Usual Adult Dose for Deep Vein Thrombosis - Prophylaxis

Recommended doses: 150 mg orally twice a day

Comments: Generally, the extent of anticoagulation does not need to be assessed with this drug; however, when necessary, use aPTT or ECT, and not INR to assess anticoagulant activity.

Uses: Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation; treatment of deep venous thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for 5 to 10 days; reduction in the risk of recurrence of deep venous thrombosis and pulmonary embolism in patients who have been previously treated.

Usual Adult Dose for Prevention of Thromboembolism in Atrial Fibrillation

Recommended doses: 150 mg orally twice a day

Comments: Generally, the extent of anticoagulation does not need to be assessed with this drug; however, when necessary, use aPTT or ECT, and not INR to assess anticoagulant activity.

Uses: Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation; treatment of deep venous thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for 5 to 10 days; reduction in the risk of recurrence of deep venous thrombosis and pulmonary embolism in patients who have been previously treated.

Usual Adult Dose for Deep Vein Thrombosis/Pulmonary Embolism Prophylaxis Following Hip Replacement Surgery

110 mg orally 1 to 4 hours after surgery and after hemostasis has been achieved, then 220 mg orally once a day for 28 to 35 days

Comments: If this drug is not started on the day of surgery, initiate treatment with 220 mg orally once a day after hemostasis has been achieved.

Use: For the prophylaxis of DVT and PE in adult patients who have undergone hip replacement surgery.

Usual Pediatric Dose for Venous Thromboembolism

Weigh-based dosage:

• 11 kg to less than 16 kg: 75 mg twice daily
• 16 kg to less than 26 kg: 110 mg twice daily
• 26 kg to less than 41 kg: 150 mg twice daily
• 41 mg to less than 61 kg: 185 mg twice daily
• 61 kg to 81 kg: 220 mg twice daily
• 81 kg or greater: 260 mg twice daily

Comments:

• This drug is to be used in children 8 years old or older that can swallow a capsule.
• In treatment of VTE, treatment should be initiated following treatment with a parenteral anticoagulant for at least 5 days. For reduction of VTE recurrence, initiate treatment following previous treatment.
• The concomitant treatment of this drug with P-gb inhibitors has not been studied in children and may increase the exposure to this drug.

Uses:

• For the treatment of venous thromboembolic events (VTE) in pediatric patients 8 and older who have been treated with a parenteral anticoagulant for at least 5 days.
• To reduce the risk of recurrence of VTE in pediatric patients 8 and older who have been previously treated.

Renal Dose Adjustments

ADULTS:
To Reduce Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation:

• CrCl greater than 30 mL/min: 150 mg orally twice a day
• CrCl 15 to 30 mL/min: 75 mg orally twice a day
• CrCl less than 15 mL/min: Dosing recommendation cannot be provided

When coadministered with dronedarone or systemic ketoconazole:

• CrCl 30 to 50 mL/min: Dose may be reduced to 75 mg twice a day

Concomitant use with P-gp inhibitors:

• CrCl 30 to 50 mL/min: No adjustment recommended
• CrCl less than 30 mL/min: Avoid coadministration

For Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism:

• CrCl greater than 30 mL/min: 150 mg orally twice a day
• CrCl less than 30 mL/min: Dosing recommendation cannot be provided

Concomitant use with P-gp inhibitors:

• CrCl less than 50 mL/min: Avoid coadministration

Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism Following Hip Replacement Surgery:

• CrCl greater than 30 mL/min: 110 mg orally 1 to 4 hours after surgery and after hemostasis has been achieved, then 220 mg orally once a day for 28 to 35 days
• CrCl 30 mL/min or less: Dosing recommendation cannot be provided

Concomitant use with P-gp inhibitors:

• CrCl less than 50 mL/min: Avoid coadministration

CHILDREN:

• eGFR less than 50 mL/min: Avoid use

Liver Dose Adjustments

Data not available

Dose Adjustments

When converting patients from warfarin therapy to dabigatran, discontinue warfarin and start dabigatran when the international normalized ratio (INR) is below 2.0.

When converting from dabigatran to warfarin, adjust the starting time of warfarin based on creatinine clearance as follows:
ADULTS:

• CrCl greater than 50 mL/min, start warfarin 3 days before discontinuing dabigatran
• CrCl 30 to 50 mL/min, start warfarin 2 days before discontinuing dabigatran
• CrCl 15 to 30 mL/min, start warfarin 1 day before discontinuing dabigatran
• CrCl less than 15 mL/min, no recommendations can be made

CHILDREN:

• CrCl greater than 50 mL/min, start warfarin 3 days before discontinuing dabigatran
• CrCl less than 50 mL/min: No data available. Avoid use.

When converting from a parenteral anticoagulant in adult and pediatric patients, start dabigatran 0 to 2 hours before the scheduled administration of the parenteral anticoagulant or at the time of discontinuation of a continuously administered parenteral anticoagulant.

When converting to a parenteral anticoagulant in adults, start the parenteral anticoagulant 12 hours (CrCl 30 mL/min or greater) or 24 hours (CrCl less than 30 mL/min) after the last dose of dabigatran. In pediatric patients, start the parenteral anticoagulant 12 hours after the last dose of dabigatran.

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

CONTRAINDICATIONS:

• Active pathological bleeding
• History of a serious hypersensitivity reaction to this drug or any of its excipients
• Any mechanical prosthetic heart valve

US BOXED WARNINGS:

• PREMATURE DISCONTINUATION OF THIS DRUG INCREASES THE RISK OF THROMBOTIC EVENTS: To reduce this risk, consider coverage with another anticoagulant if dabigatran is discontinued for a reason other than pathological bleeding or completion of a course of therapy.
• SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may occur in patients treated with dabigatran who are receiving neuraxial anesthesia or undergoing spinal puncture. These may result in long-term or permanent paralysis. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants; a history of traumatic or repeated epidural or spinal punctures; a history of spinal deformity or spinal surgery. Optimal timing between the administration of dabigatran and neuraxial procedures is not known. Monitor signs and symptoms of neurological impairment and if observed, treat urgently. Consider the benefits and risks before neuraxial intervention in patients who are or who need to be anticoagulated.

Safety and efficacy of dabigatran capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: Dosing recommendation cannot be provided
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• Assess renal function prior to initiation of treatment.
• Breaking, chewing, or emptying capsules can increase exposure to this drug.
• Swallow the capsules whole with a full glass of water.
• Take with food if gastrointestinal distress occurs with the capsules.
• Take a missed dose as soon as possible on the same day but skip if it is less than 6 hours before the next scheduled dose.
• The dose of this drug should not be doubled to make up for a missed dose.

Storage requirements:

• Store between 20C to 25C (68F to 77 F), in the original package to protect from moisture.

Monitoring:

• Cardiovascular: Hypotension.
• Hematologic: Signs of bleeding (hemoglobin, hematocrit)
• Nervous system: Signs and symptoms of neurological impairment
• Renal: Assess renal function periodically as clinically indicated and adjust therapy accordingly.

Patient advice:

• Report any experience of midline back pain, numbness, tingling, weakness in lower limbs, bowel and/or bladder dysfunction, unusual bruising, coughing or vomiting blood or if you have black or tarry stools.
• Do not stop taking this drug without medical advice.
• Female patients should inform their healthcare providers immediately if they become pregnant (or intend to become pregnant) during treatment.