FDA Approves Protease Inhibitor Lexiva
GlaxoSmithKline (GSK) and Vertex Pharmaceuticals Inc. announced today that the Food and Drug Administration (FDA) has granted marketing approval for Lexiva, an HIV-1 protease inhibitor that will be copromoted by the two companies.
Lexiva, or fosamprenavir calcium, is the calcium phosphate ester prodrug of amprenavir, another product comarketed by GSK and Vertex. The newly approved product is hydrolyzed to amprenavir in the gut epithelium.
Fosamprenavir is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. Clinical trials that led to FDA's approval of the product involved a regimen of fosamprenavir and two nucleoside reverse-transcriptase inhibitors with or without the protease inhibitor ritonavir.
GSK spokeswoman Mary Faye Dark said that fosamprenavir will be shipped to wholesalers in early to mid-November and should be available in pharmacies before the end of the month.
According to the product's labeling (PDF), fosamprenavir can be taken with or without food. HIV-infected patients who have not begun antiretroviral therapy can choose from three recommended dosages of the 700-mg film-coated tablets:
- 1,400 mg of fosamprenavir taken twice daily without ritonavir,
- 1,400 mg of fosamprenavir and 200 mg of ritonavir taken once daily, or
- 700 mg of fosamprenavir and 100 mg of ritonavir taken twice daily.
The once-daily regimen is not recommended for patients who have already undergone antiretroviral therapy with a protease inhibitor; these patients should receive 700 mg of fosamprenavir and 100 mg of ritonavir twice daily.
The product's labeling states that fosamprenavir should be coadministered cautiously or not at all with certain drug products. The protease inhibitor is contraindicated in combination with triazolam, ergot derivatives, cisapride, midazolam, and pimozide. Fosamprenavir is also contraindicated in combination with ritonavir for patients who concurrently take flecainide or propafenone.
Drugs that should not be administered with fosamprenavir include rifampin, which may decrease the antiviral effect of the protease inhibitor, and delavirdine, which may show a reduced antiviral response when coadministered with fosamprenavir. Concurrent administration of lovastatin or simvastatin with fosamprenavir may lead to muscle disease, including rhabdomyolysis. Other known and potentially significant drug interactions are described in the product's labeling.
Caution should be used when fosamprenavir, which contains a sulfonamide moiety, is administered to patients who are allergic to sulfonamide drugs. One case of Stevens-Johnson syndrome, a severe allergic rash that may be associated with sulfonamide use, was reported during clinical trials of fosamprenavir.
The most common adverse events associated with fosamprenavir in clinical trials were diarrhea, nausea, vomiting, headache, and skin rashes.