PRADAXA Coated granules Ref.[50914] Active ingredients: Dabigatran

Posology

Pradaxa coated granules can be used in children aged less than 12 years as soon as the child is able to swallow soft food. Pradaxa capsules can be used in adults and paediatric patients aged 8 years or older who are able to swallow the capsules whole. Pradaxa powder and solvent for oral solution should only be used in children aged less than 1 year.

When changing between the formulations, the prescribed dose may need to be altered. The dose stated in the relevant dosing table of a formulation should be prescribed based on the weight and age of the child.

For the treatment of VTE in paediatric patients, treatment should be initiated following treatment with a parenteral anticoagulant for at least 5 days. For prevention of recurrent VTE, treatment should be initiated following previous treatment.

Dabigatran etexilate coated granules should be taken twice daily, one dose in the morning and one dose in the evening, at approximately the same time every day. The dosing interval should be as close to 12 hours as possible.

The recommended dose of dabigatran etexilate coated granules is based on the patient’s weight and age as shown in tables 1 and 2. The dose should be adjusted according to weight and age as treatment progresses.

For weight and age combinations not listed in the dosing tables no dosing recommendation can be provided.

Table 1. Single and total daily dabigatran etexilate doses in milligrams (mg) for patients aged less than 12 months. The doses depend on weight in kilograms (kg) and age in months of the patient:

Convenient sachet combinations to achieve the single doses recommended in the dosing table are provided below. Other combinations are possible.

20 mg: One 20 mg sachet

30 mg: One 30 mg sachet

40 mg: One 40 mg sachet

50 mg: One 50 mg sachet

60 mg: Two 30 mg sachets

70 mg: One 30 mg plus one 40 mg sachet

80 mg: Two 40 mg sachets

100 mg: Two 50 mg sachets

Table 2. Single and total daily dabigatran etexilate doses in milligrams (mg) for patients aged 1 year to less than 12 years. The doses depend on weight in kilograms (kg) and age in years of the patient:

Convenient sachet combinations to achieve the single doses recommended in the dosing table are provided below. Other combinations are possible.

50 mg: One 50 mg sachet

60 mg: Two 30 mg sachets

70 mg: One 30 mg plus one 40 mg sachet

80 mg: Two 40 mg sachets

100 mg: Two 50 mg sachets

110 mg: One 110 mg sachet

140 mg: One 30 mg plus one 110 mg sachet

180 mg: One 30 mg plus one 150 mg sachet

220 mg: Two 110 mg sachets

260 mg: One 110 mg plus one 150 mg sachet

300 mg: Two 150 mg sachets

Assessment of renal function prior to and during treatment

Prior to the initiation of treatment, the estimated glomerular filtration rate (eGFR) should be estimated using the Schwartz formula (method used for creatinine assessment to be checked with local lab).

Treatment with dabigatran etexilate in paediatric patients with eGFR <50 mL/min/1.73m² is contraindicated (see section 4.3).

Patients with an eGFR ≥ 50 mL/min/1.73m² should be treated with the dose according to tables 1 and 2.

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 co-medications, etc).

Duration of use

The duration of therapy should be individualised based on the benefit risk assessment.

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 onwards, the missed dose should be omitted. A double dose to make up for missed individual doses must never be taken. If a dose has only been taken partially, there should be no attempt to administer a second dose at that time-point, and the next dose should be taken as scheduled approximately 12 hours later.

Discontinuation of dabigatran etexilate

Dabigatran etexilate treatment should not be discontinued without medical advice. Caregivers should be instructed to contact the treating physician if their treated child develops 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):

Patients should start VKA 3 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.

Method of administration

This medicinal product is for oral use.

The coated granules should be mixed with food prior to intake and only be used with apple juice or the soft foods mentioned in the instructions for use. After mixing with food or apple juice, the medicinal product has to be administered within 30 minutes. The coated granules are not compatible with milk or milk products.

This medicinal product is not compatible with feeding tubes.

Detailed instructions for the use of this medicinal product are provided in ‘Instructions for use’ in the package leaflet.

Dabigatran etexilate doses beyond those recommended, expose the patient to increased risk of bleeding.

In case of an overdose suspicion, coagulation tests can help to determine a bleeding risk (see sections 4.4 and 5.1). A calibrated quantitative dTT test or repetitive dTT measurements allow prediction of the time by when certain dabigatran levels will be reached (see section 5.1), also in case additional measures e.g. dialysis have been initiated.

Excessive anticoagulation may require interruption of dabigatran etexilate treatment. Since dabigatran is excreted predominantly by the renal route adequate diuresis must be maintained. As protein binding is low, dabigatran can be dialysed; there is limited clinical experience to demonstrate the utility of this approach in clinical studies (see section 5.2).

Management of bleeding complications

In the event of haemorrhagic complications, dabigatran etexilate treatment must be discontinued and the source of bleeding investigated. Depending on the clinical situation appropriate supportive treatment, such as surgical haemostasis and blood volume replacement, should be undertaken at the prescriber’s discretion.

Coagulation factor concentrates (activated or non-activated) or recombinant Factor VIIa may be taken into account. There is some experimental evidence to support the role of these medicinal products in reversing the anticoagulant effect of dabigatran, but data on their usefulness in clinical settings and also on the possible risk of rebound thromboembolism is very limited. Coagulation tests may become unreliable following adminstration of suggested coagulation factor concentrates. Caution should be exercised when interpreting these tests. Consideration should also be given to administration of platelet concentrates in cases where thrombocytopenia is present or long acting antiplatelet medicinal products have been used. All symptomatic treatment should be given according to the physician’s judgement.

Depending on local availability, a consultation of a coagulation expert should be considered in case of major bleedings.

3 years.

After first opening of the aluminium bag:

Once the aluminium bag containing the sachets with the coated granules and the desiccant is opened, the medicinal product must be used within 6 months.

After first opening of the sachet:

The opened sachet cannot be stored and must be used immediately after opening.

After preparation:

After mixing with soft food or apple juice, the medicinal product has to be administered within 30 minutes.

The aluminium bag containing the sachets with the coated granules should only be opened immediately prior to use of the first sachet in order to protect from moisture.

After opening of the aluminium bag, the individual sachets should be kept unopened until immediately prior to use in order to protect from moisture.

Aluminium bag containing 60 silver-coloured PET/Alu/LDPE sachets with the coated granules and one desiccant (labelled “DO NOT EAT” including pictogram and “SILICA GEL”).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.