FOSAMPRENAVIR CALCIUM
Clinical safety rating: safe
Animal studies have demonstrated safety
Fosamprenavir is a prodrug of amprenavir, an HIV-1 protease inhibitor. It binds to the active site of HIV-1 protease, preventing cleavage of viral Gag-Pol polyproteins, resulting in immature, non-infectious viral particles.
| Metabolism | Fosamprenavir is rapidly hydrolyzed to amprenavir in the gut epithelium. Amprenavir is primarily metabolized by CYP3A4. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with 14% renal excretion of unchanged drug; 68% fecal, 1% urinary as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 7.7 hours; supports twice-daily dosing. |
| Protein binding | Approximately 90% bound to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Vd/F is 6.3 L/kg (430 L for a 70 kg adult); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not determined due to lack of IV formulation; after oral administration, absorption is extensive with food increasing Cmax and AUC. |
| Onset of Action | Oral: Peak plasma concentration at 1.5-4 hours; clinical antiviral effect begins within days. |
| Duration of Action | Duration of antiviral effect supports twice-daily dosing; trough levels maintain virologic suppression. |
1400 mg orally twice daily or 1400 mg once daily plus ritonavir 100 mg or 200 mg once daily plus ritonavir 100 mg. Alternatively, fosamprenavir 700 mg plus ritonavir 100 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. Not removed by hemodialysis. |
| Liver impairment | Child-Pugh Class A: 700 mg orally twice daily without ritonavir. Child-Pugh Class B: 700 mg orally twice daily without ritonavir. Child-Pugh Class C: not recommended. |
| Pediatric use | Approved for age ≥2 years. For body weight 11-<15 kg: 18 mg/kg (max 700 mg) twice daily without ritonavir. For 15-<20 kg: 15 mg/kg (max 700 mg) twice daily without ritonavir. For ≥20 kg: 700 mg twice daily without ritonavir. If using ritonavir, dose based on weight and age, consult guidelines. |
| Geriatric use | No specific dose adjustment. Use with caution due to increased frequency of decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Induces CYP3A4 and inhibits CYP2C9 affecting many drugs Can cause severe skin reactions and hepatotoxicity.
| Breastfeeding | Amprenavir is excreted into human breast milk. In a study of HIV-positive women taking fosamprenavir/ritonavir (700 mg/100 mg twice daily), the median milk-to-plasma (M/P) ratio of amprenavir was 0.22 (range 0.02–0.63). The estimated infant daily dose via breastfeeding was 0.2% of the maternal weight-adjusted dose. While this relative infant dose is low, the absolute amount may vary with maternal dose and timing. Due to the risk of HIV transmission through breast milk, HIV-infected mothers should not breastfeed. For non-HIV indications (if applicable), caution is advised; monitor infant for potential adverse effects (e.g., diarrhea, rash, hyperbilirubinemia). |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | Rash |
| Serious Effects |
["Hypersensitivity to fosamprenavir or amprenavir.","Concomitant use with drugs highly dependent on CYP3A4 for clearance (e.g., rifampin, ergot derivatives, midazolam, triazolam, pimozide, cisapride, St. John's wort).","Concomitant use with lopinavir/ritonavir (efficacy not established).","Severe hepatic impairment (Child-Pugh class C): Use contraindicated."]
| Precautions | ["Hepatotoxicity: Severe hepatomegaly with steatosis, including fatalities, reported. Monitor liver function.","Sulfa allergy: Fosamprenavir contains a sulfonamide moiety; use caution in patients with known sulfa allergy.","Hyperglycemia/diabetes: New-onset or exacerbation reported.","Immune reconstitution syndrome: Inflammatory response to indolent or residual opportunistic infections.","Lipodystrophy: Redistribution/accumulation of body fat.","Hemolytic anemia: Cases reported, discontinue if anemia develops.","Nephrolithiasis: Cases reported, ensure adequate hydration."] |
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| Fosamprenavir calcium, a prodrug of amprenavir, is classified as FDA Pregnancy Category C. In animal studies, amprenavir caused reduced fetal body weight and delayed ossification at maternally toxic doses. There are no adequate and well-controlled studies in pregnant women. However, available data from the Antiretroviral Pregnancy Registry do not show a significantly increased risk of major birth defects overall (prevalence 2.9% compared to background 2.7%). For first trimester exposure, the registry reported a 3.1% prevalence of birth defects (not statistically different from comparator). No specific pattern of malformations has been identified. During the second and third trimesters, potential risks include maternal metabolic complications (e.g., hyperglycemia) and fetal effects from maternal toxicity. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, particularly when alternatives with more safety data (e.g., atazanavir, darunavir) are not feasible. |
| Fetal Monitoring | Monitor maternal liver function tests (especially ALT, AST, total bilirubin) due to risk of hepatotoxicity (including in pregnancy). Assess serum creatinine and glucose (risk of hyperglycemia in pregnant women). Perform fetal ultrasound monitoring for growth and anatomy, though no specific teratogenic pattern is expected. Consider therapeutic drug monitoring of amprenavir plasma concentrations during pregnancy, particularly in the third trimester, as levels may decrease; adjust dose if needed. Monitor for maternal rash, hypersensitivity reactions, and hyperlipidemia. |
| Fertility Effects | No specific human studies on fertility effects of fosamprenavir. In animal studies, no adverse effects on mating or fertility were observed in rats at exposures up to 0.8 times the human AUC at recommended doses. However, antiretroviral therapy in HIV patients may be associated with hormonal alterations (e.g., menstrual irregularities, reduced ovarian reserve) that could affect fertility, but these are likely multifactorial. In general, no direct negative impact on fertility has been established, but individual patient factors and underlying disease should be considered. |