Xarelto is a recently developed and U.S. FDA approved oral anticoagulant, or a blood-thinning drug.
Xarelto is a selective inhibitor of Factor Xa which is used in the prevention of stroke and venous embolism in patients with chronic atrial fibrillation, as well as treatment and prevention of deep venous thrombosis and pulmonary embolism.
Xarelto is available in tablets of 10, 15 and 20 mg, and the recommended dose in adults is 10 to 20 mg once daily depending upon indication and renal function.
Compared with warfarin, a traditional blood thinner, Xarelto® has some advantages, including fewer interactions with food and other drugs, rapid onset, and freedom from the need to have periodic blood test monitoring. And whereas the effects of it wane within a short time frame after they are stopped, a day or so, the effects of warfarin persist for many days after it is discontinued.
What are the Indications of Xarelto® and Who Should Use it?
Xarelto is approved to be used for the treatment of patients with following indications:
- Xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
- There are limited data on the relative effectiveness of Xarelto® and warfarin in recuding the risk of stroke and systemic embolism when warfarin is well-controlled.
- Xarelto® is indicated for the treatment of deep vein thrombosis (DVT)
- Xarelto® is indicated for the treatment of pulmonary embolism (PE)
- Xarelto® is indicated for the reduction in the risk of recurrence of DVT and of PE following initial 6 months treatment for DVT and/or PE
- Xarelto® is indicated for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery
What are the Side Effects of Xarelto?
Anticoagulants have been known for many years to produce a striking (more than 50%) decrease in the rate of stroke, but they also prevent clotting in locations and situations where clotting is desirable. In other words, they can cause bleeding.
Xarelto, like other anticoagulants, is associated with bleeding adverse events (5% to 6%, major in ~1%), but these are no more frequent than with low molecular weight heparins or warfarin. Side effects not directly attributable to the anticoagulant activity of rivaroxaban are not common, but can include nausea, abdominal discomfort, back pain, anorexia, fever, and skin rash.
- Premature discontinuation of Xarelto® increases the risk of thrombotic events
Premature discontinuation of Xarelto, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from Xarelto® to warfarin in clinical trials in atrial fibrillation patients.
- Risk of bleeding
Xarelto can cause bleeding, which can be serious, and rarely may lead to death. This is because Xarelto is a blood thinner medicine that reduces blood clotting.
While taking Xarelto®, patients are likely to bruise more easily and it may take longer for bleeding to stop.
- Risk of developing an epidural or spinal hematoma when neuraxial anesthesia or spinal puncture is employed
When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with Xarelto for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis.
Other Safety Concerns of Xarelto
While bleeding is a common complication associated with anticoagulants, it has been alleged that Xarelto® is more dangerous than traditional blood thinners because no specific antidote for Xarelto® is available yet.
Moreover, in recent years, safety concerns have been raised about hepatic safety of Xarelto®.
A case study in JAMA Internal Medicine reports on two patients that experienced severe liver injury onset during treatment with the oral anticoagulant rivaroxaban.
The first patient was a 52-year-old man who developed severe lobular hepatitis two months after initiation of rivaroxaban 10mg/day for the prevention of deep vein thrombosis (DVT) after internal fixation of a tibia fracture. The preserved lobular architecture and lack of fibrosis of portal tract were consistent with a drug-related liver injury. After cessation of rivaroxaban, the patient had a full clinical and partial biochemical recovery after 14 days. However, the patients had also been treated with other potentially hepatotoxic drugs (ibuprofen and pantoprazole).
The second patient, a 73-year-old woman prescribed 10mg/day of rivaroxaban after a total knee replacement for the prevention of DVT, experienced mixed liver injury but liver enzyme levels and bilirubin concentration restored to normal levels after 14 days of rivaroxaban cessation. This patient was also taking levothyroxine and lisinopril, which were not discontinued.
The authors speculate that rivaroxaban was most likely the cause of drug-induced liver injury (DILI) in both patients and that physicians should be aware of this potentially severe adverse drug reaction. They also emphasize that a warning regarding symptomatic liver injury should be included in the drug label.
However, a systematic review and meta-analysis of phase III randomised controlled trials (RCTs) indicate that the new oral anticoagulants (NOACs), including rivaroxaban, do not increase the risk of drug-induced liver injury.
According to NIH drug record of rivaroxaban, liver injury attributed to rivaroxaban varies from mild serum ALT elevations to liver injury with jaundice, but is usually mild and self-limited, resolving within a few weeks of stopping. Cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome due to rivaroxaban have not been reported.
- Medicine Guide of Xarelto® from U.S. FDA
- S. FDA approved Prescribing Information of Xarelto®
- NIH Drug Record of RIVAROXABAN
- Evangelia Liakoni, MD; Alexandra E. Rätz Bravo, PhD; Luigi Terracciano, MD; Markus Heim, MD4; Stephan Krähenbühl, MD, PhD; Rivaroxaban and Liver Injury: Case Studies Add to Safety Questions. JAMA Intern Med. 2014; 174(10):1683-1686. doi:10.1001/jamainternmed.2014.3912.
- Daniel Caldeira; Márcio Barra; Ana Teresa Santos; Daisy de Abreu; Fausto J Pinto; Joaquim J Ferreira; João Costa; Risk of Drug-induced Liver Injury With the New Oral Anticoagulants. Heart. 2014;100(7):550-556.