Overview
11 DESCRIPTION Fosamprenavir calcium, USP is a prodrug of amprenavir, an inhibitor of HIV protease. The chemical name of fosamprenavir calcium is (3 S )-tetrahydrofuran-3-yl (1 S ,2 R )-3-[[(4-aminophenyl) sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy) propylcarbamate monocalcium salt. Fosamprenavir calcium is a single stereoisomer with the (3 S )(1 S ,2 R ) configuration.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fosamprenavir is an HIV-1 antiretroviral agent [see Microbiology (12.4) ] . 12.3 Pharmacokinetics The pharmacokinetic properties of amprenavir after administration of fosamprenavir, with or without ritonavir, have been evaluated in both healthy adult volunteers and in HIV-1–infected subjects; no substantial differences in steady-state amprenavir concentrations were observed between the 2 populations. The pharmacokinetic parameters of amprenavir after administration of fosamprenavir (with and without concomitant ritonavir) are shown in Table 7. Table 7. Geometric Mean (95% CI) Steady-State Plasma Amprenavir Pharmacokinetic Parameters in Adults Regimen C max (mcg/mL) T max (hours) Data shown are median (range).
Indications
- 1 INDICATIONS AND USAGE Fosamprenavir calcium tablets are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection. The following points should be considered when initiating therapy with fosamprenavir plus ritonavir in protease inhibitor-experienced patients: • The protease inhibitor-experienced patient trial was not large enough to reach a definitive conclusion that fosamprenavir plus ritonavir and lopinavir plus ritonavir are clinically equivalent [see Clinical Studies (14.2) ] .
Common Doses
- 400 mg
- 200 mg
- 100 mg
- 700 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Therapy-Naive Adults: Fosamprenavir 1,400 mg twice daily; fosamprenavir 1,400 mg once daily plus ritonavir 200 mg once daily; fosamprenavir 1,400 mg once daily plus ritonavir 100 mg once daily; fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily. ( 2.2 ) • Protease Inhibitor-Experienced Adults: Fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily. ( 2.2 ) • Pregnant Patients: Fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily should only be considered in women who are already on a stable twice-daily regimen of...
Contraindications
- 4 CONTRAINDICATIONS • Fosamprenavir calcium tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome) to any of the components of this product or to amprenavir. • Fosamprenavir calcium tablets are contraindicated when coadministered with drugs that are highly dependent on cytochrome P450 (CYP)3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
Side Effects
- 6 ADVERSE REACTIONS • Severe or life-threatening skin reactions have been reported with the use of fosamprenavir [see Warnings and Precautions (5.2) ] . • The most common moderate to severe adverse reactions in clinical trials of fosamprenavir were diarrhea, rash, nausea, vomiting, and headache. • Treatment discontinuation due to adverse events occurred in 6.4% of subjects receiving fosamprenavir and in 5.9% of subjects receiving comparator treatments.
Interactions
- 7 DRUG INTERACTIONS • Coadministration of fosamprenavir with drugs that induce CYP3A4 may decrease amprenavir (active metabolite) concentrations leading to potential loss of virologic activity. ( 7 , 12.3 ) • Coadministration with drugs that inhibit CYP3A4 may increase amprenavir concentrations. ( 7 , 12.3 ) • Coadministration of fosamprenavir or fosamprenavir and ritonavir may result in clinically significant interactions with drugs metabolized by CYP3A4. ( 7 ) • Coadministration of fosamprenavir and ritonavir may result in clinically significant interactions with drugs metabolized by CYP2D6.