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Dabigatran

Aka: Dabigatran, Pradaxa, Idarucizumab, Praxbind

I. Mechanism

  1. Prodrug converted in liver to active drug
  2. Oral Direct Thrombin Inhibitor
    1. Selectively and reversibly inhibits free and clot-bound thrombin
    2. Prevents conversion of Fibrinogen to fibrin (which in turn prevents clot)

II. Pharmacokinetics

  1. Onset: 1 hour post-ingestion (and therapeutic levels within 2 hours of first dose)
  2. Half-life: 12-17 hours
  3. Renal excretion

III. Contraindications

  1. Mechanical Prosthetic Heart Valves
    1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm332949.htm
  2. Active pathologic bleeding
  3. Creatinine Clearance <15 ml/min
  4. Creatinine Clearance <30 ml/min AND concurrent P-Glycoprotein Inhibitor

IV. Indications

  1. Atrial Fibrillation (non-valvular)
    1. Poor INR control on Warfarin
    2. Barriers to INR monitoring
    3. Warfarin Drug Interactions
  2. Venous Thromboembolism
    1. Requires initial 5-10 days of Low Molecular Weight Heparin (LMWH, e.g. Enoxaparin) or standard Heparin
    2. (2009) N Engl J Med 361:2342-52 [PubMed]

V. Precautions

  1. No antidote for bleeding (until 2016 - Idarucizumab or Praxbind)
    1. Idarucizumab (Praxbind) appears very effective in initial studies
    2. See Direct Thrombin Inhibitor and Anticoagulant Reversal for other agents that may offer partial reversal
    3. Prothrombin Complex Concentrate may offer benefit in severe bleeding
    4. Dialysis is unlikely to be beneficial due to logistics of placing large bore filtered catheters in actively bleeding patients
    5. Normal PTT level suggests Pradaxa is not therapeutic and not increasing bleeding risk
  2. Bleeding typically stops spontaneously within 6-8 hours (but this is too long in exanguination)
    1. Focused control of bleeding
    2. Consider hematology Consultation

VI. Dosing

  1. Standard dose: 150 mg twice daily
    1. Same dose for Atrial Fibrillation and Venous Thromboembolism (initial, maintenance and recurrence prevention)
    2. VTE requires concurrent initial 5-10 days of Low Molecular Weight Heparin (LMWH, e.g. Enoxaparin) or standard Heparin
  2. Half-dose: 75 mg twice daily Indications
    1. Creatinine Clearance 15-30 ml/minute
      1. Contraindicated in Creatinine Clearance <15 ml/minute
    2. Creatinine Clearance 30-50 ml/minute AND concurrent Ketoconazole or Dronedarone (Multaq)
    3. This dose has not been studied
  3. Precautions
    1. Do not chew, break or open capsules
    2. Shelf life on an open bottle of Pradaxa is only 60 days
  4. Missed doses
    1. Missing 2 or more doses (1 day) risks hyerpcoagulation and complications (contrast with 3 days for Warfarin)
    2. Optimize pill taking reminders to avoid missed doses
    3. If dose missed, take when remember unless within 6 hours of next dose
  5. Transition from Pradaxa to Warfarin
    1. Creatinine Clearance 50 ml/min or greater
      1. Start Warfarin and stop Pradaxa after Warfarin day 3
    2. Creatinine Clearance 30-50 ml/min
      1. Start Warfarin and stop Pradaxa after Warfarin day 2
    3. Creatinine Clearance 15-30 ml/min
      1. Start Warfarin and stop Pradaxa after Warfarin day 1

VII. Dosing: Reversal Agent

  1. Idarucizumab (Praxbind)
    1. Monoclonal Antibody specific for Dabigatran
    2. Idarucizumab is highly effective in initial studies and FDA approval
    3. Release expected in early 2016
    4. Pollack (2015) N Engl J Med 373(6): 511-20 +PMID: 26095746 [PubMed]

VIII. Labs

  1. No routine labs needed (No monitoring of INR needed)
  2. If bleeding, expect the following results:
    1. PTT at 1-2 hours: 2x normal
    2. PTT at 12 hours: 1.5x normal
    3. PTT >2.5x normal suggests over-Anticoagulation
    4. PTT normal on Pradaxa suggests the patient is not anticoagulated
    5. Thrombin Time is most increased
    6. PT/INR is variably affected

IX. Efficacy

  1. Slightly more effective than Warfarin in prevention against thrombotic events in Atrial Fibrillation
    1. Prevent 5 more strokes per 1000 patients per year than Warfarin
    2. Connolly (2009) N Engl J Med 361(12): 1139-51 [PubMed]
  2. Appears as effective as Coumadin in Venous Thromboembolism (FDA approved)
    1. As with Warfarin, requires initial 5-10 days of Low Molecular Weight Heparin (LMWH, e.g. Enoxaparin) or standard Heparin

X. Disadvantages

  1. Cost: $260/month (contrast with Warfarin which is $80/month with monitoring)
  2. Twice daily dosing
  3. Dyspepsia is common
  4. Not as effective as Warfarin in preventing Myocardial Infarction
    1. Warfarin prevents 2 more Myocardial Infarctions per 1000 patients than Dabigatran

XI. Safety

  1. Fewer intracranial bleeding complications than with Warfarin (Coumadin)
  2. More Gastrointestinal Bleeding complications than with Coumadin
    1. http://www.fda.gov/drugs/drugsafety/ucm396470.htm

XII. Drug Interactions

  1. P-Glycoprotein Inhibitors (decreases excretion)
  2. P-Glycoprotein Inhibitors (increases excretion)
  3. Other Anticoagulants and antiplatelet agents
    1. Aspirin and other antiplatelet agents
    2. NSAIDs

XIII. References

  1. (2014) Presc Lett 21(11): 61
  2. (2011) Prescr Lett 18(12):67
  3. (2012) Prescr Lett 19(3):13
  4. Lemkin (2013) Crit Dec Emerg Med 27(4): 2-9
  5. (2009) N Engl J Med 361:1139-51 [PubMed]

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Cost: Medications

pradaxa (on 9/24/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
PRADAXA 150 MG CAPSULE $5.38 each
PRADAXA 75 MG CAPSULE $5.37 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.

Related Topics in Pharmacology

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