indication

For the treatment of HIV-1 infection in combination with other antiretroviral agents.

pharmacology

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.

biotransformation

Hepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces.

absorption

Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (T_max) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.

half life

7.1-10.6 hours

drug interactions

Abacavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored.

Acenocoumarol: Amprenavir may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.

Alprazolam: Amprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.

Aluminium: The antiacid decreases the absorption of amprenavir

Amiodarone: The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.

Anisindione: Amprenavir may increase the anticoagulant effect of anisindione by increasing its serum concentration.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atorvastatin: Amprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.

Bepridil: Amprenavir may increase the effect and toxicity of bepridil.

Bismuth Subsalicylate: The antiacid decreases the absorption of amprenavir

Calcium: The antiacid decreases the absorption of amprenavir

Cisapride: Amprenavir may increase the effect and toxicity of cisapride.

Clorazepate: Amprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.

Cyclosporine: The protease inhibitor, amprenavir, may increase the effect of cyclosporine.

Delavirdine: Decreased levels of delavirdine with increased levels of amprenavir

Diazepam: Amprenavir may increase the effect and toxicity of the benzodiazepine, diazepam.

Dicumarol: Amprenavir may increase the anticoagulant effect of dicumarol by increasing its serum concentration.

Dihydroergotamine: Amprenavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.

Dihydroxyaluminium: The antiacid decreases the absorption of amprenavir

Disulfiram: Increased irsk of side effects (oral solution)

Ergotamine: Amprenavir may increase the effect and toxicity of ergotamine.

Ethinyl Estradiol: Ritonavir could decrease the contraceptive efficacy

Fentanyl: The protease inhibitor, amprenavir, may increase the effect and toxicity of fentanyl.

Flurazepam: Amprenavir may increase the effect and toxicity of the benzodiazepine, flurazepam.

Fusidic Acid: The protease inhibitor, amprenavir, may increase the effect and toxicity of fusidic acid.

Lovastatin: Amprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated.

Magnesium: The antiacid decreases the absorption of amprenavir

Magnesium oxide: The antiacid decreases the absorption of amprenavir

Mestranol: Ritonavir could decrease the contraceptive efficacy

Methadone: The protease inhibitor, amprenavir, may decrease the effect of methadone.

Metronidazole: Increased risk of side effects (oral solution)

Midazolam: Amprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.

Pimozide: Amprenavir may increase the effect and toxicity of pimozide.

Ranolazine: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated.

Rifabutin: Amprenavir may increase the effect and toxicity of rifabutin.

Rifampin: In presence of rifampin anticipate decrease of amprenavir efficiency

Sildenafil: The protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil.

Simvastatin: Amprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated.

St. John's Wort: St. John's Wort decreases the effect of indinavir

Tacrolimus: The protease inhibitor, Amprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Amprenavir therapy is initiated, discontinued or altered.

Tadalafil: Amprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Tamoxifen: Amprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.

Tamsulosin: Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amprenavir is initiated, discontinued, or dose changed.

Telithromycin: Co-administration may result in altered plasma concentrations of Amprenavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.

Temsirolimus: Amprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Teniposide: The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Amprenavir is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tiagabine: The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Amprenavir is initiated, discontinued or dose changed.

Tolterodine: Amprenavir may decrease the metabolism and clearance of Tolterodine. Adjust the Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Amprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The protease inhibitor, Amprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amprenavir is initiated, discontinued or dose changed.

Triazolam: Amprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.

Trimipramine: The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Amprenavir is initiated, discontinued or dose changed.

Vardenafil: Amprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.

Venlafaxine: Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Amprenavir is initiated, discontinued, or dose changed.

Verapamil: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Amprenavir is initiated, discontinued or dose changed.

Vinblastine: Amprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Amprenavir is initiated, discontinued or dose changed.

Vincristine: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed.

Vinorelbine: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Amprenavir is initiated, discontinued or dose changed.

Vitamin E: Increased serum levels of vitamin E

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amprenavir by decreasing its metabolism. The serum concentration of voriconazole may be increased by amprenavir. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.

Warfarin: Amprenavir may increase the anticoagulant effect of warfarin by increasing its serum concentration.

Zolpidem: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if amprenavir is initiated, discontinued or dose changed.

Zonisamide: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if amprenavir is initiated, discontinued or dose changed.

Zopiclone: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if amprenavir is initiated, discontinued or dose changed.