FDA Notifications
VITROS anti-HIV test is approved
On March 27, 2008, the FDA approved a new HIV diagnostic test, the VITROS Anti-HIV 1+2 Reagent Pack and VITROS Anti-HIV 1+2 Calibrator, manufactured by Ortho-Clinical Diagnostics. The VITROS Anti-HIV 1+2 Reagent Pack and VITROS Anti-HIV 1+2 Calibrator is an in vitro chemiluminescent immunoassay intended for the in vitro qualitative detection of antibodies to human immunodeficiency virus types 1 and 2 in human serum and plasma using the VITROS ECi/ECiQ Immunodiagnostic System.
The results of the VITROS Anti-HIV 1+2 assay, in conjunction with other serological evidence and clinical information, may be used as an aid in the diagnosis of infection with HIV-1 and/or HIV-2 in persons with signs or symptoms of, or at risk for, HIV infection.
The assay is highly sensitive and specific for the detection of anti-HIV types 1 and 2 antibody. The VITROS ECi/ECiQ Immunodiagnostic System is fully automated, reducing the potential for operator errors, with redundant checks to ensure integrity of the system. This automation allows for increased efficiency and convenience.
FDA-approved assays for diagnosis and donor screening for HIV are listed at www.fda.gov.
Large study suggests heart attack risk from use of abacavir or didanosine
The FDA has been made aware of recent, preliminary findings from analyses of data collected from "The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study," a large observational study of 33,347 HIV-1 infected patients living in North America, Europe and Australia. Patients in this study are being followed to evaluate the short- and long-term adverse effects of treatment with anti-HIV drugs.
Analyses of data collected through Feb. 1, 2007 examined the risk of myocardial infarction (heart attack) in patients taking selected HIV drugs from the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). The NRTIs included in the analyses were zidovudine, stavudine, abacavir, didanosine, and lamivudine. No analyses were conducted evaluating the risk of heart attack when patients take tenofovir or emtricitabine, two other drugs in the class. The analyses, specifically, describe the relative risk of heart attack among cumulative use, recent use (currently using or use within the past 6 months), and past use (last use greater than 6 months ago) of these drugs.
These analyses showed that recent use of abacavir or didanosine was associated with an increased risk of heart attack. Patients taking either of these drugs had a greater chance of developing a heart attack than patients taking other medications. The risk did not appear to increase over time, but remained stable and appeared to be reversible after abacavir or didanosine were stopped.
In late 2007, GlaxoSmithKline (GSK), the manufacturer of abacavir, received the preliminary findings from the D:A:D Study analyses and conducted a search of their own clinical study databases. The results of the GSK analysis are inconclusive, but did not show an increased risk.
Bristol Myers Squibb (BMS), the manufacturer of didanosine, conducted an analysis of their clinical databases, and similarly, found no increased risk for heart attack with didanosine use. The results of the BMS analysis are also inconclusive.
Key findings from the D:A:D Study are as follows:
- The excess risk of heart attack in patients taking at least some NRTIs appears to be greater in patients with other risk factors for heart disease. Risk factors include a history of heart disease, high cholesterol, high blood pressure, diabetes, smoking, and age.
- Certain analyses found the risk of heart attack increased by 49% in patients taking didanosine and increased by 90% in patients taking abacavir.
- The increased risk for heart attack remained stable over the course of treatment and the effect was not seen 6 months after stopping the drugs.
- The FDA currently believes analyses conducted with D:A:D Study data are incomplete; no analyses were conducted evaluating the risk of heart attack when patients take tenofovir or emtricitabine, two other drugs in the class of NRTIs. However, FDA continues to evaluate the overall risks and benefits of abacavir and didanosine. This evaluation may result in the need to revise labeling for the products. Until this evaluation is complete, healthcare providers should evaluate the potential risks and benefits of each HIV-1 antiretroviral drug their patients are taking, including abacavir and didanosine.
This early communication is in keeping with FDA's commitment to inform the public about ongoing safety reviews of drugs. FDA will work with the manufacturers of abacavir and didanosine to fully evaluate the risks and benefits associated with the use of these products as part of an HIV treatment regimen. As soon as this process is complete, FDA will communicate the conclusions and recommendations to the public.
The FDA urges healthcare professionals to promptly report serious and unexpected adverse reactions associated with abacavir and didanosine, and all drugs, to the FDA MedWatch reporting program, which is available online at www.fda.gov/medwatch/report.htm or by phone at 1-800-332-1088.
Atazanavir capsule label is updated for pediatric patients
The atazanavir (Reyataz) Capsule label has been updated to include the dosing recommendations for pediatric patients 6 to 18 years of age.
Atazanavir should not be administered to pediatric patients below the age of 3 months due to the risk of kernicterus (a type of brain damage caused by excessive levels of bilirubin).
Important changes made to the product label include the following:
- Section 2.2 Recommended Pediatric Dosage was added to the label.
- The recommended dosage of atazanavir for pediatric patients (6 to less than 18 years of age) is based on body weight and should not exceed the recommended adult dosage. Atazanavir capsules must be taken with food. The data are insufficient to recommend dosing of atazanavir for any of the following: 1) patients less than 6 years of age, 2) without ritonavir in patients less than 13 years of age, and 3) treatment-experienced pediatric patients with body weight less than 25 kg.
- Therapy-Naive Pediatric Patients: The recommended dosage of atazanavir with ritonavir in treatment-naive patients at least 6 years of age is shown in Table 1.
- For treatment-naive patients at least 13 years of age and at least 39 kg, who are unable to tolerate ritonavir, the recommended dose is atazanavir 400 mg (without ritonavir) once daily with food.
- In section 6 Adverse Reactions subsection 6.2 Clinical Trial Experience in Pediatric Patients was added and includes the following information: The safety profile of atazanavir in pediatric patients (6 to less than 18 years of age) was comparable to that observed in clinical studies of atazanavir in adults. The most common Grade 2-4 adverse events (≥ 5%, regardless of causality) reported in pediatric patients were cough (21%), fever (19%), rash (14%), jaundice/scleral icterus (13%), diarrhea (8%), vomiting (8%), headache (7%), and rhinorrhea (6%). Asymptomatic second-degree atrioventricular block was reported in 2% of patients. The most common Grade 3-4 laboratory abnormality was elevation of total bilirubin (≥ 3.2 mg/dL) which occurred in 49% of pediatric patients. All other Grade 3-4 laboratory abnormalities occurred with a frequency of less than 3%.
- In section 14 Clinical Studies, subsection 14.3 Pediatric Patients was added and includes the following: Assessment of the pharmacokinetics, safety, tolerability, and efficacy of atazanavir is based on data from the open-label, multicenter clinical trial PACTG 1020A conducted in patients from 3 months to 21 years of age. In this study, 182 patients (83 antiretroviral-naive and 99 antiretroviral-experienced) received once daily atazanavir, with or without ritonavir, in combination with two NRTIs.
- Ninety-nine patients (6 to less than 18 years of age) treated with the atazanavir capsule formulation, with or without ritonavir, were evaluated. In this cohort, the overall proportions of antiretroviral-naive and -experienced patients with HIV RNA < 400 copies/mL at week 24 were 68% (28/41) and 33% (19/58), respectively. The overall proportions of antiretroviral-naive and ?experienced patients with HIV RNA < 50 copies/mL at week 24 were 59% (24/41) and 24% (14/58), respectively. The median increase from baseline in absolute CD4 count at 20 weeks of therapy was 171 cells/mm3 in antiretroviral-naive patients and 116 cells/mm3 in antiretroviral-experienced patients.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.