Dabigatran tops list again for safety issues

Once again, dabigatran led the pack in an analysis of drug safety problems directly reported to the FDA, with warfarin taking second place. Quarter Watch Report claimed risks associated with anticoagulants make them “one of the most dangerous of all outpatient drug treatments.”

The Institute of Safe Medication Practices monitors serious adverse drug events reported to the FDA through the agency’s MedWatch program. According to its Quarter Watch analysis, the FDA received 210,648 adverse events reports for therapeutic drugs in 2012, an increase of 16 percent from 2011. Reports from physicians and consumers, known as direct reports, declined by 3.3 percent and reports from manufacturers increased by 18.5 percent.

All in all, there were 6,234 cases of serious injury, including 789 patient deaths, reported either directly or by manufacturers for the anticoagulants dabigatran (Pradaxa, Boehringher Ingelheim), warfarin and rivaroxaban (Xarelto, Janssen Pharmaceuticals/Bayer HealthCare). The report found adverse events associated with dabigatran accounted for 582 of the 789 deaths. 

Dabigatran ranked first for direct reports, with 683 cases. Warfarin held the second spot, with 492 cases. Rivaroxaban placed 10th, with 226 cases.

The authors highlighted direct reports, which they called “important indicators of nation-wide safety problems because they are not influenced by factors that can expand manufacturer reporting (such as marketing activities) or suppress it (hard to identify and locate generic drug manufacturers).” They acknowledged that the number of direct reports likely is a fraction of actual adverse events, and that reporting an event does not mean the drug caused the event.

The institute raised concerns about the risk of hemorrhage and other bleeding with anticoagulants last year. “The result is tens of thousands of emergency room visits or hospitalizations each year. It is also of concern that two years after a large volume of reports of hemorrhages began, the FDA has discounted the adverse event data and focused narrowly on the question of whether dabigatran has higher risks than warfarin.” 

The authors made these recommendations to potentially reduce risks with dabigatran:

• Re-evaluate dose strategies to treat at-risk, older patients;
• Increase monitoring of kidney function; and
• Provide better information to help physicians manage patients on anticoagulants.

For warfarin they added:

• Better monitoring, including for drug interactions; and
• More careful patient selection.