Anticoagulants, Antithrombotics and Fibrinolytics
= Additional active ingredients
PRESENTATION AND DOSSAGE
VIAL(sol. for IV Inj./infus.): 2 ×50 ml.
Idarucizumab is a specific reversal agent for dabigatran and is indicated in patients treated with dabigatran etexilate when rapid reversal of the anticoagulant effects of dabigatran is required:
1. For emergency surgery/urgent procedures.
2. In life-threatening or uncontrolled bleeding.
No formal interaction studies with Idarucizumab and other medicinal products have been performed. Based on the pharmacokinetic properties and the high specificity in binding to dabigatran, clinically relevant interactions with other medicinal products are considered unlikely. Preclinical investigations with idarucizumab have shown no interactions with Volume expanders.
Coagulation factor concentrates, such as prothrombin complex concentrates (PCCs, e.g. 3 factor and 4 factor), activated PCCs (aPCCs) and recombinant factor VIIa.
Other anticoagulants (e.g. thrombin inhibitors other than dabigatran, Factor Xa inhibitors including low-molecular weight heparin, vitamin K-antagonists, heparin). Thus idarucizumab will not reverse the effects of other anticoagulants.
Idarucizumab binds specifically to dabigatran and reverses its anticoagulant effect. It will not reverse the effects of other anticoagulants. Idarucizumab treatment can be used in conjunction with standard supportive measures, which should be considered as medically appropriate.
Hypersensitivity: The risk of using Idarucizumab in patients with known hypersensitivity (e.g. anaphylactoid reaction) to idarucizumab or to any of the excipients needs to be weighed cautiously against the potential benefit of such an emergency treatment. If an anaphylactic reaction or other serious allergic reaction occurs, administration of Idarucizumab should be discontinued immediately and appropriate therapy initiated.
Hereditary fructose intolerance: The recommended dose of Idarucizumab contains 4 g sorbitol as an excipient. In patients with hereditary fructose intolerance, parenteral administration of sorbitol has been associated with reports of hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of excretory and synthetic function, and death. Therefore, in patients with hereditary fructose intolerance the risk of treatment with Idarucizumab must be weighed against the potential benefit of such an emergency treatment. If Idarucizumab is administered in these patients, intensified medical care during Idarucizumab exposure and within 24 hours of exposure is required.
Thromboembolic Events: Patients being treated with dabigatran have underlying disease states that predispose them to thromboembolic events. Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate.
See prescribing information for full details.
Urinary protein testing: Praxbind causes transient proteinuria as a physiologic reaction to renal protein overflow after bolus/short term application of 5g idarucizumab intravenously. The transient proteinuria is not indicative of renal damage, which should be taken into account for urine testing.
Sodium content: This medicinal product contains 2,2 mol (or 50 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
No adverse reactions have been identified.
The recommended dose of Idarucizumab is 5 g (2×2.5 g/50 mL). In a subset of patients, recurrence of plasma concentrations of unbound dabigatran and concomitant prolongation of clotting tests have occurred up to 24 hours after administration of idarucizumab. Administration of a second 5 g dose of idarucizumab may be considered in the following situations: Recurrence of clinically relevant bleeding together with prolonged clotting times, or If potential re-bleeding would be life-threatening and prolonged clotting times are observed, or Patients require a second emergency surgery/urgent procedure and have prolonged clotting times. Relevant coagulation parameters are activated Partial Thromboplastin Time (aPTT), diluted Thrombin Time (dTT) or Ecarin Clotting Time (ECT). A maximum daily dose has not been investigated.
Restarting Antithrombotic Therapy: Dabigatran etexilate treatment can be re-initiated 24 hours after administration of idarucizumab, if the patient is clinically stable and adequate haemostasis has been achieved. After administration of idarucizumab, other antithrombotic therapy (e.g. low-molecular weight heparin) can be started at any time, if the patient is clinically stable and adequate haemostasis has been achieved. Absence of antithrombotic therapy exposes patients to the thrombotic risk of their underlying disease or condition.
Patients with renal impairment: No dose adjustment is required in renally impaired patients. Renal impairment did not impact the reversal effect of idarucizumab.
Patients with hepatic impairment: No dose adjustment is required in hepatically impaired patients.
Elderly: No dose adjustment is required in elderly patients aged 65 years and above.
Paediatric population: The safety and efficacy of Idarucizumab in children below the age of 18 years have not yet been established. No data are available.
Method of administration
Intravenous use: Idarucizumab (2×2.5 g/50 mL) is administered intravenously as two consecutive infusions over 5 to 10 minutes each or as a bolus injection.
Urinary protein testing: Idarucizumab causes transient proteinuria as a physiologic reaction to renal protein overflow after bolus/short term application of 5g idarucizumab intravenously. The transient proteinuria is not indicative of renal damage, which should be taken into account for urine testing.
Sodium content: This medicinal product contains 2, 2 mmol (or 50 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
There is no clinical experience with overdoses of this drug.
PREGNANCY & LACTATION
Pregnancy: There are no data for the use of idarucizumab in pregnant women. Reproductive and developmental toxicity studies have not been performed, given the nature and the intended clinical use of the medicinal product. Idarucizumab may be used during pregnancy, if the expected clinical benefit outweighs the potential risks.
Lactation: It is unknown whether Idarucizumab is excreted in human milk.
For full details see prescribing information.
MANUFACTURER & DISTRIBUTER:
Manufacturer: Boehringer Ingelheim GmbH
License Holder: Boehringer Ingelheim Israel Ltd