QuickView for Fosamprenavir (compound)

Summary
General Info

PubChem

PubChem Compound 11954282

Name:	fosamprenavir
PubChem Compound ID:	11954282
Molecular formula:	C₂₅H₃₆CaN₃O₁₀PS
Molecular weight:	641.685 g/mol
Synonyms:	Lexiva; Fosamprenavir calcium hydrate; Fosamprenavir calcium hydrate (JAN); D02867; Lexiva (TN)

DrugBank

Identification

Name:	fosamprenavir
Name (isomeric):	DB01319
Drug Type:	small molecule
Brand:	Lexiva, Telzir
Category:	Prodrugs, HIV Protease Inhibitors, Anti-HIV Agents
CAS number:	226700-79-4

Pharmacology

Indication:	Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission. The use of fosamprenavir is pending revision due to a potential association between the drug and myocardial infarction and dyslipidemia in HIV infected adults.
Pharmacology:	Fosamprenavir is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. It has little or no antiviral activity until it is hydrolyzed by cellular phosphatases into amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of ampr... show more » Fosamprenavir is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. It has little or no antiviral activity until it is hydrolyzed by cellular phosphatases into amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reducing the number of pills required versus standard amprenavir. show less «
Mechanism of Action:	Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral en... show more » Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. show less «
Absorption:	The absolute oral bioavailability of amprenavir after administration of fosamprenavir in humans has not been established. After administration of a single 1,400 mg dose in the fasted state, fosamprenavir oral suspension (50 mg/mL) and fosamprenavir tablets (700 mg) provided similar amprenavir exposures (AUC), however, the C_max of amprenavir after administration of the suspension formulation was 14.5 % higher compared with the tablet.
Protein binding:	Very high (approximately 90%); primarily bound to alpha 1 -acid glycoprotein. Higher amounts of unbound amprenavir present as amprenavir serum concentrations increase.
Biotransformation:	In the gut epithelium during absorption, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system.
Route of elimination:	Excretion of unchanged amprenavir in urine and feces is minimal. The renal elimination of unchanged amprenavir represents approximately 1% of the administered dose; therefore, renal impairment is not expected to significantly impact the elimination of amprenavir. Amprenavir, the active metabolite of fosamprenavir, is metabolized in the liver by the cytochrome P450 enzyme system.
Half Life:	The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours.
Affected organisms:	Human Immunodeficiency Virus

Interactions

Food interaction:

Vitamin E increases fosamprenavir bioavailability.

Take with or without food, however avoid lipid-rich meals.

Avoid alcohol, especially with the oral solution since it contains propylene glycol which competes with alcohol for alcohol dehydrogenase metabolism.

Drug interaction:

Dantrolene	Fosamprenavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if fosamprenavir is initiated, discontinued or dose changed.
Trimipramine	The strong CYP3A4 inhibitor, Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Sildenafil	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of sildenafil.
St. John's Wort	St. John's Wort decreases the effect of indinavir
Temsirolimus	Fosamprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Dantrolene	Fosamprenavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if fosamprenavir is initiated, discontinued or dose changed.
Trimipramine	The strong CYP3A4 inhibitor, Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Sildenafil	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of sildenafil.
St. John's Wort	St. John's Wort decreases the effect of indinavir
Temsirolimus	Fosamprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Zolpidem	Fosamprenavir, 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 fosamprenavir is initiated, discontinued or dose changed.
Alprazolam	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.
Atorvastatin	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if fosamprenavir is initiated, discontinued or dose changed.
Methadone	The protease inhibitor, fosamprenavir, may decrease the effect of methadone.
Fusidic Acid	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of fusidic acid.
Ergotamine	Amprenavir increases the effect and toxicity of ergot derivative
Vinblastine	Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Dicumarol	The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of dicumarol.
Zopiclone	Fosamprenavir, 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 fosamprenavir is initiated, discontinued or dose changed.
Pimozide	Amprenavir increases the effect and toxicity of pimozide
Magnesium oxide	The antiacid decreases the absorption of amprenavir
Verapamil	Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Tamsulosin	Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fosamprenavir is initiated, discontinued, or dose changed.
Rifampin	Rifampin may decrease the effectiveness of fosamprenavir.
Lovastatin	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
Abacavir	The serum concentration of Abacavir may be decreased by protease inhibitors such as Fosamprenavir. The antiviral response should be closely monitored.
Calcium	The antiacid decreases the absorption of amprenavir
Astemizole	Increased risk of cardiotoxicity and arrhythmias
Rifabutin	Amprenavir increases the effect and toxicity of rifabutin
Tipranavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Fosamprenavir. Consider alternate therapy.
Cyclosporine	The protease inhibitor, fosamprenavir, may increase the effect of cyclosporine.
Midazolam	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.
Vinorelbine	Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Tramadol	Fosamprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Triazolam	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.
Magnesium	The antiacid decreases the absorption of amprenavir
Tamoxifen	Fosmprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Trazodone	The protease inhibitor, Fosamprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fosamprenavir is initiated, discontinued or dose changed.
Warfarin	The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of warfarin.
Tacrolimus	The protease inhibitor, Fosamprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Fosamprenavir therapy is initiated, discontinued or altered.
Diazepam	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, diazepam.
Zonisamide	Fosamprenavir, 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 fosamprenavir is initiated, discontinued or dose changed.
Acenocoumarol	The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of acenocoumarol.
Telithromycin	Fosamprevavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Tiagabine	The strong CYP3A4 inhibitor, Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Fentanyl	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of fentanyl.
Ranolazine	Increased levels of ranolazine - risk of toxicity
Simvastatin	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if fosamprenavir is initiated, discontinued or dose changed.
Amiodarone	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
Vincristine	Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Dihydroergotamine	Amprenavir increases the effect and toxicity of ergot derivative
Teniposide	The strong CYP3A4 inhibitor, Fosamprenavir, 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 Fosamprenavir is initiated, discontinued or dose changed.
Clorazepate	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.
Aluminium	The antiacid decreases the absorption of amprenavir
Venlafaxine	Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Fosamprenavir is initiated, discontinued, or dose changed.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Tolterodine	Fosamprenavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Vardenafil	Fosamprenavir, 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.
Delavirdine	Decreased levels of delavirdine with increased levels of amprenavir
Tadalafil	Fosamprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Bepridil	Amprenavir increases the effect and toxicity of bepridil
Cisapride	Amprenavir increases the effect and toxicity of cisapride
Voriconazole	Voriconazole may increase the serum concentration of fosamprenavir by decreasing its metabolism. Fosamprenavir may increase the serum concentration of voriconazole. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Anisindione	The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of anisindione.
Flurazepam	Fosamprenavir may increase the effect and toxicity of the benzodiazepine, flurazepam.
Bromazepam	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if fosamprenavir is initiated, discontinued or dose changed. Dosage adjustments may be required.

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Targets

HIV-1 protease

Enzymes

Cytochrome P450 3A4