4 out of 5 stars
Dabigatran: how the drug company withheld important analyses. Cohen D. BMJ 2014 Jul 23;349:g4670. doi: 10.1136/bmj.g4670.
As TPR has reported before, there has long been reason to doubt the claim that the anticoagulant dabigatran (Pradaxa) can be safely and effectively used for prevention of strokes in patients with non-valvular atrial fibrillation without laboratory monitoring.
This must-read investigative report uses internal company documents released in association with multiple lawsuits — recently settled for a total of $650 million — to suggest that Boehringer Ingelheim, the drug’s manufacturer, suppressed evidence that using a laboratory test to adjust dosing could reduce the incidence of major bleeds associated with the drug.
As the BMJ report points out, the claim that monitoring levels and/or anticoagulation effect was not necessary when using Pradaxa was a key talking point in marketing the drug. However, a company study had determined that blood levels of dabigatran were unpredictable, varying five-fold from patient to patient. One cardiologist who advised the FDA noted:
“I’m struck by what my eyeball tells me about a five-fold variability [in plasma levels] within the 90% confidence [interval] of the 150-dose. That seems awfully big to me in a drug that we’re proposing to use without therapeutic monitoring.”
This unpredictability was especially important because there was no available and effective way to reverse the anticoagulant effect in the event of significant hemorrhage. The Institute for Safe Medication Practices reported that in 2011 there were 3781 serious adverse effects and 542 patient deaths reported in the United States in association with dabigatran. In comparison, warfarin (Coumadin) was associated with only 72 deaths during that same time period.
The BMJ report cites the internal company documents to argue that for marketing purposes the company suppressed recommendations for monitoring and did not share all their analyses with regulatory agencies:
“In the end, the final recommendations simply stressed the need to monitor renal function and patient characteristics before and during treatment and ‘make dose reductions in certain patients’ — and not routinely measure plasma concentrations of anticoagulant activity.”
This is an important report. It’s a must-read.
Maybe Pradaxa (dabigatran) does need blood monitoring after all
Dabigatran-related bleeding: a case series
Pearl: estimating renal function in patients on dabigatran (Pradaxa)
Massive bleeding associated with dabigatran
Case report: hemodialysis for dabigatran overdose
The many potential problems with using dabigatran
New York Times on dabigatran
Case series: four patients with dabigatran-associated bleeding
Guidelines for reversing overdose of dabigatran (Pradaxa) and other new anticoagulants
Care Report: fatal GI bleed 6 days after one dose of dabigatran (Pradaxa)
Dabigatran: is laboratory monitoring really unnecessary?
Dabiagtran and the trauma patient
Dabigatran Toxicity: The Top 10 Questions
Review: the bleeding patient on dabigatran
Dabigatran and the elderly
Dabigatran etexilate: a new challenge for emergency physicians and toxicologists