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amprenavir (Agenerase)
Tradename: Agenerase.
Indication: HIV infection.
Dosage: 1200 mg PO BID
Capsules: 50 & 150 mg.
Each 150 mg capsule of Agenerase contains 109 IU of vitamin E
Solution: 15 mg/mL, containing 46 IU of vitamin E/mL
Pharmacokinetics:
1) rapidly absorbed after oral administration
2) peak serum concentration 1-2 hours after oral administration
3) may be taken with or without food, avoid high fat meals
4) wide volume of distribution (430L)
5) 90% bound to serum proteins
- high affinity for alpha-1 acid glycoprotein
6) metabolized in the liver by cyt P450 3A4
7) eliminated in urine
8) 1/2life 7.1-10.6 hours
Monitor:
- serum ALT & serum AST baseline & peridodically [5]
Adverse effects:
1) common (> 5%)
- nausea/vomiting (73%)
- diarrhea (33%)
- rash (25%)
- perioral paresthesias (26%)
- peripheral paresthesias (8%)
- taste disorder (10%)
- depression (15%)
2) uncommon (< 5%)
- hyperglycemia
- hypertriglyceridemia
- hypercholesterolemia
- hepatotoxicity [5]
Drug interactions:
1) contradindicated due to potentially serious events
a) triazolam (Halcion)
b) astemizole (Hismanal)
c) Ergot alkaloids (Cafergot)
d) cisapride (Propulsid)
e) midazolam (Versed)
f) bepridil (Vascor)
2) agents which lower plasma concentration of amprenavir:
a) rifampin lowers plasma concentration of amprenavir by 90%
b) rifabutin lowers plasma concentration of amprenavir by 15%
c) phenobarbital
d) phenytoin
e) carbamazepine
3) amprenavir increases plasma concentration of:
a) dapsone
b) erythromycin
c) itraconazole
d) benzodiazepines
1] alprazolam
2] clorazepate
3] diazepam
4] flurazepam
e) calcium channel blockers
1] diltiazem
2] nicardipine
3] nifedipine
4] nimodipine
f) HMG-CoA reductase inhibitors
1] atorvastatin
2] cerivastatin
3] lovastatin
4] pravastatin
5] simvastatin
g) clozapine
h) carbamazepine
i) loratadine
j) pimozide
k) warfarin
4) any drug, including amprenavir itself, that inhibits cyt P450 3A4 may increase levels of amprenavir
5) any drug that induces cyt P450 3A4 may diminish levels of amprenavir
Mechanism of action:
1) inhibits HIV-1 protease
2) binds to active site of HIV-1 protease
3) prevents processing of gag & gag-pol precursors
4) results in formation of immature, non-infectious viral particles
Interactions
drug interactions
drug adverse effects (more general classes)
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
fosamprenavir (Lexiva)
General
antiretroviral protease inhibitor
Properties
INHIBITS: HIV protease
SIZE: MW = 505.6 G/M
MISC-INFO: elimination route LIVER
Database Correlations
PUBCHEM correlations
References
- GlaxoWellcome package insert
- Kaiser Permanente Northern California Regional Drug
Formulary, Update 9/99
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com
- Department of Veterans Affairs, VA National Formulary
- Prescriber's Letter 17(7): 2010
Recommended Lab Monitoring for Common Medications
Liver Function Test Scheduling
Detail-Document#: 260704
(subscription needed) http://www.prescribersletter.com