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acetaminophen

General
a-seet-a-MIN-oh-fen

Tylenol

Antipyretic, non-opioid analgesic.

Pregnancy Category
Category B
acetaminophen

Action
• Inhibits the synthesis of prostaglandins that may serve as mediators of pain and fever, primarily in the CNS

• Has no significant anti-inflammatory properties or GI toxicity
acetaminophen

Dosage / Implementation
• Children ≤ 12 yr should not receive > 5 doses/24 hr without notifying physician.
• PO (Adults and Children > 12 yr): 325–650 mg q 4–6 hr or 1 g 3–4 times daily or 1300 mg q 8 hr (not to exceed 4 g or 2.5 g/24 hr in patients with hepatic/renal impairment).
• PO (Children 1–12 yr): 10–15 mg/kg/dose q 4–6 hr as needed (not to exceed 5 doses/24 hr).
• PO (Infants): 10–15 mg/kg/dose q 4–6 hr as needed (not to exceed 5 doses/24 hr).
• Rect (Adults and Children > 12 yr): 325–650 mg q 4–6 hr as needed or 1 g 3–4 times/day (not to exceed 4 g/24 hr).

Implementation:
• When combined with opioids do not exceed the maximum recommended daily dose of acetaminophen.

• PO: Administer with a full glass of water.
» May be taken with food or on an empty stomach.
acetaminophen

Contraindications
Contraindicated in:
• Previous hypersensitivity
• Products containing alcohol, aspartame, saccharin, sugar, or tartrazine (FDC yellow dye #5) should be avoided in patients who have hypersensitivity or intolerance to these compounds

Use Cautiously in:
• Hepatic disease/renal disease (lower chronic doses recommended)
• Chronic alcohol use/abuse
• Malnutrition
acetaminophen

Interactions
Drug-Drug
• Chronic high-dose acetaminophen (>2 g/day) may ↑ risk of bleeding with warfarin (PT should be monitored regularly and INR should not exceed 4)
• Hepatotoxicity is additive with other hepatotoxic substances , including alcohol
• Concurrent use of sulfinpyrazone , isoniazid , rifampin , rifabutin , phenytoin , barbiturates , and carbamazepine may ↑ the risk of acetaminophen-induced liver damage (limit self-medication); these agents will also ↓ therapeutic effects of acetaminophen
• Concurrent NSAIDs ↑ the risk of adverse renal effects (avoid chronic concurrent use)
• Propranolol↓ metabolism and may ↑ effects
• May ↓ effects of lamotrigine and zidovudine
acetaminophen

Assessment
» Assess amount, frequency, and type of drugs taken in patients self-medicating, especially with OTC drugs. Prolonged use of acetaminophen increases the risk of adverse renal effects. For short-term use, combined doses of acetaminophen and salicylates should not exceed the recommended dose of either drug given alone

• Evaluate hepatic, hematologic, and renal function periodically during prolonged, high-dose therapy
» May alter results of blood glucose monitoring. May cause falsely ↓ values when measured with glucose oxidase/peroxidase method, but probably not with hexokinase/G6PD method. May also cause falsely ↑ values with certain instruments; see manufacturer's instruction manual
» Increased serum bilirubin, LDH, AST, ALT, and prothrombin time may indicate hepatotoxicity

• If overdose occurs, acetylcysteine (Acetadote) is the antidote
acyclovir
General
Pronunciation
ay-SYE-kloe-veer

• Zovirax

Pregnancy Category
Category B (PO, IV) Category C (topical)

Ther. class.
antivirals
Pharm. class.
purine analogues
acyclovir

Action
Interferes with viral DNA synthesis

Therapeutic Effect(s):
Inhibition of viral replication, decreased viral shedding, and reduced time for healing of lesions
acyclovir

Dosage / Implementation
>>Initial Genital Herpes
• PO (Adults and Children): 200 mg q 4 hr while awake (5 times/day) for 7–10 days or 400 mg q 8 hr for 7–10 days; maximum dose in children: 80 mg/kg/day in 3–5 divided doses.

>>Acute Treatment of Herpes Zoster in Immunosuppressed Patients
• PO (Adults): 800 mg q 4 hr while awake (5 times/day) for 7–10 days. Prophylaxis—400 mg 5 times/day.
• PO (Children): 250–600 mg/m2/dose 4–5 times/day.

>> Herpes Zoster in Immunocompetent Patients
• PO (Adults and Children): 4000 mg/day in 5 divided doses for 5–7 days, maximum dose in children: 80 mg/kg/day in 5 divided doses.

>>Chickenpox
• PO (Adults and Children): 20 mg/kg (not to exceed 800 mg/dose) qid for 5 days. Start within 24 hr of rash onset.

[many more dosage protocols; consult text]

Implementation
• Acyclovir treatment should be started as soon as possible after herpes simplex symptoms appear and within 24 hr of a herpes zoster outbreak.

• PO: Acyclovir may be administered with food or on an empty stomach, with a full glass of water.
» Shake oral suspension well before administration.

IV Administration:
Maintain adequate hydration (2000–3000 mL/day), especially during first 2 hr after IV infusion, to prevent crystalluria. Observe infusion site for phlebitis. Rotate infusion site to prevent phlebitis. Acyclovir injectable should NOT be administered topically, IM, subcut, PO, or in the eye.
• Intermittent Infusion:
Reconstitute 500-mg or 1-g vial with 10 mL or 20 mL, respectively, of sterile water for injection. Do not reconstitute with bacteriostatic water with benzyl alcohol or parabens. Shake well to dissolve completely.
Diluent: Dilute in at least 100 mL of D5W, 0.9% NaCl, dextrose/saline combinations or LR.
Concentration: 7 mg/mL. Patients requiring fluid restriction: 10 mg/mL.
Rate: Administer via infusion pump over 1 hr to minimize renal tubular damage.

• Use reconstituted solution within 12 hr. Once diluted for infusion, the solution should be used within 24 hr. Refrigeration results in precipitation, which dissolves at room temperature.

• Topical: Apply to skin lesions only; do not use in the eye.
acyclovir

Contraindications
Hypersensitivity to acyclovir or valacyclovir

Use Cautiously in:
• Pre-existing serious neurologic, hepatic, pulmonary, or fluid and electrolyte abnormalities
• Renal impairment (dose alteration recommended if CCr <50 mL/min)
• Geri: Due to age related ↓ in renal function
• Obese patients (dose should be based on ideal body weight)
• Patients with hypoxia
• OB: Lactation: Safety not established
acyclovir

Interactions
Drug-Drug
• Probenecid ↑ blood levels of acyclovir
• ↑ blood levels and risk of toxicity from theophylline ; dose adjustment may be necessary
• ↓ blood levels and may ↓ effectiveness of valproic acid or hydantoins
• Concurrent use of other nephrotoxic drugs ↑ risk of adverse renal effects
• Zidovudine and IT methotrexate may ↑ risk of CNS side effects
acyclovir

Assessment
• Assess lesions before and daily during therapy

• Monitor neurologic status in patients with herpes encephalitis
Lab Test Considerations

• Monitor BUN, serum creatinine, and CCr before and during therapy. ↑ BUN and serum creatinine levels or ↓ CCr may indicate renal failure
adenosine

General
Pronunciation
a-DEN-oh-seen

• Adenocard
• Adenoscan

Pregnancy Category
Category C

Ther. class.
antiarrhythmics
adenosine

Indications
• Conversion of paroxysmal supraventricular tachycardia (PSVT) to normal sinus rhythm when vagal maneuvers are unsuccessful

• As a diagnostic agent (with noninvasive techniques) to assess myocardial perfusion defects occurring as a consequence of coronary artery disease
adenosine

Action
• Restores normal sinus rhythm by interrupting re-entrant pathways in the AV node

• Slows conduction time through the AV node

• Also produces coronary artery vasodilation
adenosine

Dosage / Implementation
• IV (Adults and Children > 50 kg): Antiarrhythmic—6 mg by rapid IV bolus; if no results, repeat 1–2 min later as 12-mg rapid bolus. This dose may be repeated (single dose not to exceed 12 mg). Diagnostic use—140 mcg/kg/min for 6 min (0.84 mg/kg total).
• IV (Children < 50 kg): Antiarrhythmic—0.05–0.1 mg/kg as a rapid bolus, may repeat in 1–2 min; if response is inadequate, may increase by 0.05–0.1 mg/kg until sinus rhythm is established or maximum dose of 0.3 mg/kg is used.

Implementation:
IV Administration:
Crystals may occur if adenosine is refrigerated. Warm to room temperature to dissolve crystals. Solution must be clear before use. Do not administer solutions that are discolored or contain particulate matter. Discard unused portions.
• Direct IV:
Diluent: Administer undiluted.
Concentration: 3 mg/mL.
Rate: Administer over 1–2 seconds via peripheral IV as proximal as possible to trunk. Slow administration may cause increased heart rate in response to vasodilation. Follow each dose with 20 mL rapid saline flush to ensure injection reaches systemic circulation.
• Intermittent Infusion:
For use in diagnostic testing.
Diluent: Administer 30-mL vial undiluted.
Concentration: 3 mg/mL.
Rate: Administer at a rate of 140 mcg/kg/min over 6 min for a total dose of 0.84 mg/kg. Thallium-201 should be injected as close to the venous access as possible at the midpoint (after 3 min) of the infusion.
adenosine

Contraindications
• Hypersensitivity
• 2nd- or 3rd-degree AV block or sick sinus syndrome, unless a functional artificial pacemaker is present

Use Cautiously in:
• Patients with a history of asthma (may induce bronchospasm)
• Unstable angina
• OB: Safety not established
adenosine

Interactions
Drug-Drug
• Carbamazepine may ↑ risk of progressive heart block
• Dipyridamole ↑ effects of adenosine (dosage reduction of adenosine recommended)
• Effects of adenosine ↑ by theophylline or caffeine (larger doses of adenosine may be required)
• Concurrent use with digoxin may ↑ risk of ventricular fibrillation
adenosine

Assessment
• Monitor heart rate frequently (every 15–30 sec) and ECG continuously during therapy. A short, transient period of 1st-, 2nd-, or 3rd-degree heart block or asystole may occur following injection; usually resolves quickly due to short duration of adenosine. After conversion to NSR, transient arrhythmias (premature ventricular contractions, atrial premature contractions, sinus tachycardia, sinus bradycardia, skipped beats, AV nodal block) may occur, but generally last a few seconds
• Monitor blood pressure during therapy
• Assess respiratory status (breath sounds, rate) following administration. Patients with history of asthma may experience bronchospasm
adenosine

Side Effects/ADRs
CNS: apprehension, dizziness, headache, head pressure, light-headedness.

EENT: blurred vision, throat tightness.
Resp: *shortness of breath*, chest pressure, hyperventilation.

CV: *facial flushing*, *transient arrhythmias*, chest pain, hypotension, palpitations.

GI: metallic taste, nausea.

Derm: burning sensation, facial flushing, sweating.

MS: neck and back pain.

Neuro: numbness, tingling.

Misc: heaviness in arms, pressure sensation in groin.
acyclovir

Side Effects/ADRs
CNS: SEIZURES, *dizziness*, *headache*, hallucinations, trembling.

GI: *diarrhea*, *nausea*, *vomiting*, elevated liver enzymes, hyperbilirubinemia, abdominal pain, anorexia.

GU: RENAL FAILURE, crystalluria, hematuria, renal pain.

Derm: STEVENS-JOHNSON SYNDROME, acne, hives, skin rashes, unusual sweating.

Endo: changes in menstrual cycle.

Hemat: THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC UREMIC SYNDROME (HIGH DOSES IN IMMUNOSUPPRESSED PATIENTS).

Local: *pain*, *phlebitis*, local irritation.

MS: joint pain.

Misc: polydipsia.
acetaminophen

Side Effects/ADRs
GI: HEPATIC FAILURE, HEPATOTOXICITY (OVERDOSE) .

GU: renal failure (high doses/chronic use).

Hemat: neutropenia, pancytopenia, leukopenia.

Derm: rash, urticaria.
albuterol

General
Pronunciation
al-BYOO-ter-ole

• Ventolin HFA and others

Pregnancy Category
Category C

Ther. class.
bronchodilators
Pharm. class.
adrenergics
albuterol

Indications
• Used as a bronchodilator to control and prevent reversible airway obstruction caused by asthma or COPD

• Inhaln: Used as a quick-relief agent for acute bronchospasm and for prevention of exercise-induced bronchospasm

• PO: Used as a long-term control agent in patients with chronic/persistent bronchospasm
albuterol

Action
• Binds to beta2-adrenergic receptors in airway smooth muscle, leading to activation of adenyl cyclase and increased levels of cAMP. Increases in cAMP activate kinases, which inhibit the phosphorylation of myosin and decrease intracellular calcium. Decreased intracellular calcium relaxes smooth muscle airways
• Relaxation of airway smooth muscle with subsequent bronchodilation
• Relatively selective for beta2 (pulmonary) receptors
>>Therapeutic Effect(s):
Bronchodilation
albuterol

Dosage / Implementation
• PO (Adults and Children >=12 yr): 2–4 mg 3–4 times daily (not to exceed 32 mg/day) or 4–8 mg of extended-release tablets twice daily.

Inhaln (Adults and Children >=4 yr): Via metered-dose inhaler—2 inhalations q 4–6 hr or 2 inhalations 15 min before exercise (90 mcg/spray); some patients may respond to 1 inhalation. NIH Guidelines for acute asthma exacerbation: Children—4–8 puffs q 20 min for 3 doses then q 1–4 hr; Adults—4–8 puffs q 20 min for up to 4 hr then q 1–4 hr prn.

Implementation:
• PO: Administer oral medication with meals to minimize gastric irritation.
» Extended-release tablets should be swallowed whole; do not break, crush, or chew.

• Inhaln: Shake inhaler well, and allow at least 1 min between inhalations of aerosol medication. Prime the inhaler before first use by releasing 4 test sprays into the air away from the face. Pedi: Use spacer for children < 8 yr of age.
» For nebulization or IPPB, the 0.5-, 0.83-, 1-, and 2-mg/mL solutions do not require dilution before administration. The 5 mg/mL (0.5%) solution must be diluted with 1–2.5 mL of 0.9% NaCl for inhalation. Diluted solutions are stable for 24 hr at room temperature or 48 hr if refrigerated.
» For nebulizer, compressed air or oxygen flow should be 6–10 L/min; a single treatment of 3 mL lasts about 10 min.
» IPPB usually lasts 5–20 min.
albuterol

Contraindications
Hypersensitivity to adrenergic amines

Use Cautiously in:
• Cardiac disease
• Hypertension
• Hyperthyroidism
• Diabetes
• Glaucoma
• Seizure disorders
• Excess inhaler use may lead to tolerance and paradoxical bronchospasm
• OB: Lactation: Pedi: Safety not established for pregnant women near term, breastfeeding women, and children <2 yr
• Geri: ↑ risk of adverse reactions; may require dose ↓
albuterol

Side Effects/ADRs
CNS: *nervousness*, *restlessness*, *tremor*, headache, insomnia (Pedi: occurs more frequently in young children than adults), hyperactivity in children.
Resp: PARADOXICAL BRONCHOSPASM (EXCESSIVE USE OF INHALERS) .
CV: *chest pain*, *palpitations*, angina, arrhythmias, hypertension.
GI: nausea, vomiting.
Endo: hyperglycemia.
F and E: hypokalemia.
Neuro: tremor.
albuterol

Interactions
Drug-Drug
• Concurrent use with other adrenergic agents will have ↑ adrenergic side effects
• Use with MAO inhibitors may lead to hypertensive crisis
• Beta blockers may negate therapeutic effect
• May ↓ serum digoxin levels
• Cardiovascular effects are potentiated in patients receiving tricyclic antidepressants
• Risk of hypokalemia ↑ concurrent use of potassium-losing diuretics
• Hypokalemia ↑ the risk of digoxin toxicity

Drug-Natural Products
Use with caffeine-containing herbs ( cola nut , guarana , tea, coffee) ↑ stimulant effect
albuterol

Assessment
• Assess lung sounds, pulse, and blood pressure before administration and during peak of medication. Note amount, color, and character of sputum produced
• Monitor pulmonary function tests before initiating therapy and periodically during therapy
• Observe for paradoxical bronchospasm (wheezing). If condition occurs, withhold medication and notify health care professional immediately

Lab Test Considerations
• May cause transient ↓ in serum potassium concentrations with nebulization or higher-than-recommended doses
allopurinol

General
Pronunciation
al-oh-PURE-i-nole

Pregnancy Category
Category C

Ther. class.
antigout agents, antihyperuricemics
Pharm. class.
xanthine oxidase inhibitors
allopurinol

Indications
• PO: Prevention of attack of gouty arthritis and nephropathy

• PO, IV: Treatment of secondary hyperuricemia, which may occur during treatment of tumors or leukemias
allopurinol

Action
Inhibits the production of uric acid by inhibiting the action of xanthine oxidase

Therapeutic Effect(s):
Lowering of serum uric acid levels
allopurinol

Dosage / Implementation
Management of Gout
• PO (Adults and Children >10 yr): Initially—100 mg/day; increase at weekly intervals based on serum uric acid (not to exceed 800 mg/day). Doses >300 mg/day should be given in divided doses; Maintenance dose—100–200 mg 2–3 times daily. Doses of <=300 mg may be given as a single daily dose.

Management of Secondary Hyperuricemia
• PO (Adults and Children >10 yr): 600–800 mg/day in 2–3 divided doses starting 1–2 days before chemotherapy or radiation.
• PO (Children 6–10 yr): 10 mg/kg/day in 2–3 divided doses (maximum 800 mg/day) or 300 mg daily in 2–3 divided doses.
• PO (Children <6 yr): 10 mg/kg/day in 2–3 divided doses (maximum 800 mg/day) or 150 mg daily in 3 divided doses.

Implementation:
PO: May be administered after milk or meals to minimize gastric irritation; give with plenty of fluid. May be crushed and given with fluid or mixed with food for patients who have difficulty swallowing.

IV Administration:
• Intermittent Infusion:
Diluent: Reconstitute each 500 mg vial with 25 mL of sterile water for injection. Solution should be clear and almost colorless with only slight opalescence. Dilute to desired concentration with 0.9% NaCl or D5W. Administer within 10 hr of reconstitution; do not refrigerate. Do not administer solutions that are discolored or contain particulate matter.
Concentration: Not > 6 mg/mL.
Rate: Infusion should be initiated 24–48 hr before start of chemotherapy known to cause tumor cell lysis. Rate of infusion depends on volume of infusate (100–300 mg doses may be infused over 30 minutes). May be administered as a single infusion or equally divided infusions at 6-, 8-, or 12-hr intervals.
allopurinol

Contraindications
Hypersensitivity

Use Cautiously in:
• Acute attacks of gout
• Renal insufficiency (dose reduction required if CCr <20 mL/min)
• Dehydration (adequate hydration necessary)
• OB: Lactation: Rarely used
• Geri: Begin at lower end of dosage range
allopurinol

Interactions
Drug-Drug
• Use with mercaptopurine and azathioprine ↑ bone marrow depressant properties—doses of these drugs should be ↓
• Use with ampicillin or amoxicillin ↑ risk of rash
• Use with oral hypoglycemic agents and warfarin ↑ effects of these drugs
• Use with thiazide diuretics or ACE inhibitors ↑ risk of hypersensitivity reactions
• Large doses of allopurinol may ↑ risk of theophylline toxicity
• May ↑ cyclosporine levels
allopurinol

Side Effects / ADRs
CV: hypotension, flushing, hypertension, bradycardia, and heart failure (reported with IV administration).

CNS: drowsiness.

GI: diarrhea, hepatitis, nausea, vomiting.

GU: renal failure, hematuria.

Derm: *rash* (discontinue drug at first sign of rash), urticaria.

Hemat: bone marrow depression.

Misc: hypersensitivity reactions.
allopurinol

Assessment
• Monitor I&Os. Decreased renal function can cause toxicity. Maintain adequate fluid intake.
» Assess patient for rash or more severe hypersensitivity reactions. D/c allopurinol immediately if rash occurs. D/c permanently if reaction severe. Titrate gradually 50 mg/day if rxn mild. If skin rash recurs, d/c permanently
>>Gout
• Prophylactic doses of colchicine or an NSAID should be administered concurrently during the first 3–6 mo of therapy because of an increased frequency of acute gout
>>Lab Test Considerations
• Serum and urine uric acid levels usually ↓ 2–3 days after initiation of oral therapy
• Monitor blood glucose in patients receiving oral hypoglycemic agents. May cause hypoglycemia
• Monitor hematologic, renal, and liver function tests before and periodically during therapy, especially during the first few months. May cause ↑ serum alkaline phosphatase, bilirubin, AST, and ALT levels. ↓ CBC and platelets may indicate bone marrow depression. ↑ BUN, serum creatinine, and CCr may indicate nephrotoxicity.
alprazolam

General
Pronunciation
al-PRAY-zoe-lam

• Xanax

Controlled Substance Schedule IV
Pregnancy Category
Category D

Ther. class.
antianxiety agents
Pharm. class.
benzodiazepines
alprazolam

Indications
• Treatment of Generalized Anxiety Disorder (GAD)
• Panic Disorder
• Management of anxiety associated with depression
>>Unlabelled Use(s):
• Management of symptoms of premenstrual syndrome (PMS)
• Insomnia, irritable bowel syndrome (IBS) and other somatic symptoms associated with anxiety
• Used as an adjunct with acute mania, acute psychosis
alprazolam

Action
• Acts at many levels in the CNS to produce anxiolytic effect

• May produce CNS depression

• Effects may be mediated by GABA, an inhibitory neurotransmitter
Therapeutic Effect(s):
Relief of anxiety
alprazolam

Dosage / Implementation
Anxiety
• PO (Adults): 0.25–0.5 mg 2–3 times daily (not >4 mg/day; begin with 0.25 mg 2–3 times daily in geriatric/debilitated patients).

Panic Attacks
• PO (Adults): 0.5 mg 3 times daily; may be increased by 1 mg or less every 3–4 days as needed (not >10 mg/day). Extended–release tablets (Xanax XR)—0.5–1 mg once daily in the morning, may be increased every 3–4 days by not more than 1 mg/day; up to 10 mg/day (usual range 3–6 mg/day).

Implementation:
» If early morning anxiety or anxiety between doses occurs, the same total daily dose should be divided into more frequent intervals.

• PO: May be administered with food if GI upset occurs. Administer greatest dose at bedtime to avoid daytime sedation.
» Tablets may be crushed and taken with food or fluids if patient has difficulty swallowing. Do not crush, break, or chew extended-release tablets
» Taper by 0.5 mg q 3 days to prevent withdrawal. Some patients may require longer tapering period (months).
» For orally disintegrating tablets: Remove tablet from bottle with dry hands just prior to taking medication. Place tablet on tongue. Tablet will dissolve with saliva; may also be taken with water. If only ½ tablet taken, discard unused portion immediately; may not remain stable.
alprazolam

Contraindications
• Hypersensitivity
• Cross-sensitivity with other benzodiazepines may exist
• Pre-existing CNS depression
• Severe uncontrolled pain
• Angle-closure glaucoma, obstructive sleep apnea, pulmonary disease
• Pregnancy and lactation. Use in pregnancy or lactation may cause CNS depression, flaccidity, feeding difficulties, and seizures in infant
• Concurrent itraconazole or ketoconazole
>>Use Cautiously in:
• Renal Impairment, Hepatic dysfunction (↓ dose required)
• Concurrent use with nefazodone, fluvoxamine, cimetidine, fluoxetine, hormonal contraceptives, propoxyphene, diltiazem, isoniazid, erythromycin, clarithromycin, grapefruit juice (↓ dose may be necessary)
• History of suicide attempt or alcohol/drug dependence, debilitated patients (↓ dose required)
• Pedi: Safety and efficacy not established. Decreased dosage and frequent monitoring required
• Geri: Elderly patients have increased sensitivity
alprazolam

Interactions
Drug-Drug
• Alcohol, antidepressants, other benzodiazepines, antihistamines, and opioid analgesics ↑ CNS depression
• Hormonal contraceptives , disulfiram , fluoxetine , isoniazid , metoprolol , propoxyphene , propranolol , valproic acid , CYP3A4 inhibitors ( erythromycin , ketoconazole , itraconazole , fluvoxamine , cimetidine , nefazodone) ↓ metabolism of alprazolam, ↑ blood levels and ↑ its actions (dose adjustments may be necessary)
• May ↓ efficacy of levodopa
• CYP3A4 inducers ( rifampin , carbamazepine , or barbiturates ) ↑ metabolism and ↓ effects of alprazolam
• Sedative effects may be ↓ by theophylline
• Cigarette smoking ↓ blood levels and effects
>>Drug-Natural Products
Kava-kava , valerian , or chamomile can ↑ CNS depression
>>Drug-Food
Concurrent ingestion of grapefruit juice ↑ blood levels
alprazolam

Side Effects/ADRs
CNS: *dizziness*, *drowsiness*, *lethargy*, confusion, hangover, headache, mental depression, paradoxical excitation.

EENT: blurred vision.

GI: constipation, diarrhea, nausea, vomiting, weight gain.

Derm: rashes.

Misc: physical dependence, psychological dependence, tolerance.
alprazolam

Assessment
• Assess degree and manifestations of anxiety and mental status (orientation, mood, behavior) prior to and periodically during therapy
• Assess patient for drowsiness, light-headedness, and dizziness. These symptoms usually disappear as therapy progresses. Dose should be reduced if these symptoms persist
• Geri: Assess CNS effects and risk of falls. Institute falls prevention strategies
• Prolonged high-dose therapy may lead to psychological or physical dependence. Risk is greater in patients taking >4 mg/day. Restrict the amount of drug available to patient. Assess regularly for continued need for treatment
>>Lab Test Considerations
• Monitor CBC and liver and renal function periodically during long-term therapy. May cause ↓ hematocrit and neutropenia
>>Toxicity and Overdose
• Flumazenil is the antidote for alprazolam toxicity or overdose. (Flumazenil may induce seizures in patients with a history of seizures disorder or who are on tricyclic antidepressants.)
amikacin

General
Pronunciation
am-i-KAY-sin

• Amikin

Pregnancy Category D

Ther. class.
anti-infectives
Pharm. class.
aminoglycosides
amikacin

Indications
IM, IV: Treatment of serious infections for which treatment with less toxic anti-infectives is contraindicated or known to be ineffective

Unlabelled Use(s):
• Part of combination treatment of Mycobacterium avium complex infections
• IT: With parenteral amikacin in the management of CNS infections
• Inhaln: By aerosol nebulization for the prevention of serious pneumonia in high-risk populations
amikacin

Action
• Inhibits protein synthesis in bacteria at the level of the 30S ribosome
• Resists the action of enzymes known to inactivate other aminoglycosides

Therapeutic Effect(s): Bactericidal action against susceptible bacteria

Spectrum: Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus, Providencia, Enterobacter, Citrobacter freundii, Serratia, Acinetobacter, Mycobacterium.\
Amikacin is also active against Staphylococci (including methicillin-resistant strains)
• Acts synergistically with beta-lactam anti-infectives against gram-negative organisms
• In the treatment of enterococcal infections, synergy with a penicillin is required
amikacin

Contraindications
Hypersensitivity to amikacin, other aminoglycosides, or bisulfites

Use Cautiously in:
• Renal or auditory impairment of any kind (dosage adjustments necessary—blood level monitoring useful in preventing ototoxicity and nephrotoxicity)
• Neuromuscular diseases such as myasthenia gravis or Parkinson's disease
• Patients with burns (may require larger, more frequent doses)
• OB: May cause fetal nephrotoxicity or deafness
• Lactation: Safety not established
• Pedi: Neonates have prolonged half-life due to renal immaturity
• Geri: Cautious use due to age-related renal impairment; may be difficult to assess vestibular and auditory function in geriatric or debilitated patients
amikacin

Side Effects / ADRs
CNS: vertigo.

EENT: *ototoxicity* (vestibular and cochlear).

GU: *nephrotoxicity*.

Neuro: enhanced neuromuscular blockade.

Resp: apnea.

Misc: hypersensitivity reactions.
amikacin

Interactions
Drug-Drug
• Inactivated by extended-spectrum penicillins when coadministered to patients with renal insufficiency
• May potentiate effects of inhalation anesthetics or neuromuscular blockers
• ↑ incidence of ototoxicity with loop diuretics
• ↑ incidence of nephrotoxicity with other nephrotoxic drugs , such as amphotericin , vancomycin , acyclovir , cisplatin , or cephalosporins
amikacin

Dosage / Implementation
• IM, IV (Adults and Children): 15 mg/kg/day divided q 8–12 hr (not to exceed 1.5 g/day). Mycobacterium avium complex infection: 7.5–15 mg/kg/day divided q 12–24 hr.
• IM, IV (Neonates): Loading dose—10 mg/kg. Maintenance dose—7.5 mg/kg q 12 hr.

Implementation:
• Keep patient well hydrated (1500–2000 mL/day) during therapy

• IV: If aminoglycosides and penicillins or cephalosporins must be administered concurrently, administer in separate sites, at least 1 hr apart.

IV Administration:
• Intermittent Infusion:
Diluent: Dilute with D5W, D10W, 0.9% NaCl, dextrose/saline combinations, or LR. Solution may be pale yellow without decreased potency. Stable for 24 hr at room temperature.
Concentration: 10 mg/mL.
Rate: Infuse over 30–60 min.
amikacin

Assessment
• Assess for infection
• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results
• Can damage CN VIII and cause vestibular dysfunction or tinnitus.
• Monitor intake and output and daily weight
• Assess for signs of superinfection (fever, upper respiratory infection, vaginal itching or discharge, increasing malaise, diarrhea)
>>Lab Test Considerations
• Monitor renal function
• May cause ↑ BUN and creatinine concentrations
>>Toxicity and Overdose
• Monitor therapeutic blood levels periodically during therapy. Timing of blood levels is important in interpreting results. Draw blood for peak levels 1 hr after IM injection and 30 min after a 30-min IV infusion is completed. Trough levels should be drawn just before next dose. Peak level range 20–30 mcg/mL; trough level <10 mcg/mL
>> Unlabeled q 24 h dosing—trough level >=1 mcg/mL
amiodarone

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
am-ee-OH-da-rone

Pregnancy Category D

Ther. class.
antiarrhythmics
(class III)
amiodarone

Indications
Life-threatening ventricular arrhythmias unresponsive to less toxic agents

Unlabelled Use(s):
• PO: Management of supraventricular tachyarrhythmias
• IV: As part of the Advanced Cardiac Life Support (ACLS) and Pediatric Advanced Life Support (PALS) guidelines for the management of ventricular fibrillation/pulseless ventricular tachycardia after cardiopulmonary resuscitation and defibrillation have failed; also for other life-threatening tachyarrhythmias
amiodarone

Action
• Prolongs action potential and refractory period

• Inhibits adrenergic stimulation

• Slows the sinus rate, increases PR and QT intervals, and decreases peripheral vascular resistance (vasodilation)
Therapeutic Effect(s):
Suppression of arrhythmias
amiodarone

Contraindications
• Patients with cardiogenic shock, Severe sinus node dysfunction, or 2nd- and 3rd-degree AV block
• Bradycardia (has caused syncope unless a pacemaker is in place)
• Hypersensitivity to amiodarone or iodine
• OB: Can cause fetal hypo- or hyperthyroidism; use alternative to breast milk
• Pedi: Safety not established; products containing benzyl alcohol should not be used in neonates
>>Use Cautiously in:
• History of CHF
• Thyroid disorders
• Corneal refractive laser surgery
• Severe pulmonary or liver disease
• Geri: Initiate therapy at the low end of the dosing range due to ↓ hepatic, renal, or cardiac function; comorbid disease; or other drug therapy
amiodarone

Side Effects / ADRs
CNS: confusional states, disorientation, hallucinations, *dizziness*, *fatigue*, *malaise*, headache, insomnia.

EENT: *corneal microdeposits*, abnormal sense of smell, dry eyes, optic neuritis, optic neuropathy, photophobia.

Resp: ADULT RESPIRATORY DISTRESS SYNDROME (ARDS), PULMONARY FIBROSIS, PULMONARY TOXICITY.

CV: CHF, WORSENING OF ARRHYTHMIAS, *bradycardia*, *hypotension*.

GI: *anorexia*, *constipation*, *nausea*, *vomiting*, abdominal pain, abnormal sense of taste, ↑ liver enzymes.

GU: ↓ libido, epididymitis.

Derm: TOXIC EPIDERMAL NECROLYSIS (RARE) , *photosensitivity*, blue discoloration.

Endo: *hypothyroidism*, hyperthyroidism.

Neuro: *ataxia*, *involuntary movement*, *paresthesia*, *peripheral neuropathy*, *poor coordination*, *tremor*.
amiodarone

Interactions
Drug-Drug
• ↑ risk of QT prolongation with fluoroquinolones , macrolides , and azole antifungals (undertake concurrent use with caution)
• ↑ levels of digoxin (↓ dose of digoxin by 50%)
• ↑ levels of class I antiarrhythmics ( quinidine , mexiletine , lidocaine , or flecainide —↓ doses of other drugs by 30–50%)
• ↑ levels of cyclosporine , dextromethorphan , methotrexate , phenytoin , carvedilol , and theophylline
• Phenytoin↓ amiodarone levels
• ↑ activity of warfarin (↓ dose of warfarin by 33–50%)
• ↑ risk of bradyarrhythmias, sinus arrest, or AV heart block with beta blockers or calcium channel blockers
• Cholestyramine may ↓ amiodarone levels
• Cimetidine and ritonavir ↑ amiodarone levels
• Risk of myocardial depression is ↑ by volatile anesthetics
• ↑ risk of myopathy with lovastatin and simvastatin (do not exceed 40 mg/day of regular-release lovastatin, 20 mg/day of extended-release lovastatin, or 20 mg/day of simvastatin)
Drug-Natural Products-Food
St. John's wort may ↓ levels and effectiveness. Grapefruit juice ↑ levels and risk of toxicity
amiodarone

Dosage / Implementation
>>Ventricular Arrhythmias
• PO (Adults): 800–1600 mg/day in 1–2 doses for 1–3 wk, then 600–800 mg/day in 1–2 doses for 1 mo, then 400 mg/day maintenance dose.
• PO (Children): 10 mg/kg/day (800 mg/1.72 m2/day) for 10 days or until response or adverse reaction occurs, then 5 mg/kg/day (400 mg/1.72 m2/day) for several weeks, then ↓ to 2.5 mg/kg/day (200 mg/1.72 m2/day) or lowest effective maintenance dose.
• IV (Adults): 150 mg over 10 min, followed by 360 mg over the next 6 hr and then 540 mg over the next 18 hr. Continue infusion at 0.5 mg/min until oral therapy is initiated. If arrhythmia recurs, a small loading infusion of 150 mg over 10 min should be given; in addition, the rate of the maintenance infusion may be ↑. Conversion to initial oral therapy—If duration of IV infusion was <1 wk, oral dose should be 800–1600 mg/day; if IV infusion was 1–3 wk, oral dose should be 600–800 mg/day; if IV infusion was >3 wk, oral dose should be 400 mg/day. ACLS guidelines for pulseless VFib/VTach—300 mg IV push, may repeat once after 3–5 min with 150 mg IV push (maximum cumulative dose 2.2 g/24 hr; unlabeled).

>>Supraventricular Tachycardia
• PO (Adults): 600–800 mg/day for 1 wk or until desired response occurs or side effects develop, then ↓ to 400 mg/day for 3 wk, then maintenance dose of 200–400 mg/day.

Implementation:
• High Alert Med!

• Hypokalemia and hypomagnesemia may decrease effectiveness or cause additional arrhythmias; correct before therapy.

» Monitor closely when converting from IV to oral therapy, especially in geriatric patients.

• PO: May be administered with meals and in divided doses if GI intolerance occurs or if daily dose exceeds 1000 mg.

IV Administration:
Administer via volumetric pump; drop size may be reduced, causing altered dosing with drop counter infusion sets. Administer through an in-line filter. Infusions exceeding 2 hr must be administered in glass or polyolefin bottles to prevent adsorption. However, polyvinyl chloride (PVC) tubing must be used during administration because concentrations and infusion rate recommendations have been based on PVC tubing.
• Direct IV:
Diluent: Administer undiluted. May also be diluted in 20–30 mL of D5W or 0.9% NaCl.
Concentration: 50 mg/mL.
Rate: administer IV push.
• Intermittent Infusion:
Diluent: Dilute 150 mg of amiodarone in 100 mL of D5W. Infusion stable for 2 hr in PVC bag, or use pre-mixed bags.
Concentration: 1.5 mg/mL.
Rate: infuse over 10 min. Do not administer IV push.
• Continuous Infusion:
Diluent: dilute 900 mg (18 mL) of amiodarone in 500 mL of D5W. Infusion stable for 24 hr in glass or polyolefin bottle.
Concentration: 1.8 mg/mL. Concentration may range from 1–6 mg/mL (concentrations >2 mg/mL must be administered via central venous catheter).
Rate: infuse at a rate of 1 mg/min for the first 6 hr, then decrease infusion rate to 0.5 mg/min and continue until oral therapy initiated.
amiodarone

Assessment
• PR prolongation, slight QRS widening, T-wave amplitude reduction with T-wave widening and bifurcation, and U waves may occur. QT prolongation may be associated with worsening of arrhythmias and should be monitored. Patients receiving IV therapy may require slowing rate, discontinuing infusion, or inserting a temporary pacemaker
• Assess pacing and defibrillation threshold in patients with pacemakers and implanted defibrillators at beginning and periodically during therapy
• Pulmonary toxicity (rales/crackles, decreased breath sounds, pleuritic friction rub, fatigue, dyspnea, cough, wheezing, pleuritic pain, fever, hemoptysis, hypoxia) possible. cont. CXR recommended. Assess for signs and symptoms of ARDS throughout therapy.
• Hypotension usually occurs during first several hours of therapy and is related to rate of infusion. If hypotension occurs, slow rate
• Assess for neurotoxicity, which may persist.
• Perform ophthalmic exams regularly and whenever visual changes (photophobia, halos around lights, decreased acuity) occur. May cause permanent loss of vision
• Assess for signs of thyroid dysfunction, especially during initial therapy.
>>Lab Test Considerations
• Monitor liver and thyroid functions before and every 6 months during therapy . Drug effects persist long after discontinuation. May cause asymptomatic ↑ in ANA titer concentrations
amitryptaline

General
a-mee-TRIP-ti-leen

Pregnancy Category C

Ther. class.
antidepressants
Pharm. class.
tricyclic antidepressants
amitryptaline

Indications
Depression

Unlabelled Use(s):
• Anxiety, insomnia, treatment-resistant depression
• Chronic pain syndromes (i.e., fibromyalgia, neuropathic pain/chronic pain, headache, low back pain)
amitryptaline

Action
• Potentiates the effect of serotonin and norepinephrine in the CNS

• Has significant anticholinergic properties
amitryptaline

Contraindications
• Angle-closure glaucoma
• Known history of QTc prolongation, recent MI, heart failure
>>Use Cautiously in:
• May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents
• Patients with pre-existing cardiovascular disease
• Prostatic hyperplasia (increased risk of urinary retention)
• History of seizures (threshold may be ↓)
• OB: Use only if clearly needed and maternal benefits outweigh risk to fetusLactation: May cause sedation in infant
• Pedi: Safety not established in children <12 yr
• Geri: Appears on Beers list. ↑ risk of adverse reactions including falls secondary to sedative and anticholinergic effects
amitryptaline

Side Effects / ADRs
CNS: SUICIDAL THOUGHTS, *lethargy*, *sedation*.

EENT: *blurred vision*, *dry eyes*, *dry mouth*.

CV: ARRHYTHMIAS, *hypotension*, ECG changes.

GI: constipation, hepatitis, paralytic ileus, increased appetite, weight gain.

GU: urinary retention, ↓ libido.

Derm: photosensitivity.

Endo: changes in blood glucose, gynecomastia.

Hemat: blood dyscrasias.
amitryptaline

Interactions
Drug-Drug
• Metabolized in the liver by the cytochrome P450 2D6 enzyme increase effect of phenothiazines, carbamazepine, class 1C antiarrhythmics. Use of other drugs that inhibit the activity of the enzyme, including cimetidine , quinidine , amiodarone , and ritonavir , may result in ↑ effects of amitriptyline
• May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (d/c 2wks before)
• Use with SSRIs may result in ↑ toxicity (d/c fluoxetine 5 wks before starting amitriptyline)
• Use with clonidine may result in hypertensive crisis
• Use with levodopa may result in delayed or ↓ absorption of levodopa or hypertension
• Effects may be ↓ by rifamycins
• Use with moxifloxacin ↑ risk of adverse cardiovascular reactions
• ↑ CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioids, and sedative/hypnotics
• Barbiturates may alter blood levels and effects
• Adrenergic and anticholinergic side effects may be ↑ with anticholinergic drugs
• Phenothiazines or oral contraceptives ↑ levels and may cause toxicity
• Nicotine may ↑ metabolism and alter effects
>>Drug-Natural Products
• St. John's wort may decrease effects. Use of kava-kava, valerian, or chamomile can increase CNS depression. Increased anticholinergic effects with jimson weed and scopolia
amitryptaline

Dosage / Implementation
• PO (Adults): 75 mg/day in divided doses; may be increased up to 150 mg/day or 50–100 mg at bedtime, may increase by 25–50 mg up to 150 mg (in hospitalized patients, may initiate with 100 mg/day, increasing total daily dose up to 300 mg).
• PO (Geriatric Patients and Adolescents): 10 mg tid and 20 mg at bedtime or 25 mg at bedtime initially, slowly increased to 100 mg/day as a single bedtime dose or divided doses.

Implementation:
• Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months. May give entire dose at bedtime. Sedative effect may be apparent before antidepressant effect is noted. May require tapering to avoid withdrawal effects.

• PO: Administer medication with or immediately after a meal to minimize gastric upset. Tablet may be crushed and given with food or fluids.
amitryptaline

Assessment
• Obtain weight and BMI initially and periodically during treatment. Assess fasting glucose and cholesterol levels in overweight/obese individuals
• Monitor blood pressure and pulse before and during initial therapy.
Depression
• Monitor mental status (orientation, mood behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults <=24 yrs. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and PRN per provider thereafter
Pain
• May require several weeks for effects to be seen. Assess for sexual dysfunction.
• Geriatric patients started on amitriptyline may be at an increased risk for falls
• Assess for anticholinergic effects (weakness and sedation)
Lab Test Considerations
• Assess leukocyte and differential blood counts, liver function, and serum glucose before and periodically during therapy. May cause an ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓
amlodipine

General
am-LOE-di-peen

Pregnancy Category C

Ther. class.
antihypertensives
Pharm. class.
calcium channel blockers
amlodipine

Indications
Alone or with other agents in the management of hypertension, angina pectoris, and vasospastic (Prinzmetal's) angina
amlodipine

Action
Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction

Therapeutic Effect(s):
• Systemic vasodilation resulting in decreased blood pressure

• Coronary vasodilation resulting in decreased frequency and severity of attacks of angina
amlodipine

Contraindications
• Hypersensitivity
• Systolic blood pressure <90 mm Hg

Use Cautiously in:
• Severe hepatic impairment (dosage reduction recommended)
• Aortic stenosis
• History of CHF
• OB: Lactation: Pedi: Safety not established
• Geri: Dose reduction recommended; ↑ risk of hypotension
amlodipine

Side Effects / ADRs
CNS: *headache*, dizziness, fatigue.

CV: *peripheral edema*, angina, bradycardia, hypotension, palpitations.

GI: gingival hyperplasia, nausea.

Derm: flushing.
amlodipine

Interactions
Drug-Drug
• Additive hypotension may occur when used concurrently with fentanyl , other antihypertensives , nitrates , acute ingestion of alcohol , or quinidine
• Antihypertensive effects may be ↓ by concurrent use of nonsteroidal anti-inflammatory agents
• May ↑ risk of neurotoxicity with lithium

Drug-Food
Grapefruit juice ↑ serum levels and effect
amlodipine

Dosage / Implementation
• PO (Adults): 5–10 mg once daily; antihypertensive in fragile or small patients or patients already receiving other antihypertensives—initiate at 2.5 mg/day, ↑ as required/tolerated (up to 10 mg/day) as an antihypertensive therapy with 2.5 mg/day in patients with hepatic insufficiency.
• PO (Geriatric Patients): Antihypertensive—Initiate therapy at 2.5 mg/day, ↑ as required/tolerated (up to 10 mg/day); antianginal—initiate therapy at 5 mg/day, ↑ as required/tolerated (up to 10 mg/day).

Hepatic Impairment
• PO (Adults): Antihypertensive—Initiate therapy at 2.5 mg/day, ↑ as required/tolerated (up to 10 mg/day); antianginal—initiate therapy at 5 mg/day, ↑ as required/tolerated (up to 10 mg/day).

PO: May be administered without regard to meals.
amlodipine

Assessment
• Monitor blood pressure and pulse before therapy, during dose titration, and periodically during therapy. Monitor ECG periodically during prolonged therapy
» Monitor intake and output ratios and daily weight. Assess for signs of CHF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention)

Angina
• Assess location, duration, intensity, and precipitating factors of patient's anginal pain

Lab Test Considerations
• Total serum calcium concentrations are not affected by calcium channel blockers
amoxicillin

General
Pronunciation
a-mox-i-SILL-in

Pregnancy Category B

Ther. class.
anti-infectives
antiulcer agents
Pharm. class.
aminopenicillins
amoxicillin

Indications
• Treatment of:
» Skin and skin structure infections.
» Otitis media.
» Sinusitis.
» Respiratory infections.
» Genitourinary infections.
• Endocarditis prophylaxis.
• Postexposure inhalational anthrax prophylaxis.
• Management of ulcer disease due to Helicobacter pylori.

Unlabelled Use:
Lyme disease in children < 8 yr.
amoxicillin

Action
Binds to bacterial cell wall, causing cell death.

Therapeutic Effect(s):
Bactericidal action; spectrum is broader than penicillins

Spectrum: Streptococci, Pneumococci, Enterococci, Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Neisseria meningitidis, N. gonorrhoeae, Shigella, Chlamydia trachomatis, Salmonella, Borrelia burgdorferi, H. pylori
amoxicillin

Contraindications
• Hypersensitivity to penicillins (cross-sensitivity exists to cephalosporins and other beta-lactams)
• Tablets for oral suspension (DisperMox) contain aspartame; avoid in patients with phenylketonuria

Use Cautiously in:
• Severe renal insufficiency (↓ dose if CCr <30 mL/min)
• Infectious mononucleosis, acute lymphocytic leukemia, or cytomegalovirus infection (↑ risk of rash)

• OB: Lactation: Has been used safely
amoxicillin

Side Effects / ADRs
CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, *diarrhea*, nausea, vomiting, ↑ liver enzymes.

Derm: *rashes*, urticaria.

Hemat: blood dyscrasias.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS , SERUM SICKNESS, superinfection.
amoxicillin

Interactions
Drug-Drug

• Probenecid↓ renal excretion and ↑ blood levels of amoxicillin—therapy may be combined for this purpose

• May ↑ effect of warfarin

• May ↓ effectiveness of oral contraceptives

• Allopurinol may ↑ frequency of rash
amoxicillin

Dosage / Implementation
Most Infections
• PO (Adults): 250–500 mg q 8 hr or 500–875 mg q 12 hr (not to exceed 2–3 g/day).

Implementation:
PO: Administer around the clock. May be given without regard to meals or with meals to decrease GI side effects. Capsule contents may be emptied and swallowed with liquids. Extended-release tablets should be swallowed whole; do not crush, break, or chew. Chewable tablets should be crushed or chewed before swallowing with liquids

» Shake oral suspension before administering. Suspension may be given straight or mixed in formula, milk, fruit juice, water, or ginger ale. Administer immediately after mixing. Discard refrigerated reconstituted suspension after 10 days

» Mix each tablet for oral suspension (DisperMox) in 2 tsp of water. Patient should drink entire mixture, rinse container with a small amount of water and drink to make sure entire dose is taken. Do not chew or swallow tablet. Tablets will not dissolve in mouth. Use only water to dissolve tablets, other liquids are not recommended. Store tablets at room temperature.
amoxicillin

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy
• Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response
• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing).
• Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results
• Diarrhea, abdominal cramping, fever, and bloody stools should be reported promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
>>Lab Test Considerations
• May cause ↑ serum alkaline phosphatase, LDH, AST, and ALT concentrations
• May cause false-positive direct Coombs' test result
amphotericin B

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

amphotericin b deoxycholate
am-foe-TER-i-sin

amphotericin B cholesterol sulfate
amphotericin b lipid complex
amphotericin b liposome

Pregnancy Category B

Ther. class.
antifungals
amphotericin B

Indications
• IV: Treatment of progressive, potentially fatal fungal infections. The cholesteryl sulfate, lipid complex, and liposome formulations should be considered for patients who are intolerant (e.g. renal dysfunction) or refractory to amphotericin B dexycholate

• Amphotericin B liposome: Management of suspected fungal infections in febrile neutropenic patients

» Treatment of visceral leishmaniasis

» Treatment of cryptococcal meningitis in HIV patients
amphotericin B

Action
• Binds to fungal cell membrane, allowing leakage of cellular contents
• Toxicity (especially acute infusion reactions and nephrotoxicity) is less with lipid formulations
>>Therapeutic Effect(s):
Can be fungistatic or fungicidal (depends on concentration achieved and susceptibility of organism)

Spectrum: Aspergillosis, Blastomycosis, Candidiasis, Coccidioidomycosis, Cryptococcosis, Histoplasmosis, Leishmaniasis (liposomal formulation only), Mucormycosis
amphotericin B

Contraindications
• Hypersensitivity

• Lactation: Potential for distribution into breast milk and toxicity in infant; discontinue nursing
Use Cautiously in:

• Renal impairment or electrolyte abnormalities

• Patients receiving concurrent leukocyte transfusions (↑ risk of pulmonary toxicity)

• OB: Has been used safely
amphotericin B

Side Effects / ADRs
CNS: anxiety, confusion, headache, insomnia.

Resp: dyspnea, hypoxia, wheezing.

CV: *chest pain*, *hypotension*, tachycardia, edema, hypertension.

GI: *diarrhea*, *hyperbilirubinemia*, ↑ liver enzymes, *nausea*, *vomiting*, abdominal pain.

GU: *nephrotoxicity*, hematuria.

F and E: hyperglycemia, hypocalcemia , hypokalemia, hypomagnesemia.

Hemat: anemia, leukopenia, thrombocytopenia.

Derm: pruritis, rashes.

Local: phlebitis.

MS: arthralgia, myalgia.

Misc: HYPERSENSITIVITY REACTIONS, chills, fever, acute infusion reactions.
amphotericin B

Interactions
Drug-Drug
• ↑ risk of nephrotoxicity, bronchospasm, and hypotension with antineoplastics
• Concurrent use with corticosteroids ↑ risk of hypokalemia
• Concurrent use with zidovudine may ↑ the risk of myelotoxicity and nephrotoxicity
• Concurrent use with flucytosine ↑ antifungal activity but may ↑ the risk of toxicity from flucytosine
• Combined use with azole antifungals may induce fungal resistance
• ↑ risk of nephrotoxicity with other nephrotoxic agents such as aminoglycosides , cyclosporine , or tacrolimus
• Hypokalemia from amphotericin ↑ the risk of digoxin toxicity
• Hypokalemia may enhance the curariform effects of neuromuscular blocking agents
amphotericin B

Dosage / Implementation
>>Amphotericin Deoxycholate
• IV (Adults): Give test dose of 1 mg. If test dose tolerated, initiate therapy with 0.25 mg/kg/day (doses up to 1.5 mg/kg/day may be used, depending on type of infection) (alternate-day dosing may also be used); Bladder irrigation—Instill 50 mcg/mL solution into bladder daily for 5–10 days.
>>Amphotericin B Cholesteryl Sulfate (Amphotec)
• IV (Adults and Children): 3–4 mg/kg q 24 hr (no test dose needed).
>>Amphotericin B Lipid Complex (Abelcet)
• IV (Adults and Children): 2.5–5 mg/kg q 24 hr (no test dose needed).
>>Amphotericin B Liposome (AmBisome)
• IV (Adults and Children): Empiric therapy—3 mg/kg q 24 hr; Documented infections—3–5 mg/kg q 24 hr; Visceral leishmaniasis (immunocompetent patients)—3 mg/kg q 24 hr on days 1–5, then 3 mg/kg q 24 hr on days 14 and 21; Visceral leishmaniasis (immunosuppressed patients)—4 mg/kg q 24 hr on days 1–5, then 4 mg/kg q 24 hr on days 10, 17, 24, 31, and 38; Cryptococcal meningitis in HIV patients—6 mg/kg q 24 hr.

Implementation:
Do not confuse amphotericin B cholesteryl sulfate (Amphotec) with amphotericin deoxycholate, amphotericin B lipid complex (Abelcet), or amphotericin B liposome (AmBisome); they are not interchangeable

» This drug should be administered IV only to hospitalized patients or those under close supervision. Diagnosis should be confirmed before administration.

Amphotericin B Deoxycholate
IV Administration:
Test dose: Reconstitute 50-mg vial with 10 mL of sterile water for injection to achieve a concentration of 5 mg/mL. Reconstituted vial stable for 24 hr at room temperature or 1 wk if refrigerated.
Diluent: Further dilute with 500 mL of D5W. May be diluted in 250 mL of D5W if being administered via a central venous catheter. Protect infusion from light. Infusion stable for 24 hr at room temperature or 2 days if refrigerated. To obtain test dose, withdraw 1 mg (10 mL) from 500 mL infusion and further dilute with D5W to a total volume of 20 mL.
Concentration: 0.05 mg/mL.
Rate: Infuse over 10–30 min to determine patient tolerance. Pedi: Infuse over 30–60 min.
• Intermittent Infusion:
Diluent: Reconstitute and dilute 50-mg vial as per the directions above.
Concentration: Final concentration of infusion should not exceed 0.1 mg/mL for peripheral infusion or 0.25 mg/mL for central line administration.
Rate: Infuse slowly over 4–6 hr.

Amphotericin B Cholesteryl Sulfate
IV Administration:
Diluent: Reconstitute 50-mg vial with 10 mL and 100-mg vial with 20 mL of sterile water for injection to achieve a concentration of 5 mg/mL. Reconstituted vials are stable for 24 hr if refrigerated. Further dilute with D5W to achieve concentration below. Do not use other diluents. Infusion stable for 24 hr if refrigerated. Protect from light. To obtain TEST DOSE, withdraw 10 mL from final preparation.
Concentration: Final concentration of infusion should be approximately 0.6 mg/mL (range 0.16–0.83 mg/mL).
Rate: Infuse over 15–30 min.
• Intermittent Infusion:
Diluent: Prepare infusion according to directions above.
Concentration: Final concentration of infusion should be approximately 0.6 mg/mL (range 0.16–0.83 mg/mL).
Rate: Infuse at a rate of 1 mg/kg/hr. If patient tolerates infusion without adverse reactions, infusion time may be shortened to a minimum of 2 hr. If reactions occur or patient cannot tolerate volume, infusion time may be extended. Rapid infusions may cause hypotension, hypokalemia, arrhythmias, and shock.

Amphotericin B Lipid Complex
IV Administration:
• Intermittent Infusion:
Diluent: Shake vial gently until yellow sediment at bottom has dissolved. Withdraw dose from required number of vials with 18-gauge needle. Replace needle from syringe filled with amphotericin B lipid complex with 5-micron filter needle. Each filter needle may be used to filter the contents of no more than 4 vials. Insert filter needle of syringe into IV bag of D5W and empty contents of syringe into bag. Protect from light. Infusion is stable for 6 hr at room temperature or 48 hr if refrigerated.
Concentration: Final concentration of infusion should be 1 mg/mL; a concentration of 2 mg/mL can be used for pediatric patients or patients who cannot tolerate large volumes of fluid.
Rate: Do not use an in-line filter. Infuse at a rate of 2.5 mg/kg/hr via infusion pump. If infusion exceeds 2 hr, mix contents by shaking infusion bag every 2 hr. If administering through an existing line, flush line with D5W before infusion or use a separate line.

Amphotericin B Liposome

IV Adminstration:
• Intermittent Infusion:
Diluent: Reconstitute each 50–mg vial with 12 mL of sterile water for injection to achieve concentration of 4 mg/mL. Immediately shake vial vigorously for at least 30 seconds until all particulate matter is completely dispersed. Reconstituted vials are stable for 24 hr if refrigerated. Withdraw appropriate volume for dilution into a syringe. Attach the 5-micron filter to the syringe and inject syringe contents into an appropriate volume of D5W. Infusion should be administered within 6 hr of dilution.
Concentration: Final concentration of infusion should be 1–2 mg/mL; a lower concentration (0.2–0.5 mg/mL) may be used for infants and small children.
Rate: Infuse over 2 hr. Infusion time may be shortened to 1 hr if patient tolerates infusion without any adverse reactions. If discomfort occurs during infusion, duration of infusion may be increased. May be administered through an in-line filter with pore diameter of at least 1 micron. If administering through an existing line, flush line with D5W before infusion or use a separate line.
amphotericin B

Assessment
• Monitor patient closely during test dose and the first 1–2 hr of each dose for fever, chills, headache, anorexia, nausea, or vomiting. Premedicating with antipyretics, corticosteroids, antihistamines, meperidine, and antiemetics may decrease these reactions. Febrile reaction usually subsides within 4 hr after the infusion is completed
• Assess injection site frequently for thrombophlebitis or leakage. Drug is very irritating to tissues
• Monitor vital signs every 15 min during test dose and every 30 min for 2–4 hr after administration Meperidine and dantrolene have been used to prevent and treat rigors. Assess respiratory status (lung sounds, dyspnea) daily. If respiratory distress occurs, discontinue infusion immediately; anaphylaxis may occur.
• Adequate hydration (2000–3000 mL/day) and maintaining sodium balance may minimize nephrotoxicity
>>Lab Test Considerations
• Monitor CBC, BUN and serum creatinine, and potassium and magnesium levels daily. If BUN and serum creatinine ↑ significantly, may need to discontinue or consider switching to cholesteryl sulfate, lipid complex, or liposomal formulation.
ampicillin

General
Pronunciation
am-pi-SIL-in

Pregnancy Category B

Ther. class.
anti-infectives
Pharm. class.
aminopenicillins
ampicillin

Indications
• Treatment of the following infections
» Skin and skin structure infections
» Soft-tissue infections
» Otitis media
» Sinusitis
» Respiratory infections
» Genitourinary infections
» Meningitis
» Septicemia
• Endocarditis prophylaxis

Unlabelled Use(s):
Prevention of infection in certain high-risk patients undergoing cesarean section
ampicillin

Action / Spectrum
Binds to bacterial cell wall, resulting in cell death.

Spectrum:
Broader than penicillin. Active against:
» Streptococci
» nonpenicillinase-producing staphylococci
» Listeria
» Pneumococci
» Enterococci
» Haemophilus influenzae
» Escherichia coli
» Enterobacter
» Klebsiella
» Proteus mirabilis
» Neisseria meningitidis
» N. gonorrhoeae
» Shigella
» Salmonella
ampicillin

Contraindications
Hypersensitivity to penicillins

Use Cautiously in:
• Severe renal insufficiency (dose ↓ required if CCr <10 mL/min)
• Infectious mononucleosis, acute lymphocytic leukemia or cytomegalovirus infection (↑ incidence of rash)
• Patients allergic to cephalosporins
• OB: Has been used during pregnancy
• Lactation: Distributed into breast milk. Can cause rash, diarrhea, and sensitization in the infant
ampicillin

Side Effects / ADRs
CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, *diarrhea*, nausea, vomiting.

Derm: *rashes*, urticaria.

Hemat: blood dyscrasias.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS AND SERUM SICKNESS , superinfection.
ampicillin

Interactions
Drug-Drug

• Probenecid↓ renal excretion and ↑ blood levels of ampicillin—therapy may be combined for this purpose

• Large doses may ↑ the risk of bleeding with warfarin

• ↑ risk of with concurrent allopurinol therapy

• May ↓ the effectiveness of oral hormonal contraceptives
ampicillin

Dosage / Implementation
Respiratory and Soft-Tissue Infections:
• PO (Adults and Children B20 kg): 250–500 mg q 6 hr.

Bacterial Meningitis Caused by H. influenzae, Streptococcus pneumoniae , Group B streptococcus or N. meningitidis or Septicemia:
• IM, IV (Adults): 500 mg to 3 g q 6 hr (not to exceed 14 g/day).

Implementation:
• Do not confuse with omnipen with imipenem.

• Reserve IM or IV route for moderately severe or severe infections or patients unable to take oral medication. Change to PO as soon as possible.

• PO: Administer around the clock on an empty stomach at least 1 hr before or 2 hr after meals with a full glass of water. Capsules may be opened and mixed with water. Reconstituted oral suspensions retain potency for 7 days at room temperature and 14 days if refrigerated. Combination with probenecid should be used immediately after reconstitution.

• IM: Reconstitute for IM or IV use by adding sterile water for injection 0.9–1.2 mL to the 125-mg vial, 0.9–1.9 mL to the 250-mg vial, 1.2–1.8 mL to the 500-mg vial, 2.4–7.4 mL to the 1-g vial, and 6.8 mL to the 2-g vial.

IV Administration:
• Direct IV:
Diluent: Sterile water for injection. Concentration: Add 5 mL of sterile water for injection to each 125-, 250-, or 500-mg vial or at least 7.4–10 mL of diluent to each 1- or 2-g vial. Solution should be used within 1 hr of reconstitution.
Rate: Doses of 125–500 mg may be given over 3–5 min (not to exceed 100 mg/min). Rapid administration may cause seizures.
• Intermittent Infusion:
Diluent: Reconstitute vials as per the directions above. Further dilute in 50 mL or more of 0.9% NaCl, D5W, D5/0.45% NaCl, or LR. Administer within 4 hr (more stable in NaCl).
Concentration: Final concentration of infusion should not exceed 30 mg/mL.
Rate: Infuse over 10–15 min.
ampicillin

Assessment
• Determine previous use/reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response
• Obtain specimens for culture and sensitivity before therapy. First dose may be given before receiving results
• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction
• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
• Assess skin for "ampicillin rash," a nonallergic, dull red, macular or maculopapular, mildly pruritic rash

Lab Test Considerations
• May cause ↑ AST and ALT
» May cause transient ↓ estradiol, total conjugated estriol, estriol-glucuronide, or conjugated estrone in pregnant women
» May cause a false-positive direct Coombs' test result
» May cause a false-positive urinary glucose
aprepitant

General
Pronunciation
a-PREP-i-tant

Trade Name(s)
• Emend

Pregnancy Category
Category B

Ther. class.
antiemetics
Pharm. class.
neurokinin antagonists
aprepitant

Indications
• Prevention of acute and delayed nausea and vomiting caused by initial/repeat treatment with highly emetogenic chemotherapy (with other antiemetics)

• Prevention of postoperative nausea and vomiting
aprepitant

Action
Acts as a selective antagonist at substance P/neurokinin 1 (NK1) receptors in the brain

Therapeutic Effect(s):
• Decreased nausea and vomiting associated with chemotherapy

• Augments the antiemetic effects of dexamethasone and 5-HT3 antagonists (ondansetron)
aprepitant

Contraindications
• Hypersensitivity

• Concurrent use with pimozide (risk of life-threatening adverse cardiovascular reactions)

• Lactation: May cause unwanted effects in nursing infants
Use Cautiously in:

• Concurrent use with any agents metabolized by CYP3A4 (see Drug-Drug Interactions)

• OB: Use only if clearly needed

• Pedi: Safety not established
aprepitant

Side Effects / ADRs
CV: dizziness, fatigue, weakness.

GI: diarrhea.

Misc: hiccups.
aprepitant

Interactions
Drug-Drug
• Aprepitant inhibits, induces, and is metabolized by the CYP3A4 enzyme system; it also induces the CYP2C9 system. Concurrent use with other medications that are metabolized by CYP3A4 may result in increased toxicity from these agents including docetaxel , paclitaxel , etoposide , irinotecan , ifosfamide , imatinib , vinorelbine , vinblastine , vincristine , midazolam , triazolam , and alprazolam ; concurrent use should be undertaken with caution
• Concurrent use with drugs that significantly inhibit the CYP3A4 enzyme system including ( ketoconazole , itraconazole , nefazodone , clarithromycin , ritonavir , nelfinavir , and diltiazem ) may ↑ blood levels and effects of aprepitant
• Concurrent use with drugs that induce the CYP3A4 enzyme system including rifampin , carbamazepine , and phenytoin may ↓ blood levels and effects of aprepitant
• ↑ blood levels and effects of dexamethasone (regimen reflects a 50% dose reduction); a similar effect occurs with methylprednisolone (↓ IV dose by 25%, ↓ PO dose by 50% when used concurrently)
• May ↓ the effects of warfarin (careful monitoring for 2 wk recommended), oral contraceptives (use alternate method), tolbutamide , and phenytoin
aprepitant

Dosage / Implementation
• PO (Adults): Chemotherapy—125 mg 1 hr prior to chemotherapy, then 80 mg once daily for 2 days (with dexamethasone 12 mg PO 30 min prior to chemotherapy, then 8 mg once daily for 3 days and ondansetron 32 mg IV 30 min prior to chemotherapy); Postoperative—40 mg given within 3 hr prior to induction of anesthesia.

Implementation:
• For chemotherapy, aprepitant is given as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist.

• PO: Administer daily for 3 days. Day 1—administer 125 mg 1 hr prior to chemotherapy. Days 2 and 3—administer 80 mg once in the morning. May be administered without regard to food.
aprepitant

Assessment
• Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following administration

• Monitor hydration, nutritional status, and intake and output. Patients with severe nausea and vomiting may require IV fluids in addition to antiemetics

Lab Test Considerations
• Monitor clotting status closely during the 2 wk period, especially at 7–10 days, following aprepitant therapy in patients on chronic warfarin therapy

» May cause mild, transient ↑ in alkaline phosphatase, AST, ALT, and BUN

» May cause proteinuria, erythrocyturia, leukocyturia, hyperglycemia, hyponatremia, and ↑ leukocytes

» May cause ↓ hemoglobin and WBC
aripiprazole

General
Pronunciation
a-ri-PIP-ra-zole

Trade Name(s)
• Abilify
Genetic Implications

Pregnancy Category
Category C

Ther. class.
antipsychotics
mood stabilizers
Pharm. class.
dihydrocarbostyril
aripiprazole

Indications
• Schizophrenia

• Acute and maintenance therapy of manic and mixed episodes associated with bipolar disorder (as monotherapy or with lithium or valproate)

• Adjunctive treatment of depression in adults

• Agitation associated with schizophrenia or bipolar disorder

• Irritability associated with autistic disorder in children
aripiprazole

Action
• Psychotropic activity may be due to agonist activity at dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at the 5-HT2A receptor

• Also has alpha1 adrenergic blocking activity
Therapeutic Effect(s):

• Decreased manifestations of schizophrenia

• Decreased mania in bipolar patients

• Decreased symptoms of depression

• Decreased agitation associated with schizophrenia or bipolar disorder

• Decreased emotional and behavioral symptoms of irritability
aripiprazole

Contraindications
• Hypersensitivity
• Lactation: Presumed to be excreted in breast milk; discontinue drug or bottle feed

Use Cautiously in:
• Known cardiovascular or cerebrovascular disease
• Conditions which cause hypotension (dehydration, treatment with antihypertensives or diuretics)
• Diabetes (may ↑ risk of hyperglycemia)
• Seizure disorders
• Patients at risk for aspiration pneumonia
• Concurrent ketoconazole or other potential CYP3A4 inhibitors (↓ aripiprazole dose by 50%)
• Concurrent quinidine, fluoxetine, paroxetine, or other potential CYP2D6 inhibitors
• Concurrent carbamazepine or other potential CYP3A4 inducers
• OB: Use only if benefit outweighs risk to fetus
• Pedi: May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children, adolescents, and young adults taking antidepressants (safe use in children/adolescents not established)
• Geri: ↑ risk of mortality in elderly patients treated for dementia-related psychosis
aripiprazole

Side Effects / ADRs
CNS: SUICIDAL THOUGHTS, *drowsiness*, *extrapyramidal reactions*, akathisia, confusion, depression, fatigue, hostility, insomnia, lightheadedness, manic reactions, impaired cognitive function, nervousness, restlessness, seizures, tardive dyskinesia.

Resp: dyspnea.

CV: bradycardia, chest pain, edema, hypertension, orthostatic hypotension, tachycardia.

EENT: blurred vision, conjunctivitis, ear pain.

GI: *constipation*, anorexia, ↑ salivation, nausea, vomiting, weight loss.

GU: urinary incontinence.

Hemat: AGRANULOCYTOSIS, anemia, leukopenia, neutropenia.

Derm: dry skin, ecchymosis, skin ulcer, sweating.

MS: muscle cramps, neck pain.

Metabolic: hyperglycemia.

Neuro: abnormal gait, *tremor*.

Misc: NEUROLEPTIC MALIGNANT SYNDROME, ↓ heat regulation.
aripiprazole

Interactions
Drug-Drug
• Ketoconazole or other potential CYP3A4 inhibitors ↓ metabolism and ↑ effects (↓ aripiprazole dose by 50%)

• Quinidine, fluoxetine , paroxetine , or other potential CYP2D6 inhibitors ↓ metabolism and ↑ effects (↓ aripiprazole dose by at least 50%)

• Concurrent carbamazepine or other potential CYP3A4 inducers ↑ metabolism and↓ effects (double aripiprazole dose; then ↓ to 10–15 mg/day when interfering drug is withdrawn)
aripiprazole

Dosage / Implementation
Schizophrenia
• PO (Adults): 10 or 15 mg daily; increments should not be made before 2 wk at a given dose.
• PO (Children 13–17 yr): 2 mg daily; ↑ to 5 mg daily after 2 days, and then to target dose of 10 mg daily after another 2 days; may further ↑ dose in 5-mg increments if needed (max: 30 mg/day).

Bipolar mania
• PO (Adults): 15 mg daily as monotherapy or with lithium or valproate; may ↑ to 30 mg daily, based on response.
• PO (Children 10–17 yr): 2 mg daily; ↑ to 5 mg daily after 2 days, and then to target dose of 10 mg daily after another 2 days; may further ↑ dose in 5-mg increments if needed (max: 30 mg/day).

Depression
• PO (Adults): 2–5 mg daily, may titrate upward at 1-wk intervals to 5–10 mg daily; not to exceed 15 mg/day.

Implementation:
• PO: Administer once daily without regard to meals. Do not open the blister until ready to administer. Do not push the tablet through the foil; may damage tablet. Immediately upon opening the blister, using dry hands, remove the tablet and place the entire orally disintegrating tablet on the tongue. Tablet disintegration occurs rapidly in saliva. Take tablet without liquid; but if needed, it can be taken with liquid. Do not attempt to split the tablet.

• IM: IM route should be used for agitation. Convert to oral dose as soon as possible. For dose of 5.25 mg use 0.7 mL, 9.75 mg use 1.3 mL, and 15 mg use 2 mL of aripiprazole solution. Solution should be clear and colorless; do not administer solutions that are discolored or contain a precipitate.
aripiprazole

Assessment
• Assess for suicidal tendencies (esp. in children, adolescents). Restrict amount of drug available to patient.
• Assess weight, blood glucose, cholesterol levels, and BMI initially and throughout therapy
• Monitor blood pressure (sitting, standing, lying), pulse, and respiratory rate before and periodically during therapy
• Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked
• Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian—difficulty speaking or swallowing, loss of balance control, pill rolling of hands, masklike face, shuffling gait, rigidity, tremors; and dystonic—muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) periodically throughout therapy.
• Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Notify physician immediately if these symptoms occur!
• Monitor for neuroleptic malignant syndrome (fever, muscle rigidity, altered mental status, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, loss of bladder control). Notify physician immediately if present!
>>Lab Test Considerations
• May cause ↑ creatinine phosphokinase
» Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs
aspirin

General
Pregnancy Category
Category D

Ther. class.
antipyretics
nonopioid analgesics

Pharm. class.
salicylates
aspirin

Indications
• Inflammatory disorders including:
» Rheumatoid arthritis
» Osteoarthritis

• Mild to moderate pain

• Fever

• Prophylaxis of transient ischemic attacks and MI

Unlabelled Use(s):
Adjunctive treatment of Kawasaki disease
aspirin

Action
• Produces analgesia and reduce inflammation and fever by inhibiting the production of prostaglandins

• Decreases platelet aggregation

• Decreased incidence of transient ischemic attacks and MI
aspirin

Contraindications
• Hypersensitivity to aspirin or other salicylates
• Cross-sensitivity with other NSAIDs may exist (less with nonaspirin salicylates)
• Bleeding disorders or thrombocytopenia
• Pedi: May increase risk of Reye's syndrome in children or adolescents with viral infections
>>Use Cautiously in:
• History of GI bleeding or ulcer disease
• Chronic alcohol use/abuse
• Severe hepatic or renal disease
• OB: Salicylates may have adverse effects on fetus and mother and should be avoided during pregnancy, especially during the 3rd trimester
• Lactation: Safety not established
• Geri: ↑ risk of adverse reactions especially GI bleeding; more sensitive to toxic levels
aspirin

Side Effects / ADRs
EENT: tinnitus.

GI: GI BLEEDING, *dyspepsia*, *epigastric distress*, *nausea*, abdominal pain, anorexia, hepatotoxicity, vomiting.

Hemat: anemia, hemolysis.

Derm: rash, urticaria.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS AND LARYNGEAL EDEMA .
aspirin

Interactions
Drug-Drug
• May ↑ the risk of bleeding with warfarin, heparin, heparin-like agents, thrombolytic agents, dipyridamole, ticlopidine, clopidogrel, tirofiban, or eptifibatide , although these agents are frequently used safely in combination and in sequence
• Ibuprofen: may negate the cardioprotective antiplatelet effects of low-dose aspirin
• May ↑ risk of bleeding with cefoperazone , cefotetan , and valproic acid
• May ↑ activity of penicillins , phenytoin , methotrexate , valproic acid , oral hypoglycemic agents , and sulfonamides
• May ↓ beneficial effects of sulfinpyrazone
• Urinary acidification ↑ reabsorption and may ↑ serum salicylate levels
• Alkalinization of the urine or the ingestion of large amounts of antacids ↑ excretion and ↓ serum salicylate levels
• May blunt the therapeutic response to diuretics and ACE inhibitors
• ↑ risk of GI irritation with NSAIDs

Drug-Natural Products-Food
↑ anticoagulant effect and bleeding risk with arnica , chamomile , clove , feverfew , garlic , ginger , ginkgo , Panax ginseng , and others. Foods capable of acidifying the urine may ↑ serum salicylate levels
aspirin

Dosage / Implementation
Pain/Fever
• PO, Rect (Adults): 325–1000 mg q 4–6 hr (not to exceed 4 g/day). Extended-release tablets—650 mg q 8 hr or 800 mg q 12 hr.
• PO, Rect (Children 2–11 yr): 10–15 mg/kg/dose q 4–6 hr; maximum dose: 4 g/day.

Inflammation
• PO (Adults): 2.4 g/day initially; increased to maintenance dose of 3.6–5.4 g/day in divided doses (up to 7.8 g/day for acute rheumatic fever).
• PO (Children): 60–100 mg/kg/day in divided doses (up to 130 mg/kg/day for acute rheumatic fever).

Implementation:
• Use lowest effective dose for shortest period of time.

• PO: Administer after meals or with food or an antacid to minimize gastric irritation. Food slows but does not alter the total amount absorbed.

» Do not crush or chew enteric-coated tablets Do not take antacids within 1–2 hr of enteric-coated tablets. Chewable tablets may be chewed, dissolved in liquid, or swallowed whole. Some extended-release tablets may be broken or crumbled but must not be ground up before swallowing.
aspirin

Assessment
• Patients who have asthma, allergies, and nasal polyps or who are allergic to tartrazine are at an increased risk for developing hypersensitivity reactions

Lab Test Considerations
• Monitor hepatic function before antirheumatic therapy and if symptoms of hepatotoxicity occur; more likely in patients, especially children, with rheumatic fever, systemic lupus erythematosus, juvenile arthritis, or pre-existing hepatic disease. May cause ↑ serum AST, ALT, and alkaline phosphatase, especially when plasma concentrations exceed 25 mg/100 mL. May return to normal despite continued use or dose reduction.
» Monitor serum salicylate levels periodically with prolonged high-dose therapy to determine dose, safety, and efficacy, especially in children with Kawasaki disease
» May alter results of serum uric acid, urine vanillylmandelic acid (VMA), protirelin-induced thyroid-stimulating hormone (TSH), urine hydroxyindoleacetic acid (5-HIAA) determinations, and radionuclide thyroid imaging
» Prolongs bleeding time for 4–7 days and, in large doses, may cause prolonged prothrombin time. Monitor hematocrit periodically in prolonged high-dose therapy to assess for GI blood loss
>>Toxicity and Overdose
• Monitor for the onset of tinnitus, headache, hyperventilation, agitation, mental confusion, lethargy, diarrhea, and sweating. If these symptoms appear, withhold medication and notify physician or other health care professional immediately
atenolol

General
Pronunciation
a-TEN-oh-lole [Pronunciation]

Trade name:
• Tenormin

Pregnancy Category
Category D

Ther. class.
antianginals
antihypertensives
Pharm. class.
beta blockers
atenolol

Indications
• Management of hypertension

• Management of angina pectoris

• Prevention of MI
atenolol

Action
Blocks stimulation of beta1(myocardial)-adrenergic receptors. Does not usually affect beta2(pulmonary, vascular, uterine)-receptor sites

Therapeutic Effects:
• Decreased blood pressure and heart rate
• Decreased frequency of attacks of angina pectoris
• Prevention of MI
atenolol

Contraindications
• Uncompensated CHF
• Pulmonary edema
• Cardiogenic shock
• Bradycardia or heart block
>>Use Cautiously in:
• Renal impairment (dosage reduction recommended if CCr C35 mL/min)
• Hepatic impairment
• Geriatric patients (increased sensitivity to beta blockers; initial dosage reduction recommended)
• Pulmonary disease (including asthma; beta selectivity may be lost at higher doses)
• Diabetes mellitus (may mask signs of hypoglycemia)
• Thyrotoxicosis (may mask symptoms)
• Patients with a history of severe allergic reactions (intensity of reactions may be increased)
• OB: Crosses the placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression
• Lactation: Pedi: Safety not established
atenolol

Side Effects / ADRs
CNS: *fatigue*, *weakness*, anxiety, depression, dizziness, drowsiness, insomnia, memory loss, mental status changes, nervousness, nightmares.

EENT: blurred vision, stuffy nose.

Resp: bronchospasm, wheezing.

CV: BRADYCARDIA, CHF, PULMONARY EDEMA, hypotension, peripheral vasoconstriction.

GI: constipation, diarrhea, liver function abnormalities, nausea, vomiting.

GU: *erectile dysfunction*, decreased libido, urinary frequency.

Derm: rashes.

Endo: hyperglycemia, hypoglycemia.

MS: arthralgia, back pain, joint pain.

Misc: drug-induced lupus syndrome.
atenolol

Interactions
Drug-Drug
• General anesthesia , IVphenytoin , and verapamil may cause additive myocardial depression
• Additive bradycardia may occur with digoxin
• Additive hypotension may occur with other antihypertensives , acute ingestion of alcohol , or nitrates
• Concurrent use with amphetamine , cocaine , ephedrine , epinephrine , norepinephrine , phenylephrine , or pseudoephedrine may result in unopposed alpha-adrenergic stimulation (excessive hypertension, bradycardia)
• Concurrent thyroid administration may decrease effectiveness
• May alter the effectiveness of insulins or oral hypoglycemic agents (dosage adjustments may be necessary)
• May decrease the effectiveness of theophylline
• May decrease the beneficial beta1-cardiovascular effects of dopamine or dobutamine
• Use cautiously within 14 days of MAO inhibitor therapy (may result in hypertension)
atenolol

Dosage / Implementation
• PO (Adults): Antianginal—50 mg once daily; may be increased after 1 wk to 100 mg/day (up to 200 mg/day). Antihypertensive—25–50 mg once daily; may be increased after 2 wk to 50–100 mg once daily. MI—50 mg, then 50 mg 12 hr later, then 100 mg/day as a single dose or in 2 divided doses for 6–9 days or until hospital discharge.

Implementation:
PO: Take apical pulse before administering drug. If <50 bpm or if arrhythmia occurs, withhold medication and notify physician.
atenolol

Assessment
• Monitor blood pressure, ECG, and pulse frequently during dosage adjustment period and periodically throughout therapy
• Monitor intake and output ratios and daily weights. Assess routinely for CHF (dyspnea, rales/crackles, weight gain, peripheral edema, jugular venous distention)
• Monitor frequency of prescription refills to determine adherence
>>Angina
• Assess frequency and characteristics of angina periodically throughout therapy
>>Lab Test Considerations
• May cause ↑ BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels
» May cause ↑ ANA titers
» May cause ↑ in blood glucose levels
>>Toxicity and Overdose
• Monitor patients receiving beta blockers for signs of overdose (bradycardia, severe dizziness or fainting, severe drowsiness, dyspnea, bluish fingernails or palms, seizures). Notify physician immediately if these signs occur
atorvastatin

General
Pronunciation
a-TORE-va-stat-in

Trade name:
• Lipitor

Pregnancy Category
Category X

Ther. class.
lipid-lowering agents
Pharm. class.
hmg coa reductase inhibitors
atorvastatin

Indications
• Adjunctive management of primary hypercholesterolemia and mixed dyslipidemia

• Primary prevention of coronary heart disease (myocardial infarction, stroke, angina, and coronary revascularization) in asymptomatic patients with increased total and low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol
atorvastatin

Action
Inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme which is responsible for catalyzing an early step in the synthesis of cholesterol

Therapeutic Effect(s):
• Lowering of total and LDL cholesterol and triglycerides. Slightly increases HDL cholesterol
• Reduction of lipids/cholesterol reduces the risk of myocardial infarction and stroke sequelae
• Slows the progression of coronary atherosclerosis with resultant decrease in coronary heart disease–related events
atorvastatin

Contraindications
• Hypersensitivity
• Active liver disease or unexplained persistent elevations in AST and ALT
• OB: Potential for fetal anomalies
• Lactation: May appear in breast milk
>>Use Cautiously in:
• History of liver disease
• Alcoholism
• Renal impairment
• Concurrent use of gemfibrozil, azole antifungals, erythromycin, clarithromycin, protease inhibitors, niacin, or cyclosporine (higher risk of myopathy/rhabdomyolysis)
• OB: Women of childbearing age
• Pedi: Children <10 yr (safety not established)
atorvastatin

Side Effects / ADRs
CNS: dizziness, headache, insomnia, weakness.

EENT: rhinitis.

Resp: bronchitis.

CV: chest pain, peripheral edema.

GI: *abdominal cramps*, *constipation*, *diarrhea*, *flatus*, *heartburn*, altered taste, drug-induced hepatitis, dyspepsia, ↑ liver enzymes, nausea, pancreatitis.

GU: erectile dysfunction.

Derm: rashes, pruritus.

MS: RHABDOMYOLYSIS, arthralgia, arthritis, myalgia, myositis.

Misc: HYPERSENSITIVITY REACTIONS INCLUDING ANGIONEUROTIC EDEMA .
atorvastatin

Interactions
Drug-Drug
• Metabolized by the hepatic CYP3A4 enzyme system
• Cholesterol-lowering effect may be additive with bile acid sequestrants (cholestyramine, colestipol)
• Bioavailability may be ↓ by bile acid sequestrants
• ↑ risk of myopathy with concurrent use of cyclosporine , gemfibrozil , erythromycin , clarithromycin , ritonavir/saquinavir , lopinavir/ritonavir large doses of niacin , and azole antifungals (combined use with gemfibrozil not recommended; temporary discontinuation of atorvastatin recommended during azole antifungals)
• May slightly ↑ serum digoxin levels
• May ↑ levels of oral contraceptives
• May ↑ effects of warfarin
Drug-Food
Grapefruit juice ↑ levels and risk of rhabdomyolysis
atorvastatin

Dosage / Implementation
• PO (Adults): 10–20 mg once daily initially; (may start with 40 mg/day if LDL-C needs to be ↓ by >45%); may be ↑ every 2–4 wk up to 80 mg/day; Concurrent cyclosporine therapy—Dose should not exceed 10 mg/day; Concurrent clarithromycin, itraconazole, ritonavir/saquinavir or lopinavir/ritonavir therapy—Use doses >20 mg/day with caution.
• PO (Children 10–17 yr): 10 mg/day initially, may be ↑ every 4 wk up to 20 mg/day; Concurrent cyclosporine therapy—Dose should not exceed 10 mg/day; Concurrent clarithromycin, itraconazole, ritonavir/saquinavir or lopinavir/ritonavir therapy—Use doses >20 mg/day with caution.

Implementation:
PO: May be administered without regard to food. Avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.
atorvastatin

Assessment
• Obtain a diet history, especially with regard to fat consumption
Lab Test Considerations

• Evaluate serum cholesterol and triglyceride levels before initiating, after 2–4 wk of therapy, and periodically thereafter

» Monitor liver function tests, including AST, prior to, at 12 wk after initiation of therapy, or after dose elevation, and then every 6 mo. If AST or ALT levels ↑ to 3 times normal, atorvastatin therapy should be reduced or discontinued. May also cause ↑ alkaline phosphatase and bilirubin levels

» If patient develops muscle tenderness during therapy, CPK levels should be monitored. If CPK levels are >10 times the upper limit of normal or myopathy occurs, therapy should be discontinued
azithromycin

General
Pronunciation
aye-ZITH-roe-mye-sin [Pronunciation]

Trade Names:
• Zithromax
• Zmax

Pregnancy Category
Category B

Ther. class.
agents atypical mycobacterium
anti-infectives
Pharm. class.
macrolides
azithromycin

Indications
• Treatment of the following infections due to susceptible organisms
» Upper respiratory tract infections, including streptococcal pharyngitis, acute bacterial exacerbations of chronic bronchitis and tonsillitis
» Lower respiratory tract infections, including bronchitis and pneumonia
» Acute otitis media
» Skin and skin structure infections
» Nongonococcal urethritis, cervicitis, gonorrhea, and chancroid

• Prevention of disseminated Mycobacterium avium complex (MAC) infection in patients with advanced HIV infection
• Extended-release suspension (ZMax) Acute bacterial sinusitis and community-acquired pneumonia in adults

Unlabelled Uses:
• Prevention of bacterial endocarditis
• Treatment of cystic fibrosis lung disease
azithromycin

Action
Inhibits protein synthesis at the level of the 50S bacterial ribosome. Bacteriostatic against susceptible bacteria.

• Active against the following gram-positive aerobic bacteria:
» Staphylococcus aureus
» Streptococcus pneumoniae
» S. pyogenes (group A strep)
• Active against these gram-negative aerobic bacteria
» Haemophilus influenzae
» Moraxella catarrhalis
» Neisseria gonorrhoeae
• Also active against
» Mycoplasma
» Legionella
» Chlamydia pneumoniae
» Ureaplasma urealyticum
» Borrelia burgdorferi
» M. avium
• Not active against methicillin-resistant S. aureus
azithromycin

Contraindications
Hypersensitivity to azithromycin, erythromycin, or other macrolide anti-infectives

Use Cautiously in:

• Severe liver impairment (dose adjustment may be required)

• Severe renal impairment (CCr <10 mL/min)

• Myasthenia gravis (may worsen symptoms)

• OB: Lactation: Safety not established

• Pedi: Safety not established in children <5 yr
azithromycin

Side Effects / ADRs
CNS: dizziness, seizures, drowsiness, fatigue, headache.

CV: chest pain, hypotension, palpitations, QT prolongation (rare).

GI: HEPATOTOXICITY, PSEUDOMEMBRANOUS COLITIS, *abdominal pain*, *diarrhea*, *nausea*, cholestatic jaundice, ↑ liver enzymes, dyspepsia, flatulence, melena, oral candidiasis, pyloric stenosis.

GU: nephritis, vaginitis.

Hemat: anemia, leukopenia, thrombocytopenia.

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, photosensitivity, rashes.

EENT: ototoxicity.

F and E: hyperkalemia.

Misc: ANGIOEDEMA.
azithromycin

Interactions
Drug-Drug
• Aluminum- and magnesium-containing antacids↓ peak levels
• Nelfinavir ↑ levels (monitor carefully); azithromycin also ↓ nelfinavir levels
• Efavirenz ↑ levels
• May ↑ the effects and risk of toxicity of warfarin and zidovudine
• Other macrolide anti-infectives have been known to ↑ levels and effects of digoxin , theophylline , ergotamine , dihydroergotamine , triazolam , carbamazepine , cyclosporine , tacrolimus , and phenytoin ; careful monitoring of concurrent use is recommended
azithromycin

Dosage / Implementation
Most Respiratory and Skin Infections
• PO (Adults): 500 mg on 1st day, then 250 mg/day for 4 more days (total dose of 1.5 g); Acute bacterial sinusitis—500 mg once daily for 3 days or single 2-g dose of extended-release suspension (Zmax).
• PO (Children B 6 mo): 10 mg/kg (not >500 mg/dose) on 1st day, then 5 mg/kg (not >250 mg/dose) for 4 more days. Pharyngitis/tonsilitis—12 mg/kg once daily for 5 days (not >500 mg/dose); Acute bacterial sinusitis—10 mg/kg/day for three days.

Otitis Media
• PO (Children < 6 mo): 30 mg/kg single dose (not >1500 mg/dose) or 10 mg/kg/day as a single dose (not >500 mg/dose) for 3 days or 10 mg/kg as a single dose (not >500 mg/dose) on 1st day, then 5 mg/kg as a single dose (not >250 mg/dose) daily for 4 more days.

Acute Bacterial Exacerbations of Chronic Bronchitis
• PO (Adults): 500 mg on 1st day, then 250 mg/day for 4 more days (total dose of 1.5 g) or 500 mg daily for 3 days.

Community-Acquired Pneumonia
• IV, PO (Adults): More severe—500 mg IV q 24 hr for at least 2 doses, then 500 mg PO q 24 hr for a total of 7–10 days; less severe—500 mg PO, then 250 mg/day PO for 4 more days or 2 g single dose as extended-release suspension (Zmax).
• PO (Children > 6 mo): 10 mg/kg on 1st day, then 5 mg/kg for 4 more days.

Pelvic Inflammatory Disease
• IV, PO (Adults): 500 mg IV q 24 hr for 1–2 days, then 250 mg PO q 24 hr for a total of 7 days.

Endocarditis Prophylaxis
• PO (Adults): 500 mg 1 hr before procedure.
• PO (Children): 15 mg/kg 1 hr before procedure.

Nongonococcal Urethritis, Cervicitis, Chancroid, Chlamydia
• PO (Adults): Single 1-g dose.
• PO (Children): Chancroid: Single 20-mg/kg dose (not >1000 mg/dose). Urethritis or cervicitis: Single 10-mg/kg dose (not >1000 mg/dose).

Gonorrhea
• PO (Adults): Single 2-g dose.

Prevention of Disseminated MAC Infection
• PO (Adults): 1.2 g once weekly (alone or with rifabutin).
• PO (Children): 5 mg/kg once daily (not >250 mg/dose) or 20 mg/kg (not >1200 mg/dose) once weekly (alone or with rifabutin).

Cystic Fibrosis
• PO (Children > 6 yrs, weight > 25 kg to < 40 kg): 250 mg q MWF. B40 kg: 500 mg q MWF.
» Zmax extended release oral suspension is not bioequivalent or interchangeable with azithromycin oral suspension.

Implementation:
• PO: Administer 1 hr before or 2 hr after meals. For administration of single 1-g packet, thoroughly mix entire contents of packet with 2 oz (60 mL) of water. Drink entire contents immediately; add an additional 2 oz of water, mix and drink to assure complete consumption of dose. Do not use the single packet to administer doses other than 1000 mg of azithromycin. Pedi: 1-g packet is not for pediatric use.

» For Zmax, shake suspension well and drink entire contents of bottle. Use within 12 hr of reconstitution. If patient vomits within 1 hr of administration, contact prescriber for instructions. Zmax may be taken without regard to antacids containing magnesium or aluminum hydroxide.

IV Adminstration:
• Intermittent Infusion:
Diluent: Reconstitute each 500-mg vial with 4.8 mL of sterile water for injection to achieve a concentration of 100 mg/mL. Reconstituted solution is stable for 24 hr at room temperature. Further dilute the 500-mg dose in 250 mL or 500 mL of 0.9% NaCl, 0.45% NaCl, D5W, LR, D5/0.45% NaCl, or D5/LR. Infusion is stable for 24 hr at room temperature or for 7 days if refrigerated.
Concentration: Final concentration of infusion is 1–2 mg/mL.
Rate: Administer the 1-mg/mL solution over 3 hr or the 2-mg/mL solution over 1 hr. Do not administer as a bolus.
azithromycin

Assessment
• Assess patient for infection.
• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing).
• Assess patient for skin rash frequently during therapy. Discontinue azithromycin at first sign of rash; may be life-threatening. Stevens-Johnson syndrome or toxic epidermal necrolysis may develop. Treat symptomatically; may recur once treatment is stopped
>>Lab Test Considerations
• May cause ↑ serum bilirubin, AST, ALT, LDH, and alkaline phosphatase concentrations.
• May cause ↑ creatine phosphokinase, potassium, prothrombin time, BUN, serum creatinine, and blood glucose concentrations.
• May occasionally cause ↓ WBC and platelet count.
baclofen

General
Pronunciation
BAK-loe-fen

Pregnancy Category
Category C

Ther. class.
antispasticity agents
skeletal muscle relaxants
(centrally acting)
baclofen

Indications
• PO: Treatment of reversible spasticity due to multiple sclerosis or spinal cord lesions

• IT: Treatment of severe spasticity originating in the spinal cord

Unlabelled Use:
Management of pain in trigeminal neuralgia
baclofen

Action
Inhibits reflexes at the spinal level

Therapeutic Effect(s):
Decreased muscle spasticity; bowel and bladder function may also be improved
baclofen

Contraindications
• Hypersensitivity
• Orally-disintegrating tablets contain aspartame and should not be used in patients with phenylketonuria

Use Cautiously in:
• Patients in whom spasticity maintains posture and balance
• Patients with epilepsy (may ↓ seizure threshold)
• Renal impairment (↓ dose may be required)
• OB: Lactation: Pedi: Safety not established
• Geri: Geriatric patients are at ↑ risk of CNS side effects
baclofen

Side Effects / ADRs
CNS: SEIZURES (IT), *dizziness*, *drowsiness*, *fatigue*, *weakness*, confusion, depression, headache, insomnia.

EENT: nasal congestion, tinnitus.

CV: edema, hypotension.

GI: *nausea*, constipation.

GU: frequency.

Derm: pruritus, rash.

Metabolic: hyperglycemia, weight gain.

Neuro: ataxia.

Misc: hypersensitivity reactions, sweating.
baclofen

Interactions
Drug-Drug
• ↑ CNS depression with other CNS depressants including alcohol, antihistamines , opioid analgesics , and sedative/hypnotics

• Use with MAO inhibitors may lead to ↑ CNS depression or hypotension

Drug-Natural Products
Concomitant use of kava-kava , valerian , or chamomile can ↑ CNS depression
baclofen

Dosage / Implementation
• PO (Adults): 5 mg 3 times daily. May increase q 3 days by 5 mg/dose up to 80 mg/day (some patients may have a better response to 4 divided doses).

• IT (Adults): 100–800 mcg/day infusion; dose is determined by response during screening phase.
• IT (Children): 25–1200 mcg/day infusion (average 275 mcg/day); dose is determined by response during screening phase.

Implementation:
• PO: Administer with milk or food to minimize gastric irritation.

» For orally disintegrating tablets, just prior to administration place tablet on tongue with dry hands. Tablet will disintegrate, then swallow with saliva or water.

• IT: For screening phase, dilute for a concentration of 50 mcg/mL with sterile preservative-free NaCl for injection. Test dose should be administered over at least 1 min. Observe patient for a significant decrease in muscle tone or frequency or severity of spasm. If response is inadequate, 2 additional test doses, each 24 hr apart, 75 mcg/1.5 mL and 100 mcg/2 mL respectively, may be administered. Patients with an inadequate response should not receive chronic IT therapy.

» Dose titration for implantable IT pumps is based on patient response. If no substantive response after dose increase, check pump function and catheter patency.
baclofen

Assessment
• Assess muscle spasticity before and periodically during therapy

» Observe patient for drowsiness, dizziness, or ataxia. May be alleviated by a change in dose

IT:
• Monitor patient closely during test dose and titration. Resuscitative equipment should be immediately available for life-threatening or intolerable side effects

Lab Test Considerations
• May cause ↑ in serum glucose, alkaline phosphatase, AST, and ALT levels
beclomethasone

General
Pronunciation
be-kloe-METH-a-sone

Pregnancy Category
Category C

Ther. class.
anti inflammatories steroidal
Pharm. class.
corticosteroids
beclomethasone

Indications
• Maintenance treatment of asthma as prophylactic therapy

• May decrease requirement for or eliminate use of systemic corticosteroids in patients with asthma
beclomethasone

Action
Potent, locally acting anti-inflammatory and immune modifier

Therapeutic Effects:
• Decreases frequency and severity of asthma attacks
• Improves asthma symptoms
beclomethasone

Contraindications
• Hypersensitivity (product contains alcohol)
• Acute attack of asthma/status asthmaticus

Use Cautiously in:
• Active untreated infections
• Diabetes or glaucoma
• Underlying immunosuppression (due to disease or concurrent therapy)
• Systemic corticosteroid therapy (should not be abruptly discontinued when inhalable therapy is started; additional corticosteroids needed in stress or trauma)
• OB: Lactation: Safety not established
• Pedi: Safety not established in children <5 yr; prolonged or high-dose therapy may lead to complications
beclomethasone

Side Effects / ADRs
CNS: *headache*.

EENT: cataracts, dysphonia, oropharyngeal fungal infections, pharyngitis, rhinitis, sinusitis.

Resp: bronchospasm, cough, wheezing.

Endo: adrenal suppression (increased dose, long-term therapy only), decreased growth (children).

MS: back pain.
beclomethasone

Interactions
Drug-Drug
None known
beclomethasone

Dosage / Implementation
• Inhaln (Adults and Children > 12 yr): Previously on bronchodilators alone-40–80 mcg twice daily (not to exceed 320 mcg twice daily). Previously on inhaled corticosteroids—40–160 mcg twice daily (not to exceed 320 mcg twice daily).

• Inhaln (Children 5–11 yr): Previously on bronchodilators alone—40 mcg twice daily (not to exceed 80 mcg twice daily). Previously on inhaled corticosteroids—40 mcg twice daily (not to exceed 80 mcg twice daily).

Implementation:
• After the desired clinical effect has been obtained, attempts should be made to decrease dose to lowest amount required to control symptoms. Gradually decrease dose every 2–4 wk as long as desired effect is maintained. If symptoms return, dose may briefly return to starting dose.

• Inhaln: Allow at least 1 min between inhalations of aerosol medication.
beclomethasone

Assessment
• Monitor respiratory status and lung sounds. Pulmonary function tests may be assessed periodically during and for several months following a transfer from systemic to inhalation corticosteroids
• Assess patients changing from systemic corticosteroids to inhalation corticosteroids for signs of adrenal insufficiency (anorexia, nausea, weakness, fatigue, hypotension, hypoglycemia) during initial therapy and periods of stress. May be life-threatening.
• Monitor for withdrawal symptoms (joint or muscular pain, lassitude, depression) during withdrawal from oral corticosteroids
• Monitor growth rate in children receiving chronic therapy; use lowest possible dose

Lab Test Considerations
• Periodic adrenal function tests may be ordered to assess degree of hypothalamic-pituitary-adrenal (HPA) axis suppression in chronic therapy. Children and patients using higher than recommended doses are at greatest risk for HPA suppression
» May cause increased serum and urine glucose concentrations if significant absorption occurs
penicillin G

General
penicillin g
pen-i-SILL-in gee

procaine penicillin g

benzathine penicillin g

Pregnancy Category
Category B

Ther. class.
anti-infectives
Pharm. class.
penicillins
penicillin G

Indications
• Treatment of a wide variety of infections including:
» Pneumococcal pneumonia
» Streptococcal pharyngitis
» Syphilis
» Gonorrhea strains

• Treatment of enterococcal infections (requires the addition of an aminoglycoside).
• Prevention of rheumatic fever.
• Should NOT be used as a single agent to treat anthrax.

Unlabelled Uses:
Treatment of Lyme disease. Prevention of recurrent Streptococcal pneumoniae septicemia in children with sickle-cell disease.
penicillin G

Action / Spectrum
Binds to bacterial cell wall, resulting in cell death

Bactericidal action against susceptible bacteria. Spectrum:
» Most gram-positive organisms, including many streptococci (Streptococcus pneumoniae, group A beta-hemolytic streptococci), staphylococci (non–penicillinase-producing strains), and Bacillus anthracis.

» Some gram-negative organisms, such as Neisseria meningitidis and N. gonorrhoeae (only penicillin susceptible strains).

» Some anaerobic bacteria and spirochetes including Borellia burgdorferi.
penicillin G

Contraindications
• Previous hypersensitivity to penicillins (cross-sensitivity exists with cephalosporins and other beta-lactam antibiotics).
• Hypersensitivity to procaine or benzathine (procaine and benzathine preparations only).
• Some products may contain tartrazine and should be avoided in patients with known hypersensitivity.

Use Cautiously in:
• Severe renal insufficiency (dosage reduction recommended).
• OB: Although safety not established, has been used safely.
• Lactation: Safety not established.
• Geri: Consider decreased body mass, age-related decrease in renal/hepatic/cardiac function, intercurrent diseases and drug therapy.
penicillin G

Side Effects / ADRs
CNS: SEIZURES.

GI: *diarrhea*, *epigastric distress*, *nausea*, *vomiting*, pseudomembranous colitis.

GU: interstitial nephritis.

Derm: *rash*, urticaria.

Hemat: eosinophilia, leukopenia.

Local: *pain at IM site*, *phlebitis at IV site*.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS AND SERUM SICKNESS , superinfection.
penicillin G

Interactions
Drug-Drug
• Penicillin may ↓ effectiveness of oral contraceptive agents

• Probenecid↓ renal excretion and ↑ blood levels of penicillin (therapy may be combined for this purpose)

• Neomycin may ↓ absorption of penicillin

• Concurrent use with methotrexate↓ methotrexate elimination and ↑ risk of serious toxicity
penicillin G

Dosage / Implementation
Aqueous Penicillin G
• IM, IV (Adults): Most infections—1–5 million units q 4–6 hr.
• IM, IV (Children): 8333–16,667 units/kg q 4 hr; 12,550–25,000 units/kg q 6 hr; up to 250,000 units/kg/day in divided doses, some infections may require up to 300,000 units/kg/day.

Benzathine Penicillin G
• IM (Adults): Streptococcal infections/erysipeloid—1.2 million units single dose. Primary, secondary, and early latent syphilis—2.4 million units single dose. Tertiary and late latent syphilis (not neurosyphilis)—2.4 million units once weekly for 3 wk. Prevention of rheumatic fever—1.2 million units q 3–4 wk.
• IM (Children >27 kg): Streptococcal infections/erysipeloid—900,000–1.2 million units (single dose). Primary, secondary, and early latent syphilis—up to 2.4 million units single dose. Late latent or latent syphilis of undetermined duration—50,000 units/kg weekly for 3 wk. Prevention of rheumatic fever—1.2 million units q 2–3 wk.

Procaine Penicillin G
• IM (Adults): Moderate or severe infections—600,000–1.2 million units/day, single dose or 2 divided doses. Neurosyphilis—2.4 million units/day with 500 mg probenecid PO 4 times daily for 10–14 days.
• IM (Children): Congenital syphilis—50,000 units/kg/day for 10–14 days.

Implementation:
• Do not confuse penicillin with penicillamine. Do not confuse penicillin G aqueous (potassium/sodium salts) with penicillin G procaine or benzathine.

IM: Reconstitute according to manufacturer's directions with sterile water for injection, D5W, or 0.9% NaCl. Shake medication well before injection. Inject penicillin deep into a well-developed muscle mass at a slow, consistent rate to prevent blockage of the needle. Massage well. Accidental injury near or into a nerve can result in severe pain and dysfunction. Penicillin G potassium or sodium may be diluted with lidocaine (without epinephrine) 1% or 2% to minimize pain from IM injection. NEVER give penicillin G benzathine or penicillin G procaine suspensions IV. May cause embolism or toxic reactions.

IV:
Change IV sites every 48 hr to prevent phlebitis. Administer slowly and observe patient closely for signs of hypersensitivity.
• Intermittent Infusion: Doses of 3 million units or less should be diluted in at least 50 mL of D5W or 0.9% NaCl; doses of more than 3 million units should be diluted with 100 mL.
Rate: Infuse over 1–2 hr in adults or 15–30 min in children.
• Continuous Infusion: Doses of 10 million units or more may be diluted in 1 or 2 L.
Rate: Infuse over 24 hr.
penicillin G

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.

• Obtain a history to determine previous use of and reactions to penicillins, cephalosporins, or other beta-lactam antibiotics. Persons with a negative history of penicillin sensitivity may still have an allergic response.

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.

Lab Test Considerations
• May cause positive direct Coombs' test results.

» Hyperkalemia may develop after large doses of penicillin G potassium.

» Monitor serum sodium concentrations in patient with hypertension or CHF. Hypernatremia may develop after large doses of penicillin sodium.

» May cause ↑ AST, ALT, LDH, and serum alkaline phosphatase concentrations.

» May cause leukopenia and neutropenia, especially with prolonged therapy or hepatic impairment.
betamethasone

General
Pronunciation
bay-ta-METH-a-sone

Trade Name(s)
• Celestone

Pregnancy Category
Category C

Ther. class.
anti inflammatories steroidal
Pharm. class.
corticosteroids
betamethasone

Indications
• Management of adrenocortical insufficiency; chronic use in other situations is limited because of mineralocorticoid activity.

• Used systemically and locally in a wide variety of chronic diseases including:
» Inflammatory
» Allergic
» Hematologic
» Neoplastic
» Autoimmune disorders

• Replacement therapy in adrenal insufficiency.

Unlabelled Use:
Short-term administration to high-risk mothers before delivery to prevent respiratory distress syndrome in the newborn.
betamethasone

Action
• In pharmacologic doses, suppresses inflammation and the normal immune response

• Has numerous intense metabolic effects (see Adverse Reactions and Side Effects)

• Suppresses adrenal function at chronic doses of 0.6 mg/day

• Has negligible mineralocorticoid activity
Therapeutic Effect(s):

• Suppression of inflammation and modification of the normal immune response

• Replacement therapy in adrenal insufficiency
betamethasone

Contraindications
• Active untreated infections (may be used in patients being treated for tuberculous meningitis).

• Traumatic brain injury (high doses may ↑ mortality).

• Lactation: Avoid chronic use.

• Some products contain bisulfites and should be avoided in patients with known hypersensitivity.

Use Cautiously in:
• Chronic treatment (will lead to adrenal suppression; use lowest possible dose for shortest period of time).

• Hypothyroidism.

• Cirrhosis.

• Ulcerative colitis.

• Stress (surgery, infections); supplemental doses may be needed.

• Potential infections may mask signs (fever, inflammation).

• OB: Safety not established.

• Pedi: Chronic use will result in ↓ growth; use lowest possible dose for shortest period of time.
betamethasone

Side Effects / ADRs
Adverse reactions/side effects are much more common with high-dose/long-term therapy

CNS: *depression*, *euphoria*, headache, ↑ intracranial pressure (children only), personality changes, psychoses, restlessness.

EENT: cataracts, ↑ intraocular pressure.

CV: *hypertension*.

GI: PEPTIC ULCERATION, *anorexia*, *nausea*, vomiting.

Derm: *acne*, *↓ wound healing*, *ecchymoses*, *fragility*, *hirsutism*, *petechiae*.

Endo: adrenal suppression, hyperglycemia.

F and E: fluid retention (long-term high doses), hypokalemia, hypokalemic alkalosis.

Hemat: THROMBOEMBOLISM, thrombophlebitis.

Metabolic: weight gain, weight loss.

MS: *muscle wasting*, *osteoporosis*, avascular necrosis of joints, muscle pain.

Misc: *cushingoid appearance (moon face, buffalo hump)*, ↑ susceptibility to infection.
betamethasone

Interactions
Drug-Drug
• Additive hypokalemia with thiazide and loopdiuretics , or amphotericin B

• Hypokalemia may ↑ risk of digitalis glycoside toxicity

• May ↑ requirement for insulins or oral hypoglycemic agents

• Phenytoin , phenobarbital , and rifampin stimulate metabolism; may ↓ effectiveness

• Oral contraceptives may block metabolism

• ↑ risk of adverse GI effects with NSAIDs (including aspirin)

• At chronic doses that suppress adrenal function, may ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines
betamethasone

Dosage / Implementation
• PO (Adults): 0.6 mg–7.2 mg/day as single daily dose or in divided doses.

• PO (Children): Adrenocortical insufficiency—17.5 mcg/kg (500 mcg/m2)/day in 3 divided doses. Other uses—62.5–250 mcg/kg (1.875–7.5 mg/m2)/day in 3 divided doses.

Implementation:
• If dose is ordered daily or every other day, administer in the morning to coincide with the body's normal secretion of cortisol.
• PO: Administer with meals to minimize GI irritation.
» Use calibrated measuring device to ensure accurate dosage of liquid forms.

• IM: Shake suspension well before drawing up. Do not dilute with other solution or admix. Do NOT administer suspensions IV.
betamethasone

Assessment
• Indicated for many conditions. Assess involved systems before and periodically during therapy

• Assess patient for signs of adrenal insufficiency (hypotension, weight loss, weakness, nausea, vomiting, anorexia, lethargy, confusion, restlessness) before and periodically during therapy

• Monitor intake and output ratios and daily weights. Observe patient for peripheral edema, steady weight gain, rales/crackles, or dyspnea. Notify health care professional if these occur

• Pedi: Children should have periodic growth evaluations
Lab Test Considerations

• Monitor serum electrolytes and glucose. May cause hyperglycemia, especially in persons with diabetes. May cause hypokalemia. Patients on prolonged courses of therapy should routinely have hematologic values, serum electrolytes, and serum glucose evaluated. May ↓ WBC counts. May ↓ serum potassium and calcium and ↑ serum sodium concentrations

» Guaiac-test stools. Promptly report presence of guaiac-positive stools

» May ↑ serum cholesterol and lipid values. May decrease uptake of thyroid 123I or 131I

» Suppress reactions to allergy skin tests

» Periodic adrenal function tests may be ordered to assess degree of hypothalamic-pituitary-adrenal axis suppression in systemic and chronic topical therapy
bethanechol

General
Pronunciation
be-THAN-e-kole

Trade Name(s)
• Duvoid
• Urabeth
• Urecholine

Pregnancy Category
Category C

Ther. class.
urinary tract stimulant
Pharm. class.
cholinergics
bethanechol

Indications
Postpartum and postoperative nonobstructive urinary retention or urinary retention caused by neurogenic bladder
bethanechol

Action
Stimulates cholinergic receptors. Effects include:

» Contraction of the urinary bladder

» Decreased bladder capacity

» Increased frequency of ureteral peristaltic waves

» Increased tone and peristalsis in the GI tract

» Increased pressure in the lower esophageal sphincter

» Increased gastric secretions

Therapeutic Effect: Bladder emptying
bethanechol

Contraindications
• Hypersensitivity

• Mechanical obstruction of the GI or GU tract

Use Cautiously in:
• History of asthma

• Ulcer disease

• Cardiovascular disease

• Epilepsy

• Hyperthyroidism

• Sensitivity to cholinergic agents or effects

• OB: Lactation: Pedi: Safety not established
bethanechol

Side Effects / ADRs
CNS: headache, malaise.

EENT: lacrimation, miosis.

Resp: bronchospasm.

CV: HEART BLOCK, SYNCOPE/CARDIAC ARREST, bradycardia, hypotension.

GI: *abdominal discomfort*, *diarrhea*, *nausea*, *salivation*, *vomiting*.

GU: *urgency*.

Misc: *flushing*, *sweating*, hypothermia.
bethanechol

Interactions
Drug-Drug
• Quinidine and procainamide may antagonize cholinergic effects.

• Additive cholinergic effects with cholinesterase inhibitors.

• Use with ganglionic blocking agents may result in severe hypotension.

• Do not use with depolarizing neuromuscular blocking agents.

• Effectiveness will be decreased by anticholinergics.

Drug-Natural Products
Cholinergic effects may be antagonized by angel's trumpet , jimson weed , or scopolia.
bethanechol

Dosage / Implementation
• PO (Adults): 25–50 mg 3 times daily. Dose may be determined by administering 5–10 mg q 1–2 hr until response is obtained or total of 50 mg administered or by starting with 10 mg, giving 25 mg 6 hr later, then, if needed, 50 mg 6 hr later.
• PO (Children): 0.2 mg/kg 3 times daily or 0.15 mg/kg 4 times daily.

Implementation:
• A test dose is usually employed before maintenance to determine minimum effective dose.

» Oral and subcut doses are NOT interchangeable.

• PO: Administer medication on an empty stomach, 1 hr before or 2 hr after meals, to prevent nausea and vomiting.

• SC: Parenteral solution is intended only for subcut administration. Do not give IM or IV. Inadvertent IM or IV administration may cause cholinergic overstimulation (circulatory collapse, drop in blood pressure, abdominal cramps, bloody diarrhea, shock, and cardiac arrest).

» Do not use if solution is discolored or contains a precipitate.
bethanechol

Assessment
• Monitor blood pressure, pulse, and respirations before administering and for at least 1 hr after subcut administration.

• Monitor intake and output ratios. Palpate abdomen for bladder distention. Notify physician or other health care professional if drug fails to relieve condition for which it was prescribed. Catheterization may be ordered to assess postvoid residual.

Lab Test Considerations
• May cause an increase in serum AST, amylase, and lipase concentrations.

Toxicity and Overdose
• Observe patient for drug toxicity (sweating, flushing, abdominal cramps, nausea, salivation). If overdosage occurs, treatment includes atropine sulfate (specific antidote).
bleomycin
Pronunciation
blee-oh-MYE-sin

Trade Name
• Blenoxane

Pregnancy Category
Category D

Ther. class.
antineoplastics
Pharm. class.
antitumor antibiotics
bleomycin

Indications
• Treatment of:
» Lymphomas

» Squamous cell carcinoma

» Testicular embryonal cell carcinoma

» Choriocarcinoma

» Teratocarcinoma

• Intrapleural administration to prevent the reaccumulation of malignant effusions.
bleomycin

Action
Inhibits DNA and RNA synthesis

Therapeutic Effect(s):
Death of rapidly replicating cells, particularly malignant ones
bleomycin

Contraindications
• Hypersensitivity.

• OB: Lactation: Potential for fetal, infant harm.

Use Cautiously in:
• Renal impairment (dose ↓ required if CCr <35 mL/min).

• Pulmonary impairment.

• Nonmalignant chronic debilitating illness.

• Patients with childbearing potential.

• Geri: ↑ risk of pulmonary toxicity and reduction in renal function.
bleomycin

Side Effects / ADRs
CNS: aggressive behavior, disorientation, weakness.

Resp: PULMONARY FIBROSIS, *pneumonitis*.

CV: hypotension, peripheral vasoconstriction.

GI: anorexia, nausea, stomatitis, vomiting.

Derm: *hyperpigmentation*, *mucocutaneous toxicity*, alopecia, erythema, rashes, urticaria, vesiculation.

Hemat: anemia, leukopenia, thrombocytopenia.

Local: pain at tumor site, phlebitis at IV site.

Metabolic: weight loss.

Misc: ANAPHYLACTOID REACTIONS, *chills*, *fever*.
bleomycin

Interactions
Drug-Drug
• Hematologic toxicity ↑ with concurrent use of radiation therapy and other antineoplastics.

• Concurrent use with cisplatin↓ elimination of bleomycin and may ↑ toxicity.

• ↑ risk of pulmonary toxicity with other antineoplastics or thoracic radiation therapy.

• General anesthesia ↑ the risk of pulmonary toxicity.

• ↑ risk of Raynaud's phenomenon when used with vinblastine.
bleomycin

Dosage / Implementation
• IV, IM, SC (Adults and Children): 0.25–0.5 unit/kg (10–20 units/m2) weekly or twice weekly initially. If favorable response, lower maintenance doses given (1 unit/day or 5 units/wk IM or IV). May also be given as continuous IV infusion at 0.25 unit/kg or 15 units/m2/day for 4–5 days.

• Intrapleural (Adults): 15–20 units instilled for 4 hr, then removed.

Implementation:
• Lymphoma patients should receive initial test doses of 2 units or less for the first 2 doses.

• High Alert Med!

• Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers.

» Lymphoma patients should receive a 1- or 2-unit test dose 2–4 hr before initiation of therapy. Monitor closely for anaphylactic reaction. May not detect reactors.

» Premedication with acetaminophen, corticosteroids, and diphenhydramine may reduce drug fever and risk of anaphylaxis.

» Reconstituted solution is stable for 24 hr at room temperature and for 14 days if refrigerated.

• IM, SC: Reconstitute vial with 1–5 mL of sterile water for injection, 0.9% NaCl, or bacteriostatic water for injection. Do NOT reconstitute with diluents containing benzyl alcohol when used for neonates.

IV Administration:
• Intermittent Infusion:
Prepare IV doses by diluting 15-unit vial with at least 5 mL of 0.9% NaCl.
Diluent: Further dilute dose in 50 to 1000 mL of D5W or 0.9% NaCl
Rate: Administer slowly over 10 min.
bleomycin

Assessment
• Monitor vital signs before and frequently during therapy

• Assess for fever and chills. May occur 3–6 hr after administration and last 4–12 hr

• Monitor for anaphylactic (fever, chills, hypotension, wheezing) and idiosyncratic (confusion, hypotension, fever, chills, wheezing) reactions. Keep resuscitation equipment and medications on hand. Lymphoma patients are at particular risk for idiosyncratic reactions that may occur immediately or several hours after therapy, usually after the first or second dose

• Assess respiratory status for dyspnea and rales/crackles. Monitor chest x-ray before and periodically during therapy. Pulmonary toxicity occurs primarily in geriatric patients (age 70 or older) who have received 400 or more units or at lower doses in patients who received other antineoplastics or thoracic radiation. May occur 4–10 wk after therapy. Discontinue and do not resume bleomycin if pulmonary toxicity occurs

• Assess nausea, vomiting, and appetite. Weigh weekly. Modify diet as tolerated. Antiemetics may be given before administration
Lab Test Considerations

• Monitor CBC before and periodically during therapy. May cause thrombocytopenia and leukopenia (nadir occurs in 12 days and usually returns to pretreatment levels by day 17)

» Monitor baseline and periodic renal and hepatic function
bromocriptine

General
Pronunciation
broe-moe-KRIP-teen

Trade Names:
• Cycloset
• Parlodel

Pregnancy Category
Category B

Ther. class.
antiparkinson agents
antidiabetics
Pharm. class.
dopamine agonists
bromocriptine

Indications
• Adjunct to levodopa in the treatment of parkinsonism (Parlodel only)

• Treatment of hyperprolactinemia (amenorrhea/galactorrhea), including associated female infertility (Parlodel only)

• Treatment of prolactin-secreting adenomas (Parlodel only)

• Treatment of acromegaly (Parlodel only)

• Treatment of type 2 diabetes (as adjunct to diet and exercise) (Cycloset only)

Unlabelled Use:
Management of neuroleptic malignant syndrome
bromocriptine

Action
• Activates dopamine receptors in the CNS

• Decreases prolactin secretion

Therapeutic Effects:
• Relief of rigidity and tremor in parkinsonism.

• Restoration of fertility in hyperprolactinemia.

• Reduction in tumor size.

• Decreased growth hormone in acromegaly.

• Lowering of blood sugar in diabetic patients.
bromocriptine

Contraindications
• Hypersensitivity to bromocriptine, ergot alkaloids, or bisulfites.

• Severe cardiovascular disease or peripheral vascular disease.

• History of syncopal migraines (↑ risk of syncope) (Cycloset only).

• Lactation.

• Concurrent use of dopamine antagonists (e.g clozapine, olanzapine, ziprasidone) or other dopamine agonists (e.g. ropinirole).

• Type 1 diabetes (Cycloset only).

• Diabetic ketoacidosis (Cycloset only).

Use Cautiously in:
• Cardiac disease.

• Mental disturbances.

• May restore fertility (additional contraception may be required if pregnancy is undesirable).

• Hepatic impairment.

• Concurrent antihypertensive therapy (↑ risk of hypotension).

• OB: Safety not established.
bromocriptine

Side Effects / ADRs
CNS: *dizziness*, *drowsiness*, confusion, hallucinations, headache, insomnia, nightmares.

EENT: burning eyes, nasal stuffiness, visual disturbances.

Resp: PULMONARY FIBROSIS, effusions, pulmonary infiltrates.

CV: MI, *orthostatic hypotension*.

GI: *nausea*, abdominal pain, anorexia, dry mouth, metallic taste, vomiting.

Derm: urticaria.

MS: leg cramps.

Misc: digital vasospasm (acromegaly only).
bromocriptine

Interactions
Drug-Drug
• Additive hypotension with antihypertensives.

• Additive CNS depression with antihistamines , alcohol , opioid analgesics , and sedative/hypnotics.

• Additive neurologic effects with levodopa.

• Effects may be antagonized by phenothiazines, haloperidol, clozapine, olanzapine, ziprasidone, aripirazole, and metoclopramide.

• ↑ risk of side effects when used with ergot derivatives (do not use within 6 hours of each other).

• CYP3A4 inhibitors may ↑ effects.

• CYP3A4 inducers may ↓ effects.
bromocriptine

Dosage / Implementation
Parkinsonism
• PO (Adults): 1.25 mg 1–2 times daily, ↑ by 2.5 mg/day in 2–4 wk intervals (range is 2.5–100 mg/day in divided doses; up to 40 mg/day have been used).

Neuroleptic Malignant Syndrome (Unlabeled)
• PO (Adults): 5 mg once daily initially, dose increased as required up to 20 mg/day.

Implementation:
• High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order and dose calculations

• Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers

» Lymphoma patients should receive a 1- or 2-unit test dose 2–4 hr before initiation of therapy. Monitor closely for anaphylactic reaction. May not detect reactors

» Premedication with acetaminophen, corticosteroids, and diphenhydramine may reduce drug fever and risk of anaphylaxis

» Reconstituted solution is stable for 24 hr at room temperature and for 14 days if refrigerated

• IM, SC: Reconstitute vial with 1–5 mL of sterile water for injection, 0.9% NaCl, or bacteriostatic water for injection. Do not reconstitute with diluents containing benzyl alcohol when used for neonates
IV Adminstration:
• Intermittent Infusion:
Prepare IV doses by diluting 15-unit vial with at least 5 mL of 0.9% NaCl.
Diluent: Further dilute dose in 50 to 1000 mL of D5W or 0.9% NaCl.
Rate: Administer slowly over 10 min
bromocriptine

Assessment
• Assess patient for allergy to ergot derivatives.

» Monitor blood pressure before and frequently during drug therapy. Instruct patient to remain supine during and for several hours after 1st dose; severe hypotension may occur. Supervise ambulation and transfer during initial dosing to prevent injury from hypotension.

Parkinson's Disease
• Assess symptoms (restlessness or desire to keep moving, rigidity, tremors, pill rolling, masklike face, shuffling gait, muscle spasms, twisting motions, difficulty speaking or swallowing, loss of balance control) before and throughout therapy.

Acromegaly
• Physical examination including ring size, heel pad thickness, and soft-tissue volume should be assessed throughout therapy.

Hyperprolactinemia
• Sella turcica should be evaluated before therapy and yearly with CT scan or MRI scan.

Type 2 Diabetes
• Observe for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety).

Neuroleptic Malignant Syndrome
• Monitor symptoms (fever, respiratory distress, tachycardia, convulsions, diaphoresis, hypertension, hypotension, pallor, tiredness) for improvement.

Lab Test Considerations
• May cause ↑ serum BUN, AST, ALT, CPK, alkaline phosphatase, and uric acid levels; usually transient and clinically insignificant.

» Female infertility: Measure serum prolactin concentrations and anterior pituitary function before therapy. Monitor ovulation during therapy.

» Acromegaly: Monitor serum growth hormone and insulin-like growth factor (IGF-I) concentrations periodically during therapy.

» Hyperprolactinemia: Measure serum prolactin concentrations monthly during initial therapy and twice yearly during maintenance therapy to determine effectiveness of therapy.

» Type 2 Diabetes: Monitor serum glucose and glycosylated hemoglobin periodically during therapy to evaluate effectiveness of treatment.
buprenorphine

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
byoo-pre-NOR-feen

Trade Name(s)

• Buprenex

• Subutex
Controlled Substance Schedule
III

Pregnancy Category
Category C

Ther. class.
opioid analgesics

Pharm. class.
opioid agonists antagonists
buprenorphine

Indications
• IM, IV: Management of moderate to severe acute pain

• SL: Treatment of opioid dependence; suppresses withdrawal symptoms in opioid detoxification
buprenorphine

Action
• Binds to opiate receptors in the CNS

• Alters the perception of and response to painful stimuli while producing generalized CNS depression

• Has partial antagonist properties that may result in opioid withdrawal in physically dependent patients when used as an analgesic
Therapeutic Effect(s):

• IM, IV: Decreased severity of pain

• SL: Suppression of withdrawal symptoms during detoxification and maintenance from heroin or other opioids. Produces a relatively mild withdrawal compared to other agents
buprenorphine

Contraindications
• Hypersensitivity

• Lactation: Enters breast milk; avoid use or discontinue nursing
Use Cautiously in:

• Increased intracranial pressure

• Severe renal, hepatic, or pulmonary disease

• Hypothyroidism

• Adrenal insufficiency

• Alcoholism

• Debilitated patients (dose reduction required)

• Undiagnosed abdominal pain

• Prostatic hyperplasia

• OB: Safety not established; neonatal withdrawal may occur in infants born to patients receiving SL buprenorphine during pregnancy

• Geri: Dose reduction required
buprenorphine

Side Effects/ADRs
CNS: *confusion*, *dysphoria*, *hallucinations*, *sedation*, dizziness, euphoria, floating feeling, headache, unusual dreams.

EENT: blurred vision, diplopia, miosis (high doses).

Resp: respiratory depression.

CV: hypertension, hypotension, palpitations.

GI: *nausea*, constipation, dry mouth, ileus, vomiting.

GU: urinary retention.

Derm: *sweating*, clammy feeling.

Misc: physical dependence, psychological dependence, tolerance.
buprenorphine

Interactions
Drug-Drug

• Use with extreme caution in patients receiving MAO inhibitors (↑ CNS and respiratory depression and hypotension—↓ buprenorphine dose by 50%; may need to ↓ MAO inhibitor dose)

• ↑ CNS depression with alcohol , antihistamines , antidepressants , and sedative/hypnotics

• May ↓ effectiveness of other opioid analgesics

• Inhibitors of the CYP3A4 enzyme system including azole antifungals (itraconazole, ketoconazole) , erythromycin , protease inhibitor antiretrovirals (ritonavir, indinavir, saquinavir) ↑ blood levels and effects; dose reduction may be necessary during concurrent use

• Inducers of the CYP3A4 enzyme system including carbamazepine , rifampin , or phenytoin↓ blood levels and effects; dose modification may be necessary during concurrent use

• Concurrent abuse of IV buprenorphine and benzodiazepines may result in coma and death
Drug-Natural Products
Concomitant use of kava-kava , valerian , chamomile , or hops can ↑ CNS depression
buprenorphine

Dosage
Analgesia

• IM, IV (Adults): 0.3 mg q 4–6 hr as needed. May repeat initial dose after 30 min (up to 0.3 mg q 4 hr or 0.6 mg q 6 hr); 0.6-mg doses should be given only IM.

• IM, IV (Children 2–12 yr): 2–6 mcg (0.002–0.006 mg)/kg q 4–6 hr.
Treatment of opioid dependence

• SL (Adults): 12–16 mg/day as a single dose.
buprenorphine

Assessment
Pain

• Assess type, location, and intensity of pain before and 1 hr after IM and 5 min (peak) after IV administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient's pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal. Single doses of 600 mcg (0.6 mg) should be administered IM. Patients requiring doses higher than 600 mcg (0.6 mg) should be converted to an opioid agonist. Buprenorphine is not recommended for prolonged use or as first-line therapy for acute or cancer pain

• Assess level of consciousness, blood pressure, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Dose may need to be decreased by 25–50%. Buprenorphine 0.3–0.4 mg has approximately equal analgesic and respiratory depressant effects to morphine 10 mg

• Assess previous analgesic history. Antagonistic properties may induce withdrawal symptoms (vomiting, restlessness, abdominal cramps, increased blood pressure and temperature) in patients who are physically dependent on opioid agonists. Symptoms may occur up to 15 days after discontinuation and persist for 1–2 wk

• Buprenorphine has a lower potential for dependence than other opioids; however, prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Most patients receiving buprenorphine for pain do not develop psychological dependence. If tolerance develops, changing to an opioid agonist may be required to relieve pain
Opioid Dependence

• Assess patient for signs and symptoms of opioid withdrawal before and during therapy
Lab Test Considerations

• May cause ↑ serum amylase and lipase levels

» Monitor liver function tests prior to and periodically during therapy for opioid dependence

Toxicity and Overdose

• If an opioid antagonist is required to reverse respiratory depression or coma, naloxone (Narcan) is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by direct IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 1–2 min. Titrate dose to avoid withdrawal, seizures, and severe pain. Naloxone may not completely reverse respiratory depressant effects of buprenorphine; may require mechanical ventilation, oxygen, IV fluids, and vasopressors
bupropion

General
Pronunciation
byoo-PROE-pee-on
Trade Name(s)

• Aplenzin

• Budeprion SR

• Budeprion XL

• Wellbutrin

• Wellbutrin SR

• Wellbutrin XL

• Zyban
Pregnancy Category
Category B

Ther. class.
antidepressants
smoking deterrents

Pharm. class.
aminoketones
bupropion

Indications
• Treatment of depression (with psychotherapy)

• Depression in patients with seasonal affective disorder (XL only)

• Smoking cessation (Zyban only)
Unlabelled Use(s):

• Treatment of ADHD in adults (SR only)

• To increase sexual desire in women
bupropion

Action
• Decreases neuronal reuptake of dopamine in the CNS

• Diminished neuronal uptake of serotonin and norepinephrine (less than tricyclic antidepressants)
Therapeutic Effect(s):

• Diminished depression

• Decreased craving for cigarettes
bupropion

Contraindications
• Hypersensitivity

• History of bulimia, and anorexia nervosa

• Concurrent MAO inhibitor or ritonavir therapy

• Lactation: Potential for serious adverse reactions in nursing infants
Use Cautiously in:

• Renal/hepatic impairment (↓ dose recommended)

• Recent history of MI

• History of suicide attempt

• Unstable cardiovascular status

• May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children

• OB: Use only if benefit to patient outweighs potential risk to fetus

• Geri: ↑ risk of drug accumulation; ↑ sensitivity to effects
Exercise Extreme Caution in:

• History of seizures, head trauma or concurrent medications that ↓ seizure threshold (theophylline, antipsychotics, antidepressants, systemic corticosteroids)

• Severe hepatic cirrhosis (↓ dose required)

• Pedi: ↑ risk of suicidal thinking and behavior. Observe carefully, especially at initiation of therapy and during ↑ or ↓ in dose
bupropion

Side Effects/ADRs
CNS: SEIZURES, SUICIDAL THOUGHTS/BEHAVIOR, *agitation*, *headache*, depression, hostility, insomnia, mania, psychoses.

GI: *dry mouth*, *nausea*, *vomiting*, change in appetite, weight gain, weight loss.

Derm: photosensitivity.

Endo: hyperglycemia, hypoglycemia, syndrome of inappropriate ADH secretion.

Neuro: *tremor*.
bupropion

Interactions
Drug-Drug

• ↑ risk of adverse reactions when used with amantadine , levodopa , or MAO inhibitors (concurrent use of MAO inhibitors is contraindicated)

• ↑ risk of seizures with phenothiazines , antidepressants , theophylline , corticosteroids , OTC stimulants/anorectics , or cessation of alcohol or benzodiazepines (avoid or minimize alcohol use)

• Blood levels ↑ by ritonavir (avoid concurrent use)

• Carbamazepine may ↓ blood levels and effectiveness

• Concurrent use with nicotine replacement may cause hypertension

• ↑ risk of bleeding with warfarin

• Bupropion and one of its metabolites inhibit the CYP2D6 enzyme system and may ↑ levels and risk of toxicity from antidepressants (SSRIs and tricyclic), some beta blockers , antiarrhythmics , and antipsychotics
bupropion

Dosage
• PO (Adults): Immediate-release—100 mg twice daily initially; after 3 days may ↑ to 100 mg 3 times daily; after at least 4 wk of therapy, may ↑ up to 450 mg/day in divided doses (not to exceed 150 mg/dose; wait at least 6 hr between doses at the 300 mg/day dose or at least 4 hr between doses at the 450-mg/day dose). Sustained-release—150 mg once daily in the morning; after 3 days, may ↑ to 150 mg twice daily with at least 8 hr between doses; after at least 4 wk of therapy, may ↑ to a maximum daily dose of 400 mg given as 200 mg twice daily. Extended-release (Wellbutrin XL)—150 mg once daily in the morning, may be ↑ after 4 days to 300 mg once daily; some patients may require up to 450 mg/day as a single daily dose.

Seasonal Affective Disorder

• PO (Adults): 150 mg/day in the morning; if dose is well tolerated, ↑ to 300 mg/day in one wk. Doses should be tapered to 150 mg/day for 2 wk before discontinuing.
bupropion

Assessment
• Monitor mood changes. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia

• Assess mental status and mood changes, especially during initial few months of therapy and during dose changes. Risk may be increased in children, adolescents, and adults C24 yrs. Inform health care professional if patient demonstrates significant increase in signs of depression (depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, suicide attempt or suicidal ideation). Restrict amount of drug available to patient
Lab Test Considerations

• Monitor hepatic and renal function closely in patients with kidney or liver impairment to prevent ↑ serum and tissue bupropion concentrations
buspirone

General
Pronunciation
byoo-SPYE-rone

Trade Name(s)

• BuSpar
Pregnancy Category
Category B

Ther. class.
antianxiety agents
buspirone

Indications
Management of anxiety
buspirone

Actions
• Binds to serotonin and dopamine receptors in the brain

• Increases norepinephrine metabolism in the brain
Therapeutic Effect(s):
Relief of anxiety
buspirone

Contraindications
• Hypersensitivity

• Severe hepatic or renal impairment

• Concurrent use of MAO inhibitors

• Ingestion of large amounts of grapefruit juice
Use Cautiously in:

• Patients receiving other antianxiety agents (other agents should be slowly withdrawn to prevent withdrawal or rebound phenomenon)

• Patients receiving other psychotropics

• Lactation: OB: Safety not established
buspirone

Side Effects/ADRs
CNS: *dizziness*, *drowsiness*, *excitement*, *fatigue*, *headache*, *insomnia*, *nervousness*, *weakness*, personality changes.

EENT: *blurred vision*, *nasal congestion*, *sore throat*, *tinnitus*, altered taste or smell, conjunctivitis.

Resp: chest congestion, hyperventilation, shortness of breath.

CV: *chest pain*, *palpitations*, *tachycardia*, hypertension, hypotension, syncope.

GI: *nausea*, abdominal pain, constipation, diarrhea, dry mouth, vomiting.

GU: changes in libido, dysuria, urinary frequency, urinary hesitancy.

Derm: *rashes*, alopecia, blisters, dry skin, easy bruising, edema, flushing, pruritus.

Endo: irregular menses.

MS: *myalgia*.

Neuro: *incoordination*, *numbness*, *paresthesia*, tremor.

Misc: *clamminess*, *sweating*, fever.
buspirone

Interactions
Drug-Drug

• Use with MAO inhibitors may result in hypertension and is not recommended

• Erythromycin , nefazodone , ketoconazole , itraconazole , ritonavir , and other inhibitors of CYP3A4 ↑ blood levels and effects of buspirone; dose reduction is recommended (decrease to 2.5 mg twice daily with erythromycin, decrease to 2.5 mg once daily with nefazodone)

• Rifampin , dexamethasone , phenytoin , phenobarbital , carbamazepine , and other inducers of CYP3A4 ↓ blood levels and effects of buspirone; dose adjustment may be necessary

• Avoid concurrent use with alcohol
Drug-Natural Products
Concomitant use of kava-kava , valerian , or chamomile can ↑ CNS depression

Drug-Food
Grapefruit juice ↑ serum levels and effect; ingestion of large amounts of grapefruit juice is not recommended
buspirone

Dosage
• PO (Adults): 7.5 mg twice daily; increase by 5 mg/day q 2–4 days as needed (not to exceed 60 mg/day). Usual dose is 20–30 mg/day (in 2 divided doses).
buspirone

Assessment
• Assess degree and manifestations of anxiety before and periodically during therapy

• Buspirone does not appear to cause physical or psychological dependence or tolerance. However, patients with a history of drug abuse should be assessed for tolerance or dependence. Restrict amount of drug available to these patients
captopril

General
Pronunciation
KAP-toe-pril

Trade Name(s)

• Capoten
Genetic Implications

Pregnancy Category
Category C (first trimester)
Category D (second and third trimesters)

Ther. class.
antihypertensives

Pharm. class.
ace inhibitors
captopril

Indications
• Alone or with other agents in the management of hypertension

• Management of heart failure

• Reduction of risk of death, heart failure-related hospitalizations, and development of overt heart failure following myocardial infarction

• Treatment of diabetic nephropathy in patients with Type 1 diabetes mellitus and retinopathy
captopril

Action
Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin levels and ↓ aldosterone levels. Net result is systemic vasodilation

Therapeutic Effect(s):

• Lowering of blood pressure in patients with hypertension

• Improved survival and reduced symptoms in patients with heart failure

• Improved survival and reduced development of overt heart failure after myocardial infarction

• Decreased progression of diabetic nephropathy with decreased need for transplantation or dialysis
captopril

Contraindications
• Hypersensitivity

• History of angioedema with previous use of ACE inhibitors

• OB: Can cause injury or death of fetus – if pregnancy occurs, discontinue immediately

• Lactation: Appears in breast milk; patient must discontinue drug or provide alternate to breast milk
Use Cautiously in:

• Patients with collagen vascular disease, renal impairment, hypovolemia, hyponatremia, and concurrent diuretic therapy

• Surgery/anesthesia (hypotension may be exaggerated)

• Black patients (monotherapy for hypertension less effective, may require additional therapy; higher risk of angioedema)

• Women of childbearing potential

• Geri: Initial dose reduction recommended

Exercise Extreme Caution in:
History of angioedema
captopril

Side Effects/ADRs
CNS: dizziness, fatigue, headache, insomnia.

Resp: *cough*.

CV: *hypotension*, chest pain, palpitations, tachycardia.

GI: *taste disturbances*, abdominal pain, anorexia, constipation, diarrhea, nausea, vomiting.

GU: proteinuria, impaired renal function.

Derm: ANGIOEDEMA, rashes, pruritis.

F and E: hyperkalemia.

Hemat: AGRANULOCYTOSIS, neutropenia.

Misc: fever.
captopril

Interactions
Drug-Drug
• Excessive hypotension may occur with concurrent use of diuretics

• Additive hypotension with other antihypertensives

• ↑ risk of hyperkalemia with concurrent use of potassium supplements , potassium-sparing diuretics , potassium-containing salt substitutes , or angiotensin II receptor antagonists

• Antihypertensive response may be blunted by NSAIDs

• ↑ levels and may ↑ the risk of lithium toxicity

Drug-Natural Products
Avoid natural licorice (causes sodium and water retention and increases potassium loss)

Drug-Food
Food significantly ↓ absorption. Administer captopril 1 hr before meals
captopril

Dosage
• Note: Use lower doses (1/2 of those listed) in patients who are sodium and water depleted due to diuretics.

Hypertension
• PO (Adults and Adolescents): 12.5–25 mg 2–3 times daily, may be ↑ at 1–2 wk intervals up to 150 mg 3 times daily (initiate therapy with 6.25–12.5 mg 2–3 times daily in patients receiving diuretics).

Heart Failure
• PO (Adults): 25 mg 3 times daily (6.25–12.5 mg 3 times daily in patients who have been vigorously diuresed); titrated up to target dose of 50 mg 3 times daily (max dose = 450 mg/day).

Left Ventricular Dysfunction Post-MI
• PO (Adults): 6.25-mg test dose, followed by 12.5 mg 3 times daily, may be ↑ up to 50 mg 3 times daily.

Diabetic Nephropathy
• PO (Adults): 25 mg 3 times daily.
captopril

Assessment
Hypertension:
• Monitor blood pressure and pulse frequently during initial dose adjustment and periodically during therapy.

» Monitor frequency of prescription refills to determine compliance

» Assess patient for signs of angioedema (dyspnea, facial swelling).

Heart Failure:
• Monitor weight and assess patient routinely for resolution of fluid overload (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention)

Lab Test Considerations
• Monitor renal function. May cause ↑ BUN and serum creatinine. If ↑ BUN or serum creatinine concentrations occur, may require dose reduction or withdrawal

» May cause hyperkalemia

» May cause ↑ AST, ALT, alkaline phosphatase, and serum bilirubin

» Assess urine protein prior to and periodically during therapy for up to 1 yr in patients with renal impairment or those receiving > 150 mg/day of captopril. If excessive or increasing proteinuria occurs, re-evaluate ACE inhibitor therapy

» May cause positive antinuclear antibody (ANA) titer

» Monitor CBC with differential prior to initiation of therapy, every 2 wk for the first 3 mo, and periodically for up to 1 yr in patients at risk for neutropenia (patients with renal impairment, or collagen-vascular disease) or at first sign of infection. Discontinue therapy if neutrophil count is <1000/mm3

» May cause false-positive test results for urine acetone
carbamazepine

General
Pronunciation
kar-ba-MAZ-e-peen

Trade Name(s)
• Apo-Carbamazepine [Canada]

• Carbatrol

• Epitol

• Equetro

• Novo-Carbamaz [Canada]

• Tegretol

• Tegretol CR [Canada]

• Tegretol-XR

• Teril

Genetic Implications

Pregnancy Category
Category D

Ther. class.
anticonvulsants
mood stabilizers
carbamazepine

Indications
• Treatment of tonic-clonic, mixed, and complex-partial seizures

• Management of pain in trigeminal neuralgia or diabetic neuropathy

• Equetro only: Acute mania and mixed mania

Unlabelled Use(s):
Other forms of neurogenic pain
carbamazepine

Action
Decreases synaptic transmission in the CNS by affecting sodium channels in neurons

Therapeutic Effect(s):

• Prevention of seizures

• Relief of pain in trigeminal neuralgia

• Decreased mania
carbamazepine

Contraindications
• Hypersensitivity

• Bone marrow suppression

• Concomitant use or use within 14 days of MAO inhibitors

• OB: Use only during pregnancy if potential benefits outweigh risks to the fetus; additional vitamin K during last weeks of pregnancy has been recommended

• Lactation: Discontinue drug or bottle feed

Use Cautiously in:
• All patients (may ↑ risk of suicidal thoughts/behaviors)

• Cardiac or hepatic disease

• Renal failure (dosing adjustment required for ClCr < 10 mL/min

• ↑ intraocular pressure

• Geri: Older men with prostatic hyperplasia may be at ↑ risk for acute urinary retention or difficulty initiating stream

Exercise Extreme Caution in:
Patients positive for HLA-B*1502 allele (unless benefits clearly outweigh the risks)
carbamazepine

Side Effects/ADRs
CNS: SUICIDAL THOUGHTS, *ataxia*, *drowsiness*, fatigue, psychosis, sedation, vertigo.

EENT: blurred vision, nystagmus, corneal opacities.

Resp: pneumonitis.

CV: CHF, edema, hypertension, hypotension, syncope.

GI: hepatitis, pancreatitis, weight gain.

GU: hesitancy, urinary retention.

Derm: photosensitivity, rashes, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria.

Endo: syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia.

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, THROMBOCYTOPENIA, eosinophilia, leukopenia.

Misc: chills, fever, lymphadenopathy, ↑ liver enzymes, multi-organ hypersensitivity reactions, hepatic failure (rare).
carbamazepine

Interactions
Drug-Drug
• May ↑ metabolism of and therefore ↓ levels/ effectiveness of corticosteroids , doxycycline , felbamate , quinidine , warfarin , estrogen-containing contraceptives , barbiturates , cyclosporine , benzodiazepines , theophylline , lamotrigine , phenytoin , topiramate , valproic acid , bupropion , and haloperidol

• Danazol ↑ blood levels (avoid concurrent use if possible)

• Concurrent use (within 2 wk) of MAO inhibitors may result in hyperpyrexia, hypertension, seizures, and death

• Verapamil , diltiazem , propoxyphene , itraconazole , ketoconazole , erythromycin , clarithromycin , SSRIs , antidepressants , or cimetidine may inhibit the hepatic metabolism of carbamazepine and ↑ levels; may cause toxicity

• Enzyme inducers such as rifampin , phenobarbital , phenytoin , primidone , and methosuximide may ↓ serum concentration of carbamazepine

• May ↑ risk of hepatotoxicity from isoniazid

• Felbamate↓ carbamazepine levels but ↑ levels of active metabolite

• May ↓ effectiveness and ↑ risk of toxicity from acetaminophen

• May ↑ risk of CNS toxicity from lithium

• May ↓ duration of action of nondepolarizing neuromuscular blocking agents

Drug-Food
Grapefruit juice ↑ serum levels and oral bioavailability by 40% and therefore may ↑ effects
carbamazepine

Dosage
• PO (Adults):
Anticonvulsant—200 mg twice daily (tablets) or 100 mg 4 times daily (suspension); increase by 200 mg/day q 7 days until therapeutic levels are achieved (range is 600–1200 mg/day in divided doses q 6–8 hr; not to exceed 1 g/day in 12–15-yr-olds. Extended-release products are given twice daily (XR, CR).
Antineuralgic—100 mg twice daily or 50 mg 4 times daily (suspension); increase by up to 200 mg/day until pain is relieved, then maintenance dose of 200–1200 mg/day in divided doses (usual range, 400–800 mg/day).

• PO (Children 6–12 yr): 100 mg twice daily (tablets) or 50 mg 4 times daily (suspension). ↑ by 100 mg weekly until therapeutic levels are obtained (usual range 400–800 mg/day; not to exceed 1 g/day). Extended-release products (XR, CR) are given twice daily.

• PO (Children <6 yr): 10–20 mg/kg/day in 2–3 divided doses; may be ↑ at weekly intervals until optimal response and therapeutic levels are achieved. Usual maintenance dose is 250–350 mg/day (not to exceed 35 mg/kg/day).
carbamazepine

Assessment
• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression

• Monitor for changes in skin condition in early therapy. Stevens-Johnson syndrome and toxic epidermal necrolysis are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502 (occurs almost exclusively in patients with Asian ancestry, including South Asian Indians).

• Assess frequency, location, duration, and characteristics of seizure activity

Trigeminal Neuralgia
• Assess for facial pain (location, intensity, duration). Ask patient to identify stimuli that may precipitate facial pain (hot or cold foods, bedclothes, touching face)

Bipolar Disorder
• Assess mental status (mood, orientation, behavior) and cognitive abilities before and periodically during therapy
Lab Test Considerations

• Monitor CBC, including platelet count, reticulocyte count, and serum iron, weekly during the first 2 mo and yearly thereafter for evidence of potentially fatal blood cell abnormalities. Medication should be discontinued if bone marrow depression occurs

» Perform genetic testing for the HLA-B*1502 allele in patients of Asian ancestry prior to beginning therapy

» Liver function tests, urinalysis, and BUN should be routinely performed. May cause ↑ AST, ALT, serum alkaline phosphatase, bilirubin, BUN, urine protein, and urine glucose levels

» Monitor serum ionized calcium levels every 6 mo or if seizure frequency increases. Thyroid function tests and ionized serum calcium concentrations may be ↓; hypocalcemia ↓ seizure threshold

» Monitor ECG and serum electrolytes before and periodically during therapy. May cause hyponatremia

» May occasionally cause ↑ serum cholesterol, high-density lipoprotein, and triglyceride concentrations

» May cause false-negative pregnancy test results with tests that determine human chorionic gonadotropin

Toxicity and Overdose
• Serum blood levels should be routinely monitored during therapy. Therapeutic levels range from 4–12 mcg/mL
carbidopa/levodopa

General
Pronunciation
KAR-bi-doe-pa/LEE -voe-doe-pa [Pronunciation]

Trade Name(s)

• Parcopa

• Sinemet

• Sinemet CR
Pregnancy Category
Category C (carbidopa/levodopa)

Ther. class.
antiparkinson agents

Pharm. class.
dopamine agonists
carbidopa/levodopa

Indications
• Parkinson's disease

• Not useful for drug-induced extrapyramidal reactions
carbidopa/levodopa

Action
• Levodopa is converted to dopamine in the CNS, where it serves as a neurotransmitter

• Carbidopa, a decarboxylase inhibitor, prevents peripheral destruction of levodopa
Therapeutic Effect(s):
Relief of tremor and rigidity in Parkinson's syndrome
carbidopa/levodopa

Contraindications
• Hypersensitivity

• Angle-closure glaucoma

• MAO inhibitor therapy

• Malignant melanoma

• Undiagnosed skin lesions

• Some products contain tartrazine, phenylalanine, or aspartame and should be avoided in patients with known hypersensitivity
Use Cautiously in:

• History of cardiac, psychiatric, or ulcer disease

• OB: Safety not established

• Lactation: May ↓ serum prolactin
carbidopa/levodopa

Side Effects/ADRs
CNS: *involuntary movements*, anxiety, dizziness, hallucinations, memory loss, psychiatric problems, urges (gambling, sexual).

EENT: blurred vision, mydriasis.

GI: *nausea*, *vomiting*, anorexia, dry mouth, hepatotoxicity.

Derm: melanoma.

Hemat: hemolytic anemia, leukopenia.

Misc: darkening of urine or sweat.
carbidopa/levodopa

Interactions
Drug-Drug
• Use with MAO inhibitors may result in hypertensive reactions

• ↑ risk of arrhythmias with inhalation hydrocarbon anesthetics (especially halothane ; if possible discontinue 6–8 hr before anesthesia)

• Phenothiazines , haloperidol , papaverine , phenytoin , and reserpine may ↓ effect of levodopa

• Large doses of pyridoxine may ↓ beneficial effects of levodopa

• Concurrent use with methyldopa may alter the effectiveness of levodopa and ↑ risk of CNS side effects

• ↑ hypotension may result with concurrent antihypertensives

• Anticholinergics may ↓ absorption of levodopa

• ↑ risk of adverse reactions with selegilene or cocaine
Drug-Natural Products
Kava may ↓ levodopa effectiveness

Drug-Food
Ingestion of foods containing large amounts of pyridoxine may ↓ effect of levodopa
carbidopa/levodopa

Dosage
Carbidopa/Levodopa
• PO (Adults): 25 mg carbidopa/100 mg levodopa 3 times daily; may be ↑ every 1–2 days until desired effect is achieved (max = 8 tablets of 25 mg carbidopa/100 mg levodopa/day).

Carbidopa/Levodopa Extended-Release
• PO (Adults): Patients not currently receiving levodopa—50 mg carbidopa/200 mg levodopa twice daily (minimum of 6 hr apart) initially. Conversion from standard carbidopa/levodopa—initiate therapy with at least 10% more levodopa content/day (may need up to 30% more) given at 4–8 hr intervals while awake. Allow 3 days between dosage changes; some patients may require larger doses and shorter dosing intervals.
carbidopa/levodopa

Assessment
• Assess parkinsonian symptoms (akinesia, rigidity, tremors, pill rolling, shuffling gait, mask-like face, twisting motions, and drooling) during therapy. "On-off phenomenon" may cause symptoms to appear or improve suddenly

• Assess blood pressure and pulse frequently during period of dose adjustment
Lab Test Considerations

• May cause false-positive test results in Coombs' test

» May cause ↑ serum glucose. Dipstick for urine ketones may reveal false-positive results

» Monitor hepatic and renal function and CBC periodically in patients on long-term therapy. May cause ↑ AST, ALT, bilirubin, alkaline phosphatase, LDH, and serum protein-bound iodine concentrations. May cause ↓ BUN, creatinine, and uric acid

» May cause ↓ hemoglobin, ↓ hematocrit, agranulocytosis, hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia, and ↑ WBC

Toxicity and Overdose
• Assess for signs of toxicity (involuntary muscle twitching, facial grimacing, spasmodic eye winking, exaggerated protrusion of tongue, behavioral changes). Consult health care professional if symptoms occur
carvedilol

General
Pronunciation
kar-VE-di-lole [Pronunciation]

Trade Name(s)

• Coreg

• Coreg CR
Genetic Implications

Pregnancy Category
Category C

Ther. class.
antihypertensives

Pharm. class.
beta blockers
carvedilol

Indications
• Hypertension

• CHF (ischemic or cardiomyopathic) with digoxin, diuretics, and ACE inhibitors

• Left ventricular dysfunction after myocardial infarction
carvedilol

Action
• Blocks stimulation of beta1(myocardial) and beta2 (pulmonary, vascular, and uterine)-adrenergic receptor sites

• Also has alpha1 blocking activity, which may result in orthostatic hypotension
Therapeutic Effect(s):

• Decreased heart rate and blood pressure

• Improved cardiac output, slowing of the progression of CHF and decreased risk of death
carvedilol

Contraindications
• History of serious hypersensitivity reaction (Stevens-Johnson syndrome, angioedema, anaphylaxis)

• Pulmonary edema

• Cardiogenic shock

• Bradycardia, heart block or sick sinus syndrome (unless a pacemaker is in place)

• Uncompensated CHF requiring IV inotropic agents (wean before starting carvedilol)

• Severe hepatic impairment

• Asthma or other bronchospastic disorders
Use Cautiously in:

• CHF (condition may deteriorate during initial therapy)

• Renal impairment

• Hepatic impairment

• Diabetes mellitus (may mask signs of hypoglycemia)

• Thyrotoxicosis (may mask symptoms)

• Peripheral vascular disease

• History of severe allergic reactions (intensity of reactions may be increased)

• OB: Crosses placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression)

• Lactation: Pedi: Safety not established

• Geri: ↑ sensitivity to beta blockers; initial dose reduction recommended
carvedilol

Side Effects/ADRs
CNS: *dizziness*, *fatigue*, *weakness*, anxiety, depression, drowsiness, insomnia, memory loss, mental status changes, nervousness, nightmares.

EENT: blurred vision, dry eyes, nasal stuffiness.

Resp: bronchospasm, wheezing.

CV: BRADYCARDIA, CHF, PULMONARY EDEMA.

GI: *diarrhea*, constipation, nausea.

GU: *erectile dysfunction*, ↓ libido.

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, itching, rashes, urticaria.

Endo: *hyperglycemia*, hypoglycemia.

MS: arthralgia, back pain, muscle cramps.

Neuro: paresthesia.

Misc: ANAPHYLAXIS, ANGIOEDEMA, drug-induced lupus syndrome.
carvedilol

Interactions
Drug-Drug
• General anesthetics , IV phenytoin , diltiazem , and verapamil may cause ↑ myocardial depression

• ↑ risk of bradycardia with digoxin

• Amiodarone or fluconazole may ↑ levels

• ↑ hypotension may occur with other antihypertensives , acute ingestion of alcohol , or nitrates

• Concurrent use with clonidine ↑ hypotension and bradycardia

• May ↑ withdrawal phenomenon from clonidine (discontinue carvedilol first)

• Concurrent administration of thyroid preparations may ↓ effectiveness

• May alter the effectiveness of insulins or oral hypoglycemic agents (dose adjustments may be necessary)

• May ↓ effectiveness of theophylline

• May ↓ beneficial beta1-cardiovascular effects of dopamine or dobutamine

• Use cautiously within 14 days of MAO inhibitor therapy (may result in hypotension/bradycardia)

• Cimetidine may ↑ toxicity from carvedilol

• Concurrent NSAIDs may ↓ antihypertensive action

• Effectiveness may be ↓ by rifampin

• May ↑ serum digoxin levels

• May ↑ blood levels of cyclosporine (monitor blood levels)
carvedilol

Dosage
• PO (Adults):
Hypertension—6.25 mg twice daily, may be ↑ q 7–14 days up to 25 mg twice daily or extended-release—20 mg once daily, dose may be doubled every 7–14 days up to 80 mg once daily;
CHF—3.125 mg twice daily for 2 wk; may be ↑ to 6.25 mg twice daily. Dose may be doubled q 2 wk as tolerated (not to exceed 25 mg twice daily in patients <85 kg or 50 mg twice daily in patients >85 kg) or extended-release—10 mg once daily, dose may be doubled every 2 wk as tolerated up to 80 mg once daily;
Left ventricular dysfunction after MI—6.25 mg twice daily, ↑ after 3–10 days to 12.5 twice daily then to target dose of 25 mg twice daily; some patients may require lower initial doses and slower titration or extended-release—20 mg once daily, dose may be doubled every 3–10 days up to 80 mg once daily.
carvedilol

Assessment
• Monitor blood pressure and pulse frequently during dose adjustment period and periodically during therapy. Assess for orthostatic hypotension when assisting patient up from supine position

• Monitor intake and output ratios and daily weight. Assess patient routinely for evidence of fluid overload (peripheral edema, dyspnea, rales/crackles, fatigue, weight gain, jugular venous distention). Patients may experience worsening of symptoms during initiation of therapy for CHF
Hypertension

• Check frequency of refills to determine adherence
Lab Test Considerations

• May cause ↑ BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels

» May cause ↑ ANA titers

» May cause ↑ in blood glucose levels

Toxicity and Overdose

• Monitor patients receiving beta blockers for signs of overdose (bradycardia, severe dizziness or fainting, severe drowsiness, dyspnea, bluish fingernails or palms, seizures). Notify health care professional immediately if these signs occur
cefazolin

General
Pronunciation
sef-A-zoe-lin

Trade Name(s)

• Ancef
Pregnancy Category
Category B

Ther. class.
anti-infectives

Pharm. class.
first generation cephalosporins
cefazolin

Indications
• Treatment of the following infections due to susceptible organisms

» Skin and skin structure infections (including burn wounds)

» Pneumonia

» Urinary tract infections

» Biliary tract infections

» Genital infections

» Bone and joint infections

» Septicemia

» Bacterial endocarditis prophylaxis for dental and upper respiratory procedures

• Perioperative prophylaxis

• Not suitable for the treatment of meningitis
cefazolin

Action
Binds to bacterial cell wall membrane, causing cell death

Therapeutic Effect(s):
Bactericidal action against susceptible bacteria

Spectrum:

• Active against many gram-positive cocci including

» Streptococcus pneumoniae

» Group A beta-hemolytic streptococci

» Penicillinase-producing staphylococci

• Not active against

» Methicillin-resistant staphylococci

» Bacteroides fragilis

» Enterococcus

• Active against some gram-negative rods including

» Proteus mirabilis

» Escherichia coli
cefazolin

Contraindications
• Hypersensitivity to cephalosporins

• Serious hypersensitivity to penicillins
Use Cautiously in:

• Renal impairment (dose reduction and/or increased dosing interval recommended if CCr <30 mL/min)

• Hepatic impairment

• History of GI disease, especially colitis

• OB: Half-life is shorter and blood levels lower during pregnancy; has been used safely.Lactation: Low concentrations of drug appear in breast milk

• Geri: Dose adjustment due to age-related ↓ in renal function may be necessary
cefazolin

Side Effects/ADRs
CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, *diarrhea*, *nausea*, *vomiting*, cramps.

Derm: STEVENS-JOHNSON SYNDROME, *rash*, pruritis, urticaria.

Hemat: leukopenia, neutropenia, thrombocytopenia.

Local: *pain at IM site*, *phlebitis at IV site*.

Misc: allergic reactions including anaphylaxis and serum sickness, superinfection.
cefazolin

Interactions
Drug-Drug
Probenecid↓ excretion and ↑ blood levels of renally excreted cephalosporins
cefazolin

Dosage
• IM, IV (Adults):
Moderate-to-severe infections—500 mg-2 g every 6–8 hr; maximum 12 g/day.
Mild infections with Gram-positive cocci-250–500 mg every 8 hr.
Uncomplicated urinary tract infection—1 g every 12 hr.
Pneumococcal pneumonia—500 mg every 12 hr.
Infective endocarditis or septicemia—1–1.5 g every 6 hr.
Perioperative prophylaxis—1 g within 30–60 min prior to incision (an additional 500 mg-1 g should be given for surgeries B 2 hr). 500 mg-1 g should then be given for all surgeries every 6–8 hr for 24 hr following the surgery.

• IM, IV (Children and Infants >1 mo): 50–100 mg/kg/day divided every 8 hr; maximum: 6 g/day.
Bacterial endocarditis prophylaxis in penicillin-allergic patients:-25 mg/kg 30 minutes prior to procedure; maximum dose: 1 g.

See text for decreased dosage protocols in renal impairment.
cefazolin

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy

• Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction

• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
Lab Test Considerations

• May cause positive results for Coombs' test in patients receiving high doses or in neonates whose mothers were given cephalosporins before delivery

» May cause ↑ serum AST, ALT, alkaline phosphatase, bilirubin, LDH, BUN, and creatinine

» May rarely cause leukopenia, neutropenia, thrombocytopenia, and eosinophilia
cefepime

General
Pronunciation
SEFF-e-peem

Trade Name(s)

• Maxipime
Pregnancy Category
Category B

Ther. class.
anti-infectives

Pharm. class.
fourth generation cephalosporins
cefepime

Indications
• Treatment of the following infections caused by susceptible organisms

» Uncomplicated skin and skin structure infections

» Bone and joint infections

» Uncomplicated and complicated urinary tract infections

» Respiratory tract infections

» Complicated intra-abdominal infections (with metronidazole)

» Septicemia

• Empiric treatment of febrile neutropenic patients
cefepime

Actions
• Similar to that of second- and third-generation cephalosporins, but activity against staphylococci is less, whereas activity against gram-negative pathogens is greater, even for organisms resistant to first-, second-, and third-generation agents

• Notable is increased action against

» Enterobacter

» Haemophilus influenzae (including ß-lactamase-producing strains)

» Escherichia coli

» Klebsiella pneumoniae

» Neisseria

» Proteus

» Providencia

» Pseudomonas aeruginosa

» Serratia

» Moraxella catarrhalis (including ß-lactamase-producing strains)

• Not active against methicillin-resistant staphylococci or enterococci
cefepime

Contraindications
• Hypersensitivity to cephalosporins

• Serious hypersensitivity to penicillins
Use Cautiously in:

• Renal impairment (↓ dosing/↑ dosing interval recommended if CCr C60 mL/min)

• History of GI disease, especially colitis

• Patients with hepatic dysfunction or poor nutritional status (may be at increased risk of bleeding)

• Geriatric patients (dose adjustment due to age-related decrease in renal function may be necessary)

• OB: Pregnancy, lactation, and children <2 mo (safety not established)
cefepime

Side Effects/ADRs
CNS: SEIZURES (HIGH DOSES IN PATIENTS WITH RENAL IMPAIRMENT) , encephalopathy, headache.

GI: PSEUDOMEMBRANOUS COLITIS, diarrhea, nausea, vomiting.

Derm: *rashes*, pruritis, urticaria.

Hemat: bleeding, eosinophilia, hemolytic anemia, neutropenia, thrombocytopenia.

Local: *pain at IM site*, *phlebitis at IV site*.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS , superinfection, fever.
cefepime

Interactions
Drug-Drug

• Probenecid↓ excretion and ↑ blood levels

• Concurrent use of loop diuretics or aminoglycosides may ↑ risk of nephrotoxicity
cefepime

Dosage
• IM (Adults):
Mild-to-moderate uncomplicated or complicated urinary tract infections due to Escherichia coli —0.5–1 g every 12 hr.

• IV (Adults):
Moderate-to-severe pneumonia—1–2 g every 12 hr. Mild-to-moderate uncomplicated or complicated urinary tract infections 0.5–1 g every 12 hr.
Severe uncomplicated or complicated urinary tract infections, moderate-to-severe uncomplicated skin and skin structure infections, complicated intra-abdominal infections—2 g every 12 hr. Empiric treatment of febrile neutropenia—2 g every 8 hr.

• IV (Children 2 mo–16 yr): Uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections, pneumonia—50 mg/kg every 12 hr (not to exceed 2 g/dose).
Febrile neutropenia—50 mg/kg every 8 hr (not to exceed 2 g/dose).

Dosing frequency changes in renal impairment.
cefepime

Assessment
• Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy

• Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction

• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
Lab Test Considerations

• May cause positive results for Coombs' test in patients receiving high doses or in neonates whose mothers were given cephalosporins before delivery

» May cause ↑ serum AST, ALT, bilirubin, BUN, and creatinine

» May rarely cause leukopenia, neutropenia, thrombocytopenia, and eosinophilia
ceftriaxone

General
Pronunciation
sef-try-AX-one

Trade Name(s)

• Rocephin
Pregnancy Category
Category B

Ther. class.
anti-infectives

Pharm. class.
third generation cephalosporins
ceftriaxone

Indications
• Treatment of

» Skin and skin structure infections

» Bone and joint infections

» Complicated and uncomplicated urinary tract infections

» Uncomplicated gynecological infections including gonorrhea

» Lower respiratory tract infections

» Intra-abdominal infections

» Septicemia

» Meningitis

» Otitis media

• Perioperative prophylaxis
ceftriaxone

Action
Binds to the bacterial cell wall membrane, causing cell death

Therapeutic Effect(s):
Bactericidal action against susceptible bacteria

Spectrum:

• Similar to that of second-generation cephalosporins, but activity against staphylococci is less, while activity against gram-negative pathogens is greater, even for organisms resistant to first- and second-generation agents

• Notable is increased action against

» Acinetobacter

» Enterobacter

» Haemophilus influenzae (including ß-lactamase-producing strains)

» Haemophilus parainfluenzae

» Escherichia coli

» Klebsiella pneumoniae

» Morganella morganii

» Neisseria

» Proteus

» Providencia

» Serratia

» Moraxella catarrhalis

• Has some activity against anaerobes, including Bacteroides fragilis

• Not active against methicillin-resistant staphylococci or enterococci
ceftriaxone

Contraindications
• Hypersensitivity to cephalosporins

• Serious hypersensitivity to penicillins

• Pedi: Neonates C28 days (use in hyperbilirubinemic neonates may lead to kernicterus)

• Pedi: Neonates C28 days requiring calcium-containing IV solutions (↑ risk of precipitation formation)
Use Cautiously in:

• Combined severe hepatic and renal impairment (dose reduction/↑ dosing interval recommended)

• History of GI disease, especially colitis

• OB: Lactation: Pregnancy and lactation
ceftriaxone

Side Effects/ADRs
CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, diarrhea, cholelithiasis, gallbladder sludging.

Derm: rashes, urticaria.

Hemat: bleeding, eosinophilia, hemolytic anemia, leukopenia, thrombocytosis.

Local: *pain at IM site*, *phlebitis at IV site*.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS , superinfection.
ceftriaxone

Interactions
Drug-Drug
Should not be administered concomitantly with any calcium-containing solutions
ceftriaxone

Dosage
• IM, IV (Adults):
Most infections—1–2 g every 12–24 hr Gonorrhea—250 mg IM (single dose).
Meningitis—2 g every 12 hr.
Perioperative prophylaxis-1 g 0.5–2 hr before surgery (single dose).

• IM, IV (Children):
Most infections—50–75 mg/kg/day (not to exceed 2 g/day) divided every 12–24 hr.
Meningitis—100 mg/kg/day (not to exceed 4 g/day) divided every 12–24 hr.
Uncomplicated gonorrhea—125 mg IM (single dose).
Acute otitis media—50 mg/kg (not to exceed 1 g) IM single dose.
ceftriaxone

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy

• Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results

• Pedi: Assess newborns for jaundice and hyperbilirubinemia; can increase bilirubinemia and should not be administered to jaundiced neonates, especially premature neonates

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction

• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
Lab Test Considerations

• May cause positive results for Coombs' test

» May cause increased serum AST, ALT, alkaline phosphatase, bilirubin, LDH, BUN, and creatinine

» May rarely cause leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, lymphocytosis, and thrombocytosis
celecoxib

General
Pronunciation
sel-e-KOX-ib [Pronunciation]

Trade Name(s)

• Celebrex
Genetic Implications

Pregnancy Category
Category C

Ther. class.
antirheumatics
nonsteroidal anti inflammatory agents

Pharm. class.
cox 2 inhibitors
celecoxib

Indications
• Relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis

• Reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (endoscopic surveillance, surgery)

• Management of acute pain including primary dysmenorrhea
celecoxib

Action
• Inhibits the enzyme COX-2. This enzyme is required for the synthesis of prostaglandins

• Has analgesic, anti-inflammatory, and antipyretic properties
Therapeutic Effect(s):

• Decreased pain and inflammation caused by arthritis or spondylitis

• Decreased number of colorectal polyps

• Decreased pain
celecoxib

Contraindications
• Hypersensitivity

• Cross-sensitivity may exist with other NSAIDs, including aspirin

• History of allergic-type reactions to sulfonamides

• History of asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs, including the aspirin triad (asthma, nasal polyps, and severe hypersensitivity reactions to aspirin)

• Advanced renal disease

• Severe hepatic dysfunction

• Peri-operative pain from coronary artery bypass graft (CABG) surgery

• OB: Should not be used in late pregnancy (may cause premature closure of the ductus arteriosus)
Use Cautiously in:

• Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use)

• Pre-existing renal disease, heart failure, liver dysfunction, concurrent diuretic or ACE inhibitor therapy (↑ risk of renal impairment)

• Hypertension or fluid retention

• Renal insufficiency (may precipitate acute renal failure)

• Serious dehydration (correct deficits before administering)

• Patients who are known or suspected to be poor CYP2C9 metabolizers (↓ initial dose by 50%)

• Pre-existing asthma

• Pedi: Safety not established in children <2 yrs or for longer than 6 mo

• Geri: Concurrent therapy with corticosteroids or anticoagulants, long duration of NSAID therapy, history of smoking, alcoholism, geriatric patients, or poor general health status (↑ risk of GI bleeding)

• Lactation: Lactation
Exercise Extreme Caution in:
History of ulcer disease or GI bleeding
celecoxib

Side Effects/ADRs
CNS: dizziness, headache, insomnia.

CV: MYOCARDIAL INFARCTION, STROKE, THROMBOSIS, edema.

GI: GI BLEEDING, abdominal pain, diarrhea, dyspepsia, flatulence, nausea.

Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash.
celecoxib

Interactions
Drug-Drug

• CYP2C9 inhibitors may ↑ levels

• May ↓ effectiveness of ACE inhibitors , thiazide diuretics , and furosemide

• Fluconazole ↑ levels (use lowest recommended dosage)

• May ↑ risk of bleeding with warfarin and aspirin

• May ↑ serum lithium levels

• Does not inhibit the cardioprotective effect of low-dose aspirin
celecoxib

Dosage
• PO (Adults): Osteoarthritis—200 mg once daily or 100 mg twice daily. Rheumatoid arthritis—100–200 mg twice daily. Ankylosing spondylitis—200 mg once daily or 100 mg twice daily; dose may be ↑ after 6 wk to 400 mg daily. Familial adenomatous polyosis—400 mg twice daily. Acute pain, including dysmenorrhea—400 mg initially, then a 200-mg dose if needed on the first day; then 200 mg twice daily as needed.

Dosing changed in hepatic impairment.
celecoxib

Assessment
• Assess range of motion, degree of swelling, and pain in affected joints before and periodically throughout therapy

• Assess patient for allergy to sulfonamides, aspirin, or NSAIDs. Patients with these allergies should not receive celecoxib

• Monitor patient for signs of Stevens-Johnson syndrome and toxic epidermal necrolysis. Discontinue celecoxib at first sign of rash
Lab Test Considerations

• May cause ↑ AST and ALT levels

» May cause hypophosphatemia and ↑ BUN
cephalexin

General
Pronunciation
sef-a-LEX-in

Trade Name(s)

• Apo-Cephalex [Canada]

• DOM-Cephalexin [Canada]

• Keflex

• Nu-Cephalex [Canada]

• PMS Cephalexin [Canada]
Pregnancy Category
Category B

Ther. class.
anti-infectives

Pharm. class.
first generation cephalosporins
cephalexin

Indications
Treatment of the following infections caused by susceptible organisms

» Skin and skin structure infections

» Respiratory tract infections

» Otitis media

» Urinary tract infections

» Bone infections
cephalexin

Action
Binds to bacterial cell wall membrane, causing cell death

Therapeutic Effect(s):
Bactericidal action against susceptible bacteria

Spectrum:

• Active against many gram-positive cocci including

» Streptococcus pneumoniae

» Group A beta-hemolytic streptococci

» Staphylococci (including penicillinase-producing strains)

• Active against the following gram-negative organisms

» Escherichia coli

» Haemophilus influenzae

» Klebsiella pneumoniae

» Moraxella catarrhalis

» Proteus

• Not active against methicillin-resistant staphylococci or enterococci

» Enterococcus

• Not active against anaerobes
cephalexin

Contraindications
• Hypersensitivity to cephalosporins

• Serious hypersensitivity to penicillins
Use Cautiously in:

• Renal impairment

• History of GI disease, especially colitis

• OB: Lactation: Pregnancy and lactation (has been used safely)
cephalexin

Side Effects/ADRs
CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, *diarrhea*, abdominal pain, nausea, vomiting.

Derm: rashes, urticaria.

Hemat: eosinophilia, hemolytic anemia, neutropenia, thrombocytopenia.

Misc: allergic reactions including anaphylaxis, superinfection.
cephalexin

Interactions
Drug-Drug

• Probenecid↓ excretion and ↑ blood levels of renally excreted cephalosporins

• Concurrent use of loop diuretics or aminoglycosides may ↑ risk of renal toxicity
cephalexin

Dosage
• PO (Adults):
Most infections—250–500 mg every 6 hr.
Uncomplicated cystitis, skin and soft tissue infections, streptococcal pharyngitis—500 mg every 12 hr. Maximum dose: 4 g/day.

• PO (Children): Most infections—25–50 mg/kg/day divided every 6–8 hr (can be administered every 12 hr in skin/skin structure infections or streptococcal pharyngitis).
Otitis media—75–100 mg/kd/day divided every 6 hr. Maximum dose: 4 g/day.
cephalexin

Assessment
• Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy

• Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction
Lab Test Considerations

• May cause positive results for Coombs' test

» May cause ↑ serum AST, ALT, alkaline phosphatase, bilirubin, LDH, BUN, creatinine

» May rarely cause neutropenia, thrombocytopenia, and eosinophilia
chlorproPAMIDE

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
klor-PROE-pa-mide

Trade Name(s)

• Apo-Chlorpropamide [Canada]

• Diabinese

• Novo-Propamide [Canada]
Pregnancy Category
Category C

Ther. class.
antidiabetics

Pharm. class.
sulfonylureas
chlorproPAMIDE

Indications
Control of blood sugar in type 2 diabetes mellitus when diet therapy fails. Requires some pancreatic function.

Unlabelled Use(s):
Management of neurogenic diabetes insipidus.
chlorproPAMIDE

Action
• Lowers blood sugar by stimulating the release of insulin from the pancreas and increasing the sensitivity to insulin at receptor sites

• May also decrease hepatic glucose production

Therapeutic Effect(s):
Lowering of blood sugar in diabetic patients
chlorproPAMIDE

Contraindications
• Hypersensitivity

• Cross-sensitivity with sulfonamides (including thiazide diuretics) may occur

• Type 1 diabetes

• Diabetic coma or ketoacidosis

• Severe renal or hepatic disease

• Uncontrolled infection, serious burns, or trauma

• Lactation: Discontinue or bottle feed

Use Cautiously in:
• Severe cardiovascular disease

• Glucose 6-phosphate dehydrogenase deficiency (↑ risk of hemolytic anemia)

• Hepatic or renal impairment (↑ risk of hypoglycemia)

• Infection, stress, or changes in diet may alter requirements for control of blood sugar

• Impaired thyroid, pituitary, or adrenal function

• Malnutrition, high fever, prolonged nausea, or vomiting

• OB: Safety not established; insulin recommended during pregnancy

• Geri: Prolonged half-life in geriatric patients may cause hypoglycemia, dosage reduction may be required. Appears on Beers list.
chlorproPAMIDE

Side Effects/ADRs
CNS: anorexia, dizziness, headache.

GI: constipation, diarrhea, drug-induced hepatitis, ↑ appetite, nausea, vomiting.

Derm: *photosensitivity*, rash, pruritis, urticaria.

Endo: *hypoglycemia*, syndrome of inappropriate antidiuretic hormone (SIADH) secretion.

F and E: hyponatremia.

Hemat: APLASTIC ANEMIA, agranulocytosis, eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.

Misc: disulfiram-like reaction.
chlorproPAMIDE

Interactions
Drug-Drug

• Ingestion of alcohol may result in disulfiram-like reaction

• Effectiveness may be ↓ by concurrent use of diuretics , calcium channel blockers , corticosteroids , phenothiazines , hormonal contraceptives , estrogens , thyroid agents , phenytoin , nicotinic acid , adrenergics , and isoniazid

• Alcohol , androgens (testosterone) , chloramphenicol , fluoroquinolones , MAO inhibitors , miconazole , NSAIDs ), probenecid , salicylates , sulfonamides , and warfarin may ↑ the risk of hypoglycemia

• Concurrent use with warfarin may alter the response to both agents (may ↑ effects of both; close monitoring recommended during any changes in dose)

• Beta blockers may alter the response to oral hypoglycemic agents (↑ or ↓ requirements; nonselective agents may cause prolonged hypoglycemia)
Drug-Natural Products
Glucosamine may worsen hypoglycemia. Fenugreek, chromium, and coenzyme Q-10 may produce additive hypoglycemic effects
chlorproPAMIDE

Dosage
• PO (Adults): 250 mg once daily, initially; may ↑ dose by 50–125 mg/day at 3–5 day intervals. Maximum daily dose is 750 mg.Older, debilitated or malnourished patients—initiate therapy with 100–125 mg once daily; may ↑ dose by 50–125 mg/day at 3–5 day intervals. Maximum daily dose is 750 mg.Antidiuretic dose—100–250 mg/day.

Dosage altered in hepatic/renal impairment,
chlorproPAMIDE

Assessment
• Observe patient for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety). Long half-life of chlorpropamide increases the risk of recurrent hypoglycemia. Monitor patients who experience a hypoglycemic episode closely for 3–5 days

• Assess patient for allergy to sulfonamides
Lab Test Considerations

• Monitor serum glucose and glycosylated hemoglobin periodically during therapy to evaluate effectiveness

» Monitor CBC periodically during therapy. Notify health care professional promptly if ↓ in blood counts occurs

» May cause an ↑ in ASTand LDH

» Monitor urine periodically for glucose, ketones, and protein

» Monitor serum sodium levels and plasma osmolarity periodically during therapy in patients

Toxicity and Overdose

• Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated with administration of oral glucose. Severe hypoglycemia should be treated with IV D50W followed by continuous IV infusion of more dilute dextrose solution at a rate sufficient to keep serum glucose at approximately 100 mg/dL
cholestyramine

General
Pronunciation
koe-less-TEAR-a-meen [Pronunciation]

Trade Name(s)

• LoCHOLEST

• LoCHOLEST Light

• Prevalite

• Questran

• Questran Light
Pregnancy Category
Category C

Ther. class.
lipid-lowering agents

Pharm. class.
bile acid sequestrants
cholestyramine

Indications
• Management of primary hypercholesterolemia

• Pruritus associated with elevated levels of bile acids
Unlabelled Use(s):
Diarrhea associated with excess bile acids
cholestyramine

Action
Bind bile acids in the GI tract, forming an insoluble complex. Result is increased clearance of cholesterol

Therapeutic Effect(s):

• Decreased plasma cholesterol and low-density lipoproteins (LDLs)

• Decreased pruritus
cholestyramine

Contraindications
• Hypersensitivity

• Complete biliary obstruction

• Some products contain aspartame and should be avoided in patients with phenylketonuria
Use Cautiously in:
History of constipation

Exercise Extreme Caution in:
Children (may cause intestinal obstruction; deaths have occurred)
cholestyramine

Side Effects/ADRs
EENT: irritation of the tongue.

GI: *abdominal discomfort*, *constipation*, *nausea*, fecal impaction, flatulence, hemorrhoids, perianal irritation, steatorrhea, vomiting.

Derm: irritation, rashes.

F and E: hyperchloremic acidosis.

Metabolic: vitamin A, D, and K deficiency.
cholestyramine

Interactions
Drug-Drug

• May decrease absorption/effects of orally administered acetaminophen , amiodarone , clindamycin , clofibrate , digoxin , diuretics , gemfibrozil , glipizide , corticosteroids , imipramine , mycophenolate , methotrexate , methyldopa , niacin , NSAIDs , penicillin , phenytoin , phosphates , propranolol , tetracyclines , tolbutamide , thyroid preparations , ursodiol , warfarin , and fat-soluble vitamins (A, D, E, and K)

• May decrease absorption of other orally administered medications
cholestyramine

Dosage
• PO (Adults): 4 g 1–2 times daily (initially, may be increased as needed/tolerated up to 24 g/day in 6 divided doses).

• PO (Children): 240 mg/kg/day in 2–3 divided doses (not >8 g/day).
cholestyramine

Assessment
Hypercholesterolemia

• Obtain a diet history, especially in regard to fat consumption
Pruritus

• Assess severity of itching and skin integrity. Dose may be decreased when relief of pruritus occurs
Diarrhea

• Assess frequency, amount, and consistency of stools
Lab Test Considerations

• Serum cholesterol and triglyceride levels should be evaluated before initiating, frequently during first few months and periodically throughout therapy. Discontinue medication if paradoxical increase in cholesterol level occurs

» May cause an increase in AST, ALT, phosphorus, chloride, and alkaline phosphatase and a decrease in serum calcium, sodium, and potassium levels

» May also cause prolonged prothrombin times
cimetidine

General
Pronunciation
sye-ME-ti-deen

Trade Name(s)

• Apo-Cimetidine [Canada]

• Novocimetine [Canada]

• Peptol [Canada]

• Tagamet

• Tagamet HB
Pregnancy Category
Category B

Ther. class.
antiulcer agents

Pharm. class.
histamine h2 antagonists
cimetidine

Indications
• Short-term treatment of active duodenal ulcers and benign gastric ulcers

• Maintenance therapy for duodenal ulcers after healing of active ulcer(s)

• Management of gastroesophageal reflux disease (GERD)

• Treatment of heartburn, acid indigestion, and sour stomach (OTC use)

• Management of gastric hypersecretory states (Zollinger-Ellison syndrome)

• IV: Prevention and treatment of stress-induced upper GI bleeding in critically ill patients
Unlabelled Use(s):

• Management of GI symptoms associated with the use of NSAIDs

• Prevention of stress ulceration or aspiration pneumonitis

• Prevention of acid inactivation of supplemental pancreatic enzymes in patients with pancreatic insufficiency

• Management of urticaria
cimetidine

Action
Inhibits the action of histamine at the H2-receptor site located primarily in gastric parietal cells, resulting in inhibition of gastric acid secretion

Therapeutic Effect(s):

• Healing and prevention of ulcers

• Decreased symptoms of gastroesophageal reflux

• Decreased secretion of gastric acid
cimetidine

Contraindications
• Hypersensitivity

• Oral liquid contains alcohol and should be avoided in patients with known intolerance
Use Cautiously in:

• Renal impairment (more susceptible to adverse CNS reactions; increased dose interval recommended if renal impairment is severe)

• OB: /Lactation: Safety not established

• Geri: Appears on Beers list. Geriatric patients are more susceptible to adverse CNS reactions (dose reduction recommended)
cimetidine

Side Effects/ADRs
CNS: *confusion*, dizziness, drowsiness, hallucinations, headache.

CV: ARRHYTHMIAS.

GI: constipation, diarrhea, drug-induced hepatitis, nausea.

GU: decreased sperm count, erectile dysfunction.

Endo: gynecomastia.

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, anemia, neutropenia, thrombocytopenia.

Local: pain at IM site.

Misc: hypersensitivity reactions.
cimetidine

Interactions
Drug-Drug

• Cimetidine inhibits drug-metabolizing enzymes in the liver; may lead to ↑ blood levels and toxicity with the following—some benzodiazepines (especially chlordiazepoxide , diazepam , and midazolam ), some beta blockers ( labetalol , metoprolol , propranolol ), caffeine , calcium channel blockers , carbamazepine , chloroquine , lidocaine , metronidazole , moricizine , pentoxifylline , phenytoin , propafenone , quinidine , quinine , metformin , sulfonylureas , theophylline , triamterene , tricyclic antidepressants , and warfarin

• The effects of succinylcholine , flecainide , procainamide , carmustine , and fluorouracil are ↑ by cimetidine

• ↓ absorption of ketoconazole

• Antacids and sucralfate↓ absorption
Drug-Natural Products
↑ caffeine levels and side effects with caffeine-containing herbs ( cola nut , guarana , mate , tea, coffee)
cimetidine

Dosage
• PO (Adults):
Short-term treatment of active ulcers—300 mg 4 times daily or 800 mg at bedtime or 400–600 mg twice daily (not to exceed 2.4 g/day).
Duodenal ulcer prophylaxis—300 mg twice daily or 400 mg at bedtime.
GERD—800–1600 mg/day in divided doses.
Gastric hypersecretory conditions—300–600 mg q 6 hr (up to 12 g/day have been used).
OTC use—up to 200 mg may be taken twice daily (for no more than 2 wk).

• IM, IV (Adults):
Short-term treatment of active ulcers—300 mg q 6 hr (not to exceed 2.4 g/day).
Continuous IV infusion—900 mg infused over 24 hr (37.5 mg/hr); may be preceded by a 150-mg bolus dose.
Gastric hypersecretory conditions—300–600 mg q 6 hr (up to 12 g/day have been used).
Prevention of aspiration pneumonitis—300 mg IM 1 hr before anesthesia, then 300 mg IV q 4 hr until patient is conscious (unlabeled).
Prevention of upper GI bleeding in critically ill patients—50 mg/hr (25 mg/hr if CCr <30 mL/min).

Other dosages exist.
cimetidine

Assessment
• Assess patient for epigastric or abdominal pain and frank or occult blood in the stool, emesis, or gastric aspirate

• Assess geriatric and debilitated patients routinely for confusion. Report promptly
Lab Test Considerations

• CBC with differential should be monitored periodically throughout therapy

» Antagonize effects of pentagastrin and histamine during gastric acid secretion testing. Avoid administration for 24 hr preceding the test

» May cause false-negative results in skin tests using allergenic extracts. Histamine H antagonists should be discontinued 24 hr prior to the test

» May cause ↑ serum transaminases and serum creatinine

» Serum prolactin concentration may be ↑ following IV bolus of cimetidine. May also cause ↓ parathyroid concentrations
ciprofloxacin

General
Pronunciation
sip-roe-FLOX-a-sin

Trade Name(s)
• Cipro

Pregnancy Category
Category C

Ther. class.
anti-infectives
Pharm. class.
fluoroquinolones
ciprofloxacin

Indications
• PO, IV: Treatment of the following bacterial infections

» Urinary tract and gynecologic infections, including cystitis, gonorrhea, and prostatitis

» Respiratory tract infections including acute sinusitis, acute exacerbations of chronic bronchitis, and pneumonia

» Skin and skin structure infections

» Bone and joint infections

» Infectious diarrhea

» Complicated intra-abdominal infections (with metronidazole)

» Typhoid fever

• Post-exposure prophylaxis of inhalational anthrax

• Cutaneous anthrax
Unlabelled Use(s):
Febrile neutropenia
ciprofloxacin

Action
Inhibits bacterial DNA synthesis by inhibiting DNA gyrase enzyme

• Active against gram-positive pathogens, including S. aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Bacillus anthracis
• Gram-negative spectrum notable for activity against E. coli, Klebsiella pneumoniae, Enterobacter cloacae, Salmonella typhi, Shigella spp, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Providencia rettgeri, Morganella morganii, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, Campylobacter jejuni
ciprofloxacin

Contraindications
• Hypersensitivity (cross-sensitivity within class may exist)

• OB: Do not use unless potential benefit outweighs potential fetal risk

• Pedi: Use only for treatment of anthrax and complicated urinary tract infections in children 1–17 years due to possible arthropathy
Use Cautiously in:

• Known or suspected CNS disorder

• Renal impairment (dose reduction if CCr C50 mL/min)

• Concurrent use of corticosteroids (↑ risk of tendinitis/tendon rupture)

• Kidney, heart, or lung transplant patients (↑ risk of tendinitis/tendon rupture)

• Lactation: Safety not established except for treatment of anthrax

• Geri: ↑ risk of adverse reactions
ciprofloxacin

Side Effects/ADRs
CNS: SEIZURES, dizziness, drowsiness, headache, insomnia, agitation, confusion.

GI: PSEUDOMEMBRANOUS COLITIS, abdominal pain, *diarrhea*, abnormal liver enzymes , *nausea*.

GU: vaginitis.

Derm: photosensitivity, rash.

Endo: hyperglycemia, hypoglycemia.

Hemat: eosinophilia .

Local: phlebitis at IV site.

MS: tendinitis, tendon rupture.

Neuro: peripheral neuropathy.

Misc: hypersensitivity reactions including —ANAPHYLAXIS .
ciprofloxacin

Interactions
Drug-Drug

• Concurrent use with theophylline may result in ↑ theophylline concentrations and therefore serious and potentially fatal reactions due to theophylline toxicity; if concurrent use cannot be avoided serum theophylline levels should be monitored

• Administration with antacids , iron salts , bismuth subsalicylate , sucralfate , and zinc salts↓ absorption

• May alter the effects of warfarin

• May ↓ blood levels and effectiveness of phenytoin

• Serum levels may be ↓ by antineoplastics

• Cimetidine may interfere with elimination

• Beneficial effects may be antagonized by nitrofurantoin

• Probenecid↓ renal elimination

• May ↑ risk of nephrotoxicity from cyclosporine

• Concurrent use with foscarnet may ↑ risk of seizures

• Concurrent therapy with corticosteroids may ↑ risk of tendon rupture
Drug-Natural Products
Fennel decreases bioavailability

Drug-Food

• Absorption is impaired by concurrent enteral feeding (because of metal cations)

• Absorption of norfloxacin is decreased by food and/or dairy products (take 1 hr before or 2 hr after)
ciprofloxacin

Dosage
Most infections

• PO (Adults): 500–750 mg q 12 hr.

• IV (Adults): —400 mg q 12 hr.

Urinary tract infections

• PO (Adults): 250–500 mg q 12 hr; or 1000 mg q 24 hr for 10–14 days as extended-release tablets.Uncomplicated urinary tract infections—100 mg q 12 hr for 3 days or 500 mg q 24 hr for 3 days as extended-release tablets.

• PO (Children 1–17 yr): Complicated urinary tract infections—10–20 mg/kg every 12 hr (not to exceed 750 mg/dose)for 10–21 days.

Gonorrhea

• PO (Adults): 250 mg single dose.
Inhalational Anthrax

• PO, IV (Adults): 400 mg q 12 hr IV, change to 500 mg PO twice daily when clinically appropriate for a total of 60 days; one or two other anti-infectives may be added initially, depending on clinical situation.

• PO, IV (Children): 10–15 mg/kg q 12 hr IV, change to 10–15 mg/kg PO q 12 hr when clinically appropriate for a total of 60 days; one or two other anti-infectives may be added initially, depending on clinical situation.
Cutaneous anthrax

• PO (Adults): 500 mg twice daily for 60 days; some patients may require intravenous therapy initially depending on clinical situation (for IV dose see inhalational anthrax above).

• PO (Children): 10–15 mg/kg q 12 hr for 60 days; some patients may require intravenous therapy initially depending on clinical situation (for IV dose see inhalational anthrax above).

See text for less common dosages.
ciprofloxacin

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC; urinalysis; frequency and urgency of urination; cloudy or foul-smelling urine) at beginning of and throughout therapy

• Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results

• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction

• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy
Lab Test Considerations

» May cause ↑ serum AST, ALT, LDH, bilirubin, and alkaline phosphatase

» May also cause ↑ or ↓ serum glucose
cisplatin

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
sis-PLA-tin

Trade Name(s)

• Platinol [Canada]

• Platinol-AQ
Pregnancy Category
Category D

Ther. class.
antineoplastics

Pharm. class.
alkylating agents
cisplatin

Indications
• Metastatic testicular and ovarian carcinoma

• Advanced bladder cancer

• Head and neck cancer

• Cervical cancer

• Lung cancer

• Other tumors
cisplatin

Action
Inhibits DNA synthesis by producing cross-linking of parent DNA strands (cell-cycle phase–nonspecific)

Therapeutic Effect(s):
Death of rapidly replicating cells, particularly malignant ones
cisplatin

Contraindications
• Hypersensitivity

• Pregnancy or lactation
Use Cautiously in:

• Hearing loss

• Renal impairment (dosage ↓ recommended)

• CHF

• Electrolyte abnormalities

• Active infections

• Bone marrow depression

• Geriatric patients (↑ risk of nephrotoxicity, peripheral neuropathy)

• Chronic debilitating illnesses

• Patients with childbearing potential
cisplatin

Side Effects/ADRs
CNS: SEIZURES, malaise, weakness.

EENT: *ototoxicity*, *tinnitus*.

GI: *severe nausea*, *vomiting*, diarrhea, hepatotoxicity.

GU: nephrotoxicity, sterility.

Derm: alopecia.

F and E: *hypocalcemia*, *hypokalemia*, *hypomagnesemia*.

Hemat: LEUKOPENIA, THROMBOCYTOPENIA, *anemia*.

Local: phlebitis at IV site.

Metabolic: hyperuricemia.

Neuro: peripheral neuropathy.

Misc: anaphylactoid reactions.
cisplatin

Interactions
Drug-Drug

• ↑ nephrotoxicity and ototoxicity with other nephrotoxic and ototoxic drugs (aminoglycosides, loop diuretics)

• ↑ risk of hypokalemia and hypomagnesemia with loopdiuretics and amphotericin B

• May ↓phenytoin levels

• ↑ bone marrow depression with other antineoplastics or radiation therapy

• May ↓ antibody response to live-virus vaccines and ↑ adverse reactions
cisplatin

Dosage
• IV (Adults): Metastatic testicular tumors—20 mg/m2 daily for 5 days repeated q 3–4 wk. Metastatic ovarian cancer—75–100 mg/m2, repeat q 4 wk in combination with cyclophosphamide or 100 mg/m2 q 3 wk if used as a single agent. Advanced bladder cancer—50–70 mg/m2 q 3–4 wk as a single agent.

Other regimens are used.
cisplatin

Assessment
• Monitor vital signs frequently during administration. Report significant changes

• Monitor intake and output and specific gravity frequently during therapy. Report discrepancies immediately. To reduce the risk of nephrotoxicity, maintain a urinary output of at least 100 mL/hr for 4 hr before initiating and for at least 24 hr after administration

• Encourage patient to drink 2000–3000 mL/day to promote excretion of uric acid. Allopurinol and alkalinization of the urine may be used to help prevent uric acid nephropathy

• Assess patency of IV site frequently during therapy. Cisplatin may cause severe irritation and necrosis of tissue if extravasation occurs. If a large amount of highly concentrated cisplatin solution extravasates, mix 4 mL of 10% sodium thiosulfate with 6 mL of sterile water or 1.6 mL of 25% sodium thiosulfate with 8.4 mL of sterile water and inject 1–4 mL (1 mL for each mL extravasated) through existing line or cannula. Inject subcut if needle has been removed. Sodium thiosulfate inactivates cisplatin

• Severe and protracted nausea and vomiting usually occur 1–4 hr after a dose; vomiting may last for 24 hr. Administer parenteral antiemetic agents 30–45 min before therapy and routinely around the clock for the next 24 hr. Monitor amount of emesis and notify health care professional if emesis exceeds guidelines to prevent dehydration. Nausea and anorexia may persist for up to 1 wk

• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension

• Monitor for signs of anaphylaxis (facial edema, wheezing, dizziness, fainting, tachycardia, hypotension). Discontinue medication immediately and report symptoms. Epinephrine and resuscitation equipment should be readily available

• Medication may cause ototoxicity and neurotoxicity. Assess patient frequently for dizziness, tinnitus, hearing loss, loss of coordination, loss of taste, or numbness and tingling of extremities; may be irreversible. Notify health care professional promptly if these occur. Audiometry should be performed before initiation of therapy and before subsequent doses. Hearing loss is more frequent with children and usually occurs first with high frequencies and may be unilateral or bilateral

• Monitor for inadvertent cisplatin overdose. Doses >100 mg/m2/cycle once every 3–4 wk are rarely used. Differentiate daily doses from total dose/cycle. Symptoms of high cumulative doses include muscle cramps (localized, painful involuntary skeletal muscle contractions of sudden onset and short duration) and are usually associated with advanced stages of peripheral neuropathy.

Lab Test Considerations

• Monitor CBC with differential and platelet count before and routinely throughout therapy. The nadir of leukopenia, thrombocytopenia, and anemia occurs within 18–23 days and recovery 39 days after a dose. Withhold further doses until WBC is >4000/mm3 and platelet count is >100,000/mm3

» Monitor BUN, serum creatinine, and CCr before initiation of therapy and before each course of cisplatin to detect nephrotoxicity. May cause ↑ BUN and creatinine and ↓ calcium, magnesium, phosphate, sodium, and potassium levels that usually occur the 2nd wk after a dose. Do not administer additional doses until BUN is <25 mg/100 mL and serum creatinine is <1.5 mg/100 mL. May cause ↑ uric acid level, which usually peaks 3–5 days after a dose

» May cause transiently ↑ serum bilirubin and AST concentrations

» May cause positive Coombs' test result
citalopram

General
Pronunciation
si-TAL-oh-pram [Pronunciation]

Trade Name(s)

• Celexa
Pregnancy Category
Category C

Ther. class.
antidepressants

Pharm. class.
selective serotonin reuptake inhibitors ssris
citalopram

Indications
Depression

Unlabelled Use(s):
• Premenstrual dysphoric disorder (PMDD)
• Obsessive-compulsive discorder (OCD)
• Panic disorder
• Generalized anxiety disorder (GAD)
• Post-traumatic stress disorder (PTSD)
• Social anxiety disorder (social phobia)
citalopram

Action
Selectively inhibits the reuptake of serotonin in the CNS

Therapeutic Effect(s):
Antidepressant action
citalopram

Contraindications
• Hypersensitivity

• Concurrent MAO inhibitor or pimozide therapy
Use Cautiously in:

• History of mania

• History of suicide attempt/ideation (↑ risk during early therapy and during dose adjustment)

• History of seizure disorder

• Illnesses or conditions that are likely to result in altered metabolism or hemodynamic responses

• Severe renal or hepatic impairment

• OB: Use during third trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support

• Lactation: Present in breast milk and may result in lethargy with ↓ feeding in infants; weigh risk/benefits

• Pedi: May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment in children/adolescents (unlabeled for pediatric use)

• Geri: ↓ doses recommended
citalopram

Side Effects/ADRs
CNS: NEUROLEPTIC MALIGNANT SYNDROME, SUICIDAL THOUGHTS, *apathy*, *confusion*, *drowsiness*, *insomnia*, *weakness*, agitation, amnesia, anxiety, ↓ libido, dizziness, fatigue, impaired concentration, ↑ depression, migraine headache.

EENT: abnormal accommodation.

Resp: cough.

CV: postural hypotension, tachycardia.

GI: *abdominal pain*, *anorexia*, *diarrhea*, *dry mouth*, *dyspepsia*, *flatulence*, *↑ saliva*, *nausea*, altered taste, ↑ appetite, vomiting.

GU: amenorrhea, dysmenorrhea, ejaculatory delay, erectile dysfunction, polyuria.

Derm: *sweating*, photosensitivity, pruritus, rash.

Metabolic: weight loss, weight gain.

F and E: hyponatremia.

MS: arthralgia, myalgia.

Neuro: *tremor*, paresthesia.

Misc: SEROTONIN SYNDROME, fever, yawning.
citalopram

Interactions
Drug-Drug

• May cause serious, potentially fatal reactions when used with MAO inhibitors ; allow at least 14 days between citalopram and MAO inhibitors

• Concurrent use with pimozide may result in prolongation of the QTc interval and is contraindicated

• Drugs that affect serotonergic neurotransmitter systems, including linezolid , tramadol , and triptans ↑ risk of serotonin syndrome

• Use cautiously with other centrally acting drugs (including alcohol , antihistamines , opioid analgesics , and sedative/hypnotics ; concurrent use with alcohol is not recommended)

• Cimetidine may ↑ levels

• Serotonergic effects may be ↑ by lithium (concurrent use should be carefully monitored)

• Ketoconazole , itraconazole , erythromycin , and omeprazole may ↑ levels

• Carbamazepine may ↓ blood levels

• May ↑ levels of metoprolol

• Use cautiously with tricyclic antidepressants due to unpredictable effects on serotonin and norepinephrine reuptake

• ↑ risk of bleeding with aspirin , NSAIDs , clopidogrel , or warfarin

Drug-Natural Products
↑ risk of serotonergic side effects including serotonin syndrome with St. John's wort and SAMe
citalopram

Dosage
• PO (Adults): 20 mg once daily initially, may be ↑ by 20 mg/day at weekly intervals, up to 60 mg/day (usual dose is 40 mg/day).

• PO (Geriatric Patients): 20 mg once daily initially, may be ↑ to 40 mg/day only in nonresponding patients.

40mg max dosage absolute in nonresponders w/ renal impairment
citalopram

Assessment
• Monitor mood changes during therapy

» Assess for suicidal tendencies, especially during early therapy and dose changes. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults C24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for the next 4 wk, and on advice of health care professional thereafter

• Assess for sexual dysfunction (erectile dysfunction; decreased libido)

• Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile blood pressure, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans)
clindamycin

General
Pronunciation
klin-da-MYE-sin

Trade Name(s)

• Cleocin

• Cleocin T

• Clinda-Derm

• Clindagel

• Clindesse

• ClindaMax

• Clindets

• C/T/S

• Dalacin C [Canada]

• Dalacin T [Canada]

• Evoclin
Pregnancy Category
Category B

Ther. class.
anti-infectives
clindamycin

Indications
• PO, IM, IV: Treatment of

» Skin and skin structure infections

» Respiratory tract infections

» Septicemia

» Intra-abdominal infections

» Gynecologic infections

» Osteomyelitis

» Endocarditis prophylaxis

• Topical: Severe acne

• Vag: Bacterial vaginosis
Unlabelled Use(s):
PO, IM, IV: Treatment of Pneumocystis carinii pneumonia, CNS toxoplasmosis, and babesiosis
clindamycin

Action
Inhibits protein synthesis in susceptible bacteria at the level of the 50S ribosome

Therapeutic Effect(s):
Bactericidal or bacteriostatic, depending on susceptibility and concentration

Spectrum:

• Active against most gram-positive aerobic cocci, including

» Staphylococci

» Streptococcus pneumoniae

» other streptococci, but not enterococci

• Has good activity against those anaerobic bacteria that cause bacterial vaginosis, including Bacteroides fragilis , Gardnerella vaginalis , Mobiluncus spp, Mycoplasma hominis , and Corynebacterium

• Also active against P. jirovecii and Toxoplasma gondii
clindamycin

Contraindications
• Hypersensitivity

• Previous pseudomembranous colitis

• Severe liver impairment

• Diarrhea

• Known alcohol intolerance (topical solution, suspension)
Use Cautiously in:

• OB: Safety not established for systemic and topical; approved for vaginal use in 3rd trimester of pregnancy

• Lactation: Has been used safely but appears in breast milk and exposes infant to drug and its side effects
clindamycin

Side Effects/ADRs
CNS: dizziness, headache, vertigo.

CV: arrhythmias, hypotension.

GI: PSEUDOMEMBRANOUS COLITIS, *diarrhea*, bitter taste (IV only), nausea, vomiting.

Derm: rashes.

Local: phlebitis at IV site.
clindamycin

Interactions
Drug-Drug

• Kaolin/pectin may ↓ GI absorption

• May enhance the neuromuscular blocking action of other neuromuscular blocking agents

• Topical: Concurrent use with irritants , abrasives , or desquamating agents may result in additive irritation
clindamycin

Dosage
• PO (Adults): Most infections—150–450 mg q 6 hr. P. carinii pneumonia—1200–1800 mg/day in divided doses with 15–30 mg Primaquine/day (unlabeled). CNS toxoplasmosis—1200–2400 mg/day in divided doses with pyrimethamine 50–100 mg/day (unlabeled); Bacterial endocarditis prophylaxis—600 mg 1 hr before procedure.

• PO (Children >1 mo): 10–30 mg/kg/day divided q 6–8 hr; maximum dose 1.8 g/day. Bacterial endocarditis prophylaxis—20 mg/kg 1 hr before procedure.

• IM, IV (Adults): Most infections—300–600 mg q 6–8 hr or 900 mg q 8 hr (up to 4.8 g/day IV has been used; single IM doses of >600 mg are not recommended). P. cariniipneumonia—2400–2700 mg/day in divided doses with Primaquine (unlabeled). Toxoplasmosis—1200–4800 mg/day in divided doses with pyrimethamine. Bacterial endocarditis prophylaxis—600 mg 30 min before procedure.

• IM, IV (Children >1 mo): 25–40 mg/kg/day divided q 6–8 hr; maximum dose: 4.8 g/day. Bacterial endocarditis prophylax
clindamycin

Assessment
• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy

• Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results

• Monitor bowel elimination. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. This may begin up to several weeks following the cessation of therapy

• Assess patient for hypersensitivity (skin rash, urticaria)
Lab Test Considerations

• Monitor CBC; may cause transient ↓ in leukocytes, eosinophils, and platelets

» May cause ↑ alkaline phosphatase, bilirubin, CPK, AST, and ALT concentrations
clindamycin

Implementation
• PO: Administer with a full glass of water. May be given with or without meals. Shake liquid preparations well. Do not refrigerate. Stable for 14 days at room temperature

• IM: Do not administer >600 mg in a single IM injection
IV Adminstration:

• Intermittent Infusion:

Diluent: Vials must be diluted before use. Dilute a dose of 300 mg or 600 mg in 50 mL and a dose of 900 mg or 1200 mg in 100 mL. Compatible diluents include D5W, 0.9% NaCl, D5/0.9% NaCl, D5/0.45% NaCl, or LR. Admixed solution stable for 16 days at room temperature. Premixed infusion is already diluted and ready to use
Concentration: Not to exceed 18 mg/mL

• Rate:
Not exceed 30 mg/min. Hypotension and cardiopulmonary arrest have been reported following rapid IV administration
clonazepam

General
Pronunciation
kloe-NA-ze-pam

Trade Name(s)

• Klonopin

• Rivotril [Canada]

• Syn-Clonazepam [Canada]
Controlled Substance Schedule
IV

Pregnancy Category
Category C

Ther. class.
anticonvulsants

Pharm. class.
benzodiazepines
clonazepam

Indications
• Prophylaxis of

» Petit mal

» Petit mal variant

» Akinetic

» Myoclonic seizures

• Panic disorder with or without agoraphobia
Unlabelled Use(s):

• Uncontrolled leg movements during sleep

• Neuralgias

• Sedation

• Adjunct management of acute mania, acute psychosis, or insomnia
clonazepam

Action
• Anticonvulsant effects may be due to presynaptic inhibition

• Produces sedative effects in the CNS, probably by stimulating inhibitory GABA receptors
Therapeutic Effect(s):

• Prevention of seizures

• Decreased manifestations of panic disorder
clonazepam

Contraindications
• Hypersensitivity to clonazepam or other benzodiazepines

• Severe liver disease
Use Cautiously in:

• All patients (may ↑ risk of suicidal thoughts/behaviors)

• Angle-closure glaucoma

• Obstructive sleep apnea

• Chronic respiratory disease

• History of porphyria

• Do not discontinue abruptly

• OB: Safety not established; chronic use during pregnancy may result in withdrawal in the neonate

• Lactation: May enter breast milk; discontinue drug or bottle feed

• Pedi: Safety not established

• Geri: May experience excessive sedation at usual doses; decreased dosage recommended
clonazepam

Side Effects/ADRs
CNS: SUICIDAL THOUGHTS, *behavioral changes*, *drowsiness*, fatigue, slurred speech, ataxia, sedation, abnormal eye movements, diplopia, nystagmus.

Resp: increased secretions.

CV: palpitations.

GI: constipation, diarrhea, hepatitis, weight gain.

GU: dysuria, nocturia, urinary retention.

Hemat: anemia, eosinophilia, leukopenia, thrombocytopenia.

Neuro: *ataxia*, hypotonia.

Misc: fever, physical dependence, psychological dependence, tolerance.
clonazepam

Interactions
Drug-Drug

• Alcohol , antidepressants , antihistamines , other benzodiazepines , and opioid analgesics —concurrent use results in ↑ CNS depression

• Cimetidine , hormonal contraceptives , disulfiram , fluoxetine , isoniazid , ketoconazole , metoprolol , propoxyphene , propranolol , or valproic acid may ↓ metabolism of clonazepam, ↑ its actions

• May ↓ efficacy of levodopa

• Rifampin or barbiturates may ↑ metabolism and ↓ effectiveness of clonazepam

• Sedative effects may be ↓ by theophylline

• May ↑ serum phenytoin levels

• Phenytoin may ↓ serum clonazepam levels
Drug-Natural Products
Concomitant use of kava-kava , valerian , or chamomile can ↑ CNS depression
clonazepam

Dosage
• PO (Adults): 0.5 mg 3 times daily; may ↑ by 0.5–1 mg q 3 days. Total daily maintenance dose not to exceed 20 mg. Panic disorder—0.125 mg twice daily; ↑ after 3 days toward target dose of 1 mg/day (some patients may require up to 4 mg/day).
clonazepam

Assessment
• Observe and record intensity, duration, and location of seizure activity

• Assess degree and manifestations of anxiety and mental status (orientation, mood, behavior) prior to and periodically during therapy

• Assess need for continued treatment regularly

• Assess patient for drowsiness, unsteadiness, and clumsiness. These symptoms are dose related and most severe during initial therapy; may decrease in severity or disappear with continued or long-term therapy

• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression
Lab Test Considerations

• Patients on prolonged therapy should have CBC and liver function test results evaluated periodically. May cause an ↑ in serum bilirubin, AST, and ALT

» May cause ↓ thyroidal uptake of sodium iodide, 123I, and 131I

Toxicity and Overdose

• Therapeutic serum concentrations are 20–80 mg/mL. Flumazenil antagonizes clonazepam toxicity or overdose (may induce seizures in patients with history of seizure disorder or who are on tricyclic antidepressants)
clonidine

General
Pronunciation
KLON-i-deen

Trade Name(s)

• Catapres

• Catapres-TTS

• Dixarit [Canada]

• Duraclon
Pregnancy Category
Category C

Ther. class.
antihypertensives

Pharm. class.
adrenergics
centrally acting
clonidine

Indications
• PO, Transdermal: Management of mild to moderate hypertension

• Epidural: Management of cancer pain unresponsive to opioids alone
Unlabelled Use(s):

• Management of opioid withdrawal

• Treatment of attention-deficit hyperactivity disorder (ADHD)

• Adjunctive treatment of neuropathic pain
clonidine

Action
• Stimulates alpha-adrenergic receptors in the CNS, which results in decreased sympathetic outflow inhibiting cardioacceleration and vasoconstriction centers

• Prevents pain signal transmission to the CNS by stimulating alpha-adrenergic receptors in the spinal cord
Therapeutic Effect(s):

• Decreased blood pressure

• Decreased pain
clonidine

Contraindications
Contraindicated in:

• Hypersensitivity

• Epidural—injection site infection, anticoagulant therapy, or bleeding problems
Use Cautiously in:

• Serious cardiac or cerebrovascular disease

• Renal insufficiency

• Pedi: Evaluation for cardiac disease should precede initiation of therapy for ADHD in children

• Geri: Appear on Beers list due to increased risk of orthostatic hypotension and adverse CNS effects in geriatric patients (↓ dose recommended)

• OB: Lactation: Safety not established
clonidine

Side Effects/ADRs
CNS: *drowsiness*, depression, dizziness, nervousness, nightmares.

CV: bradycardia, hypotension (↑ with epidural), palpitations.

GI: *dry mouth*, constipation, nausea, vomiting.

GU: erectile dysfunction.

Derm: rash, sweating.

F and E: sodium retention.

Metabolic: weight gain.

Misc: *withdrawal phenomenon*.
clonidine

Interactions
Drug-Drug

• Additive sedation with CNS depressants , including alcohol , antihistamines , opioid analgesics , and sedative/hypnotics

• Additive hypotension with other antihypertensives and nitrates

• Additive bradycardia with beta blockers , diltiazem , verapamil , or digoxin

• MAO inhibitors , amphetamines , or tricyclic antidepressants may ↓ antihypertensive effect

• Withdrawal phenomenon may be ↑ by discontinuation of beta blockers

• Epidural clonidine prolongs the effects of epidurally administered local anesthetics

• May ↓ effectiveness of levodopa
clonidine

Dosage
• PO (Adults and Adolescents >= 12 yrs): 100 mcg (0.1 mg) bid, ↑ by 100–200 mcg (0.1–0.2 mg)/day q 2–4 days.
Usual maintenance dose is 200–600 mcg (0.2–0.6 mg)/day in 2–3 divided doses (up to 2.4 mg/day).
Urgent treatment—200 mcg (0.2 mg) loading dose, then 100 mcg (0.1 mg) q hr until blood pressure is controlled or 800 mcg (0.8 mg) total has been administered; follow with maintenance dosing.
Opioid withdrawal—300 mcg (0.3 mg)–1.2 mg/day, may be ↓ by 50%/day for 3 days, then discontinued or ↓ by 100–200 mcg (0.1–0.2 mg)/day.
clonidine

Assessment
• Monitor intake and output ratios and daily weight, and assess for edema daily, especially at beginning of therapy

• Monitor blood pressure and pulse frequently during initial dose adjustment and periodically throughout therapy. Report significant changes
Pain

• Assess location, character, and intensity of pain prior to, frequently during first few days, and routinely throughout administration

» Monitor for fever as potential sign of catheter infection

Opioid Withdrawal

• Monitor patient for signs and symptoms of opioid withdrawal (tachycardia, fever, runny nose, diarrhea, sweating, nausea, vomiting, irritability, stomach cramps, shivering, unusually large pupils, weakness, difficulty sleeping, gooseflesh)
Lab Test Considerations

• May cause transient ↑ in blood glucose levels

» May cause ↓ urinary catecholamine and vanillylmandelic acid (VMA) concentrations; these may ↑ on abrupt withdrawal

» May cause weakly positive Coombs' test result
clopidogrel

General
Pronunciation
kloh-PID-oh-grel

Trade Name(s)

• Plavix
Genetic Implications

Pregnancy Category
Category B

Ther. class.
antiplatelet agents

Pharm. class.
platelet aggregation inhibitors
clopidogrel

Indications
Reduction of atherosclerotic events (MI, stroke, vascular death) in patients at risk for such events including recent MI, acute coronary syndrome (unstable angina/non–Q-wave MI), stroke, or peripheral vascular disease.
clopidogrel

Actions
Inhibits platelet aggregation by irreversibly inhibiting the binding of ATP to platelet receptors.

Therapeutic Effect(s):
Decreased occurrence of atherosclerotic events in patients at risk.
clopidogrel

Contraindications
• Hypersensitivity

• Pathologic bleeding (peptic ulcer, intracranial hemorrhage)

• Lactation
Use Cautiously in:

• Patients at risk for bleeding (trauma, surgery, or other pathologic conditions)

• History of GI bleeding/ulcer disease

• Concurrent use of strong CYP2C19 inhibitors

• Severe hepatic impairment

• OB: Lactation: Pedi: Safety not established; use in pregnancy only if clearly indicated
clopidogrel

Side Effects/ADRs
Incidence of adverse reactions similar to that of aspirin

CNS: depression, dizziness, fatigue, headache.

EENT: epistaxis.

Resp: cough, dyspnea.

CV: chest pain, edema, hypertension.

GI: GI BLEEDING, abdominal pain, diarrhea, dyspepsia, gastritis.

Derm: pruritus, purpura, rash.

Hemat: BLEEDING, NEUTROPENIA, THROMBOTIC THROMBOCYTOPENIC PURPURA.

Metabolic: hypercholesterolemia.

MS: arthralgia, back pain.

Misc: fever, hypersensitivity reactions.
clopidogrel

Interactions
Drug-Drug
• Concurrent abciximab , eptifibatide , tirofiban , aspirin , NSAIDs , heparin , LMWHs , thrombolytic agents , ticlopidine , or warfarin may ↑ risk of bleeding

• May ↓ metabolism and ↑ effects of phenytoin , tolbutamide , tamoxifen , torsemide , fluvastatin , and many NSAIDs

• Concurrent use of strong CYP2C19 inhibitors (e.g. omeprazole , esomeprazole , cimetidine , fluconazole , ketoconazole , voriconazole , etravirine , felbamate , fluoxetine , or fluvoxamine ) may ↓ antiplatelet effects (concurrent use not recommended)

Drug-Natural Products
↑ bleeding risk with anise , arnica , chamomile , clove , fenugreek , feverfew , garlic , ginger , ginkgo , Panax ginseng , and others
clopidogrel

Dosage
Recent MI, Stroke, or Peripheral Vascular Disease

• PO (Adults): 75 mg once daily.
Acute Coronary Syndrome

• PO (Adults): 300 mg initially, then 75 mg once daily; aspirin 75–325 mg once daily should be given concurrently.
clopidogrel

Assessment
• Assess patient for symptoms of stroke, peripheral vascular disease, or MI periodically during therapy
• Monitor patient for signs of thrombotic thrombocytic purpura (thrombocytopenia, microangiopathic hemolytic anemia, neurologic findings, renal dysfunction, fever). May rarely occur, even after short exposure (<2 wk). Requires prompt treatment
Lab Test Considerations
• Monitor bleeding time during therapy. Prolonged bleeding time, which is time- and dose-dependent, is expected
» Monitor CBC with differential and platelet count periodically during therapy. Neutropenia and thrombocytopenia may rarely occur
» May cause ↑ serum bilirubin, hepatic enzymes, total cholesterol, nonprotein nitrogen (NPN), and uric acid concentrations
clozapine

General
Pronunciation
KLOE-za-peen

Trade Name(s)

• Clozaril

• FazaClo
Genetic Implications

Pregnancy Category
Category B

Ther. class.
antipsychotics
clozapine

Indications
• Schizoprenia unresponsive to or intolerant of standard therapy with other antipsychotics (treatment refractory)

• To reduce recurrent suicidal behavior in schizophrenic patients
clozapine

Action
• Binds to dopamine receptors in the CNS

• Also has anticholinergic and alpha-adrenergic blocking activity

• Produces fewer extrapyramidal reactions and less tardive dyskinesia than standard antipsychotics but carries high risk of hematologic abnormalities
Therapeutic Effect(s):

• Diminished schizophrenic behavior

• Diminished suicidal behavior
clozapine

Contraindications
• Hypersensitivity

• Bone marrow depression

• Severe CNS depression/coma

• Uncontrolled epilepsy

• Granulocytopenia

• Lactation: Discontinue drug or bottle-feed
Use Cautiously in:

• Prostatic enlargement

• Angle-closure glaucoma

• Malnourished patients or patients with cardiovascular, hepatic, or renal disease (use lower initial dose, titrate more slowly)

• Diabetes

• Seizure disorder

• Pedi: Children <16 yr (safety not established)

• Geri: ↑ risk of mortality in elderly patients treated for dementia-related psychosis
clozapine

Side Effects/ADRs
CNS: NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, *dizziness*, *sedation*.

EENT: visual disturbances.

CV: MYOCARDITIS, *hypotension*, *tachycardia*, ECG changes, hypertension.

GI: *constipation*, abdominal discomfort, dry mouth, ↑ salivation, nausea, vomiting, weight gain.

Derm: rash, sweating.

Endo: hyperglycemia.

Hemat: AGRANULOCYTOSIS, LEUKOPENIA.

Neuro: extrapyramidal reactions.

Misc: fever.
clozapine

Interactions
Drug-Drug

• ↑ anticholinergic effects with other agents having anticholinergic properties, including antihistamines , quinidine , disopyramide , and antidepressants

• Concurrent use with SSRI antidepressants (especially fluvoxamine ), cimetidine , ciprofloxacin , and erythromycin ↑ blood levels and risk of toxicity

• ↑ CNS depression with alcohol , antidepressants , antihistamines , opioid analgesics , or sedative/hypnotics

• ↑ hypotension with nitrates , acute ingestion of alcohol , or antihypertensives

• ↑ risk of bone marrow suppression with antihypertensives or radiation therapy

• Use with lithium ↑ risk of adverse CNS reactions, including seizures

• Phenytoin , nicotine , and rifampin may ↓ levels and lead to ↓ efficacy
Drug-Natural Products

• Caffeine-containing herbs ( cola nut , tea, coffee) may ↑ serum levels and side effects

• St. John's wort may ↓ blood levels and efficacy
clozapine

Dosage
• PO (Adults): 25 mg 1–2 times daily initially; ↑ by 25–50 mg/day over a period of 2 wk up to target dose of 300–450 mg/day. May ↑ by up to 100 mg/day once or twice further (not to exceed 900 mg/day). Treatment should be continued for at least 2 yr in patients with suicidal behavior.
clozapine

Assessment
• Monitor patient's mental status (orientation, mood, behavior) before and periodically during therapy

• Monitor blood pressure (sitting, standing, lying) and pulse rate before and frequently during initial dose titration

• Assess weight and BMI initially and throughout therapy

• Assess fasting blood glucose and cholesterol levels initially and throughout therapy. Refer as appropriate for nutritional/weight management and medical management

• Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked

• Monitor for signs of myocarditis (unexplained fatigue, dyspnea, tachypnea, fever, chest pain, palpitations, other signs and symptoms of heart failure, ECG changes, such as ST-T wave abnormalities, arrhythmias, or tachycardia during first month of therapy). If these occur, clozapine should be discontinued and not restarted

• Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects ( parkinsonian—difficulty speaking or swallowing, loss of balance control, pill-rolling motion of hands, mask-like face, shuffling gait, rigidity, tremors and dystonic muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Notify health care professional if these symptoms occur; reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benzotropine may be used to control these symptoms

• Although not yet reported for clozapine, monitor for possible tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities, lip smacking or puckering, puffing of cheeks, uncontrolled chewing, rapid or worm-like movements of tongue). Report these symptoms immediately; may be irreversible

• Monitor frequency and consistency of bowel movements. Increasing bulk and fluids in the diet may help to minimize constipation

• Clozapine lowers the seizure threshold. Institute seizure precautions for patients with history of seizure disorder

• Transient fevers may occur, especially during first 3 wk of therapy. Fever is usually self-limiting but may require discontinuation of medication. Also, monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur

Lab Test Considerations

• Monitor WBC, absolute neutrophil count (ANC), and differential count before initiation of therapy and WBC and ANC weekly for the first 6 months, then biweekly during therapy and weekly for 4 wk after discontinuation of clozapine. Because of the risk of agranulocytosis, clozapine is available only in a 1-wk supply through the Clozaril Patient Management System,which combines WBC testing, patient monitoring, and controlled distribution through participating pharmacies. If WBC is <3000 mm3 or granulocyte count is <1500 mm3, withhold clozapine, increase frequency of WBC monitoring according to management system guidelines, and monitor patient for signs and symptoms of infection. If acceptable WBC and ANC levels were maintained during first 6 months of continuous therapy, monitoring may decrease to every 2 wk. If levels are maintained for second 6 months, WBC and ANC may be monitored every 4 wk thereafter
Toxicity and Overdose

• Overdose is treated with activated charcoal and supportive therapy. Monitor patient for several days because of risk of delayed effects

» Avoid use of epinephrine and its derivatives when treating hypotension, and avoid quinidine and procainamide when treating arrhythmias
codeine

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
KOE-deen

Trade Name(s)

• Paveral [Canada]
Genetic Implications

Controlled Substance Schedule
II, III, IV, V(depends on content)

Pregnancy Category
Category C

Ther. class.
allergy, cold and cough remedies
antitussives
opioid analgesics

Pharm. class.
opioid agonists
codeine

Indications
• Management of mild to moderate pain

• Antitussive (in smaller doses)
Unlabelled Use(s):
Management of diarrhea
codeine

Action
• Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression

• Decreases cough reflex

• Decreases GI motility
Therapeutic Effect(s):

• Decreased severity of pain

• Suppression of the cough reflex

• Relief of diarrhea
codeine

Contraindications
Hypersensitivity

Use Cautiously in:

• Head trauma

• Increased intracranial pressure

• Severe renal, hepatic, or pulmonary disease

• Hypothyroidism

• Adrenal insufficiency

• Alcoholism

• Geri: Geriatric or debilitated patients (dose reduction required; more susceptible to CNS depression, constipation)

• Undiagnosed abdominal pain

• Geri: Prostatic hyperplasia

• OB: Has been used during labor; respiratory depression may occur in the newborn

• OB: Lactation: Avoid chronic use
codeine

Side Effects/ADRs
CNS: *confusion*, *sedation*, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams.

EENT: blurred vision, diplopia, miosis.

Resp: respiratory depression.

CV: *hypotension*, bradycardia.

GI: *constipation*, *nausea*, *vomiting*.

GU: urinary retention.

Derm: flushing, sweating.

Misc: physical dependence, psychological dependence, tolerance.
codeine

Interactions
Drug-Drug
• Use with extreme caution in patients receiving MAO inhibitors (↓ initial dose to 25% of usual dose)

• Additive CNS depression with alcohol , antidepressants , antihistamines , and sedative/hypnotics

• Administration of partial antagonists ( buprenorphine , butorphanol , nalbuphine , or pentazocine) may precipitate opioid withdrawal in physically dependent patients

• Nalbuphine or pentazocine may ↓ analgesia

Drug-Natural Products
Concomitant use of kava-kava , valerian , skullcap , chamomile , or hops can ↑ CNS depression
codeine

Dosage
• PO (Adults):
Analgesic—15–60 mg q 3–6 hr as needed.
Antitussive—10–20 mg q 4–6 hr as needed (not to exceed 120 mg/day).
Antidiarrheal —30 mg up to 4 times daily.

• PO (Children 6–12 yr): Analgesic—0.5 mg/kg (15 mg/m2) q 4–6 hr (up to 4 times daily) as needed.
Antitussive—5–10 mg q 4–6 hr as needed (not to exceed 60 mg/day). Antidiarrheal—0.5 mg/kg up to 4 times daily.

See text for less common dosages.
codeine

Assessment
• Assess blood pressure, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Dose may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use

» Assess bowel function routinely. Prevention of constipation should be instituted with increased intake of fluids, bulk, and laxatives to minimize constipating effects. Stimulant laxatives should be administered routinely if opioid use exceeds 2–3 days, unless contraindicated

Pain

• Assess type, location, and intensity of pain before and 1 hr (peak) after administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient's pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal

» An equianalgesic chart (see Equianalgesic Dosing Guidelines) should be used when changing routes or when changing from one opioid to another

» Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Most patients who receive codeine for pain do not develop psychological dependence. If progressively higher doses are required, consider conversion to a stronger opioid

Cough

• Assess cough and lung sounds during antitussive use
Lab Test Considerations

• May cause ↑ plasma amylase and lipase concentrations
Toxicity and Overdose

• If an opioid antagonist is required to reverse respiratory depression or coma, naloxone (Narcan) is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by direct IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain
colchicine

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
KOL-chi-seen

Trade Name(s)

• Colcrys
Pregnancy Category
Category D

Ther. class.
antigout agents
colchicine

Indications
• Acute attacks of gouty arthritis

• Familial Mediterranean fever

Unlabelled Use(s):
Treatment of hepatic cirrhosis and prevention of recurrences of gout
colchicine

Action
Interferes with the functions of WBCs in initiating and perpetuating the inflammatory response to monosodium urate crystals

Therapeutic Effect(s):

• Decreased pain and inflammation in acute attacks of gout

• Reduced number of attacks of familial Mediterranean fever
colchicine

Contraindications
• Hypersensitivity

• Use of P-glycoprotein inhibitors or strong CYP3A4 inhibitors in patients with renal or hepatic impairment
Use Cautiously in:

• Geri: Elderly or debilitated patients (toxicity may be cumulative)

• Renal impairment (dose ↓ suggested if CCr <80 mL/min)

• OB: Lactation: Pedi: Safety not established
colchicine

Side Effects/ADRs
GI: *diarrhea*, *nausea*, *vomiting*, abdominal pain.

Derm: alopecia.

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, leukopenia, thrombocytopenia.

Neuro: peripheral neuritis.
colchicine

Interactions
Drug-Drug
• Additive bone marrow depression may occur with bone marrow depressants or radiation therapy

• Strong CYP3A4 inhibitors (e.g., atazanavir , clarithromycin , indinavir , itraconazole , ketoconazole , nefazodone , nelfinavir , ritonavir , saquinavir , or telithromycin ) moderate CYP3A4 inhibitors (e.g., aprepitant , diltiazem , erythromycin , fluconazole , fosamprenavir , or verapamil ) and P-glycoprotein inhibitors (e.g., cyclosporine or ranolazine ) may ↑ levels and risk of toxicity (↓ colchicine dose)

• ↑ risk of rhabdomyolysis with HMG-CoA reductase inhibitors , gemfibrozil , or fenofibrate

• Additive adverse GI effects with NSAIDs

• May cause reversible malabsorption of vitamin B12

Drug-Food
Grapefruit juice may ↑ levels and risk of toxicity (↓ colchicine dose)
colchicine

Dosage
Acute Gout Attacks
• PO (Adults): 1.2 mg initially, then 0.6 mg 1 hr later (maximum dose of 1.8 mg in 1 hr); Concomitant use of strong CYP3A4 inhibitors—0.6 mg initially, then 0.3 mg 1 hr later (do not repeat treatment course for B3 days); Concomitant use of moderate CYP3A4 inhibitors—1.2 mg × 1 dose (do not repeat for >= days); Concomitant use of P-glycoprotein inhibitors—0.6 mg x 1 dose (do not repeat for >= days).

Prevention of Recurrent Gout Attacks (unlabeled use)
• PO (Adults): 0.6 mg daily (may be used up to 3 times daily or as little as 1–4 times weekly).

Familial Mediterranean Fever
• PO (Adults and Children >12 yr): 1.2–2.4 mg daily (in 1–2 divided doses); may ↑ or ↓ dose in 0.3 mg/day increments based on safety and efficacy; Concomitant use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors—Do not exceed 0.6 mg/day (may be given as 0.3 mg twice daily); Concomitant use of moderate CYP3A4 inhibitors—Do not exceed 1.2 mg/day (may be given as 0.6 mg twice daily).

• PO (Children 6–12 yr): 0.9–1.8 mg daily (in 1–2 divided doses).

• PO (Children 4–6 yr): 0.3–1.8 mg daily (in 1–2 divided doses).
colchicine

Assessment
• High Alert: Assess patient for toxicity (weakness, abdominal discomfort, nausea, vomiting, diarrhea, delirium, seizures, sense of suffocation, dilated pupils, difficulty swallowing, ascending paralysis, oliguria), withhold drug and report symptoms immediately

• Monitor intake and output ratios. Fluids should be encouraged to promote a urinary output of at least 2000 mL/day

Gout
• Assess involved joints for pain, mobility, and edema throughout therapy. During initiation of therapy, monitor for drug response every 1–2 hr

Familial Mediterranean fever
• Assess for signs and symptoms of familial Mediterranean fever (abdominal pain, chest pain, fever, chills, recurrent joint pain, red and swollen skin lesions) periodically during therapy
Lab Test Considerations
• In patients receiving prolonged therapy, monitor baseline and periodic CBC; report significant ↓ in values. May cause ↓ platelet count, leukopenia, aplastic anemia, and agranulocytosis

» May cause ↑ in AST and alkaline phosphatase

» May cause false-positive results for urine hemoglobin

» May interfere with results of urinary 17-hydroxycorticosteroid concentrations

Toxicity and Overdose
• Assess patient for toxicity (weakness, abdominal discomfort, nausea, vomiting, diarrhea). If these symptoms occur, discontinue medication and notify physician or other health care professional. Opioids may be needed to treat diarrhea
colchicine

Implementation
• High Alert: Colchicine overdose can be fatal. Cumulative dose should not exceed 4 mg. Cumulative dose should not exceed 2 mg in geriatric and renal patients. After dosing limit has been reached, do not administer any additional colchicine by any route for 21 days

• Intermittent therapy with 3 days between courses may be used to decrease risk of toxicity

• PO: Administer oral doses with food to minimize gastric irritation
cortisone

General
Pronunciation
KOR-ti-sone

Trade Name(s)

• Cortone [Canada]
Pregnancy Category
Category C

Ther. class.
anti inflammatories steroidal

Pharm. class.
corticosteroids
cortisone

Indications
• Management of adrenocortical insufficiency; chronic use in other situations is limited because of mineralocorticoid activity

• Replacement therapy in adrenal insufficiency
cortisone

Action
• In pharmacologic doses, suppresses inflammation and the normal immune response

• Has numerous intense metabolic effects (see Adverse Reactions and Side Effects)

• Suppresses adrenal function at chronic doses of 20 mg/day

• Replaces endogenous cortisol in deficiency states

• Also has potent mineralocorticoid (sodium-retaining) activity
Therapeutic Effect(s):

• Suppression of inflammation and modification of the normal immune response

• Replacement therapy in adrenal insufficiency
cortisone

Contraindications
• Active untreated infections (may be used in patients being treated for tuberculous meningitis)

• Lactation: Avoid chronic use
Use Cautiously in:

• Chronic treatment (will lead to adrenal suppression; use lowest possible dose for shortest period of time), unless being used to treat adrenal insufficiency

• Stress (surgery, infections); supplemental doses may be needed

• Hypothyroidism

• Cirrhosis

• Ulcerative colitis

• Potential infections may mask signs (fever, inflammation)

• OB: Safety not established

• Pedi: Chronic use will result in ↓ growth; use lowest possible dose for shortest period of time
cortisone

Side Effects/ADRs
Adverse reactions/side effects are much more common with high-dose/long-term therapy

CNS: *depression*, *euphoria*, headache, ↑ intracranial pressure (children only), personality changes, psychoses, restlessness.

EENT: cataracts, ↑ intraocular pressure.

CV: *hypertension*.

GI: PEPTIC ULCERATION, *anorexia*, *nausea*, vomiting.

Derm: *acne*, *↓ wound healing*, *ecchymoses*, *fragility*, *hirsutism*, *petechiae*.

Endo: *adrenal suppression*, hyperglycemia.

F and E: fluid retention (long-term high doses), hypokalemia, hypokalemic alkalosis.

Hemat: THROMBOEMBOLISM, thrombophlebitis.

Metabolic: weight gain, weight loss.

MS: *avascular necrosis of joints*, *muscle wasting*, *osteoporosis*, muscle pain.

Misc: *cushingoid appearance* (moon face, buffalo hump), ↑ susceptibility to infection.
cortisone

Interactions
Drug-Drug

• Additive hypokalemia with thiazide or loop diuretics , or amphotericin B

• Hypokalemia may ↑ risk of digoxin toxicity

• May ↑ requirement for insulins or oral hypoglycemic agents

• Phenytoin , phenobarbital , and rifampin stimulate metabolism; may ↓ effectiveness

• Oral contraceptives may ↓ metabolism

• ↑ risk of adverse GI effects with NSAIDs (including aspirin)

• At chronic doses that suppress adrenal function, may ↓ antibody response to and ↑ the risk of adverse reactions from live-virus vaccines
cortisone

Dosage
• PO (Adults): 25–300 mg/day in divided doses every 12–24 hr.

• PO (Children):
Adrenocortical insufficiency—0.7 mg/kg/day (20–25 mg/m2/day) in divided doses every 8 hr.
Other uses—2.5–10 mg/kg/day (75–300 mg/m2/day) in divided doses every 6–8 hr.
cortisone

Assessment
• Indicated for many conditions. Assess involved systems before and periodically during therapy

• Assess patient for signs of adrenal insufficiency (hypotension, weight loss, weakness, nausea, vomiting, anorexia, lethargy, confusion, restlessness) before and periodically during therapy

• Monitor intake and output ratios and daily weights. Observe patient for peripheral edema, steady weight gain, rales/crackles, or dyspnea. Notify health care professional if these occur

• Children should have periodic evaluations of growth
Lab Test Considerations

• Monitor serum electrolytes and glucose. May cause hyperglycemia, especially in persons with diabetes. May cause hypokalemia. Patients on prolonged courses of therapy should routinely have hematologic values, serum electrolytes, and serum electrolytes evaluated. May decrease WBC counts. May decrease serum potassium and calcium and increase serum sodium concentrations

» Guaiac-test stools. Promptly report presence of guaiac-positive stools

» May ↑ serum cholesterol and lipid values. May ↓ uptake of thyroid 123I or 131I

» Suppresses reactions to allergy skin tests

» Periodic adrenal function tests may be ordered to assess degree of hypothalamic-pituitary-adrenal axis suppression in systemic and chronic topical therapy
cyclophosphamide

General
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
sye-kloe-FOS-fa-mide

Trade Name(s)

• Procytox [Canada]
Pregnancy Category
Category D

Ther. class.
antineoplastics
immunosuppressants

Pharm. class.
alkylating agents
cyclophosphamide

Indications
• Alone or with other modalities in the management of

» Hodgkin's disease

» Malignant lymphomas

» Multiple myeloma

» Leukemias

» Mycosis fungoides

» Neuroblastoma

» Ovarian carcinoma

» Breast carcinoma, and a variety of other tumors

• Minimal change nephrotic syndrome in children
Unlabelled Use(s):
Severe active rheumatoid arthritis or Wegener's granulomatosis
cyclophosphamide

Action
Interferes with DNA replication and RNA transcription, ultimately disrupting protein synthesis (cell-cycle phase–nonspecific)

Therapeutic Effect(s):

• Death of rapidly replicating cells, particularly malignant ones

• Also has immunosuppressant action in smaller doses
cyclophosphamide

Contraindications
• Hypersensitivity

• OB: Lactation: Pregnancy or lactation
Use Cautiously in:

• Active infections

• Bone marrow depression

• Other chronic debilitating illnesses

• OB: Patients with childbearing potential
cyclophosphamide

Side Effects/ADRs
Resp: PULMONARY FIBROSIS.

CV: MYOCARDIAL FIBROSIS, hypotension.

GI: *anorexia*, *nausea*, *vomiting*.

GU: HEMORRHAGIC CYSTITIS, *hematuria*.

Derm: *alopecia*.

Endo: gonadal suppression, syndrome of inappropriate antidiuretic hormone (SIADH).

Hemat: LEUKOPENIA, *thrombocytopenia*, anemia.

Metabolic: hyperuricemia.

Misc: secondary neoplasms.
cyclophosphamide

Interactions
Drug-Drug

• Phenobarbital or rifampin may ↑ toxicity of cyclophosphamide

• Concurrent allopurinol or thiazidediuretics may exaggerate bone marrow depression

• May prolong neuromuscular blockade from succinylcholine

• Cardiotoxicity may be additive with other cardiotoxic agents (e.g., cytarabine , daunorubicin , doxorubicin )

• May ↓ serum digoxin levels

• Additive bone marrow depression with other antineoplastics or radiation therapy

• May potentiate the effects of warfarin

• May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions

• Prolongs the effects of cocaine
cyclophosphamide

Dosage
• Many regimens are used

• PO (Adults): 1–5 mg/kg/day.

• PO (Children): Induction—2–8 mg/kg/day (60–250 mg/m2/day) in divided doses for 6 days or longer. Maintenance—2–5 mg/kg (50–150 mg/m2/day) twice weekly.

• IV (Adults): 40–50 mg/kg in divided doses over 2–5 days or 10–15 mg/kg q 7–10 days or 3–5 mg/kg twice weekly or 1.5–3 mg/kg/day. Other regimens may use larger doses.

• IV (Children): Induction—2–8 mg/kg/day (60–250 mg/m2/day) in divided doses for 6 days or longer. Total dose for 7 days may be given as a single weekly dose. Maintenance—10–15 mg/kg every 7–10 days or 30 mg/kg q 3–4 wk.
cyclophosphamide

Assessment
• Monitor blood pressure, pulse, respiratory rate, and temperature frequently during administration. Report significant changes

• Monitor urinary output frequently during therapy. To reduce the risk of hemorrhagic cystitis, fluid intake should be at least 3000 mL/day for adults and 1000–2000 mL/day for children. May be administered with mesna

• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension

• Assess nausea, vomiting, and appetite. Weigh weekly. Antiemetics may be given 30 min before administration of medication to minimize GI effects. Anorexia and weight loss can be minimized by feeding frequent light meals

• Encourage patient to drink 2000–3000 mL/day to promote excretion of uric acid. Alkalinization of the urine may be used to help prevent uric acid nephropathy

• Assess cardiac and respiratory status for dyspnea, rales/crackles, weight gain, edema. Pulmonary toxicity may occur after prolonged therapy. Cardiotoxicity may occur early in therapy and is characterized by symptoms of CHF
Lab Test Considerations

• Monitor CBC with differential and platelet count before and periodically during therapy. The nadir of leukopenia occurs in 7–12 days (recovery in 17–21 days). Leukocytes should be maintained at 2500–4000/mm3. May also cause thrombocytopenia (nadir 10–15 days), and rarely causes anemia

» Monitor BUN, creatinine, and uric acid before and frequently during therapy to detect nephrotoxicity

» Monitor ALT, AST, LDH, and serum bilirubin before and frequently during therapy to detect hepatotoxicity

» Urinalysis should be evaluated before initiating therapy and frequently during therapy to detect hematuria or change in specific gravity indicative of SIADH

» May suppress positive reactions to skin tests for Candida , mumps, Trichophyton , and tuberculin purified-protein derivative (PPD). May also produce false-positive results in Papanicolaou smears
cycloSPORINE

General
Pronunciation
SYE-kloe-spor-een

Trade Name(s)

• Neoral

• Sandimmune

• Gengraf
Pregnancy Category
Category C

Ther. class.
immunosuppressants
antirheumatics
(DMARD)

Pharm. class.
polypeptides
cyclic
cycloSPORINE

Indications
• PO, IV: Prevention and treatment of rejection in renal, cardiac, and hepatic transplantation (with corticosteroids)

• PO: Treatment of severe active rheumatoid arthritis (Neoral only)

• Treatment of severe recalcitrant psoriasis in adult nonimmunocompromised patients (Neoral only)
Unlabelled Use(s):

• Management of recalcitrant ulcerative colitis

• Treatment of steroid resistant nephrotic syndrome

• Treatment of severe steroid resistant autoimmune disease

• Prevention and treatment of graft vs. host disease in bone marrow transplant patients
cycloSPORINE

Action
Inhibits normal immune responses (cellular and humoral) by inhibiting interleukin-2, a factor necessary for initiation of T-cell activity

Therapeutic Effect(s):

• Prevention of rejection reactions

• Slowed progression of rheumatoid arthritis or psoriasis
cycloSPORINE

Contraindications
• Hypersensitivity to cyclosporine or polyoxyethylated castor oil (vehicle for IV form)

• OB: Lactation: Should not be given unless benefits outweigh risks

• Disulfiram therapy or known alcohol intolerance (IV and oral liquid dose forms contain alcohol)

• Psoriasis patients receiving immunosuppressants or radiation

• Uncontrolled hypertension
Use Cautiously in:

• Severe hepatic impairment (dose ↓ recommended)

• Renal impairment (frequent dose changes may be necessary)

• Active infection

• Pedi: Larger or more frequent doses may be required
cycloSPORINE

Side Effects/ADRs
CNS: SEIZURES, *tremor*, confusion, flushing, headache, psychiatric problems.

CV: *hypertension*.

GI: *diarrhea*, *hepatotoxicity*, *nausea*, *vomiting*, abdominal discomfort, anorexia, pancreatitis.

GU: *nephrotoxicity*.

Derm: *hirsutism*, acne.

F and E: hyperkalemia, hypomagnesemia.

Hemat: anemia, leukopenia, thrombocytopenia.

Metabolic: hyperlipidemia, hyperuricemia.

Neuro: hyperesthesia, paresthesia.

Misc: *gingival hyperplasia*, *hypersensitivity reactions*, *infections (including activation of latent viral infections such as BK virus-associated nephropathy)*.
cycloSPORINE

Interactions
Drug-Drug
• ↑ blood levels and/or risk of toxicity with azithromycin, clarithomycin , amphotericin B , aminoglycosides , amiodarone , anabolic steroids , some calcium channel blockers , cimetidine , colchicine , danazol , erythromycin , fluconazole , fluoroquinolones , ketoconazole , itraconazole , metoclopramide , methotrexate, miconazole , nefazodone NSAIDs , melphalan , protease inhibitors quinupristin/dalfopristin , or hormonal contraceptives

• ↑ nephrotoxicity with acyclovir, amphotericin B, aminoglycosides, NSAIDs , trimethoprim , ciprofloxacin , and vancomycin

• ↑ immunosuppression with other immunosuppressants (cyclophosphamide, azathioprine, corticosteroids)

• Barbiturates , phenytoin , rifampin , rifabutin, carbamazepine , oxcarbamazepine or sulfonamides may ↓ effect of cyclosporine

• ↑ risk of hyperkalemia with potassium-sparing diuretics , potassium supplements , or ACE inhibitors

• ↑ serum levels/risk of toxicity from digoxin (↓ digoxin dose by 50%)

• Prolongs the action of neuromuscular blocking agents

• ↑ risk of seizures with imipenem/cilastatin

• May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions

• ↑ risk of rhabdomyolysis with HMG-CoA reductase inhibitors

• May ↑ levels and risk of toxicity from etoposide

• Concurrent use with tacrolimus should be avoided

• Orlistat↓ absorption; avoid concurrent use

• May ↑ levels and the risk of hypoglycemia from repaglinide
Drug-Natural Products

• Concomitant use with echinacea and melatonin may interfere with immunosuppression

• Use with St. John's wort may cause ↓ serum levels and organ rejection for transplant patients
Drug-Food

• Concurrent ingestion of grapefruit or grapefruit juice ↑ absorption and should be avoided

• Food↓ absorption of microemulsion products (Neoral)
cycloSPORINE

Dosage
• Doses are adjusted on the basis of serum level monitoring
Prevention of Transplant Rejection (Sandimmune)

• PO (Adults and Children): 14–18 mg/kg/dose 4–12 hr before transplant then 5–15 mg/kg/day divided q 12–24 hr postoperatively, taper by 5% weekly to maintenance dose of 3–10 mg/kg/day.

• IV (Adults and Children): 5–6 mg/kg/dose 4–12 hr before transplant, then 2–10 mg/kg/day in divided doses q 8–24 hr; change to PO as soon as possible.
Prevention of Transplant Rejection (Neoral)

• PO (Adults and Children): 4–12 mg/kg/day divided q 12 hr (dose varies depending on organ transplanted).
Rheumatoid Arthritis (Neoral only)

• PO (Adults and Children): 2.5 mg/kg/day given in 2 divided doses; may ↑ by 0.5–0.75 mg/kg/day after 8 and 12 weeks, up to 4 mg/kg/day. ↓ dose by 25–50% if adverse reactions occur.
Severe Psoriasis (Neoral only)

• PO (Adults): 2.5 mg/kg/day given in 2 divided doses, for at least 4 wk; then may ↑ by 0.5 mg/kg/day q 2 wk, up to 4 mg/kg/day. ↓ dose by 25–50% if adverse reactions occur.
Autoimmune Diseases (Neoral only)

• PO (Adults and Children): 1–3 mg/kg/day.
cycloSPORINE

Assessment
• Monitor serum creatinine level, intake and output ratios, daily weight, and blood pressure during therapy. Report significant changes
Prevention of Transplant Rejection

• Assess for symptoms of organ rejection throughout therapy
IV

• Monitor patient for signs and symptoms of hypersensitivity (wheezing, dyspnea, flushing of face or neck) continuously during at least the first 30 min of each treatment and frequently thereafter. Oxygen, epinephrine, and equipment for treatment of anaphylaxis should be available with each IV dose
Arthritis

• Assess pain and limitation of movement prior to and during administration

» Prior to initiating therapy, perform a physical exam including blood pressure on 2 occasions to determine baseline. Monitor blood pressure every 2 wk during initial 3 mo, then monthly if stable. If hypertension occurs, dose should be reduced

Psoriasis

• Assess skin lesions prior to and during therapy
Lab Test Considerations

• Measure serum creatinine, BUN, CBC, magnesium, potassium, uric acid, and lipids at baseline, every 2 wk during initial therapy, and then monthly if stable. Nephrotoxicity may occur; report significant increases

» May cause hepatotoxicity; monitor for ↑ AST, ALT, alkaline phosphatase, amylase, and bilirubin

» May cause ↑ serum potassium and uric acid levels and ↓ serum magnesium levels

» Serum lipid levels may be ↑

Toxicity and Overdose

• Evaluate serum cyclosporine levels periodically during therapy. Dose may be adjusted daily, in response to levels, during initiation of therapy. Guidelines for desired serum levels will vary among institutions