Amprenavir

Oral
HIV infection

Do not use oral solution. Capsules: moderate impairment (Child-Pugh score 5-8): 450 mg bid and severe impairment (Child-Pugh score 9-12): 300 mg bid.

May be taken with or without food. Do not take w/ high fat meal.

Hypersensitivity; sulfonamide allergy. Oral solution: Infants, child <4 yr old; renal or hepatic failure; concomitant metronidazole or disulfiram therapy. Pregnancy and lactation.

Elderly; renal impairment, hepatic impairment, DM, haemophilia; sensitivity to sulfonamides; use of sildenafil, vitamin E supplements. Always use with other antiretroviral agents in HIV treatment. Use oral solution only when capsule and other protease inhibitors are not therapeutic options. Capsule and oral solution not interchangeable on a mg-per-mg basis. Monitor for propylene glycol-associated adverse effect when oral solution is admin.

Tremors, oral or perioral paraesthesia; mood disorders, dyslipidaemia, redistribution of body fat causing "protease paunch", buffalo hump, facial atrophy and breast enlargement; rash; GI effects e.g. nausea, vomiting and diarrhoea.
Potentially Fatal: Hypersensitivity, Stevens-Johnson syndrome and acute haemolytic anaemia.

Monitor patient and institute supportive care as necessary.

Clorazepate, alprazolam, diazepam, erythromycin and midazolam increase risk of prolonged sedation and respiratory depression. Plasma concentrations of cilostazol, rifabutin, sertindole and terfenadine (risk of ventricular arrhythmias), sildenafil, antiarrhythmics may be increased. May increase warfarin effects. St. John's wort. Ethanol. Oestrogens; dexamethasone; delavirdine; efavirenz and veriparine; methadone.
Potentially Fatal: Drugs with narrow therapeutic index e.g. cisapride and terfenadine, pimozide, guanidine and rifampicin. Ergot alkaloids; lovastatin and simvastatin.

High fat meals increase amprenavir levels by about 6-folds.

Description:
Mechanism of Action: Amprenavir, a selective, competitive, reversible inhibitor of HIV-1 protease, inhibits the cleavage of viral polyprotein precursors into individual functional proteins found, thus forming immature, noninfectious viral particles.
Pharmacokinetics:
Absorption: Rapidly absorbed. Takes about 1-2 hr to reach peak plasma concentrations after an oral dose.
Distribution: 90% bound to plasma proteins.
Metabolism: Metabolised by liver cytochrome CYP3A4.
Excretion: Elimination half-life: about 7.1-10.6 hr. Mainly excreted as metabolites in faeces (about 75%).

Store at 25°C.

Antivirals