Zidovudine approved for pediatric use
On July 23, 2009, FDA granted approval for zidovudine 60 mg scored tablets for pediatric use, manufactured by Aurobindo Pharma Limited of Hyderabad, India. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
This 60 mg tablet is an alternate formulation to oral syrup for pediatric use, and facilitates distribution and storage in settings where weight can negatively affect shipping/distribution, and high temperatures can shorten product shelf life.
This product will not be marketed in the United States, where the oral syrup formulation serves pediatric dosing needs.
Zidovudine is a Nucleoside Reverse Transcriptase Inhibitor (NRTI) anti-viral drug indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Lamivudine/zidovudine combination approved for pediatric use
On July 23, 2009, the FDA granted tentative approval to fixed dose combination lamivudine/zidovudine scored tablets, 30mg/60mg, for pediatric use, manufactured by Aurobindo Pharma Limited of Hyberdad, India. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
Zidovudine and lamivudine are anti-viral drugs indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. Combination products such as this one can decrease pill burden and may result in improved dosing compliance for HIV infected individuals. The scored tablets permit greater flexibility in dosing small children.
"Tentative approval" means that FDA has concluded that a drug product meets all required quality, safety and efficacy standards, but is not presently eligible for final approval for marketing in the U.S. because of existing patents and/or exclusivity rights. However, tentative approval does make the product eligible for purchase and use outside the United States under PEPFAR.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.
FDA gives tentative approval for stavudine, lamivudine & nevirapine tablet
On July 16, 2009, the Food and Drug Administration (FDA) granted tentative approval for stavudine, lamivudine, and nevirapine fixed dose combination tablets, 40mg/150mg/200mg & 30mg/150mg/200mg manufactured by Emcure Pharmaceuticals Limited of Pune, India. The combination product is indicated for use alone as a complete regimen, or in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Combination products like this one can decrease pill burden and may result in improved dosing compliance for HIV infected individuals.
The FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product has been shown to meet all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and thus qualifies for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
As with all generic applications, 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.
Tentative approval given for combination of abacavir, lamivudine & zidovudine tablets
On July 15, 2009, the FDA granted tentative approval to a fixed-dose combination tablet containing abacavir sulfate, lamivudine and zidovudine Tablets, 300 mg/150 mg/300 mg, manufactured by Matrix Laboratories Limited of Hyberdad, India, indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Fixed dose combination tablets significantly reduce pill burden and may help to improve adherence to drug regimens containing these products.
Tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, but that it may not be marketed in the U.S. due to existing patents rights. However, tentative approval makes the product eligible to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program. Existing patent information is available in the FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.
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 of these applications. This is done to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.
A list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan can be found on the FDA website.
The abacavir sulfate/lamivudine/zidovudine fixed dose combination tablets are a version of the FDA approved Trizivir Tablets, 300 mg/150 mg/300 mg, manufactured by GlaxoSmithKline.
FDA approves raltegravir for HIV-1 treatment-naïve patients
On July 8, 2009, the FDA granted approval to raltegravir (Isentress), for the treatment of HIV-1 infection in treatment-naïve patients. The recommended dose for treatment-naïve adult patients is raltegravir 400 mg twice daily, with or without food.
The use of raltegravir in treatment-naïve patients is based on a 48-week randomized, double-blind, active control trial to evaluate the safety and efficacy of Isentress 400 mg twice daily + emtricitabine + tenofovir versus efavirenz (Sustiva) 600 mg + emtricitabine + tenofovir. The proportion of patients with HIV RNA < 50 copies/mL was 87% for the raltegravir group compared to 82% for the efavirenz group. The difference between raltegravir and efavirenz with respect to HIV RNA < 50 copies/mL and the 95% confidence intervals is 4.7% (-1.3%, 10.6%).
Several other changes were made to the package insert and include the following major revisions:
• Highlights Section:
- DRUG INTERACTIONS heading was included along with a warning about use with UGT (UDP-glucuronosyltransferases) inducers other than rifampin, specifically, "Coadministration of ISENTRESS with drugs that are strong inducers of UGT1A1 may result in reduced plasma concentrations of raltegravir."
• Full Prescribing Information Section:
- Section 1: INDICATIONS AND USAGE was changed to incorporate use in treatment-naïve patients: "ISENTRESS is indicated in combination with other anti-retroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adult patients. This indication is based on analyses of plasma HIV-1 RNA levels up through 48 weeks in three double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, NRTI, PI) treatment-experienced adults and one was conducted in treatment-naïve adults. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response."
• Section 5.2: WARNINGS AND PRECAUTIONS, Drug Interactions: this section removed because the information is sufficiently included in Section 7: DRUG INTERACTIONS.
• Section 6.1: Clinical Trials Experience, Treatment-Naïve Studies: This section now includes 48 week safety and laboratory data from Protocol 021.
• Section 6.2: Postmarketing Experience: addition of paranoia and anxiety.
• Section 7.1 Effect of Raltegravir on the Pharmacokinetics of Other Agents adds information for CYP1A2, CYP2B6 and methadone.
• Section 12.4 Microbiology was updated to include the following headings and information:
- Antiviral Activity in Cell Culture;
- In addition, 5 clinical isolates of HIV-1 subtype B had EC95 values ranging from 9 to 19 nM in cultures of mitogen-activated human peripheral blood mononuclear cells.
- Resistance: Treatment-Naïve Subjects: By Week 48 in the STARTMRK trial, the primary raltegravir resistance-associated substitutions were observed in 3 (1 with Y143R and 2 with Q148H/R) of the 6 virologic failure subjects with evaluable paired genotypic data.
• Section 14 CLINICAL STUDIES includes 48 week efficacy data from Protocol 02.
Minor editorial changes were made to the patient package insert for consistency with other antiretrovirals.
The revised label will be available soon on the FDA web site at Drugs@FDA or through the National Library of Medicine's DailyMed site.
Raltegravir (Isentress) is an integrase inhibitor made by Merck & Co.
On July 23, 2009, FDA granted approval for zidovudine 60 mg scored tablets for pediatric use, manufactured by Aurobindo Pharma Limited of Hyderabad, India. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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