Dabigatran

Aka: Dabigatran, Pradaxa

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II. Indications

  1. Atrial Fibrillation (non-valvular)
    1. Poor INR control on Warfarin
    2. Barriers to INR monitoring
    3. Warfarin Drug Interactions
  2. Venous Thromboembolism Treatment or prophylaxis
    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]
  3. Heparin Induced Thrombocytopenia (HIT)
    1. Off-label use

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 <30 ml/min
  4. Creatinine Clearance <50 ml/min AND concurrent P-Glycoprotein Inhibitor

IV. 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)

V. Pharmacokinetics

  1. Oral Bioavailability: 3 to 7%
  2. Onset: 1 hour post-ingestion (and therapeutic levels within 2 hours of first dose)
  3. Half-Life: 12-17 hours
  4. Primarily renal excretion (80%)

VI. Precautions: Hemorrhage

  1. See Emergent Reversal of Anticoagulation
  2. Idarucizumab (Praxbind)
    1. Monoclonal Antibody antidote specific to Dabigatran (available in 2016)
    2. Appears very effective with rapid activity in initial studies
  3. Other reversal agents if Idarucizumab (Praxbind) is not available
    1. See Direct Thrombin Inhibitor and Anticoagulant Reversal for other agents that may offer partial reversal
    2. Prothrombin Complex Concentrate may offer benefit in severe bleeding
    3. Hemodialysis does remove Dabigatran
      1. However Hemodialysis is unlikely to be practical
      2. Logistics of placing large bore filtered catheters in actively bleeding patients
    4. Normal PTT level suggests Dabigatran is not therapeutic and not increasing bleeding risk
    5. Consider Activated Charcoal if Dabigatran Overdose and taken within 2-4 hours of presentation
  4. Bleeding typically stops spontaneously within 6-8 hours (but this is too long in exanguination)
    1. Focused control of bleeding
    2. Consider hematology Consultation

VII. 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. VTE Prophylaxis following hip or knee surgery
    1. Avoid if GFR <30 ml/min (or with strong P-Glycoprotein Inhibitor AND GFR <50 ml/min)
    2. Start 220 mg orally daily on postoperative day 1
      1. May give a first dose of 110 mg one to four hours after surgery
    3. Continue for 28 to 35 days after hip surgery (or 10 days after knee surgery)
  4. Precautions
    1. Do not chew, break or open capsules
    2. Shelf life on an open bottle of Pradaxa is only 60 days
  5. 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
  6. 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

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 Warfarin 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
  3. 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
    5. High renal elimination (80%)
      1. Exercise caution in Chronic Kidney Disease

X. Safety

  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation
  3. Fewer Intracranial Bleeding complications than with Warfarin (Coumadin)
  4. More Gastrointestinal Bleeding complications than with Coumadin
    1. http://www.fda.gov/drugs/drugsafety/ucm396470.htm

XI. Drug Interactions

  1. P-Glycoprotein Inhibitors (decreases excretion with increased absorption and bleeding risk)
    1. Simvastatin
    2. Lovastatin
    3. Does not appear to occur significantly with Rosuvastatin or Atorvastatin
    4. (2017) Presc Lett 24(2):12
  2. Other Anticoagulants and antiplatelet agents
    1. Aspirin and other antiplatelet agents
    2. NSAIDs

XII. Reources

  1. Dabigatran (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ba74e3cd-b06f-4145-b284-5fd6b84ff3c9

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]
  6. Wilbur (2017) Am Fam Physician 95(5): 295-302 [PubMed]

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Related Studies

Cost: Medications

dabigatran (on 3/22/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
DABIGATRAN ETEXILATE 150 MG CP Generic $6.69 each
DABIGATRAN ETEXILATE 75 CAP Generic $6.13 each
pradaxa (on 1/10/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PRADAXA 110 MG CAPSULE $7.91 each
PRADAXA 150 MG CAPSULE Generic $6.69 each
PRADAXA 75 MG CAPSULE $7.92 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. GoodRx is another tool for finding lower drug prices.

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