Posology : מינונים

4.2     Posology and method of administration
Posology

Prevention of stroke and systemic embolism in adult patients with NVAF (SPAF) Treatment of deep vein thrombosis ( DVT) and pulmonary embolism ( PE), and prevention of recurrent DVT and PE in adults (DVT/PE)

The recommended doses of dabigatran etexilate in the indications SPAF, DVT and PE are shown in table 1.


Boehringer Ingelheim Israel                                                                                 Page 2 of 38 Pradaxa 150                                                                          Prescribing Information Boehringer Ingelheim                                                                            January 2022 
Table 1: Dose recommendations for SPAF, DVT and PE

Dose recommendation
Prevention of stroke and systemic embolism        300 mg dabigatran etexilate taken as one 150 mg in adult patients with NVAF (SPAF)                capsule twice daily Treatment of (DVT) and (PE), and                  300 mg dabigatran etexilate taken as one 150 mg prevention of recurrent DVT, and PE in            capsule twice daily following treatment with a adults (DVT/PE)                                   parenteral anticoagulant for at least 5 days 
Dose reduction recommended
Patients aged ≥80 years daily dose of 220 mg dabigatran etexilate taken as one
Patients who receive concomitant verapamil        110 mg capsule twice daily 
Dose reduction for consideration
Patients between 75-80 years
Patients with moderate renal impairment
(CrCL 30-50 mL/min)                               daily dose of dabigatran etexilate of 300 mg or 220 mg should be selected based on an individual assessment
Patients with gastritis, esophagitis or of the thromboembolic risk and the risk of bleeding gastroesophageal reflux
Other patients at increased risk of bleeding
For DVT/PE the recommendation for the use of 220 mg dabigatran etexilate taken as one 110 mg capsule twice daily is based on pharmacokinetic and pharmacodynamic analyses and has not been studied in this clinical setting. See further down and sections 4.4, 4.5, 5.1 and 5.2.

In case of intolerability to dabigatran etexilate, patients should be instructed to immediately consult their treating physician in order to be switched to alternate acceptable treatment options for prevention of stroke and systemic embolism associated with atrial fibrillation or for DVT/PE.

Assessment of renal function prior to and during dabigatran etexilate treatment 
In all patients and especially in the elderly (>75 years), as renal impairment may be frequent in this age group:
•      Renal function should be assessed by calculating the creatinine clearance (CrCL) prior to initiation of treatment with dabigatran etexilate to exclude patients with severe renal impairment (i.e. CrCL <30 mL/min) (see sections 4.3, 4.4 and 5.2).
•      Renal function should also be assessed when a decline in renal function is suspected during treatment (e.g.
hypovolaemia, dehydration, and in case of concomitant use of certain medicinal products).

Additional requirements in patients with mild to moderate renal impairment and in patients aged over 75 years:
•     Renal function should be assessed during treatment with dabigatran etexilate at least once a year or more frequently as needed in certain clinical situations when it is suspected that the renal function could decline or deteriorate (e.g.
hypovolaemia, dehydration, and in case of concomitant use of certain medicinal products).

The method to be used to estimate renal function (CrCL in mL/min) is the Cockcroft-Gault method.

Boehringer Ingelheim Israel                                                                                      Page 3 of 38 Pradaxa 150                                                                         Prescribing Information Boehringer Ingelheim                                                                           January 2022 
Duration of use

The duration of use of dabigatran etexilate in the indications SPAF, DVT and PE are shown in table 2.
Table 2: Duration of use for SPAF and DVT/PE

Indication       Duration of use
SPAF             Therapy should be continued long term.
DVT/PE           The duration of therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding (see section 4.4).
Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation) and longer durations should be based on permanent risk factors or idiopathic DVT or PE.

Missed dose

A forgotten dabigatran etexilate dose may still be taken up to 6 hours prior to the next scheduled dose. From 6 hours prior to the next scheduled dose on, the missed dose should be omitted.

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

Discontinuation of dabigatran etexilate
Dabigatran etexilate treatment should not be discontinued without medical advice. Patients should be instructed to contact the treating physician if they develop gastrointestinal symptoms such as dyspepsia (see section 4.8).

Switching

Dabigatran etexilate treatment to parenteral anticoagulant:
It is recommended to wait 12 hours after the last dose before switching from dabigatran etexilate to a parenteral anticoagulant (see section 4.5).

Parenteral anticoagulants to dabigatran etexilate:
The parenteral anticoagulant should be discontinued and dabigatran etexilate should be started 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)) (see section 4.5).

Dabigatran etexilate treatment to Vitamin K antagonists (VKA):
The starting time of the VKA should be adjusted based on CrCL as follows:
•     CrCL ≥50 mL/min, VKA should be started 3 days before discontinuing dabigatran etexilate
•     CrCL ≥30-<50 mL/min, VKA should be started 2 days before discontinuing dabigatran etexilate 
Because dabigatran etexilate can impact the International Normalised Ratio (INR), the INR will better reflect VKA’s effect only after dabigatran etexilate has been stopped for at least 2 days. Until then, INR values should be interpreted with caution.

VKA to dabigatran etexilate:
The VKA should be stopped. Dabigatran etexilate can be given as soon as the INR is <2.0.
Boehringer Ingelheim Israel                                                                                   Page 4 of 38 Pradaxa 150                                                                          Prescribing Information Boehringer Ingelheim                                                                            January 2022 
Cardioversion (SPAF)

Patients can stay on dabigatran etexilate while being cardioverted.
Catheter ablation for atrial fibrillation (SPAF)

Catheter ablation can be conducted in patients on 150 mg twice daily dabigatran etexilate treatment. Dabigatran etexilate treatment does not need to be interrupted (see section 5.1).

Percutaneous coronary intervention (PCI) with stenting (SPAF)

Patients with non valvular atrial fibrillation who undergo a PCI with stenting can be treated with dabigatran etexilate in combination with antiplatelets after haemostasis is achieved (see section 5.1).

Special populations

Elderly
For dose modifications in this population see table 1 above.

Patients at risk of bleeding

Patients with an increased bleeding risk (see sections 4.4, 4.5, 5.1 and 5.2) should be closely monitored clinically (looking for signs of bleeding or anaemia). Dose adjustment should be decided at the discretion of the physician, following assessment of the potential benefit and risk to an individual patient (see table 1 above). A coagulation test (see section 4.4) may help to identify patients with an increased bleeding risk caused by excessive dabigatran exposure. When excessive dabigatran exposure is identified in patients at high risk of bleeding, a reduced dose of 220 mg taken as one 110 mg capsule twice daily is recommended. When clinically relevant bleeding occurs, treatment should be interrupted.

For subjects with gastritis, esophagitis, or gastroesophageal reflux, a dose reduction may be considered due to the elevated risk of major gastro-intestinal bleeding (see table 1 above and section 4.4).

Renal impairment

Treatment with dabigatran etexilate in patients with severe renal impairment (CrCL <30 mL/min) is contraindicated (see section 4.3).

No dose adjustment is necessary in patients with mild renal impairment (CrCL 50- ≤80 mL/min). For patients with moderate renal impairment (CrCL 30-50 mL/min) the recommended dose of dabigatran etexilate is also 300 mg taken as one 150 mg capsule twice daily. However, for patients with high risk of bleeding, a dose reduction of dabigatran etexilate to 220 mg taken as one 110 mg capsule twice daily should be considered (see sections 4.4 and 5.2). Close clinical surveillance is recommended in patients with renal impairment.

Concomitant use of dabigatran etexilate with mild to moderate P-glycoprotein (P-gp) inhibitors, i.e. amiodarone, quinidine or verapamil

No dose adjustment is necessary for concomitant use of amiodarone or quinidine (see sections 4.4, 4.5 and 5.2).


Boehringer Ingelheim Israel                                                                                     Page 5 of 38 Pradaxa 150                                                                       Prescribing Information Boehringer Ingelheim                                                                        January 2022 Dose reductions are recommended for patients who receive concomitantly verapamil (see table 1 above and sections 4.4 and 4.5). In this situation dabigatran etexilate and verapamil should be taken at the same time.

Weight

No dose adjustment is necessary (see section 5.2), but close clinical surveillance is recommended in patients with a body weight <50 kg (see section 4.4).

Gender

No dose adjustment is necessary (see section 5.2).
Paediatric population

There is no relevant use of dabigatran etexilate in the paediatric population for the indication of prevention of stroke and systemic embolism in patients with NVAF.

For the indication DVT/PE, the safety and efficacy of Pradaxa in children from birth to less than 18 years of age have not yet been established. Currently available data are described in section 4.8 and 5.1, but no recommendation on a posology can be made.

Method of administration

This medicinal product is for oral use.
The capsules can be taken with or without food. The capsules should be swallowed as a whole with a glass of water, to facilitate delivery to the stomach.
Patients should be instructed not to open the capsule as this may increase the risk of bleeding (see sections 5.2 and 6.6).