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Rivaroxaban
Aka: Rivaroxaban, Xarelto- Mechanism
- Oral direct Xa inhibitor
- Factor Xa is the first step in the Common Clotting Cascade
- Indications
- Atrial Fibrillation
- Bridging to Transesophageal Echocardiogram and early cardioversion in Atrial Fibrillation (ideal indication)
- Alternative to Warfarin (where Pradaxa Dyspepsia not tolerated, or twice daily dosing difficult)
- Poor INR control on Warfarin
- Barriers to INR monitoring
- Warfarin Drug Interactions
- Deep Vein Thrombosis prophylaxis post-hip or knee replacement
- Venous Thromboembolism (DVT or PE) management
- Atrial Fibrillation
- Contraindications
- Avoid if Creatinine Clearance <30 ml/min (especially if using to treat VTE)
- Moderate to severe hepatic Impairment
- Lumbar Puncture or spinal Anesthesia (risk of Epidural Hematoma or spinal hematoma)
- Active bleeding
- Pregnancy or Lactation
- Pharmacokinetics
- Oral bioavailability: 60%
- Half-life
- Young: 5-9 hours in young patients
- Elderly: 11-13 hours in the elderly
- Onset: 1-4 hours post-ingestion
- Maximal Factor Xa inhibition by 3 hours
- Mixed renal (66%) and hepatic excretion
- Contrast with Dabigatran which has primarily renal excretion
- Precautions
- Emergent Reversal of Anticoagulation (e.g. Hemorrhage)
- Andexxa released in 2018
- Consider Prothrombin Complex Concentrate, activated PCC or recombinant factor VIIa
- Increased stroke risk if stopped abruptly without other Anticoagulation in nonvalvular Atrial Fibrillation
- Emergent Reversal of Anticoagulation (e.g. Hemorrhage)
- Dosing
- Taken with evening meal increases absorption
- Atrial Fibrillation
- Creatinine Clearance >50 ml/minute: 20 mg daily
- Creatinine Clearance 15-50 ml/minute: 15 mg daily
- Do not use in patients with Creatinine Clearance <15 ml/minute
- Deep Vain Thrombosis prophylaxis (hemostasis must be achieved before starting; start 6-10 hours post-op)
- Post hip surgery: 10 mg once daily for 35 days
- Post knee surgery: 10 mg once daily for 12 days
- Venous Thromboembolism management
- Initial: 15 mg orally twice daily for 21 days
- Maintenance: 20 mg orally daily
- Prevention of recurrence: 20 mg orally daily
- Continue for at least 3 months or as per the indicated VTE circumstances
- Vascular prevention (CAD or PAD)
- Xarelto 2.5 mg twice daily added to Aspirin 81 mg in stable chronic CAD or PAD
- However, NNT 71 for serious CAD related event, NNT 147 for PAD related amputation
- NNH 80 to cause one major bleeding event
- (2018) Presc Lett 25(12): 68
- Efficacy
- Atrial Fibrillation
- Same efficacy as Warfarin in prevention against thrombotic events (e.g. CVA) in Atrial Fibrillation
- Deep Vein Thrombosis
- FDA approved for treatment of Venous Thromboembolism or VTE (Deep Vein Thrombosis, Pulmonary Embolism)
- As effective, safe as Low Molecular Weight Heparin in DVT short-term and long-term management (without bridging)
- Bauersachs (2010) N Engl J Med 363(26): 2499-510 [PubMed]
- Buller (2012) N Engl J Med 366(14): 1287-97 [PubMed]
- Pulmonary Embolism
- Not yet mainstream usage (may be considered in small Pulmonary Embolism in an otherwise healthy patient)
- Effective in studies using the same dosing as for Deep Vein Thrombosis (see above)
- Atrial Fibrillation
- Disadvantages
- Cost: $260/month (contrast with Warfarin which is $80/month with monitoring)
- However, in acute management, Rivoroxaban is $14/day versus $100-200/day for Enoxaparin (Lovenox)
- Cost: $260/month (contrast with Warfarin which is $80/month with monitoring)
- Safety
- Longterm data is less available than for Warfarin
- Fewer Intracranial Bleeding complications than with Warfarin (Coumadin)
- More Gastrointestinal Bleeding complications than with Coumadin
- Contraindications
- Active pathologic bleeding
- Moderate to severe liver disease (significantly increases drug levels)
- Coagulopathies secondary to hepatic disease
- Creatinine Clearance <15 ml/min
-
Drug Interactions
- Strong Cytochrome P450 3A4 inducers
- Rifampin (also induces P-Glycoprotein)
- Phenytoin
- Carbamazepine
- Phenobarbital
- P-Glycoprotein Inhibitors
- Ketoconazole
- Itraconazole
- Voriconazole
- Ritonavir
- Conivaptan
- Clarithromycin
- Dronedarone
- Verapamil
- Other Anticoagulants and antiplatelet agents
- Strong Cytochrome P450 3A4 inducers
- References
- (2014) Presc Lett 21(11): 61
- (2012) Prescr Lett 19(3):13
- (2011) Prescr Lett 18(12):67
- Lemkin (2013) Crit Dec Emerg Med 27(4): 2-9
- Patel (2011) N Engl J Med 365(10): 883-91 [PubMed]
- Wilbur (2017) Am Fam Physician 95(5): 295-302 [PubMed]
- Wigle (2019) Am Fam Physician 100(7): 426-34 [PubMed]