Brands, Medical Use, Clinical Data
- Anti-HIV Agents
Brands / Synonyms
For the treatment of HIV-1 infection in combination with other antiretroviral agents.
Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism of Action
Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Biotrnasformation / Drug Metabolism
AGENERASE should not be administered concurrently with astemizole, bepridil, cisapride,
dihydroergotamine, ergotamine, midazolam, and triazolam. Although these drugs have not been specifically studied,
coadministration may result in competitive inhibition of metabolism of these products and may cause serious or
life-threatening adverse events.
AGENERASE is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to
any of the components of this product.
Amprenavir is metabolized in the liver by the cytochrome P450 enzyme system. Amprenavir inhibits CYP3A4. Caution should be used when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4, or potentially toxic medications that are metabolized by CYP3A4. Amprenavir does not inhibit CYP2D6, CYP1A2, CYP2C9, CYP2C19, CYP2E1, or uridine glucuronosyltransferase (UDPGT).
HIV Protease Inhibitors: The effect of amprenavir on total drug concentrations of other HIV protease inhibitors in subjects receiving both agents was evaluated using comparisons to historical data. Indinavir steady-state Cmax, A.C. and Cmin were decreased by 22%, 38%, and 27%, respectively, by concomitant amprenavir. Similar decreases in Cmax and AUC were seen after the first dose. Saquinavir steady-state Cmax, A.C. and Cmin were increased 21%, decreased 19%, and decreased 48%, respectively, by concomitant amprenavir. Nelfinavir steady-state Cmax, A.C. and Cmin were increased by 12%, 15%, and 14%, respectively, by concomitant amprenavir.
Methadone: Coadministration of amprenavir and methadone can decrease plasma levels ofmethadone.
Coadministration of amprenavir and methadone as compared to a non-matched historicalcontrol group resulted in a 30%, 27%, and 25% decrease in serum amprenavir AUC, Cmax, andCmin, respectively.
Amprenavir is an inhibitor of cytochrome P450 C.P.A. metabolism and therefore should not be administered concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4. There are other agents that may result in serious and/or life-threatening drug interactions.
Laboratory Tests: The combination of Amprenavir and low-dose ritonavir has been associated with elevations of cholesterol and triglycerides, SGOT (AST), and SGPT (ALT) in some patients. Appropriate laboratory testing should be considered prior to initiating combination therapy with Amprenavir and ritonavir and at periodic intervals or if any clinical signs or symptoms of hyperlipidemia or elevated liver function tests occur during therapy. For comprehensive information concerning laboratory test alterations associated with ritonavir, physicians should refer to the complete prescribing information for NORVIR (ritonavir).