Drug Interactions With Haart

Front 1

types of pharmacodynamic changes that change drug effect w/o PK changes

Back 1

additive, synergistic, antagonistic

Front 2

4 categories/types of PK changes include

Back 2

A - absorption
D - distribution
M - metabolism
E - elimnation

Front 3

when used concomitantly, these two medications - and "interference with absorption" occurs

Back 3

Atazanavir + PPIs/H-2 blockers

Front 4

Atazanavir needs an ???? environment for proper absorption

Back 4

acidic

Front 5

PPI's are CONTRAINDICATED with what medication?

Back 5

Atazanavir***

there is loss of absorption if administered together; pt should be counseled on this!

Front 6

when Atazanavir is given with H2 blockers..how should the two be administered?

Back 6

12 hours apart

Front 7

interactions with HAART are more commonly PK or PD?

Back 7

PK

Front 8

****discuss metabolism of NRTIs and enfuvirtide (entry inhibitor)****

Back 8

minimal of no CYP3A4 activity

absorption drug interactions occur (drug-drug interactions)

Front 9

****NNRTI --- class effect regarding metabolism

Back 9

ALL NNRTIs are substrates of cyp3A4

Front 10

delavirdine aka Rescriptor -- is it an inducer or inhibitor of any CYP enzymes?

Back 10

potent inhibitor of cyp3A4

Front 11

efavirenz aka Sustiva -- is it an inducer or inhibitor of any CYP enzymes?

Back 11

mixed inhibitor (10%)/inducer (90%) of CYP 3A4

Front 12

nevirapine aka Viramune -- is it an inducer or inhibitor of any CYP enzymes?

Back 12

potent inducer of CYP3a4

Front 13

in regards to ALL protease inhibitors; what is the class effect regarding metabolism?

Back 13

ALL PIs are substrates of CYP3A4

Front 14

are PI's (as a class) inhibitors or inducers? of what CYP enzyme?

Back 14

inhibitors of CYP3A4 (including other pathways)

some may act as inducers (PI vs. PI)

differ in interaction potency

Front 15

what can be said about the metabolism of enfuvirtide (Fuzeon) - an entry inhibitor?

Back 15

it does not significantly affect nor is affected by CYP450

Front 16

CCR5 antagonist: Maraviroc -- is it a substrate, an inhibitor, an inducer???

Back 16

its a substrate of CYP3A4

NOT an inhibitor or inducer

Front 17

integrase inhibitor: raltegravir --- what can be said about its metabolism?

Back 17

metabolized via glucuronidation

does NOT affect CYP450 3A4 pathway

Front 18

what is the time frame of CYP450 inhibition?? (slow vs. fast)

Back 18

inhibition occurs RAPIDLY, as soon as adequate concentrations of inhibitor are reached

Front 19

what is the time frame of CYP450 induction?

Back 19

peak effect occurs SLOWLY based on half-life of drug and time to synthesize new CYP450 enzymes

Front 20

cyp450 inhibition leads to [increase or decrease] in drug levels? what about induction?

Back 20

inhibition -- leads to increased levels

induction -- leads to decreased levels

Front 21

list some antituberculosis meds that are a RED FLAG drug interaction with HAART meds

Back 21

rifampin, rifabutin - potent INDUCERS of cyp3a4

Front 22

list some azole antifungal meds that are a RED FLAG drug interaction with HAART meds

Back 22

itraconazole, voriconazole, ketoconazole - INHIBITORS of cyp3a4

Front 23

list some statins that are a RED FLAG drug interaction with HAART meds

Back 23

simvastatin, lovastatin, atorvastatin -- 3A4 SUBSTRATES

Front 24

list some anticonvulsant meds that are a RED FLAG drug interaction with HAART meds

Back 24

carbamazepine, phenobarbital, phenytoin -- potent 3A4 INDUCERS

Front 25

list some macrolide antibiotics that are a RED FLAG drug interaction with HAART meds

Back 25

clarythromycin, erythromycin -- 3A4 INHIBITORS


exception: azithro - no effect

Front 26

list some erectyle dysfunction meds that are a RED FLAG drug interaction with HAART meds

Back 26

sildenafil, vardenafil, tadalafil -- 3A4 SUBSTRATES

Front 27

list some benzodiazepines that are a RED FLAG drug interaction with HAART meds

Back 27

midazolam, triazolam -- SUBSTRATES

Front 28

why is methadone a RED FLAG drug interaction with HAART meds??

Back 28

HAART causes decreased levels of methadone, which could trigger withdrawl symptoms

Front 29

list some herbal remedies that are a RED FLAG drug interaction with HAART meds

Back 29

st. john's wart, garlic supplements -- 3A4 INDUCERS

Front 30

list some HAART combinations that should not be used together

Back 30

PI + PI

PI + NNRTI


Tenofovir + didanosine/atazanavir

Front 31

which two medications should not be given together due to concerns for LA, PN, pancreatitis, fatal acute renal failure???

Back 31

didanosine + tenofovir

increased risk w/ buffered tab and even more so with enteric coated

Front 32

Didanosine EC + tenovofir

when combined in pts weighing >60kg, what should be done in regards to dosing?

Back 32

dosing of tenofovir (EC) reduced from 400mg to 250mg po qd

Front 33

Didanosine EC + tenovofir

when combined in pts weighing <60kg, what should be done in regards to dosing?

Back 33

no recommendations exist, but might want to reduce dose to 200mg po qd

Front 34

rifampin vs. rifabutin effects on PIs...which one is more potent, which one is less?

Back 34

rifabutin is LESS LIKELY to cause decreased PI/NNRTI levels

Front 35

Rifampin is contraindicated with what antiretroviral class?

Back 35

PI

when pts on PI therapy need rifamycin therapy, rifampin should be replaced by rifabutin and the rifabutin should be dose reduced!

Front 36

what happens to statin levels with PI use?

Back 36

statin levels are increased

Front 37

which statin should be used in treatment of HIV pt dyslipidemia? and whY?

Back 37

PRAVASTATIN

cleared via renal elimination, not liver

consider reduced dose of atorvastatin (if using it)

why not use simva/PI combo? fatalities reported

Front 38

which statins should absolutely be avoided during HAART therapy?

Back 38

simvastatin (zocor)

lovastatin (mevacor)

Front 39

which two statins CAN be used concomitantly with HAART?

Back 39

atorvastatin is safe at LOW doses (start at 10mg and titrate up according to response and tolerability)

PRAVASTATIN***

Front 40

can rosuvastatin be used concomitantly w/HAART?

Back 40

no. interaction is still seen with UNKNOWN mechanism

- its not metabolized through CYP450 3A4

Front 41

are other agents (fenofibrates, zetia, niacin) okay to use with HAART?

Back 41

YES

Front 42

viagra interacts with which medications in HAART regimen?

Back 42

PIs (esp ritonavir)

NNRTI (delavirdine - Rescriptor)

Front 43

what happens during viagra + HAART interaction and what should be done about it?

Back 43

Viagra AUC increased 2-11 fold depending on the PI involved

Start with 25mg, do not repeat dose for at least 48 hours

May consider increasing subsequent doses in 25mg increments for those not responding

Toxicity would include priapism, severe hypotension, visual changes

Similar dose reduction recommendations available for other available ED medications

Front 44

St. Johns wort should be avoided with which HAART meds? why?

Back 44

Concern for treatment failure, resistance, or both

Avoid SJW with PI and NNRTI

Front 45

Garlic should be avoided with which HAART meds? why?

Back 45

Cmax and trough decreased

Concern for treatment failure, resistance, or both

Avoid garlic supplements with PI and NNRTI

Front 46

Maraviroc dosing changes according to the type of concomitant med given with it...

Back 46

150mg bid (w/CYP3A4 inhibitors)

300mg bid (not strong inhibitors or inducers)

600mg bid (w/strong CYP3A4 inducers)