Fosamprenavir

Uses

Fosamprenavir is an antiretroviral agent used for the treatment and postexposure prophylaxis of human immunodeficiency virus (HIV-1) infection.

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.

Fosamprenavir is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Fosamprenavir works

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.

Food Interaction

• Avoid alcohol. Drug impairs alcohol metabolism.
• Avoid fatty foods.
• Take with or without food.

[Moderate] ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension.

The mechanism of interaction has not been described.

According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state.

The time to reach peak plasma level (Tmax) was delayed by 0.72 hours.

In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance.

If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated.

Fosamprenavir tablets may be taken with or without food.

Fosamprenavir Cholesterol interaction

[Moderate] Hyperlipidemia has been observed in 10% of patients receiving ritonavir during clinical trials.

Increases of 30% to 40% from baseline have been reported for total cholesterol and 200% to 300% or more for triglycerides.

These effects have also been reported during postmarketing experience with other protease inhibitors (PIs) but may be the most dramatic with ritonavir.

The clinical significance of these elevations is unclear.

Severe hyperlipidemia is known to sometimes cause pancreatitis.

In addition, some patients have reportedly developed symptomatic atherosclerosis and coronary artery disease after initiating PI treatment.

Patients with preexisting hyperlipidemia may require closer monitoring during PI therapy, and adjustments made accordingly in their lipid-lowering regimen.

PI therapy should be administered cautiously in patients with coronary artery disease or a history of ischemic heart disease.

Fosamprenavir Drug Interaction

Unknown: charcoal, charcoal, heparin, heparin, ritonavir, ritonavir, vitamin a topical, vitamin a topical, bioflavonoids, bioflavonoids, sotalol, sotalol, vortioxetine, vortioxetine, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, cholecalciferol, cholecalciferol

Fosamprenavir Disease Interaction

Major: hemophiliaModerate: nephrolithiasis, hyperglycemia, hyperlipidemia

Elimination Route

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.

Half Life

The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours.

Elimination Route

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.

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