Pradaxa capsules 110mg №30

Packaging

Indications and usage

Prevention of venous thromboembolism in patients after orthopedic surgery.

Contraindications

- Known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.
- Patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).
- Hemorrhagic disorders, patients with hemorrhagic diathesis, patients with spontaneous or pharmacologically induced impaired hemostasis.
- Active clinically significant bleeding.
- Liver dysfunction and liver disease that may affect survival.
- Simultaneous intake of quinidine.
- Organ damage as a result of clinically significant bleeding,including hemorrhagic stroke during the previous 6 months before the start of therapy.
- Age of patients less than 18 years.

Pregnancy and Breastfeeding

In an animal experiment, reproductive toxicity was identified.

Clinical data on the use of dabigatran etexilate during pregnancy is not available. The potential risk to humans is not known.

Women of reproductive age should avoid pregnancy in the treatment of Pradaxa ®. When pregnancy occurs, the use of dabigatran etexilate is not recommended, except in cases where the expected benefit outweighs the possible risk.

In the case of dabigatran etexilate, breastfeeding should be discontinued (as a precautionary measure), clinical data are not available.

Dosage and administration

Inside While eating or on an empty stomach, drinking water.

Special instructions for removing the capsules from the blister: Remove the capsules from the blister, peeling off the foil. Do not squeeze the capsules through the foil. Remove the foil so that it is convenient to remove the capsules.

Adults:
Prevention of venous thromboembolism (BT) in patients after orthopedic surgery: The recommended dose is 220 mg once a day (2 capsules of 110 mg each). In patients with moderate renal impairment, the risk of bleeding is increased, the recommended dose is 150 mg once daily (2 capsules, 75 mg each).

Prevention of VT after knee replacement: TreatmentPRADAXA ® should be started 1–4 hours after completion of the operation from taking one capsule (110 mg) followed by increasing the dose to 2 capsules once a day for the next 10 days. If hemostasis is not achieved, treatment should be postponed. If treatment does not start on the day of surgery, therapy should begin with taking 2 capsules once a day.

Prevention of BT after hip joint endoprosthesis: PRADAXA ® should be started 1-4 hours after the operation is completed with one capsule (110 mg) followed by increasing the dose to 2 capsules once a day for the next 28-35 days. If hemostasis is not achieved, treatment should be postponed. If treatment does not start on the day of surgery, therapy should begin with taking 2 capsules once a day.

Use in violation of liver function: Patients with moderate or severe liver dysfunction (degree B and C according to Child-Pugh classification) or with liver disease that may affect survival, or with an increase of more than 2 times the upper limit of liver enzymes from clinical studies. In this regard, the use of PRADAXA ® in these patients is not recommended.

Use in violation of kidney function: After intravenous administration, 85% of dabigatran plasma is excreted through the kidneys. In patients with moderate renal impairment (creatinine clearance 30-50 ml / min) there is a high risk of bleeding.In such patients, the dose should be reduced to 150 mg per day. Creatinine clearance can be determined using the Cockroft-Gault formula: Creatinine clearance (ml / min) men = ((140 - age (in years)) x body weight (kg)): (72 x serum creatinine (mg / 100 ml) ) Creatinine clearance (ml / min) women = (0.85 x (140 - age (in years)) x body weight (kg)) :( 72 x serum creatinine (mg / 100 ml)) There are no data on the use of the drug patients with severe impaired renal function (creatinine clearance less than 30 ml / min); treatment of Pradaxa ® in such patients is not recommended. Dabigatran is displayed during dialysis; no clinical studies have been conducted in such patients.

Elderly patients (over 75): Patient experience is limited. The recommended dose of 150 mg (2 capsules of 75 mg once). When conducting pharmacokinetic studies in elderly patients who have decreased kidney function with age, an increase in the content of the drug in the body has been found. The dose of the drug should be calculated in the same way as for patients with impaired renal function.

Transition from treatment with dabigatran etexilate to parenteral administration of anticoagulants: Wait 24 hours from the last dose before switching to PRADAXA ® on parenteral anticoagulants.

Transition from treatment with parenteral anticoagulants to therapy with dabigatran etexilate: There are no relevant data, therefore, it is not recommended to start PRADAXA therapy until the planned introduction of another dose of parenteral anticoagulant.

Adverse reactions

In controlled studies, some patients received PRADAXA ® at 150-220 mg / day, some less than 150 mg / day, and some more than 220 mg / day.

Possible bleeding of any localization. Extensive bleeding is rare. The development of undesirable reactions was similar to the reactions in the case of the use of enoxaparin sodium.

Hematopoietic and lymphatic system disorders: Anemia, thrombocytopenia.

Vascular disorders: Hematoma, bleeding wounds.

Disturbances from the respiratory, chest and mediastinal organs: Bleeding from the nose.

Gastrointestinal disorders: Gastrointestinal bleeding, rectal bleeding, hemorrhoidal bleeding.

Hepatobiliary disorders: Impaired liver function, increased activity of hepatic transaminases, hyperbilirubinemia.

Laboratory indicators: Reduced hemoglobin and hematocrit.

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

Musculoskeletal: disorders, disorders of the connective tissue and bones Hemarthrosis.

Changes in the kidneys and urinary tract: Hematuria.

Violations of a general nature and changes in the injection site: Bleeding from the injection site, bleeding from the site of the catheter, bloody sections from wounds.

Damage, toxicity and complications from the procedures: Bloody discharge from the wound, hematoma after the procedures, bleeding after the procedures, postoperative anemia, post-traumatic hematoma, bloody discharge after the procedures, bleeding from the incision site.

Surgical and therapeutic procedures: Drainage after the procedure, wound drainage.

The frequency of the observed undesirable reactions when taking dabigatran etexilate did not go beyond the range of the frequency of undesirable reactions developing when using enoxaparin sodium.

Special notes

Risk of hemorrhage: Unfractionated Heparin can be used to preserve the function of the central venous or arterial catheter. PRADAXA ® should not be used at the same time: unfractionated heparins or its derivatives, low molecular weight heparins, sodium fondaparinux, desirudin, thrombolytic agents, GPIIb / IIIa receptor antagonists, Clopidogrel, ticlopidine, dextran, sulfate pyramone and antagonists, in a case-quest, in size and weight loss rate, in size and weight loss rate in size 15% in size and in size 15% quest can not be used in regards, costumes and costumes, and in case of weight loss rate, weight loss rate, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, weight loss ratio, GPIIb / IIIa receptors for the treatment of deep vein thrombosis, doses of Acetylsalicylic acid in doses of 75-320 mg increase the risk of bleeding. There is no evidence of an increased risk of bleeding associated with dabigatran when PRADAXA ® is taken in the recommended dose by patients receiving small doses of acetylsalicylic acid to prevent cardiovascular diseases. However, the available information is limited, so when combined with the use of acetylsalicylic acid in a low dose and PRADAXA ®, it is necessary to monitor the condition of the patients in order to timely diagnose bleeding.Careful observation (for symptoms of bleeding or anemia) should be carried out in cases in which you may increase the risk of developing hemorrhagic complications:
- Recently completed biopsy or injury.
- The use of drugs that increase the risk of hemorrhagic complications. The combination of PRADAXA ® with drugs that affect hemostasis or coagulation processes.
- Bacterial endocarditis.

Appointment of a NSAID for a short time when used together with PRADAXA ® for the purpose of analgesia after operations does not increase the risk of bleeding. There are limited data on the systematic administration of NSAIDs with a half-life of less than 12 hours in combination with PRADAXA ®, and there is no evidence of an increased risk of bleeding.

Renal failure: In pharmacokinetic studies, it was shown that patients with a decrease in renal function, including those associated with age, showed an increase in the effectiveness of the drug. In patients with moderately reduced renal function (creatinine clearance 50-30 ml / min) it is recommended to reduce the daily dose to 150 mg per day. PRADAXA ® is contraindicated in patients with severe renal impairment (CC <30 ml / min). With the development of acute renal failure, the drug should be discontinued.

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 spinal bleeding or epidural hematoma may increase.The first dose of PRADAXA ® should be taken no earlier than 2 hours after the catheter is removed. Such patients should be monitored for the purpose of possible detection of neurological symptoms.

Effects on ability to drive mechanisms: The effects of dabigatran etexilate on the ability to drive vehicles and control mechanisms have not been studied.

Combined use of PRADAXA ® with drugs affecting hemostasis or coagulation processes, including vitamin K antagonists, can significantly increase the risk of bleeding.

Dabigatran etexilate and dabigatran are not metabolized with the participation of the cytochrome P450 system and do not affect in vitro the human cytochrome P450 enzymes. Therefore, when combined with PRADAXA ®, drug interactions are not expected.

When combined with Atorvastatin interaction is not observed.

With the combined use of 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 nonsteroidal anti-inflammatory drugs (NSAIDs), and therefore requires careful monitoring of the patient's condition.

Digoxin: pharmacokinetic interaction of this combination was not detected.

Pantoprazole: AUC reduction of approximately 30% has been established.In clinical studies, no effect of the combination of pantoprazole or other proton pump inhibitors and PRADAXA ® on the development of bleeding or pharmacological effects was detected.

Ranitidine: when combined with PRADAXA ®, the degree of absorption of dabigatran does not change.

- Interaction at the level of Amiodarone transporters: when PRADAXA ® and amiodarone are used together, the rate and extent of absorption of the latter and the formation of its active metabolite, deethylamidarodon, does not change. AUC and C max increased by 60% and 50%, respectively. With the joint use of dabigatran etexilate and amiodarone, it is necessary to reduce the dose of PRADAXA ® to 150 mg per day. Due to the long half-life of amiodarone, potential drug interactions may persist for several weeks after discontinuation of amiodarone.
- P-glycoprotein inhibitors. Care should be taken when PRADAXA ® is used together with active P-glycoprotein inhibitors, such as, for example, 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. Simultaneous use of PRADAXA ® with quinidine is contraindicated.

- P-glycoprotein inducers Potential inductors such as rifampicin and St. John's wort herb extract may reduce the effect of dabigatran.Care should be taken when sharing dabigatran with similar drugs.

With the joint use of dabigatran with antacids and means that inhibit gastric secretion, changes in the dose of dabigatran are not required.

No interaction of dabigatran with the most commonly used drugs was found: opioid analgesics, diuretics, Paracetamol, nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, hydroxymethylglutaryl-coenzyme A reductase inhibitors; drugs that reduce cholesterol / triglycerides (not related to statins), angiotensin II receptor blockers, ACE inhibitors, beta-adrenergic receptor blockers; Calcium channel blockers; prokinetics; benzodiazepine derivatives.

There is no antidote to dabigatran etexilate or dabigatran.

The use of doses of the drug in excess of the recommended, increases the risk of bleeding. If bleeding develops, treatment should be stopped to determine the causes of bleeding. Given the main route of elimination of dabigatran through the kidneys, it is recommended to ensure adequate diuresis. If necessary, surgical hemostasis or transfusion of fresh frozen plasma is possible.

Dabigatran is removed during dialysis; however, clinical experience with this method is missing.

Store in a dry place at a temperature not higher than 25? WITH