FDA Notifications: Revised guidelines for pregnant women
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Revised guidelines for pregnant women
The Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States have undergone a complete revision and reorganization to reflect important new information, and to make them more user-friendly. The guidelines have been restructured into principles for medical management of the woman and her infant during the antepartum, intrapartum, and postpartum period, including panel recommendations for each section.
Changes to the report include the following:
- Due to contamination with ethyl methane sulfonate (EMS), nelfinavir is no longer recommended for use in pregnant HIV-infected women.
- New sections on antepartum management of HIV-infected pregnant women in special situations, including HBV and HCV co-infection.
- New information on ARV drug choice and continuation during labor, and management of women not receiving antepartum ARVs.
- New sections on choice and management of infant ARV prophylaxis.
- Two new tables: "Results of Major Studies on ARV Prophylaxis to Prevent Mother-to-Child HIV Transmission" and "Clinical Scenario Summary Recommendations for ARV Use by Pregnant HIV-Infected Women and Prevention of Perinatal HIV-1 Transmission in the U.S."
- Updated information for emtricitabine, tenofovir, amprenavir, atazanavir, lopinavir/ritonavir, nelfinavir, maraviroc, and raltegravir.
- Updated information for tenofovir, saquinavir-HGC, atazanavir, nelfinavir, maraviroc, and raltegravir.
- The updated guidelines are available in the "Guidelines" section of the AIDS info Web site under " Perinatal Guidelines." You can download the guidelines or can request to receive them by e-mail or regular mail on the AIDSinfo Web site.
FDA draft guidance is\about new drug development
On Oct. 25, 2007, the FDA published draft guidance intended to assist the pharmaceutical industry and other investigators who are conducting new drug development in assessing the potential for a drug to cause severe liver injury (i.e., fatal, or requiring liver transplantation). The document may be of interest to those involved in drug development related to HIV/AIDS, although the guidance is broader in scope.
In particular, the guidance addresses how laboratory measurements that signal the potential for such drug-induced liver injury (DILI) can be obtained and evaluated during drug development. This evaluation is important because most drugs that cause severe DILI do so infrequently; typical drug development databases with up to a few thousand subjects exposed to a new drug may not show any cases. Databases do, however, often show evidence of a drug's potential for severe DILI if the clinical and laboratory data are properly evaluated for evidence of lesser injury that may not be severe, but may predict the ability to cause more severe injuries.
The guidance describes an approach that can be used to distinguish signals of DILI that identify drugs likely to cause significant hepatotoxicity from signals that do not suggest such a potential. The guidance does not address issues of preclinical evaluation for potential DILI, nor the detection and assessment of DILI after drug approval and marketing.
FDA is soliciting comments on the proposed guidance during the next 60 days. Comments and suggestions regarding this draft document should be submitted before Dec. 24, 2007, to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, room 1061, Rockville, MD 20852. Comments should be identified with docket number 2007D-0396.
You can view the draft guidance on the FDA web site at http://www.fda.gov/cder/guidance/7507dft.htm. The Federal Register Notice can be found at http://www.fda.gov/OHRMS/DOCKETS/98fr/E7-21060.htm.
Tentative approval for generic stavudine, oral solution
On Oct. 29, 2007, FDA granted tentative approval for a generic formulation of stavudine for oral solution, manufactured by Cipla, Limited, of Mumbai, India.
Stavudine is a Nucleoside Reverse Transcriptase Inhibitors (NRTI) indicated for used in combination with other antiretroviral agents in the treatment of HIV infection. This is the second tentatively approved generic version of the approved product, Zerit for oral solution, manufactured by Bristol-Myers Squibb. This child-friendly product is indicated for use in pediatric patients with HIV from birth through adolescence.
"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 President's Emergency Fund for AIDS Relief, commonly referred to as the PEPFAR program.
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.
FDA approves NDA for Lexiva
On Oct. 12, 2007, the Food and Drug Administration (FDA) approved a supplemental new drug application for Lexiva (fosamprenavir calcium; FPV) Oral Tablets, adding a new indication for once-daily dosing of 1400 mg of Lexiva with 100 mg ritonavir for the treatment of HIV infection in therapy-naïve adults. The approval was based on a bioavailability study demonstrating that this dosing regimen produced drug levels bracketed within those of the already approved 1400 mg once daily plus ritonavir 200 mg once daily regimen, and the Lexiva1400 mg twice daily dosing regimen.
Lexiva is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, and is distributed by GlaxoSmithKline, Research Triangle Park, NC.
Accelerated approval for raltegravir tablets
The Food and Drug Administration (FDA), on Oct. 12, 2007, granted accelerated approval for raltegravir tablets (400 mg) for treatment of Human Immunodeficiency Virus (HIV)-1 infection in combination with other antiretroviral agents. Raltegravir, sold under the trade name Isentress, is the first agent of the pharmacological class of antiretroviral agents known as HIV integrase strand transfer inhibitors, commonly referred to as integrase inhibitors. They are designed to slow the advancement of HIV-1 infection by blocking the HIV integrase enzyme that the virus needs in order to multiply.
When used with other anti-HIV medicines, raltegravir may reduce the amount of HIV in the blood and may increase white blood cells, called CD4+ (T) cells, that help fight other infections.
Raltegravir received a priority review by the FDA. The review and approval of the New Drug Application was completed in within six months.
FDA's approval of raltegravir is based on efficacy and safety data from two double-blind, placebo-controlled studies (BENCHMRK 1 and BENCHMRK 2) in 699 highly antiretroviral treatment-experienced HIV-1 infected adult patients (16 years or older, with documented resistance to at least 1 drug in each of 3 Classes (NNRTIs, NRTIs, PIs) of antiretroviral therapies). Four hundred sixty-two patients used the recommended 400 mg dose twice daily in combination with other currently available HIV medications; 237 patients received a placebo in combination with other currently available HIV medications. The mean changes in plasma HIV-1 RNA from baseline were -1.85 log10 copies/mL in the raltegravir 400 mg twice daily arm and -0.84 log10 copies/mL for the control arm. The mean increase from baseline in CD4+ cell counts was higher in the arm receiving raltegravir 400 mg twice daily (89 cells/mm3) than in the control arm (35 cells/mm3).
The most common adverse events reported with raltegravir were diarrhea, nausea, and headache. Blood tests showed abnormal elevated levels of a muscle enzyme in some patients receiving raltegravir. Caution is advised when using raltegravir in patients at increased risk for certain types of muscle problems, such as patients taking other medications that can cause muscle problems.
Raltegravir has not been studied in pregnant women. Women who are taking HIV medications when they get pregnant are advised to ask their physician about registering with the Antiretroviral Pregnancy Registry.
As with other treatments for HIV, patients taking raltegravir may still develop infections, including opportunistic infections or other conditions that may develop in patients living with HIV-1 infection, and can still pass the virus on to others through sexual contact, sharing needles, or being exposed to blood.
The long-term effects of raltegravir are not known at this time, and its safety and effectiveness in children less than 16 years of age has not been studied.
Raltegravir is distributed by New Jersey-based Merck & Co., Inc.
Tentative approval to Aptivus for combination ART
On Oct. 4, 2007, FDA granted traditional approval to Aptivus (tipranavir), for combination antiretroviral treatment of HIV-1 infected adults with evidence of viral replication, who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor. Aptivus was granted accelerated approval on June 22, 2005, based on analysis of plasma HIV-1 RNA levels in two controlled phase 3 studies, of 24 weeks duration, of Aptivus/ritonavir. The traditional approval is based on continuation of the RESIST trials through 48 weeks and beyond, confirming durability of the virologic response. Aptivus is a product of Boehringer Ingelheim.
The Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States have undergone a complete revision and reorganization ...Subscribe Now for Access
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