Description
Latin name
PRADAXA
Release form
Capsules.
Packing
30 pcs
Pharmacological action
Pradax – anticoagulant. Direct thrombin inhibitor. Dabigatran etexilate is a low molecular weight prodrug that does not have pharmacological activity. After oral administration, it is rapidly absorbed and is converted to 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, then inhibition of its activity prevents the formation of a blood clot. Dabigatran inhibits free thrombin, fibrin-binding thrombin and thrombin-mediated platelet aggregation.
In vivo and ex vivo in animal studies using various models of thrombosis demonstrated the antithrombotic efficacy and anticoagulant activity of dabigatran after iv administration and dabigatran etexilate after oral administration.
A close correlation was found between the concentration of dabigatran in plasma and the severity of the anticoagulant effect. Dabigatran lengthens activated partial thromboplastin time (APTT).
Indications
Prevention of venous thromboembolism in patients after orthopedic surgery.
Contraindications
– severe renal failure (CC less than 30 ml / min)
– hemorrhagic disorders, hemorrhagic diathesis, spontaneous or pharmacologically induced hemostasis
– active clinically significant bleeding
– which can affect liver function and liver survival
– concomitant use of quinidine
– organ damage due to clinically significant bleeding, including hemorrhagic stroke within the previous 6 months before onset and
therapy – less than 18 years of age
– known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.
Special instructions
Risk of developing hemorrhages: Unfractionated heparin can be used to maintain the functioning of a central venous or arterial catheter. It should not be used simultaneously with PRADAXA В®: unfractionated heparins or its derivatives, low molecular weight heparins, fondaparinux sodium, desirudin, thrombolytic agents, GPIIb / IIIa receptor antagonists, clopidogrel, ticlopidine, dextran, sulfinpyrazone and vitamin K antagonists. The combined use of PRADAXAВ® in the doses recommended for the treatment of deep vein thrombosis and acetylsalicylic acid in doses of 75-320 mg increases the risk of bleeding. Data indicating an increased risk of bleeding associated with dabigatran when taking PRADAX В® in the recommended dose for patients, receiving small doses of acetylsalicylic acid in order to prevent cardiovascular disease, are absent. However, the available information is limited, therefore, with the combined use of acetylsalicylic acid in a low dose and PRADAXA В®, it is necessary to monitor the condition of patients with the aim of timely diagnosis of bleeding. Careful monitoring (for symptoms of bleeding or anemia) should be carried out in cases where it is possible to increase the risk of hemorrhagic complications: – A recent biopsy or trauma.
– The use of drugs that increase the risk of hemorrhagic complications. The combination of PRADAXA В® with drugs that affect hemostasis or coagulation processes.
– Bacterial endocarditis.
Prescribing NSAIDs for a short time when used together with PRADAXA В® for analgesia after surgery does not increase the risk of bleeding. There is limited data on the systematic administration of NSAIDs with a half-life of less than 12 hours in combination with PRADAXA В®, there is no evidence of an increased risk of bleeding.
Renal failure: Pharmacokinetic studies have shown that in patients with impaired renal function, including age-related, an increase in the effectiveness of the drug was noted. In patients with moderately reduced renal function (creatinine clearance of 50-30 ml / min), it is recommended to reduce the daily dose to 150 mg per day. PRADAXA В® is contraindicated in patients with severe impaired renal function (CC
Spinal anesthesia / Epidural anesthesia / Lumbar puncture: In the case of traumatic or repeated spinal puncture and prolonged use of an epidural catheter, the risk of developing cerebrospinal bleeding or epidural hematoma should not be taken. earlier than 2 hours after removal of the catheter, these patients should be monitored for possible detection of neurological symptoms.
Effect on ability to control mechanisms: The effects of dabigatran etexilate on the ability to drive vehicles and control mechanisms have not been studied.
Composition
Dabigatran etexilate mesylate 75 mg.
Excipients: acacia gum, coarse tartaric acid, tartaric acid powder, crystalline tartaric acid, hypromellose, dimethicone, talc, hyprolose (hydroxypropyl cellulose).
Dosage and administration
The drug is prescribed orally.
Adults for the prevention of venous thromboembolism (BT) in patients after orthopedic surgery, the recommended dose is 220 mg / day once (2 capsules of 110 mg).
In patients with moderate impaired renal function, the risk of bleeding is increased, the recommended dose is 150 mg / day once (2 caps. 75 mg each).
For the prevention of BT after knee replacement, treatment should begin 1-4 hours after completion of the operation with a dose of 110 mg, followed by a dose increase to 220 mg once for the next 10 days. If hemostasis is not achieved, treatment should be delayed. If treatment has not started on the day of surgery, therapy should be started with a dose of 220 mg / day once.
For the prevention of BT after hip replacement, treatment should be started 1-4 hours after surgery with a dose of 110 mg, followed by a dose increase to 220 mg / day, once for the next 28-35 days. If hemostasis is not achieved, treatment should be delayed. If treatment has not started on the day of surgery, therapy should be started with a dose of 220 mg / day once.
Patients with severe hepatic impairment (Child-Pugh class B and C) or with liver diseases that could affect survival, or with a more than 2-fold increase in hepatitis V, the liver enzymes were excluded from clinical trials. In this regard, the use of Pradaxa in this category of patients is not recommended.
Side effects
Disorders from the hematopoietic and lymphatic systems: anemia, thrombocytopenia.
Immune system disorders: hypersensitivity reactions, including urticaria, rash and itching, bronchospasm.
Disorders of the nervous system: intracranial bleeding.
Vascular disorders: hematoma, bleeding.
Disorders of the respiratory system, chest and mediastinum: 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 from the hepatobiliary system: increased activity of “hepatic” transaminases, impaired liver function, hyperbilirubinemia.
Changes in the skin and subcutaneous tissue: skin hemorrhagic syndrome.
Musculoskeletal disorders, disorders of the connective tissue and bones: hemarthrosis.
Changes in the kidneys and urinary tract: urogenital bleeding, hematuria.
General disorders and changes in the injection site: bleeding from the injection site, bleeding from the injection site of the catheter.
Damage, toxicity and complications from procedures: post-traumatic hematoma, bleeding from the site of surgical access.
Vascular disorders: bleeding from an operating 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.
Drug interactions
The combined use of PRADAX ® with drugs that affect hemostasis or coagulation processes, including vitamin K antagonists, can significantly increase the risk of bleeding.
Dabigatran etexilate and dabigatran are not metabolized by the P450 cytochrome system and do not affect human in vitro cytochrome P450 enzymes. Therefore, when combined with PRADAXA ®, drug interactions are not expected.
When combined with atorvastatin, no interaction is observed.
When combined, the pharmacokinetics of diclofenac and dabigatran etexilate does not change, indicating a slight interaction. The use of NSAIDs for a short time to reduce pain after surgery did not increase the risk of bleeding.
There is limited experience with PRADAXA ® in combination with long-term systematic administration of non-steroidal anti-inflammatory drugs (NSAIDs), which requires careful monitoring of patients.
digoxin: pharmacokinetic interaction of this combination was not detected.
Pantoprazole: AUC reduction of about 30% was found. In clinical studies, no effect of a combination of pantoprazole or other proton pump inhibitors and PRADAX ® on the development of bleeding or pharmacological effects was revealed.
Ranitidine: when used together with PRADAXA ®, the degree of absorption of dabigatran does not change.
– Interaction at the level of transporters Amiodarone: with the combined use of PRADAX® and amiodarone, the rate and degree of absorption of the latter and the formation of its active metabolite desethylamiodarone do not change. AUC and C max increased by 60% and 50%, respectively. With the combined use of dabigatran etexilate and amiodarone, it is necessary to reduce the dose of PRADAX ® to 150 mg per day. Due to the long half-life of amiodarone, the potential interaction of the drugs may persist for several weeks after canceling amiodarone.
– P-glycoprotein inhibitors Caution should be exercised when combined with PRADAXA ® with active P-glycoprotein inhibitors, such as verapamil, clarithromycin. Repeated administration of verapamil over several days led to an increase in the concentration of dabigatran by 50-60%. This effect can be reduced by prescribing dabigatran at least two hours before taking verapamil. The concomitant use of PRADAX ® with quinidine is contraindicated.
– P-Glycoprotein Inductors Potential inducers such as rifampicin and St. John’s wort herb extract can reduce the effect of dabigatran. Caution should be exercised when sharing dabigatran with similar drugs.
With the combined use of dabigatran with antacids and drugs that inhibit gastric secretion, a change in the dose of dabigatran is not required.
No interaction of dabigatran with the most commonly used drugs was found: opioid analgesics, diuretics, paracetamol, non-steroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, hydroxymethylglutaryl coenzyme A inhibitors, drugs that lower cholesterol / receptor triglycerides, triglycerides II, ACE inhibitors, beta-adrenergic blockers, calcium channel blockers, prokinetics, benzodiazepine derivatives.
Overdose
Symptoms: use of drug doses, exceeding the recommended leads to an increased risk of bleeding.
Treatment: In case of bleeding, treatment should be stopped to find out the causes of bleeding. Given the major route of excretion of dabigatran through the kidneys, it is recommended to provide adequate diuresis. If necessary, surgical hemostasis or transfusion of fresh frozen plasma is possible. Dabigatran is removed by dialysis, however, there is no clinical experience with this method. There is no antidote to dabigatran etexilate or dabigatran.
Storage Conditions
At a temperature not exceeding 25C.
Shelf life
3 years.
Terms of dispatch from
pharmacies Prescription from pfroaf from
pharmacies Prescription
Dosage form
capsule
Appointment
Appointment
Adults doctor’s prescription
