Possible Rivaroxaban Failure during the Postpartum Period

Abstract

Rivaroxaban, a factor Xa inhibitor, is a direct-acting oral anticoagulant (DOAC) indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for reducing the risk of DVT and PE recurrence. To our knowledge, no data are presently available to guide DOAC dosing in the postpartum period when pharmacokinetic and pharmacodynamic changes induced by pregnancy have an impact on drug clearance and increase hypercoagulability for a period of 6-8 weeks after delivery. We describe the case of a 35-year-old postpartum woman who presented to the emergency department with a diagnosis of a new multiple segmental PE 5 days after starting rivaroxaban therapy for a diagnosis of DVT. No precipitating cause, including noncompliance, was identified as a source of thrombosis embolization or extension. The patient was admitted, a heparin infusion was started for the management of PE, and rivaroxaban was discontinued. She was transitioned to enoxaparin 1 mg/kg (90 mg) subcutaneously every 12 hours the next day, bridged to warfarin, and discharged home on the overlapping regimen with close follow-up by the pharmacist-managed outpatient Anticoagulation Management Service. To our knowledge, this is the first case report of potential failure associated with rivaroxaban therapy in the postpartum period, possibly due to pharmacokinetic alterations seen in the postpartum period contributing to decreased drug exposure, yielding reduced anticoagulant efficacy. Clinicians should carefully weigh the risks and benefits of DOAC therapy in postpartum patients or other special populations requiring anticoagulation therapy. This report also highlights the need for further research identifying the impact of pharmacokinetic changes induced by special populations and the need to develop monitoring assays for such clinical situations.

Incomplete Resolution of Deep Vein Thromboses during Rivaroxaban Therapy

“…The recent addition of factor Xa inhibitors to anticoagulant agents is not without fault (i.e., failure, bleeding, and lack of reversal agents), as demonstrated in this case report and other papers [6, 7, 12]. The risk factors for failure of anticoagulation therapy are vast and vary from patient to patient; pharmacodynamics, pharmacokinetics, metabolism, and elimination all have a hand in how a drug interacts in a given patient and are further discussed below [13–15].…”

“…A thorough literature review revealed little in the way of reports of rivaroxaban failure in the treatment of DVT, although a few case reports in which potential rivaroxaban failure is noted have emerged recently [6, 7]. Postmarketing surveillance is clearly an important factor in the further development, safety, and efficacy of any novel drug.…”

“…On the other hand, rivaroxaban's disadvantages have been documented as well. The major disadvantages include internal bleeding, particularly gastrointestinal bleeding [5], as well as documented cases in which thromboembolisms do not completely resolve [6, 7]. …”

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

“…Further, we suggest that practitioners carefully weigh the risks and benefits when selecting these medications. We note that Rudd et al have reported independently on possible rivaroxaban failure in patients treated during the postpartum period, possibly due to pharmacokinetic alterations seen in the postpartum period that can contribute to decreased drug exposure and reduced anticoagulant efficacy [16]. In fact, rivaroxaban is well known to be metabolized by the cytochrome P450 isoenzyme CYP 3A4 and binds to P-glycoprotein; hence, leading to risks of pharmacokinetic interactions that may alter its anticoagulant properties [17].…”

Possible Rivaroxaban Failure during the Postpartum Period: An Alternative Viewpoint

“…Anticoagulation decreases the risk of recurrent venous thromboembolism (VTE) in patients with DVT to 6.3/100 patientyears. 1,2 However, this is after the discontinuation of anticoagulant therapy. 2 The risk of recurrent VTE is not static and decreases over time.…”