Hematology and Oncology Book

Tranfusion

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Rivaroxaban

Aka: Rivaroxaban, Xarelto
  1. Mechanism
    1. Oral direct Xa inhibitor
    2. Factor Xa is the first step in the Common Clotting Cascade
  2. Indications
    1. Atrial Fibrillation
      1. Bridging to Transesophageal Echocardiogram and early cardioversion in Atrial Fibrillation (ideal indication)
      2. Alternative to Warfarin (where Pradaxa Dyspepsia not tolerated, or twice daily dosing difficult)
      3. Poor INR control on Warfarin
      4. Barriers to INR monitoring
      5. Warfarin Drug Interactions
    2. Deep Vain Thrombosis prophylaxis post-hip or knee replacement
    3. Venous Thromboembolism (DVT or PE) management
  3. Contraindications
    1. Avoid if Creatinine Clearance <30 ml/min (especially if using to treat VTE)
    2. Moderate to severe hepatic Impairment
    3. Lumbar Puncture or spinal anesthesia (risk of Epidural Hematoma or spinal hematoma)
    4. Active bleeding
    5. Pregnancy or Lactation
  4. Pharmacokinetics
    1. Oral bioavailability: 60%
    2. Half-life
      1. Young: 5-9 hours in young patients
      2. Elderly: 11-13 hours in the elderly
    3. Onset: 1-4 hours post-ingestion
      1. Maximal Factor Xa inhibition by 3 hours
    4. Mixed renal (66%) and hepatic excretion
      1. Contrast with Dabigatran which has primarily renal excretion
  5. Precautions
    1. No antidote for bleeding
      1. Consider Prothrombin Complex Concentrate, activated PCC or recombinant factor VIIa
    2. Increased stroke risk if stopped abruptly without other Anticoagulation in nonvalvular Atrial Fibrillation
  6. Dosing
    1. Taken with evening meal increases absorption
    2. Atrial Fibrillation
      1. Creatinine Clearance >50 ml/minute: 20 mg daily
      2. Creatinine Clearance 15-50 ml/minute: 15 mg daily
        1. Do not use in patients with Creatinine Clearance <15 ml/minute
    3. Deep Vain Thrombosis prophylaxis (hemostasis must be achieved before starting; start 6-10 hours post-op)
      1. Post hip surgery: 10 mg once daily for 35 days
      2. Post knee surgery: 10 mg once daily for 12 days
    4. Venous Thromboembolism management
      1. Initial: 15 mg orally twice daily for 21 days
      2. Maintenance: 20 mg orally daily
      3. Prevention of recurrence: 20 mg orally daily
      4. Continue for at least 3 months or as per the indicated VTE circumstances
  7. Efficacy
    1. Atrial Fibrillation
      1. Same efficacy as Warfarin in prevention against thrombotic events (e.g. CVA) in Atrial Fibrillation
    2. Deep Vein Thrombosis
      1. FDA approved for treatment of Venous Thromboembolism or VTE (Deep Vein Thrombosis, Pulmonary Embolism) as of Nov, 2012
      2. As effective and safe as Low Molecular Weight Heparin in DVT short-term and long-term management (without bridging)
      3. Bauersachs (2010) N Engl J Med 363(26): 2499-510 [PubMed]
      4. Buller (2012) N Engl J Med 366(14): 1287-97 [PubMed]
    3. Pulmonary Embolism
      1. Not yet mainstream usage (may be considered in small Pulmonary Embolism in an otherwise healthy patient)
      2. Effective in studies using the same dosing as for Deep Vein Thrombosis (see above)
        1. (2012) N Engl J Med 366(14):1287-97 [PubMed]
  8. Disadvantages
    1. Cost: $260/month (contrast with Warfarin which is $80/month with monitoring)
      1. However, in acute management, Rivoroxaban is $14/day versus $100-200/day for Enoxaparin (Lovenox)
  9. Safety
    1. Longterm data is less available than for Warfarin
    2. Fewer intracranial bleeding complications than with Warfarin (Coumadin)
    3. More Gastrointestinal Bleeding complications than with Coumadin
  10. Contraindications
    1. Active pathologic bleeding
    2. Moderate to severe liver disease (significantly increases drug levels)
    3. Coagulopathies secondary to hepatic disease
    4. Creatinine Clearance <15 ml/min
  11. Drug Interactions
    1. Strong cytochrome P450 3A4 inducers
      1. Rifampin (also induces P-Glycoprotein)
      2. Phenytoin
      3. Carbamazepine
      4. Phenobarbital
    2. P-Glycoprotein Inhibitors
      1. Ketoconazole
      2. Itraconazole
      3. Voriconazole
      4. Ritonavir
      5. Conivaptan
    3. Other Anticoagulants and antiplatelet agents
      1. Aspirin and other antiplatelet agents
      2. NSAIDs
  12. References
    1. (2014) Presc Lett 21(11): 61
    2. (2012) Prescr Lett 19(3):13
    3. (2011) Prescr Lett 18(12):67
    4. Lemkin (2013) Crit Dec Emerg Med 27(4): 2-9
    5. Patel (2011) N Engl J Med 365(10): 883-91 [PubMed]
    6. Wilbur (2017) Am Fam Physician 95(5): 295-302 [PubMed]
Medication Costs
xarelto (on 3/22/2017 at Medicaid.Gov Pharmacy Drug pricing)
XARELTO 10 MG TABLET $12.38 each
XARELTO 15 MG TABLET $12.44 each
XARELTO 20 MG TABLET $12.41 each
XARELTO STARTER PACK $12.25 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

rivaroxaban (C1739768)

Definition (NCI) An orally bioavailable oxazolidinone derivative and direct inhibitor of the coagulation factor Xa with anticoagulant activity. Upon oral administration, rivaroxaban selectively binds to both free factor Xa and factor Xa bound in the prothrombinase complex. This interferes with the conversion of prothrombin (factor II) to thrombin and eventually prevents the formation of cross-linked fibrin clots. Rivaroxaban does not affect existing thrombin levels.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C503223
SnomedCT 442539005, 442031002
LNC LP135650-2, MTHU042952
English Rivaroxaban, Rivaroxaban (substance), Rivaroxaban (product), 5-chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide, rivaroxaban, RIVAROXABAN, 5-Chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)- 1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide, anticoagulants rivaroxaban, anticoagulants rivaroxaban (medication)
Spanish rivaroxabán (producto), rivaroxabán, rivaroxabán (sustancia)
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Xarelto (C3159309)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C503223
English Xarelto, Janssen brand of rivaroxaban
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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