Doctors urge caution after critical report on Pradaxa

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As the maker of the stroke-prevention drug Pradaxa disputed a report Wednesday that it withheld safety data from regulators, local doctors recommended cautious use of a medication widely marketed for its convenience to patients.

The British medical journal BMJ said drug maker Boehringer Ingelheim tells Pradaxa users that they don’‍t need periodic blood tests to check for excessive blood thinning, even though the company‘‍s own research showed that such monitoring would help reduce the risk of bleeding. It said the Germany-based company withheld those findings from U.S. and European regulators, who approved the drug’‍s use in 2010 and 2011, respectively.

The company said it did not share certain “preliminary, exploratory simulations” with regulators but had provided the data behind them. It called the journal report misleading, and said it feared frightened patients might stop taking the drug without their doctor’s approval.

Srinivas Murali, medical director of Allegheny Health Network’‍s Cardiovascular Institute, cited a need for comprehensive data on doctor and patient experience with the drug.

But for now, he envisions no major shifts in when he prescribes the drug, noting he already uses other medications for high-risk patients, such as those with kidney problems.

Roy Smith, professor in the hematology/​oncology division of the University of Pittsburgh School of Medicine, said he’s already inclined to prescribe an older medication, warfarin, instead of Pradaxa. He said that’‍s partly because Pradaxa’s medical benefits are only slightly better than warfarin’‍s and because there’‍s no antidote to reverse Pradaxa’s effects in patients who experience bleeding problems.

UPMC can perform dialysis to reverse the effects of Pradaxa, but not all health-care systems may be able to provide the same care. Antidotes for Pradaxa and similar drugs are in development, Dr. Smith said.

There is no accurate way currently to measure the impact of Pradaxa on the blood, and, with only two doses available, it isn’t really possible to customize dosages for the patient anyway, he said.

Both doctors said the dispute over Pradaxa research highlights the need for full disclosure during the drug-approval process. “That’‍s one lesson here,” Dr. Murali said.

The older drug warfarin, known by such brand names as Coumadin and Jantoven, requires periodic blood testing and, based on the results, a patient’s dose may be adjusted to reduce the risk of internal or external bleeding. The bleeding could occur spontaneously or as the result of an injury or medical procedure.

Pradaxa has been marketed as a convenient alternative requiring no blood monitoring. “If monitoring is needed, that advantage goes away,” Dr. Murali said.

The journal also questioned regulators’ actions, saying they approved the drug’s use even though they had concerns about the clinical research used to assess the drug’s benefits and risks and wondered whether it was prudent for Pradaxa users to forgo blood monitoring.

In the United States, the drug accounted for 542 deaths and nearly 2,400 hemorrhages in 2011, the journal said. In comparison, warfarin accounted for 72 deaths that year.

In defending its research and the drug‘‍s record, Boehringer Ingelheim said, “Contrary to the BMJ’s accusation that BI withheld analyses, here are the facts: in 2012, our scientists performed preliminary, exploratory simulations with mathematical models to understand whether dose adjustments based on plasma concentrations might further improve Pradaxa’s benefits and safety. Because the simulations did not offer reliable predictions of actual patient outcomes, they were not provided to regulators. However, all of the data that was used for the simulations had already been provided.”

The U.S. Food and Drug Administration is standing behind Pradaxa.

“Our most recent safety notice on Pradaxa from May 2014 notes that we still consider Pradaxa to have a favorable benefit-to-risk profile and have made no changes to the current label or to the recommendations for use,” FDA spokeswoman Sandy Walsh said in an email.

Direct-to-consumer marketing has influenced Pradaxa's popularity, Dr. Smith said. Many patients take the drug because they’ve asked for it or because of physician convenience, he said.

In the wake of the journal’‍s report, Dr. Murali said, “we should inform our patients that perhaps there is additional information that is forthcoming regarding this drug.”

Joe Smydo: or 412-263-1548. First Published July 23, 2014 12:00 AM

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