FDA Notifications

FDA approves generic abacavir sulfate tablets

The FDA, on November 6, 2006, granted tentative approval for a generic formulation of abacavir sulfate tablets, 300 mg, manufactured by Cipla Limited of Mumbai, India. The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR).

The FDA's tentative approval means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and can thus be considered for purchase under PEPFAR.

As with all generic applications, the FDA conducts an on-site inspection of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to these applications to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.

This tentatively approved product, a generic version of Ziagen tablets manufactured by GlaxoSmithKline, is a nucleoside reverse transcriptase inhibitor (NRTI) for use in combination with other antiretroviral agents in the treatment of HIV infection.

Pediatric HIV infection ART guidelines revised

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection have been revised. The revision represents a major rewriting of the main document to improve its organization and readability. Because the main document has been almost completely rewritten, there is no highlighting of changes to either its text or tables.

The document's appendix, "Characteristics of Available Antiretroviral Drugs, and Supplement I: Pediatric Antiretroviral Drug Information," has also been updated. Changes to those sections appear highlighted in yellow.

Changes in recommendations include:

  • Revised guidelines on when to initiate therapy in antiretroviral-naïve children, with recommendations for four age categories (< 12 months, 1 to < 4 years, 4 to 12 years, and > 13 years).
  • Revised discussion and tables of rationale for antiretroviral drug choice for antiretroviral-naïve children, with revised preferred and alternative treatment regimen recommendations.
  • Revised recommendations for adolescents, including issues related to drug dosing, use of contraception, pregnancy, and transition into adult care.
  • Updated Characteristics of Available Antiretroviral Drugs drug-dosing appendix and updated Supplement I: Pediatric Antiretroviral Drug Information, including information on newly approved antiretroviral agents, such as darunavir, and new pediatric studies.

Also new to the guidelines are:

  • Recommendations for antiretroviral resistance testing for all antiretroviral-naïve children prior to initiation of antiretroviral therapy.
  • New section and table on monitoring of children on antiretroviral therapy and management of antiretroviral toxicity/intolerance.
  • New section on management of the treatment-experienced child.
  • New section and tables on assessment and management of antiretroviral treatment failure and choice of new antiretroviral regimen in children with treatment failure.
  • New section on therapeutic drug monitoring.
  • New section on discontinuation or interruption of antiretroviral therapy.
  • Inclusion of darunavir information.

The updated guidelines are available on the Pediatric Guidelines page of the Clinical Guidelines section of AIDSinfo.

FDA provides new guidance on fixed-dose combinations

The FDA announced, on October 18, 2006, the availability of a guidance for industry entitled "Fixed Dose Combinations (FDC), Co-Packaged Drug Products and Single Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV."

The guidance encourages sponsors to develop various drug product versions of previously approved antiretroviral drugs and encourages sponsors to submit drug applications for these products to FDA for review. The availability of a wide range of safe and effective antiretroviral drug products is hoped to facilitate a wider distribution of anti-HIV drugs to better meet the demands of the global HIV/AIDS pandemic.

The draft version of this guidance entitled "Fixed Dose Combination and Co-Packaged Drug Products for Treatment of HIV," was first posted on May 2004.

The guidance has been updated to address public comments to the draft version. Significant changes to the draft are:

  1. The inclusion of single entity versions, in addition to combination products, in the expedited FDA review pathway for these products;
  2. The addition of tables that supply references supporting the clinical efficacy and safety of antiretroviral combinations;
  3. The inclusion of more details and clarification on the amount and type of data that should be submitted in a drug application to support a potential approval or tentative approval.

The full guidance is available on the FDA Web site www.fda.gov (343 KB).

FDA approves 300 mg atazanavir capsule

On October 16, 2006, the Food and Drug Administration approved a new 300 mg capsule form of Reyataz (atazanavir).

Reyataz is now available as 100 mg, 150 mg, 200 mg, and the new 300 mg capsules.

The new 300 mg capsules give treatment-experienced patients the option to take either one 300 mg capsule, or two 150 mg capsules of Reyataz, once daily, plus ritonavir 100 mg once daily, with food.

The recommended dose for treatment-naïve patients remains unchanged and is Reyataz 400 mg (two 200 mg capsules) once daily with food. Reyataz is a product of Bristol-Myers Squibb.