This New Generation Of Oral Anticoagulants Has Bleeding-Related Adverse Reactions Including Gastrointestinal And Intracranial Bleeds
The ISMP Quarterwatch published on September 23, 2015 includes an examination of the safety profiles of Eliquis, Pradaxa, and Xarelto, which are characterized as "novel" oral anticoagulants. Savaysa is not included in this ISMP study because it draws on FDA data from the second half of 2014 and Savaysa was not approved by the FDA until January 2015.
These new oral anticoagulants which have been associated with bleeding-related adverse reactions including gastrointestinal and intracranial bleeds. And that problem is the primary complaint that the Institute for Safe Medications (ISMP) has with these blood thinners.
Here is a brief excerpt from the ISMP Quarterwatch report that captures the tone of this report about Pradaxa, Xarelto, and Eliquis:
The adverse event reports for oral anticoagulants confirm the evidence that long-term use remains one of the highest-risk drug treatments in older patients, with injury rates of 15-20% per year. As previously noted in this publication, bringing a new generation of oral anticoagulants to market based on ease of use rather than improved safety was a major wrong turn.... But the risks of bleeding are so high that individualizing the dose—as with warfarin—promises to improve the safety profile of this risky class of drugs.
This September 2015 edition of the ISMP QuarterWatch publication then goes on to cover a safety issue with Savaysa, Eliquis, Pradaxa, and Xarelto that has not received much attention: The effect of platelet inhibitors in combination with those new anticoagulants.
From the ISMP report, we get these points about the effect of platelet inhibitors:
- The adverse event data for 2014 raised questions about why no clear guidelines existed about when or even whether patients should take two different kinds of drugs that inhibited the formation of blood clots. The anticoagulants reduce blood clot formation by inhibiting the enzyme that triggers the formation of fibrin threads that help seal the platelets that aggregate to plug bleeding site. Aspirin, clopidogrel, and other nonsteroidal anti-inflammatory drugs inhibit the aggregation of platelets.
- In the adverse event data, we found that concomitant therapy with platelet inhibitors increased the odds of a hemorrhage event by threefold (OR 3.01 p < 0.01). The increased risk was found across all three of the novel anticoagulants and warfarin.
- The prescribing information for all three drugs [Xarelto, Pradaxa, and Eliquis] contains no guidance on the concomitant use of antiplatelet agents other than a warning that an increased risk of bleeding was observed.
It seems sensible that the FDA should require studies be done to develop clear and definitive guidelines for whether to use these new anticoagulant drugs at the same time, i.e., concomitant use, that a patient is taking one or more of the platelet inhibitors.
I suggest to the pharmaceutical companies responsible for Savaysa, Eliquis, Xarelto, and Pradaxa that they spend some of the "big" money now used for their direct-to-consumer (DTC) advertising campaigns on such a drug safety study.