Pradaxa, 110 mg capsules 180 pcs

PRADAXA – dabigatran etexilate is a low molecular weight prodrug that has no pharmacological activity. After oral administration, it is rapidly absorbed and is converted to dabigatran by esterase-catalyzed hydrolysis. Dabigatran is an active, competitive, reversible direct thrombin inhibitor and acts mainly in plasma.

Since thrombin (a serine protease) converts fibrinogen to fibrin during the coagulation cascade, inhibition of its activity prevents thrombus formation. Dabigatran inhibits free thrombin, fibrin-binding thrombin and thrombin-induced platelet aggregation.

In vivo and ex vivo animal studies using various models of thrombosis have demonstrated the antithrombotic efficacy and anticoagulant activity of dabigatran after intravenous administration and dabigatran etexilate after oral administration.

A close correlation between the concentration of dabigatran in plasma and the severity of anticoagulant effect was revealed. Dabigatran prolongs activated partial thromboplastin time (ATTB).

Indications

— prevention of venous thromboembolism in patients after orthopedic operations;
– prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation;
– treatment of acute deep vein thrombosis and/or pulmonary embolism and prevention of deaths caused by these diseases;
– prevention of recurrent deep vein thrombosis and/or pulmonary embolism and deaths caused by these diseases.

Pharmacological effect

PRADAXA – dabigatran etexilate is a low molecular weight prodrug that does not have pharmacological activity. After oral administration, it is rapidly absorbed and is converted into dabigatran by hydrolysis catalyzed by esterases. Dabigatran is an active, competitive, reversible direct thrombin inhibitor and acts primarily in plasma.

Since thrombin (serine protease) converts fibrinogen into fibrin during the coagulation cascade, inhibition of its activity prevents the formation of a blood clot. Dabigatran inhibits free thrombin, fibrin-binding thrombin, and thrombin-induced platelet aggregation.

In vivo and ex vivo animal studies using various thrombosis models have demonstrated the antithrombotic efficacy and anticoagulant activity of dabigatran after intravenous administration and dabigatran etexilate after oral administration.

A close correlation was found between the plasma concentration of dabigatran and the severity of the anticoagulant effect. Dabigatran prolongs the activated partial thromboplastin time (aPTT).

Special instructions

Risk of hemorrhage: Unfractionated heparin can be used to preserve the functioning of a central venous or arterial catheter.

Active ingredient

Dabigatran etexilate

Composition

1 caps:
dabigatran etexilate mesylate 126.83 mg, which corresponds to the content of dabigatran etexilate 110 mg.

Contraindications

– known sensitivity to dabigatran or dabigatran etexilate or to any of the excipients;
— severe renal failure (creatinine clearance <30 ml/min);
– active clinically significant bleeding, hemorrhagic diathesis, spontaneous or pharmacologically induced disorder of hemostasis;
– organ damage as a result of clinically significant bleeding, including hemorrhagic stroke during the previous 6 months before the start of therapy;
– significant risk of major bleeding from existing or recent gastrointestinal ulceration, presence of malignancies with a high risk of bleeding, recent injury to the brain or spinal cord, recent brain or spinal cord or ophthalmic surgery, recent intracranial hemorrhage, presence or suspicion of esophageal varices, congenital arteriovenous defects, vascular aneurysms or large intravertebral or intracerebral vascular disorders;
– simultaneous administration of any other anticoagulants, incl. unfractionated heparin, low molecular weight heparins (including enoxaparin, dalteparin), heparin derivatives (including fondaparinux), oral anticoagulants (including warfarin, rivaroxaban, apixaban), except in cases of switching treatment from or to Pradaxa® or in the case of using unfractionated heparin in doses necessary to maintain central venous or arterial catheter;
– simultaneous administration of ketoconazole for systemic use, cyclosporine, itraconazole, tacrolimus and dronedarone;
– liver dysfunction and liver disease that may affect survival;
— presence of a prosthetic heart valve;
– children and adolescents under 18 years of age (no clinical data).
The drug should be used with caution in conditions that increase the risk of bleeding:
— age 75 years and older;
— moderate decrease in renal function (creatinine clearance 30-50 ml/min);
– simultaneous use of P-glycoprotein inhibitors (except for those indicated in the “Contraindications” section);
— body weight <50 kg;
– simultaneous use of NSAIDs (including acetylsalicylic acid), clopidogrel, selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, as well as other drugs, the use of which may impair hemostasis;
— congenital or acquired diseases of the blood coagulation system;
– thrombocytopenia or functional platelet defects;
– recent biopsy or major trauma;
— bacterial endocarditis;
– esophagitis, gastritis or gastroesophageal reflux disease.

Side Effects

Disorders of the hematopoietic and lymphatic system: anemia, thrombocytopenia.

Immune system disorders: hypersensitivity reactions, including urticaria, rash and itching, bronchospasm.

Nervous system disorders: intracranial bleeding.

Vascular disorders: hematoma, bleeding.

Respiratory, thoracic and mediastinal disorders: nosebleeds, hemoptysis.

Gastrointestinal disorders: gastrointestinal bleeding, rectal bleeding, hemorrhoidal bleeding, abdominal pain, diarrhea, dyspepsia, nausea, ulceration of the gastrointestinal mucosa, gastroesophagitis, gastroesophageal reflux disease, vomiting, dysphagia.

Disorders of the hepatobiliary system: increased activity of liver transaminases, impaired liver function, hyperbilirubinemia.

Changes in the skin and subcutaneous tissues: cutaneous hemorrhagic syndrome.

Musculoskeletal disorders, connective tissue and bone disorders: hemarthrosis.

Changes in the kidneys and urinary tract: urogenital bleeding, hematuria.

General disorders and changes at the injection site: bleeding from the injection site, bleeding from the catheter insertion site.

Damage, toxicity and complications from procedures: post-traumatic hematoma, bleeding from the surgical access site.

Vascular disorders: bleeding from the surgical wound.

General disorders and disorders at the injection site: spotting.

Damage, toxicity and complications of postoperative treatment: hematoma after wound treatment, bleeding after wound treatment, anemia in the postoperative period, discharge from the wound after procedures, secretion from the wound.

Surgical and therapeutic procedures: wound drainage, drainage after wound treatment.

Interaction

Pharmacokinetic interaction. Dabigatran etexilate and dabigatran are not metabolized by liver microsomal enzymes and are neither inducers nor inhibitors of the activity of cytochrome P450 isoenzymes. Therefore, it is assumed that dabigatran does not have a clinically significant pharmacokinetic drug interaction with drugs that are metabolized by cytochrome P450 isoenzymes. In clinical studies in healthy volunteers, no interaction of dabigatran with atorvastatin (CYP3A4 substrate) and diclofenac (CYP2C9 substrate) was detected.

Overdose

Symptoms: overdose when using Pradaxa® may be accompanied by hemorrhagic complications, which is due to the pharmacodynamic properties of the drug.

Storage conditions

The drug in vials should be stored at a temperature not exceeding 25°C. The bottle should be kept tightly sealed to protect it from moisture. After opening the bottle, the drug should be used within 4 months.

Shelf life

3 years.

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co.KG, Germany