Emma Hitt, PhD

August 16, 2007 — Use of entecavir (Baraclude) by patients coinfected with HIV and hepatitis B virus who are not already receiving highly active antiretroviral therapy (HAART) may result in resistance to nucleoside reverse transcriptase inhibitors (NRTIs), according to an alert sent today from MedWatch, the US Food and Drug Administration (FDA) adverse event and reporting program. The full prescribing information for entecavir, including the boxed warning, has been updated to include this information. Entecavir, manufactured by Bristol-Myers Squibb (BMS), is indicated for the treatment of chronic hepatitis B virus in adults who show evidence of active viral replication and who have either histologically active disease or persistent elevations in serum aminotransferases (ALT or AST).The microbiology section of the entecavir prescribing information was also updated to include a statement about the inhibitory activity of entecavir against HIV-1 isolates. Entecavir selected for an M184I substitution in HIV reverse transcriptase at micromolar concentrations in cell culture, indicating inhibitory pressure at high entecavir concentrations, and HIV variants containing the M184V substitution showed loss of susceptibility to entecavir.In addition, the warnings section has been updated to state that before starting therapy with entecavir, all patients should be offered HIV antibody testing and that entecavir has not been evaluated for treatment of HIV infection.

Black-Box Heart-Failure Warning for Rosiglitazone, Pioglitazone

from Heartwire — a professional news service of WebMD

Shelley Wood

August 15, 2007 (Rockville, MD) - At the FDA's behest, GlaxoSmithKline and Takeda will be adding black-box warnings to their thiazolidinedione drugs for type 2 diabetes--rosiglitazone (Avandia) and pioglitazone (Actos), respectively--reminding physicians that these drugs should not be used in people with heart failure, the FDA announced today. The news is no surprise: FDA commissioner Andrew C von Eschenbach first promised this labeling change during a hearing of the US Congress House Committee on Oversight and Government Reform in June, as reported by Heartwire. But the recent brouhaha over rosiglitazone has had to do with risk of ischemic events, not heart failure, and an FDA press release states that the agency's review of Avandia and the possible increased risk of heart attacks is ongoing." On July 30, a joint meeting of the FDA's Endocrine and Metabolic Advisory Committee and its Drug Safety and Risk Management Advisory Committee recommended that the FDA also include labeling about ischemic risk, noting that there is a signal of increased MI and cardiac death with the drug in some studies. The heart-failure warning, however, merely strengthens the existing labeling caveats about use of this class of drugs in heart-failure patients. The boxed warning will now advise physicians to look carefully for heart-failure signs and symptoms, including edema, shortness of breath, and rapid weight gain. The warning will also appear on other brands made by these companies that combine rosiglitazone or pioglitazone with other antidiabetic agents.

FDA Safety Changes: Zerit

News Author: Yael Waknine
CME Author: Yael Waknine

Stavudine (Zerit) Use With Didanosine and Hydroxyurea-Based Regimens Linked to Hepatotoxicity

On April 20, the FDA approved safety labeling changes for stavudine (Zerit capsules and oral solution, made by Bristol-Myers Squibb Company) to advise of the increased risk for hepatotoxicity associated with its use with didanosine and hydroxyurea. The FDA previously warned that combination antiretroviral therapy has yielded an increased frequency of abnormalities of liver function (including severe and potentially fatal hepatic adverse events) in patients with preexisting liver dysfunction, including chronic active hepatitis. Monitoring is advised according to standard practice, and interruption or discontinuation of treatment is considered on evidence of worsening liver disease.
The agency now warns that cases of fatal hepatotoxicity and hepatic failure have been reported during postmarketing surveillance of patients infected with HIV, particularly among those receiving concomitant treatment with hydroxyurea, didanosine, and stavudine. Therefore, this drug combination should be avoided. Stavudine is indicated for use with other antiretroviral agents for the treatment of HIV-1 infection.