Washington Editor

The FDA has released two more lists of drugs and classes of medications, such as oral bisphosphonates and antidepressants, currently being evaluated by regulators for potential safety problems.

The public lists, which were derived from reports to the agency's Adverse Event Reporting Systems (AERS) and were mandated by Congress under the FDA Amendments Act, were supposed to be issued quarterly.

However, the first list for the quarter ending March 31, 2008, which included 20 drugs and classes of medications, was not issued by the FDA until September 2008, and the reports for the quarters ending June 30, 2008, and Sept. 30, 2008, were released together late Wednesday afternoon. (See BioWorld Today, Sept. 8, 2008.)

Officials in September said it had taken the FDA several months to get its process under way for communicating the information to the public, and therefore, would take it a while to get caught up.

FDA spokeswoman Karen Riley emphasized that the appearance of a drug on the list does not mean that regulators have firmly concluded that there is a causal relationship between the medication or drug class and the suspected safety issue.

It simply means the agency is analyzing AERS reports to determine whether there is a safety problem and if any regulatory action is needed, Riley told reporters Wednesday afternoon.

Some of the concerns raised about the drugs in the two new quarterly reports already have been made public in the past year by the FDA through various alerts, such as labeling revisions, public health advisories or MedWatch alerts.

For instance, the FDA in August 2008 issued a public alert about the risk of rhabdomyolysis, a rare condition of muscle injury that can lead to kidney failure or death, when patients mix simvastatin with amiodarone. Although the labeling for the drugs had been revised in 2002 to alert prescribers and patients about the risk of rhabdomyolysis when mixing the medications at certain dosages, the FDA said it continues to receive reports about the adverse event.

Some of the drugs on the list already have been under scrutiny for certain safety issues, but new concerns have recently arisen. For example, the FDA last month issued an alert about the possibility of severe and sometimes incapacitating bone, joint or musculoskeletal pain in patients taking bisphosphonates. The agency last fall also alerted the public about a potential increased risk for atrial fibrillation related to the drugs.

In its report for the quarter ending Sept. 30, 2008, the FDA said it is now reviewing 23 reports of esophageal cancer in patients taking Merck & Co.'s bisphosphonate Fosamax (alendronate).

The FDA's Diane K. Wysowski had published an article about those reports in the Jan. 1, 2009, issue of the New England Journal of Medicine.

Regulators said they are continuing to evaluate the esophageal cancer reports to determine whether there is a need for any regulatory action.

The FDA in July 2008 required makers of fluoroquinolones, such as ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin, to include a black-box warning in product labeling alerting prescribers and patients about an increased risk of tendinitis and tendon rupture with the drugs. In its report for the quarter ending June 30, 2008, the FDA acknowledged that it had considered adding an alert about an increased risk of adverse central nervous system (CNS) events, such as seizures, related to the drugs.

However, the FDA said in the quarterly report that it had decided that the CNS events already were adequately addressed in the "Warnings" section of the labeling.

While the controversy continues about the black-box warning added to the labeling for antidepressants alerting prescribers and patients about an increased risk of suicidal thoughts and behaviors in patients taking the drugs - something for which the FDA has been criticized for not warning the public soon enough about - the agency said in its September 2008 report that it now is investigating a link between the medications and birth defects. Regulators said they are continuing to evaluate that concern.

The FDA also said it was reviewing reports of torsades de pointes, hepatotoxicity and blood dyscrasias in patients taking Bristol-Myer Squibb Co.'s Abilify (aripiprazole). Those safety concerns were identified as part of the FDA's Post-Marketing Safety Evaluation New Molecular Entity pilot program, initiated by the agency in January 2007, the agency said.

Regulators also said they had received reports of adverse neuropsychiatric events in patients taking Tibotec Inc.'s HIV drug Intelence (etravirine), which was approved last year.

However, the FDA said it its June 2008 quarterly report that it decided that no action is necessary at this time based on limited available information, but is continuing to monitor the issue.

The June 2008 report listed 14 drugs or classes of medications with safety concerns under review, while the September 2008 report included nine.