PRADAXA®

Prevention of venous thromboembolic events (VTE) following major orthopedic surgery of the lower limbs in patients with a high risk for VTE:

Patients following elective knee replacement surgery

The recommended dose of PRADAXA® is 150 mg once daily taken as 2 capsules of 75 mg or 220 mg once daily taken as 2 capsules of 110 mg. Treatment should be initiated orally within 1-4 hours of completed surgery with a single capsule and continuing with 2 capsules once daily thereafter for a total of 10 days.

Patients following elective hip replacement surgery

The recommended dose of PRADAXA® is 150 mg once daily taken as 2 capsules of 75 mg or 220 mg once daily taken as 2 capsules of 110 mg. Treatment should be initiated orally within 1-4 hours of completed surgery with a single capsule and continuing with 2 capsules once daily thereafter for a total of 28-35 days. For the following groups the recommended daily dose of PRADAXA® is 150 mg taken once daily as 2 capsules of 75 mg. Treatment should be initiated orally within 1-4 hours of completed surgery with a single capsule of 75 mg and continuing with 2 capsules once daily thereafter for a total of 10 days (knee replacement surgery) or 28-35 days (hip replacement surgery):

• Patients with moderate renal impairment (creatinine clearance (CrCL) 30-50 mL/min)
• Patients who receive concomitant verapamil, amiodarone, quinidine
• Patients aged 75 or above

For both surgeries, if hemostasis is not secured, initiation of treatment should be delayed. If treatment is not started on the day of surgery then treatment should be initiated with 2 capsules once daily.

Assessment of renal function (prevention of VTE):

In all patients:

• Renal function should be assessed by calculating the creatinine clearance (CrCL) prior to initiation of treatment with PRADAXA® to exclude patients with severe renal impairment (i.e. CrCL < 30 mL/min). PRADAXA® is contraindicated in patients with severe renal impairment
• Renal function should also be assessed when a decline in renal function is suspected during treatment (e.g. hypovolemia, dehydration, and in case of concomitant use of certain medicinal products)

Special populations

Renal impairment (prevention of VTE)

Treatment with PRADAXA® in patients with severe renal impairment (CrCL < 30 mL/min) is contraindicated.

In patients with moderate renal impairment (CrCL 30 50 mL/min), there is limited clinical experience. These patients should be treated with caution. The recommended dose is 150 mg taken once daily as 2 capsules of 75 mg.

Switching (prevention of VTE)

PRADAXA® treatment to parenteral anticoagulant

It is recommended to wait 24 hours after the last dose before switching from PRADAXA® to a parenteral anticoagulant.

Parenteral anticoagulants to PRADAXA®

Dabigatran etexilate should be given 0-2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment (e.g. intravenous Unfractionated Heparin (UFH).

Paediatric population (prevention of VTE)

There is no relevant use of PRADAXA® in the pediatric population in the indication: Prevention of venous thromboembolic events (VTE) following major orthopedic surgery of the lower limbs in patients with a high risk for VTE.

Missed dose (prevention of VTE)

It is recommended to continue with the remaining daily doses of dabigatran etexilate at the same time of the next day.

No double dose should be taken to make up for missed individual doses.

Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

Recommended Dose:

The recommended daily dose of PRADAXA is 110-150 mg taken orally, twice daily, with or without food, depending on the individual condition and clinical situation. One capsule of 150mg can be substituted by 2 capsules of 75mg.

For patients with a higher risk of bleeding, e.g. age ≥ 75 years, CHADS₂ score of ≥3, body weight < 50 kg, previous gastro-intestinal bleed or moderate renal impairment (30-50 ml CrCL/min), the dose of 110 mg taken orally, twice daily, may be considered.

Instruct patients to swallow the capsules whole. Breaking, chewing, or emptying the contents of the capsule can result in increased exposure

If a dose of PRADAXA is not taken at the scheduled time, the dose should be taken as soon as possible on the same day; the missed dose should be skipped if it cannot be taken at least 6 hours before the next scheduled dose. The dose of PRADAXA should not be doubled to make up for a missed dose.

Renal impairment

Renal function should be assessed by calculating the creatinine clearance (CrCl) prior to initiation of treatment with PRADAXA to exclude patients for treatment with severe renal impairment (i.e. CrCl < 30ml/min). There are no data to support use in patients with severe renal impairment (< 30 mL/min creatinine clearance); treatment in this population with PRADAXA is not recommended. While on treatment renal function should be assessed in certain clinical situations when it is suspected that the renal function could decline or deteriorate (such as hypovolemia, dehydration, and with certain comedications, etc). Dabigatran can be dialysed; there is limited clinical experience to demonstrate the utility of this approach in clinical studies.

In patients with moderate renal impairment (CrCl 30-50ml/min) the renal function should be assessed at least once a year.

Switching from PRADAXA treatment to parenteral anticoagulant

Wait 12 hours after the last dose before switching from PRADAXA to a parenteral anticoagulant.

Switching from parenteral anticoagulants treatment to PRADAXA

PRADAXA should be given 0-2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment (e.g. intravenous UFH).

Switching from Vit. K antagonists to PRADAXA

The Vit. K antagonist should be stopped. PRADAXA can be given as soon as the INR is < 2.0.

Switching from PRADAXA to Vit. K antagonists (VKA)

The starting time of the VKA should be adjusted according to the patient´s CrCL as follows:

• CrCL ≥ 50 ml/min, start VKA 3 days before discontinuing dabigatran etexilate.
• CrCL ≥ 30-< 50 ml/min, start VKA 2 days before discontinuing dabigatran etexilate.
• CrCL < 30 ml/min: contraindicated in this population.

Because PRADAXA® can increase INR, the INR will better reflect warfarin’s effect only after PRADAXA® has been stopped for at least 2 days.

Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE):

Adults

The recommended daily dose of PRADAXA is 300 mg taken orally as 150 mg hard capsules twice daily following treatment with a parenteral anticoagulant for at least 5 days. Therapy should be continued for up to 6 months.

Children

PRADAXA has not been investigated in patients <18 years of age. The safety and efficacy in children has not yet been established. Treatment of children with PRADAXA is therefore not recommended.

Renal impairment

Renal function should be assessed by calculating the creatinine clearance (CrCl) prior to initiation of treatment with PRADAXA to exclude patients for treatment with severe renal impairment (i.e. CrCl < 30 mL/min).There are no data to support use in patients with severe renal impairment (< 30 mL/min CrCl); treatment in this population with PRADAXA is not recommended.

While on treatment renal function should be assessed in certain clinical situations when it is suspected that the renal function could decline or deteriorate (such as hypovolemia, dehydration, and with certain comedications, etc).

Dabigatran can be dialyzed; there is limited clinical experience to demonstrate the utility of this approach in clinical studies.

No dose adjustment necessary in patients with renal function over CrCl 30 mL/min. Patients should be treated with a daily dose of 300 mg taken orally as 150 mg hard capsules twice daily.

Switching from PRADAXA treatment to parenteral anticoagulant

Wait 12 hours after the last dose before switching from PRADAXA to a parenteral anticoagulant.

Switching from parenteral anticoagulants treatment to PRADAXA

PRADAXA should be given 0-2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment (e.g. intravenous UFH).

Switching from Vit. K antagonists to PRADAXA

The Vit. K antagonist should be stopped. PRADAXA can be given as soon as the INR is < 2.0.

Switching from PRADAXA to Vit. K antagonists (VKA)

The starting time of the VKA should be adjusted according to the patient´s CrCl as follows:

• CrCl ≥50 mL/min, start VKA 3 days before discontinuing dabigatran etexilate.
• CrCl ≥ 30-< 50 mL/min, start VKA 2 days before discontinuing dabigatran etexilate.
• CrCl < 30 mL/min, contraindicated in this population.

Because PRADAXA can increase INR, the INR will better reflect warfarin's effect only after PRADAXA has been stopped for at least 2 days.