FDA Notifications

Tentative approval granted for combo antiretroviral drug

The FDA, on Aug. 13, 2007, granted tentative approval for a new fixed dose three-drug combination pill containing generic lamivudine, stavudine and nevirapine, to treat human immunodeficiency virus (HIV-1) infection in children outside the United States.

This is the first combination of its kind available to meet the needs of children less than 12 years of age, and represents a major advance in global AIDS treatment efforts. The generic combination drug tablet is manufactured by Cipla Limited, of Mumbai, India.

The new combination constitutes a complete HIV regimen that is taken twice daily, once patients have tolerated 14 days of lead-in treatment with nevirapine taken once daily in combination with separate doses of lamivudine and stavudine. The combination tablet can be dissolved in water for children who cannot swallow tablets.

Each ingredient of this generic tablet is currently approved to treat HIV-1 in combination with other antiretroviral agents. The safety and effectiveness of the combination of lamivudine-stavudine-nevirapine in lowering viral load and increasing CD4+ cells has been demonstrated in previously conducted, controlled studies of the individual ingredients used together.

The three drugs, combined in a single twice-a-day tablet, are not only easier to administer to children, increasing access and adherence to therapy, but also facilitate storage and distribution. This new combination represents a significant advance in the treatment of children infected with HIV in PEPFAR countries.

Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards. But because of existing patents and/or exclusivity rights, it may not be marketed in the U.S. The tentative approval, does however, make the product eligible for consideration for purchase under the PEPFAR program.

As with all generic applications, FDA conducts on-site inspections of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application, ensuring that antiretroviral drugs purchased by PEPFAR meet the same safety, efficacy, and manufacturing standards as drugs used in the United States.

This product was reviewed under guidance titled Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously approved Antiretrovirals for the Treatment of HIV developed by FDA to clarify what regulatory requirements apply to such applications, what issues might be of concern, how these issues should be addressed, and to encourage sponsors to submit applications for combination and co-packaged products to FDA.

The tentative approvals of nevirapine and this triple fixed dose combination tablet of lamivudine, stavudine and nevirapine represent the 50th and 51st approvals or tentative approvals, respectively, by FDA under the expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR). A list of all approvals and tentative approvals under these provisions can be found at http://www.fda.gov/oia/pepfar.htm.

Abbot sends out provider letter about Kaletra for kids

Abbott has sent out a Dear Healthcare Provider letter highlighting important information about Kaletra dosing for children. A pdf copy of the letter and the accompanying dosing guidelines for children receiving the recommended dose of lopinavir/ritonavir using Kaletra Oral Solution is available on the FDA Web site.

The FDA website has a pediatric HIV drug page that provides additional information about pediatric dosing, at www.fda.gov/oashi/aids/pedlbl.html.

Tentative approval for generic nevirapine tablets

The FDA, on Aug. 13, 2007, granted tentative approval for a generic formulation of nevirapine tablets, 200 mg, manufactured by Hetero Drugs Limited, Hyderabad, India, under expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR).

"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. However, tentative approval does make the product eligible for consideration for purchase under the PEPFAR program.

As with all generic applications, FDA conducts on-site inspections of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval 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 is a generic formulation of FDA approved Viramune Tablets, 200 mg, made by Boehringer Ingelheim Pharmaceuticals, Inc., which is subject to existing patent and pediatric exclusivity protections.

Effective patent dates and additional marketing exclusivities can be found in the agency's publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "Orange Book"

Nevirapine is a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) indicated for used in combination with other antiretroviral agents in the treatment of HIV infection.

Tentative approval for generic lamivudine/zidovudine

Tentative approval was granted on Aug. 8, 2007, for a generic formulation of a combination product, lamivudine and zidovudine tablets, 150 mg/300 mg, manufactured by Emcure Pharmaceuticals Inc. of Pune, India, under expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR).

"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. However, tentative approval does make the product eligible for consideration for purchase under the PEPFAR program.

As with all generic applications, FDA conducts on-site inspections of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval 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 is a generic formulation of FDA approved Combivir Tablets, 150 mg/300 mg, marketed by GlaxoSmithKline, which is subject to patent and pediatric exclusivity protections.

Effective patent dates and additional marketing exclusivities can be found in the agency's publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "Orange Book"

Lamivudine and zidovudine are both Nucleoside Reverse Transcriptase Inhibitors (NRTI) indicated for used in combination with other antiretroviral agents in the treatment of HIV infection.

Public Reporting: Strategies to Promote Trust Within Your Service Community