Dabigatran Sandoz Dosage/Direction for Use

Posology: Primary prevention of Venous Thromboembolism in Orthopaedic Surgery: The recommended doses of Dabigatran etexilate and the duration of therapy for primary prevention of venous thromboembolism in orthopaedic surgery are shown in Table 2. (See Table 2.)

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For both surgeries, if haemostasis 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 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 Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
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).
The method to be used to estimate renal function (CrCL in mL/min) is the Cockcroft-Gault method.
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.
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 Adverse Reactions).
Switching: Dabigatran etexilate treatment to parenteral anticoagulant: It is recommended to wait 24 hours after the last dose before switching from Dabigatran etexilate to a parenteral anticoagulant (see Interactions).
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 Interactions).
Special populations: Renal impairment: Treatment with Dabigatran etexilate in patients with severe renal impairment (CrCL <30 mL/min) is contraindicated (see Contraindications).
In patients with moderate renal impairment (CrCL 30-50 mL/min), a dose reduction is recommended (see Table 2 as previously mentioned, Precautions and Pharmacology: Pharmacodynamics under Actions).
Concomitant use of Dabigatran etexilate with mild to moderate P-glycoprotein (P-gp) inhibitors, i.e. amiodarone, quinidine or verapamil: Dosing should be reduced as indicated in Table 2 (see also Precautions and Interactions). In this situation Dabigatran etexilate and these medicinal products should be taken at the same time.
In patients with moderate renal impairment and concomitantly treated with verapamil, a dose reduction of Dabigatran etexilate to 75 mg daily should be considered (see Precautions and Interactions).
Elderly: For elderly patients >75 years, a dose reduction is recommended (see Table 2 as previously mentioned, and Precautions and Pharmacology: Pharmacodynamics under Actions).
Weight: There is very limited clinical experience in patients with a body weight <50 kg or >110 kg at the recommended posology. Given the available clinical and kinetic data no adjustment is necessary (see Pharmacology: Pharmacokinetics under Actions), but close clinical surveillance is recommended (see Precautions).
Gender: No dose adjustment is necessary (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: There is no relevant use of Dabigatran etexilate in the paediatric population for the indication of primary prevention of venous thromboembolic events in patients who have undergone elective total hip replacement surgery or total knee replacement surgery.
Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors (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 3. (See Table 3.)

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For DVT/PE the recommendation for the use of Dabigatran etexilate 220 mg 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 following text and Precautions, Interactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions.
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 Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
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.
Duration of use: The duration of use of Dabigatran etexilate in the indications SPAF, DVT and PE are shown in Table 4. (See Table 4.)

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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 Adverse Reactions).
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 Interactions).
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 Interactions).
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 Normalized 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.
Cardioversion (SPAF): Patients can stay on Dabigatran etexilate while being cardioverted.
Catheter ablation for atrial fibrillation (SPAF): There are no data available for 110 mg twice daily Dabigatran etexilate treatment.
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 Pharmacology: Pharmacodynamics under Actions).
Special populations: Elderly: For dose modifications in this population see Table 3 as previously mentioned.
Patients at risk of bleeding: Patients with an increased bleeding risk (see Precautions, Interactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions) 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 3 as previously mentioned). A coagulation test (see Precautions) 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 3 as previously mentioned and Precautions).
Renal impairment: Treatment with Dabigatran etexilate in patients with severe renal impairment (CrCL <30 mL/min) is contraindicated (see Contraindications).
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 Precautions and Pharmacology: Pharmacokinetics under Actions). 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 Precautions, Interactions and Pharmacology: Pharmacokinetics under Actions).
Dose reductions are recommended for patients who receive concomitantly verapamil (see Table 3 as previously mentioned and Precautions and Interactions). In this situation Dabigatran etexilate and verapamil should be taken at the same time.
Weight: No dose adjustment is necessary (see Pharmacology: Pharmacokinetics under Actions), but close clinical surveillance is recommended in patients with a body weight <50 kg (see Precautions).
Gender: No dose adjustment is necessary (see Pharmacology: Pharmacokinetics under Actions).
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 Dabigatran etexilate in children from birth to less than 18 years of age have not yet been established. Currently available data are described in Adverse Reactions and Pharmacology: Pharmacodynamics under Actions, but no recommendation on a posology can be made.
Method of administration: Dabigatran etexilate is for oral use.
The capsules can be taken with or without food. Dabigatran etexilate 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 Pharmacology: Pharmacokinetics under Actions and Special precautions for disposal and other handling under Cautions for Usage).