Safety group flags bleeding reports on Pradaxa, Xarelto and old standby warfarin

The Institute for Safe Medication Practices (ISMP) has flagged its latest set of side-effect reports to the FDA--and once again, anticoagulant drugs are at the top. Boehringer Ingelheim's Pradaxa, a new-generation pill, and the old standard therapy warfarin together accounted for more than 1,100 of the adverse events reported direcctly to the FDA. Rounding out the top 5 were the antibiotic Levaquin, the antidepressant Cymbalta and the hypertension treatment Prinivil.

In both blood-thinner cases, serious bleeding was the side effect most often reported--and given the nature of anticoagulants, which cut down on blood clotting, that's no surprise. The difference in the two is that warfarin, which is difficult to dose and requires ongoing monitoring, has a quick-acting antidote, vitamin K. Pradaxa, designed to be easier to use, has no such antidote, though Boehringer is working to develop one. It's worth noting as well that Bayer and Johnson & Johnson's ($JNJ) latest anticoagulant Xarelto, which hit the stroke-prevention market more than a year after Pradaxa, also accounted for a significant number of reports, ranking 10th on the ISMP's QuarterWatch list.

Among the other three drugs in the top 5, lisinopril, originally sold under the brand name Prinivil, accounted for the biggest number of side-effect reports; the most common were hives and angioedema, or swelling, which most often affected the face, tongue and lips. Levaquin (levofloxacin), the Johnson & Johnson antibiotic that has been associated with ruptured tendons--and carries a black-box warning to that effect--came in fourth.

In fifth place is Eli Lilly's ($LLY) Cymbalta (duloxetine), its top-selling antidepressant. The CenterWatch tally included withdrawal symptoms in patients trying to stop their Cymbalta therapy; according to the watchdog organization, about half of patients in long-term trials had troublesome side effects when coming off the drug.

The organization also highlighted some reports related to three anti-TNF drugs, used to fight rheumatoid arthritis, psoriasis and other inflammatory disorders. Abbvie's ($ABBV) Humira, Amgen's ($AMGN) Enbrel and J&J's Remicade accounted for more than 11,000 serious adverse events. That number includes thousands of reports directly from the manufacturers, intended to flag side effects that aren't prominently highlighted in drug-label warnings, the QuarterWatch update states. Overall, the reported side effects included infections, skin cancer and nerve-fiber demyelination.

- read the ISMP report (PDF)

Editor's note: This story was corrected to show that Boehringer is working on a Pradaxa antidote alone, rather than with a partner as originally stated.