Factor Xa Inhibitor Has Stern Renal Function Warning

Factor Xa inhibitors help decrease the formation of a blood clot in the circulatory system. Simply stated, these anticoagulant drugs work by blocking factor Xa, which is directly responsible for producing thrombin, a necessary ingredient in clot production.

Four drugs in this class are currently available: dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and the recently approved edoxaban (Savaysa).

All of these factor Xa inhibitors share the following black box warnings:

• There is an increased risk of a thrombotic event and stroke when the factor Xa inhibitor is stopped in patients with nonvalvular atrial fibrillation (NVAF). If the drug must be stopped for reasons other than bleeding, then consider administering another anticoagulant.

• There is an increased risk of hematoma in the spinal column after spinal puncture or epidural catheter for anesthesia if performed with concomitant use of drugs that affect bleeding, such as anticoagulants, platelet inhibitors, or NSAIDs. A spinal hematoma may result in long-term paralysis. Monitor for tingling, weakness, or numbness.

The recently approved factor Xa inhibitor, edoxaban, has an additional black box warning:

• This medication has a reduced efficacy in NVAF patients with a creatinine clearance (CrCl) >95 ml/min. Patients in this category show an increased risk of ischemic stroke compared with patients on warfarin. Use another anticoagulant in these patients.

Normal CrCl values range from 97 ml/min to 137 ml/min in adult males and 88 ml/min to 128 ml/min in adult females, according to the US National Library of Medicine. Therefore, there is no scenario where edoxaban could be appropriately used to treat NVAF in adult males with normal renal function, and there is limited opportunity for it to be used in adult females with normal renal function.

My outpatient pharmacy has been detailed on edoxaban no less than 5 times in the past 2 months. The representatives have shared efficacy studies and discussed the all-important patient assistance program and co-pay cards.

Not once has a representative discussed the renal function contraindication with our staff. In fact, my first encounter with this contraindication was when we received the medication on our store shelf, and I opened up the package insert to review the black box warnings.

Edoxban may very well have a place in the treatment of NVAF, but pharmacists must be aware that this medication should not be used in any patient with a CrCl >95 ml/min.