FDA Notifications

FDA approves generic foscarnet sodium injection

The FDA issued an approval on May 31 for a generic formulation of foscarnet sodium injection, 24 mg/mL, 250 mL, and 500 mL single-dose containers, manufactured by Pharmaforce Inc. of Columbus, OH. The product is indicated for the treatment of CMV retinitis in patients with AIDS, making a generic alternative formulation available in the United States.

The product is a generic version of Foscavir (foscarnet sodium injection) 24 mg/mL, 250 mL and 500 mL single-dose containers, manufactured by AstraZeneca, originally approved in 1991.

Tentative approval of generic lamivudine

The FDA granted a tentative approval for a generic formulation of lamivudine tablets, 150 mg, manufactured by Ranbaxy Laboratories Limited (India), for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in adults. The tentative approval was issued May 27.

A tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity. It does, however, make the product eligible for use under the President’s Emergency Plan for AIDS Relief (PEPFAR) program outside the United States.

The lamivudine tablets are a generic version of Epivir (lamivudine) Tablets, 150 mg, manufactured by Glaxo Smith Kline.

Pediatric HIV Infection Guidelines updated

The Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were updated March 24, 2005. Please note that the Appendix, Characteristics of Available Antiretroviral Drugs, has been extensively modified to include up-to-date drug information, including updated information about pediatric dosing and new drug formulations. The updated Appendix also includes a matrix based on Table 18 in the Adult Guidelines (adverse drug reactions) and three matrices based on Tables 19-21 in the Adult Guidelines (drug interactions between antiretrovirals and other drugs).

The Pediatric Guidelines are developed by the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, which reviews new data on an ongoing basis and provides regular updates to the guidelines.

The updated guidelines document is available in the Pediatric Guidelines section of the Guidelines page on the AIDSinfo web site.

The AIDSinfo web site (AIDSinfo.nih.gov) also is a valuable source of other information related to HIV/AIDS, including other treatment and prevention guidelines, downloadable databases for PDAs (Personal Digital Assistants), and HIV/AIDS-related clinical trials information.

Entecavir is approved for chronic hepatitis B infection in adults

On March 29, FDA approved entecavir (Bara-clude) for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication, and either evidence of persistent elevations in serum aminotransferases (ALT or AST), or histologically active disease.

This indication is based on histologic, virologic, biochemical, and serologic responses after one year of treatment in nucleoside-treatment-naive and lamivudine-resistant adult patients with HbeAg (hepatitis B e antigen)-positive, or HBeAg-negative chronic HBV infection with compensated liver disease, and on more limited data in adult patients with HIV/HBV coinfection who have received prior lamivudine therapy.

Limited data about entecavir in patients with HIV/HBV coinfection who received prior lamivudine therapy are presented in the label. Please refer to the attached label and the Special Population section under Description of Clinical Studies for information on HIV/HBV coinfected patients.

In summary, Study AI463038 was a randomized, double-blind, placebo-controlled study of entecavir versus placebo in 68 patients coinfected with HIV and HBV who experienced recurrence of HBV viremia while receiving a lamivudine-containing highly active antiretroviral therapy (HAART) regimen. Patients continued their lamivudine-containing HAART regimen (lamivudine dose 300 mg/day) and were assigned to add either entecavir 1 mg once daily (51 patients) or placebo (17 patients) for 24 weeks followed by an open-label (nonblinded) phase for an additional 24 weeks where all patients received entecavir.

At baseline, patients had a mean serum HBV DNA level by PCR of 9.13 log10 copies/mL. Ninety-nine percent of patients were HBeAg-positive at baseline, with a mean baseline ALT level of 71.5 U/L. Median HIV RNA level remained stable at approximately 2 log10 copies/ mL through 24 weeks of blinded therapy.

The proportion of HIV/HBV coinfected patients with HBV DNA < 300 copies/mL was 6% for the entecavir 1 mg group vs. 0% for the placebo group. The mean change from baseline for HBV DNA was -3.65 log10 copies/mL for the Baraclude 1 mg group vs. +0.11 log10 copies/mL for the placebo group. Thirty-four percent of patients in the entecavir 1 mg group had ALT normalization (< 1 x ULN) compared to 8% of patients in the placebo group. There are no data for patients with HIV/HBV coinfection who have not received prior lamivudine therapy.

Roche issues letter about saquinavir

Roche Pharmaceuticals of Nutley, NJ, has issued a "Dear Health Care Provider" letter to inform the clinical community that commercial distribution of Fortovase, the 200-mg softgel formulation of saquinavir, will be discontinued by Feb. 15, 2006.

The letter cites decreased demand for Fortovase as the reason for the product’s discontinuation.

Roche suggests that physicians refrain from starting Fortovase treatment in their HIV-positive patients at this time, and encourages prescribing health care providers to discuss appropriate alternative treatment regimens with patients currently receiving Fortovase.

Invirase, another formulation of saquinavir manufactured by Roche Pharmaceuticals, will continue to be available in 200-mg and 500-mg formulations.

The complete Dear Health Care Provider letter is available at www.invirase.com/pdf/FTVDear DoctorFINAL.pdf.