Pradaxa instructions for use reviews. Pradaxa tablets: instructions, price and real consumer reviews

In this article you can find instructions for use medicinal product Pradaxa. Feedback from site visitors - consumers - is presented of this medicine, as well as the opinions of specialist doctors on the use of Pradaxa in their practice. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications were observed and side effects, perhaps not stated by the manufacturer in the annotation. Analogues of Pradaxa in the presence of existing structural analogues. Use for the treatment of thrombosis, embolism and the prevention of strokes in adults, children, as well as during pregnancy and lactation. Composition of the drug.

Pradaxa- anticoagulant. Direct thrombin inhibitor. Dabigatran etexilate (the active ingredient of Pradaxa) is a low molecular weight precursor that does not have pharmacological activity. active form dabigatran. After oral administration of dabigatran etexilate is rapidly absorbed into the gastrointestinal tract and, by hydrolysis catalyzed by esterases, is converted into dabigatran in the liver and blood plasma. Dabigatran is a potent competitive reversible direct thrombin inhibitor and the main active substance in blood plasma.

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

Experimental studies on various models of thrombosis confirmed the antithrombotic effect and anticoagulant activity of dabigatran after intravenous administration and dabigatran etexilate - after oral administration.

A direct correlation has been established between the concentration of dabigatran in the blood plasma and the severity of the anticoagulant effect. Dabigatran prolongs the aPTT, ecarin clotting time (ECT) and thrombin time (TT).

results clinical trials in patients who underwent orthopedic surgery - knee and hip joint replacement - confirmed the preservation of hemostasis parameters and the equivalence of the use of 75 mg or 110 mg of dabigatran etexilate 1-4 hours after surgery and a subsequent maintenance dose of 150 or 220 mg 1 time per day for 6- 10 days (for surgery on knee joint) and 28-35 days (at hip joint) compared with enoxaparin at a dose of 40 mg 1 time per day, which was used before and after surgery.

When used to prevent venous thromboembolism after endoprosthetics large joints demonstrated the equivalence of the antithrombotic effect of dabigatran etexilate at doses of 150 mg or 220 mg compared with enoxaparin at a dose of 40 mg per day when assessing the primary endpoint, which included all cases of venous thromboembolism and mortality from any cause.

When used to prevent stroke and systemic thromboembolism in patients with atrial fibrillation and at moderate or high risk of stroke, it was shown that dabigatran etexilate at a dose of 110 mg 2 times a day was not inferior to warfarin in preventing stroke and systemic thromboembolism in patients with fibrillation atria; There was also a reduction in the risk of intracranial bleeding and the overall incidence of bleeding in the dabigatran group. The use of a higher dose of dabigatran etexilate (150 mg 2 times a day) significantly reduced the risk of ischemic and hemorrhagic strokes, cardiovascular death, intracranial bleeding and overall bleeding incidence compared with warfarin. The lower dose of dabigatran was associated with a significantly lower risk of major bleeding compared with warfarin. Clean clinical effect was assessed by determining a combined endpoint that included the incidence of stroke, systemic thromboembolism, pulmonary thromboembolism, acute heart attack myocardium, cardiovascular mortality and major bleeding. The annual incidence of these events in patients receiving dabigatran etexilate was lower than in patients receiving warfarin. Changes in laboratory tests of liver function in patients receiving dabigatran etexilate were observed with comparable or less frequency compared to patients receiving warfarin.

Compound

Dabigatran etexilate mesylate + excipients.

Pharmacokinetics

After oral administration of Pradaxa, there is a rapid dose-dependent increase in its concentration in the blood plasma. The absolute bioavailability of dabigatran after oral administration of dabigatran etexilate in hypromellose-coated capsules is about 6.5%. Food intake does not affect the bioavailability of dabigatran etexilate.

When using dabigatran etexilate 1-3 hours in patients after surgical treatment there is a decrease in the rate of absorption of the drug compared to healthy volunteers.

It should be noted that factors such as anesthesia, gastrointestinal paresis and surgery may have a role in slowing absorption, regardless of dosage form drug. A decrease in the rate of absorption of dabigatran is usually observed only on the day of surgery.

After oral administration, during hydrolysis under the influence of esterase, dabigatran etexilate is quickly and completely converted into dabigatran, which is the main active metabolite in the blood plasma. When dabigatran is conjugated, 4 isomers of pharmacologically active acyl glucuronides are formed: 1-O, 2-O, 3-O, 4-O, each of which constitutes less than 10% of general content dabigatran in blood plasma. Traces of other metabolites are only detected using highly sensitive analytical methods.

Dabigatran is excreted unchanged, mainly by the kidneys (85%), and only 6% through the gastrointestinal tract. It has been established that 168 hours after administration of a radioactive drug, 88-94% of its dose is excreted from the body.

Dabigatran has a low binding ability to plasma proteins (34-35%), it does not depend on its concentration.

Indications

• prevention of venous thromboembolism in patients after orthopedic surgery;
• prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation.

Release forms

Capsules 75 mg, 110 mg and 150 mg (sometimes mistakenly called tablets).

Instructions for use and dosage regimen

Depending on the indications, the daily dose is 110-300 mg. The frequency of administration is 1-2 times a day. The treatment regimen and duration of use depend on the indications and clinical situation.

Use in patients with increased risk bleeding

The presence of factors such as age 75 years or older, moderate decrease in renal function (creatinine clearance 30-50 ml/min), simultaneous use of P-glycoprotein inhibitors, or indication of gastrointestinal bleeding history may increase the risk of bleeding. In patients with one or more of these risk factors, at the discretion of the physician, the daily dose of Pradaxa may be reduced to 220 mg (take 1 capsule 110 mg 2 times a day).

Transition from the use of Pradaxa to parenteral use of anticoagulants

Prevention of venous thromboembolism in patients after orthopedic surgery: parenteral administration of anticoagulants should begin 24 hours after taking the last dose of Pradaxa.

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation: parenteral anticoagulants should be started 12 hours after the last dose of Pradaxa.

Transition from parenteral anticoagulants to Pradaxa

The first dose of Pradaxa is prescribed instead of the discontinued anticoagulant in the interval 0-2 hours before the next injection of alternative therapy or simultaneously with the cessation of continuous infusion (for example, intravenous use unfractionated heparin (UFH)).

Switching from vitamin K antagonists to Pradaxa

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

The use of vitamin K antagonists is discontinued; the use of Pradaxa is possible with MHO less than 2.0.

Switching from Pradaxa to Vitamin K Antagonists

With a CC of more than 50 ml/min, the use of vitamin K antagonists is possible 3 days, and with a CC of 30-50 ml/min - 2 days before discontinuation of the Pradaxa drug.

Cardioversion

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

Planned or emergency cardioversion does not require discontinuation of Pradaxa therapy.

Missed dose

Prevention of venous thromboembolism in patients after orthopedic surgery: it is recommended to take the usual daily dose Pradaxa at the usual time the next day. If you miss individual doses, you should not take a double dose of the drug.

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation: a missed dose of Pradaxa can be taken if 6 hours or more remain before the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Treatment and prevention of acute DVT and/or PE deaths caused by these diseases: a missed dose of Pradaxa can be taken if there are 6 hours or more left before taking the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Prevention of recurrent DVT and/or PE and deaths caused by these diseases: a missed dose of Pradaxa can be taken if 6 hours or more remain before the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Side effect

• anemia;
• thrombocytopenia;
• hypersensitivity reactions, including urticaria, rash and itching, bronchospasm;
• intracranial bleeding;
• hematoma;
• nose bleed;
• hemoptysis;
• gastrointestinal bleeding;
• rectal bleeding;
• hemorrhoidal bleeding;
• abdominal pain;
• diarrhea;
• dyspepsia;
• nausea, vomiting;
• ulceration of the gastrointestinal mucosa;
• gastroesophagitis;
• gastroesophageal reflux disease;
• dysphagia
• increased activity of liver transaminases;
• liver dysfunction;
• hyperbilirubinemia;
• cutaneous hemorrhagic syndrome;
• hemarthrosis;
• urogenital bleeding;
• hematuria;
• bleeding from the injection site;
• bleeding from the catheter insertion site;
• post-traumatic hematoma;
• bleeding from the surgical wound;
• bloody issues;
• wound drainage;
• drainage after wound treatment.

Contraindications

• severe renal failure (creatinine clearance less than 30 ml/min);
• active clinically significant bleeding, hemorrhagic diathesis, spontaneous or pharmacologically induced disturbance of hemostasis;
• organ damage resulting from clinically significant bleeding, including hemorrhagic stroke, within the previous 6 months before the start of therapy;
• simultaneous administration of ketoconazole for systemic use;
• liver dysfunction and liver disease that may affect survival;
• age under 18 years (no clinical data);
• known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.

Use during pregnancy and breastfeeding

There are no data on the use of Pradaxa during pregnancy. The potential risk in humans is unknown.

Experimental studies have not shown any adverse effects on fertility or postnatal development of newborns.

Women reproductive age Reliable methods of contraception should be used in order to exclude the possibility of pregnancy while being treated with Pradaxa. During pregnancy, the use of the drug is not recommended, except in cases where the expected benefit outweighs the possible risk.

If it is necessary to use the drug during breastfeeding, due to the lack of clinical data, breast-feeding it is recommended to stop (as a precaution).

Use in children

The effectiveness and safety of Pradaxa have not been studied in patients under 18 years of age, so use in children is not recommended.

Use in elderly patients

Due to the fact that increased drug exposure in elderly patients (over 75 years of age) is often due to decreased renal function, renal function should be assessed before prescribing the drug. Renal function should be assessed at least once a year or more frequently depending on the clinical situation. Dose adjustments should be made depending on the severity of renal dysfunction.

special instructions

Risk of bleeding

The use of Pradaxa, as well as other anticoagulants, is recommended with caution in conditions characterized by an increased risk of bleeding. During therapy with Pradaxa, bleeding of various locations may develop. A decrease in the concentration of hemoglobin and/or hematocrit in the blood, accompanied by a decrease in blood pressure, is the basis for searching for the source of bleeding.

Treatment with Pradaxa does not require monitoring of anticoagulant activity. The test to determine MHO should not be used, since there is evidence of a false increase in MHO levels.

Thrombin or ecarin clotting time tests should be used to detect excessive anticoagulant activity of dabigatran. When these tests are not available, the APTT test should be used.

In a study of patients with atrial fibrillation, an aPTT level exceeding 2-3 times the normal limit before taking the next dose of the drug was associated with an increased risk of bleeding.

Pharmacokinetic studies of Pradaxa have shown that in patients with reduced renal function (including elderly patients), there is an increase in drug exposure. The use of Pradaxa is contraindicated in the case of pronounced violations renal function (creatinine clearance less than 30 ml/min).

If acute renal failure develops, Pradaxa should be discontinued.

The following factors can lead to an increase in the concentration of dagibatran in plasma: decreased renal function (creatinine clearance 30-50 ml/min), age over 75 years, simultaneous use of a P-glycoprotein inhibitor. The presence of one or more of these factors may increase the risk of bleeding.

Concomitant use of Pradaxa with the following drugs has not been studied, but may increase the risk of bleeding: unfractionated heparin (except for doses required to maintain the patency of a venous or arterial catheter) and heparin derivatives, low molecular weight heparins (LMWH), fondaparinux sodium, thrombolytic drugs, glycoprotein blockers GP 2b/3a platelet receptors, ticlopidine, dextran, rivaroxaban, ticagrelor, vitamin K antagonists and P-glycoprotein inhibitors (itraconazole, tacrolimus, cyclosporine, ritonavir, nelfinavir and saquinavir). The risk of bleeding is increased in patients taking selective serotonin reuptake inhibitors concomitantly. Also, the risk of bleeding may increase with the simultaneous use of antiplatelet agents and other anticoagulants.

Concomitant use of dronedarone and dabigatran is not recommended.

If the risk of bleeding increases (for example, with a recent biopsy or major trauma, bacterial endocarditis), monitoring the patient's condition is required in order to promptly detect signs of bleeding.

Prevention of venous thromboembolism in patients after orthopedic surgery

It has been established that the use of non-steroidal anti-inflammatory drugs (NSAIDs) for short-term anesthesia during surgery concomitantly with Pradaxa is not associated with an increased risk of bleeding. There is limited data on the regular use of NSAIDs (those with a half-life of less than 12 hours) during treatment with Pradaxa; there is no evidence of an increased risk of bleeding.

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

Concomitant use of Pradaxa, antiplatelet agents (including ASA and clopidogrel) and NSAIDs increases the risk of bleeding.

The use of fibrinolytic drugs can only be considered if the patient's TV, EVS or APTT values ​​do not exceed upper limit local reference range standards.

Interaction with P-glycoprotein inducers

Oral administration of the P-glycoprotein inducer rifampicin with Pradaxa decreased the plasma concentrations of dabigatran. It is expected that other P-glycoprotein inducers, such as St. John's wort or carbamazepine, may also reduce plasma concentrations of dabigatran and should be used with caution.

Surgical operations and interventions

Patients using Pradaxa during surgery or invasive procedures have an increased risk of bleeding. Therefore, during surgical interventions, Pradaxa should be discontinued.

Preoperative period

Pradaxa should be discontinued before invasive procedures or surgery. at least, 24 hours before they take place. In patients with an increased risk of bleeding or undergoing major surgery requiring complete hemostasis, use of Pradaxa should be discontinued 2-4 days before surgery. In patients with renal failure clearance of dabigatran may be prolonged.

Pradaxa is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min), but if the drug is still used, it should be discontinued at least 5 days before surgery.

If emergency surgery is necessary, Pradaxa should be temporarily discontinued. Surgical intervention If such a possibility exists, it is advisable to perform it no earlier than 12 hours after the last Pradaxa dose.

Spinal anesthesia/epidural anesthesia/lumbar puncture

Procedures such as spinal anesthesia, may require full recovery hemostasis. In case of traumatic or repeated spinal tap and prolonged use of an epidural catheter may increase the risk of developing spinal bleeding or epidural hematoma. The first dose of Pradaxa should be taken no earlier than 2 hours after removal of the catheter. It is necessary to monitor the condition of patients to exclude neurological symptoms which may be caused by spinal bleeding or epidural hematoma.

Period after the procedure

The use of Pradaxa can be continued once complete hemostasis is achieved.

Impact on the ability to drive vehicles and operate machinery

The effect of Pradaxa on the ability to drive vehicles and potentially engage in others dangerous species activities requiring increased concentration attention and psychomotor speed have not been studied, but given that the use of Pradaxa may be accompanied by an increased risk of bleeding, caution should be exercised when performing such activities.

Drug interactions

Combined use with medicines drugs that affect hemostasis or coagulation processes, including vitamin K antagonists, can significantly increase the risk of bleeding.

Pharmacokinetic interactions

Studies have not established an inducing or inhibitory effect of dabigatran on cytochrome P450. In studies in healthy volunteers, no interaction was observed between dabigatran etexilate and atorvastatin (CYP3A4 substrate) and diclofenac (CYP2C9 substrate).

Interaction with P-glycoprotein inhibitors/inducers

The substrate for the transport molecule P-glycoprotein is dabigatran etexilate. The simultaneous use of P-glycoprotein inhibitors (amiodarone, verapamil, quinidine, ketoconazole for systemic use or clarithromycin) leads to an increase in the concentration of dabigatran in the blood plasma.

Concomitant use with P-glycoprotein inhibitors

Dose selection in the case of using the listed P-glycoprotein inhibitors for the prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation is not required. If used for the prevention of venous thromboembolism in patients after orthopedic surgery, see sections “Dosage regimen” and Drug interactions.”

Amiodarone. With simultaneous use of dabigatran etexilate with a single dose of amiodarone (600 mg) taken orally, the degree and rate of absorption of amiodarone and its active metabolite, desethylamiodarone, did not change. The AUC and Cmax values ​​of dabigatran increased approximately 1.6 and 1.5 times (60% and 50%), respectively. In a study in patients with atrial fibrillation, dabigatran concentrations increased by no more than 14%, and no increased risk of bleeding was observed.

Verapamil. When dabigatran etexilate was co-administered with verapamil administered orally, the Cmax and AUC values ​​of dabigatran increased depending on the time of administration and the dosage form of verapamil. The greatest increase in the effect of dabigatran was observed when using the first dose of verapamil in the immediate release dosage form, which was administered 1 hour before dosing with dabigatran etexilate (Cmax increased by 180% and AUC increased by 150%). When using the sustained release formulation of verapamil, this effect was progressively reduced (Cmax increased by 90% and AUC by 70%), as well as when using multiple doses of verapamil (Cmax increased by 60% and AUC by 50%), which may be explained by the induction of P-glycoprotein in the gastrointestinal tract with long-term use of verapamil. When verapamil was used 2 hours after taking dabigatran etexilate, no clinically significant interaction was observed (Cmax increased by 10% and AUC by 20%), since dabigatran was completely absorbed after 2 hours. In a study in patients with atrial fibrillation, dabigatran concentrations increased by no more than 21%, and no increased risk of bleeding was observed. There are no data on the interaction of dabigatran etexilate with verapamil administered parenterally; no clinically significant interaction is expected.

Ketoconazole. Ketoconazole for systemic use after a single dose of 400 mg increases the AUC and Cmax of dabigatran by approximately 2.4 times (by 138% and 135%), respectively, and after repeated administration of ketoconazole at a dose of 400 mg per day - by approximately 2.5 times (by 153%). and 149%) respectively. Ketoconazole did not affect Tmax and final T1/2. The simultaneous use of Pradaxa and ketoconazole for systemic use is contraindicated.

Clarithromycin. With simultaneous use of clarithromycin at a dose of 500 mg 2 times a day with dabigatran etexilate, no clinically significant pharmacokinetic interaction was observed (Cmax increased by 15% and AUC by 19%).

Quinidine. The AUCt,ss and Cmax,ss values ​​of dabigatran when administered twice daily when co-administered with quinidine at a dose of 200 mg every 2 hours until a total dose of 1000 mg were increased on average by 53% and 56%, respectively.

Concomitant use with P-glycoprotein substrates

Digoxin. With simultaneous use of dabigatran etexilate with digoxin, which is a substrate of P-glycoprotein, no pharmacokinetic interaction was observed. Neither dabigatran nor the prodrug dabigatran etexilate are clinically significant P-gp inhibitors.

Concomitant use with P-glycoprotein inducers

The simultaneous use of Pradaxa and P-glycoprotein inducers should be avoided, since combined use leads to a decrease in the exposure of dabigatran.

Rifampicin. Pretreatment with the test inducer rifampicin at a dose of 600 mg per day for 7 days resulted in decreased exposure to dabigatran. After discontinuation of rifampicin, this inductive effect decreased; on day 7, the effect of dabigatran was close to the initial level. Over the next 7 days, no further increase in the bioavailability of dabigatran was observed.

It is expected that other P-glycoprotein inducers, such as St. John's wort or carbamazepine, may also reduce plasma concentrations of dabigatran and should be used with caution.

Concomitant use with antiplatelet agents

Acetylsalicylic acid (ASA). When studying the simultaneous use of dabigatran etexilate at a dose of 150 mg 2 times a day and ASA in patients with atrial fibrillation, it was found that the risk of bleeding may increase from 12% to 18% (when using ASA at a dose of 81 mg) and up to 24% (when using ASA at a dose of 325 mg). It has been shown that ASA or clopidogrel, used simultaneously with dabigatran etexilate at a dose of 110 mg or 150 mg 2 times a day, may increase the risk of major bleeding. Bleeding is also observed more often with the simultaneous use of warfarin with ASA or clopidogrel.

NSAIDs. NSAIDs used for short-term analgesia after surgery did not increase the risk of bleeding during simultaneous use with dabigatran etexilate. Experience long-term use NSAIDs with a half-life of less than 12 hours are limited with dabigatran etexilate, there is no data on additional increase risk of bleeding.

Clopidogrel. It has been established that the simultaneous use of dabigatran etexilate and clopidogrel does not lead to an additional increase in time capillary bleeding compared with clopidogrel monotherapy. In addition, it was shown that the AUCt,ss and Cmax,ss values ​​of dabigatran, as well as the coagulation parameters that were monitored to evaluate the effect of dabigatran (aPTT, ecarin clotting time or thrombin time (anti F2a), as well as the degree of inhibition of platelet aggregation (main the effect index of clopidogrel) during combination therapy did not change compared with the corresponding indicators in monotherapy. When using a “loading” dose of clopidogrel (300 or 600 mg), the AUCt,ss and Cmax,ss values ​​of dabigatran increased by 30-40%.

Concomitant use with drugs that increase the pH of the gastric contents

The interaction of Pradaxa with alcohol remains unknown. Sharing is prohibited.

Pantoprazole. At joint use dabigatran etexilate and pantoprazole, a 30% decrease in dabigatran AUC was observed. Pantoprazole and other inhibitors proton pump co-administered with dabigatran etexilate in clinical studies, no effect on bleeding risk or efficacy was observed.

Ranitidine. Ranitidine, when used concomitantly with dabigatran etexilate, did not have a significant effect on the degree of absorption of dabigatran. Changes in the pharmacokinetic parameters of dabigatran under the influence of proton pump inhibitors and antacids turned out to be clinically insignificant, since the severity of these changes was small (the decrease in bioavailability was not significant for antacids, but for proton pump inhibitors it was 14.6%). It was found that the simultaneous use of proton pump inhibitors is not accompanied by a decrease in the concentration of dabigatran and, on average, only slightly reduces the concentration of the drug in the blood plasma (by 11%). Therefore, concomitant use of proton pump inhibitors does not appear to lead to an increase in the incidence of stroke or systemic thromboembolism, especially when compared with warfarin, and therefore the decrease in dabigatran bioavailability caused by simultaneous use pantoprazole is probably of no clinical significance.

Analogues of the drug Pradaxa

Structural analogues according to active substance the medicine Pradaxa does not have.

Analogues pharmacological group(anticoagulants):

• Angiox;
• Angioflux;
• Anfiber;
• Acenocoumarol;
• Warfarex;
• Warfarin;
• Venabos;
• Venolife;
• Viatromb;
• Hemapaxan;
• Gepalpan;
• Heparin;
• Heparin ointment;
• Heparoid;
• Hepatrombin;
• Dolobene;
• Ellon gel;
• Calciparin;
• Clexane;
• Klivarin;
• Xarelto;
• Lavenum;
• Lyoton 1000;
• Marewan;
• Nigepan;
• Pelentan;
• Piyawit;
• Seprotin;
• Sinkumar;
• Skinlight;
• Troxevasin Neo;
• Trombless;
• Trombless Plus;
• Thrombogel;
• Thrombophobe;
• Troparin;
• Phenilin;
• Fluxum;
• Fragmin;
• Fraxiparine;
• Fraxiparine Forte;
• Cibor;
• Exanta;
• Eliquis;
• Emeran;
• Enixum;
• Enoxaparin sodium;
• Essaven.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Anticoagulant. Direct thrombin inhibitor. Dabigatran etexilate is a low molecular weight, non-pharmacologically active precursor to the active form of dabigatran. After oral administration of dabigatran etexilate is rapidly absorbed into the gastrointestinal tract and, by hydrolysis catalyzed by esterases, is converted into dabigatran in the liver and blood plasma. Dabigatran is a potent competitive reversible direct thrombin inhibitor and the main active substance in blood plasma.

Because 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-induced platelet aggregation.

Experimental studies on various models of thrombosis in vivo and ex vivo confirmed the antithrombotic effect and anticoagulant activity of dabigatran after intravenous administration and dabigatran etexilate after oral administration.

A direct correlation has been established between the concentration of dabigatran in the blood plasma and the severity of the anticoagulant effect. Dabigatran prolongs the aPTT, ecarin clotting time (ECT) and thrombin time (TT).

The results of clinical studies in patients who underwent orthopedic surgery - knee and hip joint replacement - confirmed the preservation of hemostasis parameters and the equivalence of the use of 75 mg or 110 mg of dabigatran etexilate 1-4 hours after surgery and a subsequent maintenance dose of 150 mg or 220 mg 1 time / day for 6-10 days (for knee surgery) and 28-35 days (for hip surgery) compared with enoxaparin at a dose of 40 mg 1 time / day, which was used before and after surgery.

When used to prevent venous thromboembolism after major joint replacement, the antithrombotic effect of dabigatran etexilate at doses of 150 mg or 220 mg was shown to be equivalent to enoxaparin at a dose of 40 mg/day when assessing the primary endpoint, which included all cases of venous thromboembolism and mortality from any reasons.

When used for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation and with a moderate or high risk of stroke, it was shown that dabigatran etexilate at a dose of 110 mg 2 times / day was not inferior to warfarin in preventing stroke and systemic thromboembolism in patients with fibrillation atria; There was also a reduction in the risk of intracranial bleeding and the overall incidence of bleeding in the dabigatran group. Use of a higher dose of dabigatran etexilate (150 mg 2 times / day) significantly reduced the risk of ischemic and hemorrhagic strokes, cardiovascular death, intracranial bleeding and the overall incidence of bleeding, compared with warfarin. The lower dose of dabigatran was associated with a significantly lower risk of major bleeding compared with warfarin. The net clinical effect was assessed by determining a composite endpoint that included the incidence of stroke, systemic thromboembolism, pulmonary thromboembolism, acute myocardial infarction, cardiovascular mortality, and major bleeding. The annual incidence of these events in patients receiving dabigatran etexilate was lower than in patients receiving warfarin. Changes in laboratory tests of liver function in patients receiving dabigatran etexilate were observed with comparable or less frequency compared to patients receiving warfarin.

Pharmacokinetics

After oral administration of dabigatran etexilate, there is a rapid dose-dependent increase in its plasma concentration and AUC. Cmax of dabigatran etexilate is achieved within 0.5-2 hours.

After reaching Cmax, plasma concentrations of dabigatran decrease biexponentially, the final T1/2 averages about 11 hours (in elderly people). The final T1/2 after repeated use was about 12-14 hours. T1/2 does not depend on the dose. However, in case of renal dysfunction, T1/2 is prolonged.

Food intake does not affect the bioavailability of dabigatran etexilate, however, the time to reach Cmax increases by 2 hours.

When using dabigatran etexilate after 1-3 hours in patients after surgical treatment, a decrease in the rate of absorption is observed active substance compared to healthy volunteers. AUC is characterized by a gradual increase in amplitude without the appearance high values With max. Cmax in blood plasma is observed 6 hours after the use of dabigatran etexilate or 7-9 hours after surgery.

It should be noted that factors such as anesthesia, gastrointestinal tract palsy and surgery may play a role in delaying absorption, regardless of the dosage form. A decrease in the rate of absorption of dabigatran is usually observed only on the day of surgery. In the following days, absorption of dabigatran occurs rapidly, reaching C max 2 hours after oral administration.

V d of dabigatran is 60-70 l and exceeds the volume of total water content in the body, which indicates a moderate distribution of dabigatran in tissues.

After oral administration, during hydrolysis under the influence of esterase, dabigatran etexilate is quickly and completely converted into dabigatran, which is the main active metabolite in the blood plasma. When dabigatran is conjugated, 4 isomers of pharmacologically active acyl glucuronides are formed: 1-O, 2-O, 3-O, 4-O, each of which constitutes less than 10% of the total content of dabigatran in the blood plasma. Traces of other metabolites are only detected using highly sensitive analytical methods.

Dabigatran is excreted unchanged, mainly by the kidneys (85%), and only 6% through the gastrointestinal tract. It was found that 168 hours after administration of radiolabeled dabigatran etexilate, 88-94% of its dose is excreted from the body.

Dabigatran has a low binding ability to plasma proteins (34-35%), it does not depend on its concentration.

In elderly people, the AUC value is higher than in young people by 1.4-1.6 times (by 40-60%), and C max by more than 1.25 times (by 25%). The observed changes correlated with an age-related decrease in CC.

In elderly women (over 65 years old), the AUC t,ss and C max,ss values ​​were approximately 1/9 times and 1/6 times higher than in women young(18-40 years), and in older men - 2.2 and 2.0 times higher than in young men. A study in patients with atrial fibrillation confirmed the effect of age on dabigatran exposure: baseline concentrations of dabigatran in patients aged >75 years were approximately 1.3 times (31%) higher, and in patients aged<65 лет - примерно на 22% ниже, чем у пациентов возрасте 65-75 лет.

In volunteers with moderate renal impairment (creatinine clearance 30-50 ml/min), the AUC value of dabigatran after oral administration was approximately 3 times greater than in individuals with unchanged renal function.

In patients with severe renal impairment (creatinine clearance 10-30 ml/min), the AUC values ​​of dabigatran etexilate and T1/2 increased by 6 and 2 times, respectively, compared with similar indicators in individuals without impaired renal function.

In patients with atrial fibrillation and moderate renal failure (creatinine clearance 30-50 ml/min), dabigatran concentrations before and after drug use were on average 2.29 and 1.81 times higher than in patients without renal impairment.

When using hemodialysis in patients without atrial fibrillation, it was found that the amount of active substance excreted is proportional to the speed of blood flow. The duration of dialysis, with a dialysate flow rate of 700 ml/min, was 4 hours, and the blood flow rate was 200 ml/min or 350-390 ml/min. This resulted in the removal of 50% and 60% of free and total dabigatran concentrations, respectively. The anticoagulant activity of dabigatran decreased as plasma concentrations decreased, and the relationship between pharmacokinetics and pharmacological action did not change.

Release form

The capsules are oblong, opaque; size No. 0; with a cream-colored body with an overprint "R 150" and a light blue cap with a printed Boehringer Ingelheim symbol, the overprint color is black; the contents of the capsules are yellowish pellets.

Excipients: acacia gum - 8.86 mg, tartaric acid (coarse) - 44.28 mg, tartaric acid (powder) - 59.05 mg, tartaric acid (crystalline) - 73.81 mg, hypromellose - 4.46 mg, dimethicone - 0.08 mg, talc - 34.31 mg , hyprolose (hydroxypropylcellulose) - 34.59 mg.

Capsule shell composition: carrageenan (E407) - 0.285 mg, potassium chloride - 0.4 mg, titanium dioxide (E171) - 5.4 mg, indigo carmine (E132) - 0.054 mg, sunset yellow dye (E110) - 0.004 mg, hypromellose (hydroxypropyl methylcellulose) - 79.35 mg, purified water - 4.5 mg.
Composition of black Colorcon S-1-27797 ink: shellac 52.5%, butanol 6.55%, denatured ethanol (methylated alcohol) 0.65%, black iron oxide dye (E172) 33.77%, isopropanol 3.34%, propylene glycol 1.25%, purified water 1.94%.

10 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (3) - cardboard packs.
10 pieces. - blisters (6) - cardboard packs.
60 pcs. - polypropylene bottles (1) - cardboard packs.
10 pieces. - blisters (6) - cardboard packs (3) - polypropylene film (for hospitals).

Dosage

Depending on the indications, the daily dose is 110-300 mg. Frequency of administration - 1-2 times/day. The treatment regimen and duration of use depend on the indications and clinical situation.

If necessary, simultaneous use of dabigatran etexilate with active inhibitors of P-glycoprotein (amiodarone, quinidine, verapamil), as well as in patients aged 75 years and older, with moderate renal impairment (creatinine clearance 30-50 ml/min) or indication of gastrointestinal tract a history of intestinal bleeding requires adjustment of the dosage regimen.

The transition from the use of dabigatran to the parenteral use of anticoagulants and vice versa, as well as from the use of dabigatran etexilate to the use of vitamin K antagonists and vice versa, is carried out according to a special scheme, depending on the indications and clinical situation.

Interaction

Concomitant use with drugs that affect hemostasis or coagulation processes, including vitamin K antagonists, can significantly increase the risk of bleeding.

The substrate for the transport molecule P-glycoprotein is dabigatran etexilate. The simultaneous use of P-glycoprotein inhibitors (amiodarone, verapamil, quinidine, ketoconazole for systemic use or clarithromycin) leads to an increase in the concentration of dabigatran in the blood plasma.

With simultaneous use of dabigatran etexilate with a single dose of amiodarone (600 mg) taken orally, the degree and rate of absorption of amiodarone and its active metabolite, desethylamiodarone, did not change. The AUC and Cmax values ​​of dabigatran increased approximately 1.6 and 1.5 times (60% and 50%), respectively. In a study in patients with atrial fibrillation, dabigatran concentrations increased by no more than 14%, and no increased risk of bleeding was observed.

After simultaneous use of dabigatran etexilate and dronedarone at a dose of 400 mg once, the AUC 0-∞ and Cmax of dabigatran increased by 2.1 and 1.9 times (by 114% and 87%), respectively, and after repeated use of dronedarone at a dose of 400 mg/day - by 2.4 and 2.3 (by 136% and 125%), respectively. After single and multiple doses of dronedarone, 2 hours after administration of dabigatran etexilate, AUC 0-∞ increased by 1.3 and 1.6 times, respectively. Dronedarone did not affect the final half-life and renal clearance of dabigatran.

When dabigatran etexilate was co-administered with verapamil administered orally, the Cmax and AUC values ​​of dabigatran increased depending on the time of use and the dosage form of verapamil. The greatest increase in the effect of dabigatran was observed when using the first dose of verapamil in the immediate release dosage form, which was administered 1 hour before dosing with dabigatran etexilate (Cmax increased by 180% and AUC increased by 150%). When using the sustained release formulation of verapamil, this effect was progressively reduced (Cmax increased by 90% and AUC by 70%), as well as when using multiple doses of verapamil (Cmax increased by 60% and AUC by 50%) , which may be explained by the induction of P-glycoprotein in the gastrointestinal tract with long-term use of verapamil. When verapamil was used 2 hours after taking dabigatran etexilate, no clinically significant interaction was observed (C max increased by 10% and AUC by 20%), since dabigatran was completely absorbed after 2 hours. In a study in patients with atrial fibrillation, dabigatran concentrations increased by no more than 21%, and no increased risk of bleeding was observed. There are no data on the interaction of dabigatran etexilate with verapamil administered parenterally; no clinically significant interaction is expected.

Ketoconazole for systemic use after a single dose of 400 mg increases the AUC 0-∞ and Cmax of dabigatran by approximately 2.4 times (by 138% and 135%), respectively, and after repeated administration of ketoconazole at a dose of 400 mg/day - by approximately 2.5 times (by 153% and 149%), respectively. Ketoconazole did not affect Tmax and final T1/2. The combination of dabigatran etexilate and ketoconazole for systemic use is contraindicated.

With simultaneous use of clarithromycin at a dose of 500 mg 2 times / day with dabigatran etexilate, no clinically significant pharmacokinetic interaction was observed (C max increased by 15% and AUC by 19%).

The AUC t, ss and C max, ss values ​​of dabigatran when used 2 times a day in the case of simultaneous administration with quinidine at a dose of 200 mg every 2 hours until a total dose of 1000 mg were increased on average by 53% and 56%, respectively.

With simultaneous use of dabigatran etexilate with digoxin, which is a substrate of P-glycoprotein, no pharmacokinetic interaction was observed. Neither dabigatran nor the prodrug dabigatran etexilate are clinically significant P-gp inhibitors.

Concomitant use of dabigatran etexilate and P-gp inducers should be avoided as concomitant use will result in decreased exposure to dabigatran.

Pretreatment with the test inducer rifampicin at a dose of 600 mg/day for 7 days resulted in a decrease in exposure to dabigatran. After discontinuation of rifampicin, this inductive effect decreased; on day 7, the effect of dabigatran was close to the initial level. Over the next 7 days, no further increase in the bioavailability of dabigatran was observed.

It is assumed that other P-gp inducers, such as St. John's wort or carbamazepine, are also capable of reducing plasma concentrations of dabigatran; such combinations should be used with caution.

When studying the simultaneous use of dabigatran etexilate at a dose of 150 mg 2 times / day and acetylsalicylic acid in patients with atrial fibrillation, it was found that the risk of bleeding may increase from 12% to 18% (with a dose of acetylsalicylic acid 81 mg) and up to 24% (when using acetylsalicylic acid at a dose of 325 mg). It has been shown that acetylsalicylic acid or clopidogrel, used simultaneously with dabigatran etexilate at a dose of 110 mg or 150 mg 2 times a day, may increase the risk of major bleeding. Bleeding is also observed more often with the simultaneous use of warfarin with acetylsalicylic acid or clopidogrel.

NSAIDs used for short-term analgesia after surgery did not increase the risk of bleeding when used concomitantly with dabigatran etexilate. Experience with long-term use of NSAIDs, half-life of which is less than 12 hours, with dabigatran etexilate is limited, and there is no evidence of an additional increase in the risk of bleeding.

It was found that the simultaneous use of dabigatran etexilate and clopidogrel does not lead to an additional increase in capillary bleeding time compared to clopidogrel monotherapy. In addition, it was shown that the AUC t,ss and Cmax,ss values ​​of dabigatran, as well as the coagulation parameters that were monitored to evaluate the effect of dabigatran (aPTT, ecarin clotting time or thrombin time (anti-Flla), as well as the degree of inhibition of platelet aggregation (the main indicator of the effect of clopidogrel) during combination therapy did not change compared with the corresponding indicators in monotherapy. When using a “loading” dose of clopidogrel (300 or 600 mg), the AUC t, ss and C max, ss values ​​of dabigatran increased by 30-40 %.

When dabigatran etexilate and pantoprazole were co-administered, a 30% decrease in the AUC of dabigatran was observed. Pantoprazole and other proton pump inhibitors were used with dabigatran etexilate in clinical studies and no effect on bleeding risk or efficacy was observed.

Side effects

From the hematopoietic and lymphatic system: anemia, thrombocytopenia.

From the immune system: hypersensitivity reactions, including urticaria, rash and itching, bronchospasm.

From the nervous system: intracranial bleeding.

From the side of blood vessels: hematoma, bleeding, bleeding from the surgical wound.

From the respiratory system: nosebleeds, hemoptysis.

From the digestive system: gastrointestinal bleeding, rectal bleeding, hemorrhoidal bleeding, abdominal pain, diarrhea, dyspepsia, nausea, ulceration of the gastrointestinal mucosa, gastroesophagitis, gastroesophageal reflux disease, vomiting, dysphagia, increased activity of liver transaminases, impaired liver function, hyperbilirubinemia.

From the skin and subcutaneous tissues: cutaneous hemorrhagic syndrome.

From the musculoskeletal system: hemarthrosis.

From 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; hematoma after wound treatment, bleeding after wound treatment, anemia in the postoperative period, discharge from the wound after procedures, secretion from the wound; wound drainage, drainage after wound treatment.

Indications

Prevention of venous thromboembolism in patients after orthopedic surgery; prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation.

Contraindications

Severe renal failure (creatinine clearance less than 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 within the previous 6 months before the start of therapy; simultaneous administration of ketoconazole for systemic use; liver dysfunction and liver disease that may affect survival; children and adolescents up to 18 years of age; hypersensitivity to dabigatran or dabigatran etexilate.

Features of application

Use during pregnancy and breastfeeding

There are no data on the use of dabigatran etexilate during pregnancy. The potential risk in humans is unknown.

Experimental studies have not shown any adverse effects on fertility or postnatal development of newborns.

Women of reproductive age should use reliable methods of contraception in order to exclude the possibility of pregnancy while being treated with dabigatran etexilate. During pregnancy, the use of dabigatran etexilate is not recommended, unless the expected benefit of treatment outweighs the possible risk.

If it is necessary to use dabigatran etexilate during breastfeeding, due to the lack of clinical data, it is recommended to stop breastfeeding (as a precaution).

special instructions

Use with caution in conditions characterized by an increased risk of bleeding. During therapy with dabigatran etexilate, bleeding of various locations may develop. A decrease in the concentration of hemoglobin and/or hematocrit in the blood, accompanied by a decrease in blood pressure, is the basis for searching for the source of bleeding.

To detect excessive anticoagulant activity of dabigatran, tests to determine TV or EVS should be used. When these tests are not available, the APTT test should be used.

If acute renal failure develops, dabigatran etexilate should be discontinued.

The following factors may lead to an increase in the concentration of dagibatran in plasma: decreased renal function (creatinine clearance 30-50 ml/min), age ≥75 years, simultaneous use of a P-glycoprotein inhibitor. The presence of one or more of these factors may increase the risk of bleeding.

Concomitant use of dabigatran etexilate with the following drugs has not been studied, but may increase the risk of bleeding: unfractionated heparin (except for doses required to maintain the patency of a venous or arterial catheter) and heparin derivatives, low molecular weight heparins (LMWH), fondaparinux sodium, thrombolytic drugs, glycoprotein blockers GP IIb/IIIa platelet receptors, ticlopidine, dextran, rivaroxaban, ticagrelor, vitamin K antagonists and P-glycoprotein inhibitors (itraconazole, tacrolimus, cyclosporine, ritonavir, nelfinavir and saquinavir). The risk of bleeding is increased in patients taking selective serotonin reuptake inhibitors concomitantly. Also, the risk of bleeding may increase with the simultaneous use of antiplatelet agents and other anticoagulants.

Concomitant use of dronedarone and dabigatran is not recommended.

If the risk of bleeding increases (for example, with a recent biopsy or major trauma, bacterial endocarditis), monitoring the patient's condition is required in order to promptly detect signs of bleeding.

Concomitant use of dabigatran etexilate, antiplatelet agents (including acetylsalicylic acid and clopidogrel) and NSAIDs increases the risk of bleeding.

The use of fibrinolytic drugs should only be considered if the patient's TT, EVS, or APTT values ​​do not exceed the upper limit of the local reference range.

Patients receiving dabigatran etexilate have an increased risk of bleeding during surgery or invasive procedures. Therefore, during surgical interventions, dabigatran etexilate should be discontinued.

Before invasive procedures or surgical operations, dabigatran etexilate is discontinued at least 24 hours before the procedure. In patients with an increased risk of bleeding or undergoing major surgery requiring complete hemostasis, dabigatran etexilate should be discontinued 2-4 days before surgery. In patients with renal impairment, the clearance of dabigatran may be prolonged.

Dabigatran etexilate is contraindicated in patients with severe renal impairment (KR).<30 мл/мин), но если его все же применяют, отмену следует провести не менее чем за 5 дней до операции.

If emergency surgery is necessary, dabigatran etexilate should be temporarily discontinued. Surgical intervention, if possible, should be performed no earlier than 12 hours after the last dose. If surgery cannot be delayed, the risk of bleeding may increase. In this case, the risk of bleeding should be assessed against the need for emergency intervention.

Procedures such as spinal anesthesia may require complete restoration of hemostasis. 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 dabigatran should be taken no earlier than 2 hours after catheter removal. It is necessary to monitor the condition of patients to exclude neurological symptoms that may be caused by spinal bleeding or epidural hematoma.

Impact on the ability to drive vehicles and operate machinery

Given that the use of dabigatran etexilate may be associated with an increased risk of bleeding, caution should be exercised when performing such activities.

Pradaxa is a drug from the group of anticoagulants.

What is Pradaxa's composition and release form?

Pradaxa is produced in oblong capsules, they are opaque, the body is cream-colored with an overprint “R 75”, the cap is light bluish in color with the symbol of the manufacturing company Boehringer Ingelheim, printed in black ink, there are yellow pellets inside the dosage form. The active compound is 75 milligrams of dabigatran etexilate.

The capsules' excipients are as follows: acacia gum, coarse and crystalline tartaric acid, dimethicone, tartaric acid powder, hypromellose, talc, hydroxypropylcellulose.

Capsules identical to those presented above are produced, but with a different dosage of the active compound, which is reflected in the form of an overprint “R 110”, which indicates the amount of the active ingredient dabigatran etexilate in a dose of 110 milligrams.

There are capsules in size No. 0, overprinted “R 150”, which reflects the dosage of the active ingredient dabigatran etexilate, equal to 150 milligrams. The medicine is placed in aluminum blisters with perforations; in addition, polypropylene bottles with medicine are produced, containing 60 pieces.

Pradaxa should be stored away from moisture, in a tightly sealed bottle, which should be used within four months after opening the container with the medicine. Shelf life is three years. The drug is available with a prescription.

What does Pradaxa do?

The active compound of the drug, dabigatran etexilate, is quickly absorbed into the gastrointestinal tract, after which it is converted into dabigatran, which is a powerful reversible thrombin inhibitor.

Inhibition of thrombin activity prevents thrombus formation. Dabigatran inhibits free thrombin. The half-life is 11 hours. Protein binding reaches 35%. Absolute bioavailability is about 6.5 percent. It is excreted primarily by the kidneys.

What are Pradaxa's indications for use?

Pradaxa capsules instructions for use allow use for medicinal purposes in the following cases:

After orthopedic operations to prevent venous thromboembolism;
Prevention of stroke, in addition, systemic thromboembolism in patients with atrial fibrillation;
Prevention of diseases such as pulmonary embolism and recurrent venous thrombosis.

In addition, the pharmaceutical is prescribed as a treatment for acute venous thrombosis and thromboembolism.

What are Pradaxa's contraindications for use?

Pradaxa (capsules) instructions for use do not allow use for medicinal purposes in the following cases:

Hypersensitivity to the components of the drug;
Kidney failure;
With active bleeding, with hemorrhagic diathesis;
With a significant risk of major bleeding in the following situations: from recent ulceration of the gastrointestinal tract, in the presence of malignant tumors, recent damage to the spinal cord and brain, as well as intracranial hemorrhage;
You should not simultaneously use several different anticoagulants, including low molecular weight heparins, oral anticoagulants;
Severe liver diseases;
Up to 18 years old;
With a prosthetic heart valve.

Pradaxa is used with caution in the following situations: age over 75 years; weight less than 50 kg; simultaneously with taking NSAIDs; thrombocytopenia; bacterial endocarditis; suffered extensive trauma in the recent past; esophagitis, gastritis.

What is the use of Pradaxa? What is the dosage of Pradaxa?

Pradaxa capsules should be taken orally once or twice a day with a glass of water. To remove the capsule, it is recommended to carefully peel off the foil; you should not squeeze out the capsule, since disruption of the capsule shell may affect the bioavailability of the drug.

To prevent venous thromboembolism after orthopedic surgery, 220 mg of the drug is prescribed once a day. In patients with mild renal impairment, 150 mg of the drug should be used due to the risk of possible bleeding.

Prevention of stroke in patients with atrial fibrillation involves a daily dose of Pradaxa equal to 300 mg, in particular 150 mg twice a day. Therapy with this medicine should last for life.

Pradaxa - drug overdose

An overdose of Pradaxa can lead to hemorrhagic complications. In such a situation, the patient is indicated for urgent gastric lavage, as in case of poisoning, after which, if necessary, symptomatic treatment is carried out.

What are the side effects of Pradaxa?

The use of the pharmaceutical drug Pradaxa can provoke the following adverse reactions: allergies develop, this is especially typical with prolonged use of the medication, the appearance of hives, as well as rashes and itching of the skin, and bronchospasm is possible.

Other adverse reactions to taking the drug include the development of diarrhea, abdominal pain, thrombocytopenia, anemia, reflux esophagitis, hyperbilirubinemia, hematuria, urogenital bleeding, and cutaneous hemorrhagic syndrome.

special instructions

The use of Pradaxa, like other anticoagulants, should be used with caution in conditions that are characterized by an increased risk of bleeding. During treatment it is necessary to monitor anticoagulant activity.

How to replace Pradaxa, what analogues should I use?

Dabigatran etexilate.

Conclusion

Taking the pharmaceutical drug Pradaxa should be previously agreed with your doctor.

Registration Certificate Holder:
BOEHRINGER INGELHEIM INTERNATIONAL GmbH

Produced:
BOEHRINGER INGELHEIM PHARMA GmbH & Co. KG

ATX code for PRADAX

B01AE07 (Dabigatran etexilate)

You should consult your doctor before using PRADAXA. These instructions for use are for informational purposes only. For more complete information, please refer to the manufacturer's instructions.

Clinical and pharmacological group

20.026 (Anticoagulant. Direct inhibitor)

Release form, composition and packaging

The capsules are oblong, opaque, a cream-colored body with an overprint “R 75” and a light blue cap with a printed symbol of the Boehringer Ingelheim company, the overprint color is black; the contents of the capsules are yellowish pellets.

Excipients: acacia gum, crystalline tartaric acid, hypromellose, dimethicone, talc, hyprolose (hydroxypropylcellulose).

The capsules are oblong, opaque, a cream-colored body with an overprint “R 110” and a light blue cap with a printed symbol of the Boehringer Ingelheim company, the overprint color is black; the contents of the capsules are yellowish pellets.

Excipients: acacia gum, coarse tartaric acid, tartaric acid powder, crystalline tartaric acid, hypromellose, dimethicone, talc, hyprolose (hydroxypropylcellulose).

Composition of the capsule shell: carrageenan (E407), potassium chloride, titanium dioxide (E171), indigo carmine (E132), sunset yellow dye (E110), hypromellose (hydroxypropyl methylcellulose), purified water. Composition of black Colorcon S-1-27797 ink: shellac , butanol, denatured ethanol (methylated alcohol), black iron oxide dye (E172), isopropanol, propylene glycol, purified water.

10 pieces. - blisters (1) - cardboard packs. 10 pcs. - blisters (3) - cardboard packs. 10 pcs. - blisters (6) - cardboard packs. 60 pcs. - polypropylene bottles (1) - cardboard packs.

pharmachologic effect

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 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-mediated 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).

Pharmacokinetics

Suction

After taking the drug, the pharmacokinetic profile of dabigatran in the blood plasma of healthy volunteers is characterized by a rapid increase in plasma concentration with Cmax achieved within 0.5-2 hours.

After reaching Cmax, plasma concentrations of dabigatran decrease biexponentially, the final T1/2 averages about 14-17 hours in young people and 12-14 hours in elderly people. T1/2 does not depend on dose. Cmax and AUC vary proportionally to the dose. Food does not affect the bioavailability of dabigatran etexilate, but Tmax is delayed by 2 hours.

The absolute bioavailability of dabigatran is about 6.5%.

A study examining the absorption of dabigatran etexilate 1-3 hours after surgery demonstrated a slower absorption compared to healthy volunteers. A smooth increase in AUC without the appearance of Cmax in plasma was revealed. Cmax was observed at 6 hours after administration or at 7-9 hours after surgery. It should be noted that factors such as anesthesia, gastrointestinal paralysis and surgery may play a role in slowing absorption, regardless of the dosage form of the drug. Another study showed that slow absorption or delayed absorption is usually observed only on the day of surgery. In the following days, absorption of dabigatran occurs rapidly, reaching Cmax 2 hours after administration.

Distribution

A low ability (34-35%) of binding of dabigatran to human plasma proteins has been established, regardless of the concentration of the drug. The Vd of dabigatran is 60-70 L and exceeds the volume of total body water, indicating a moderate distribution of dabigatran in tissues.

Metabolism and excretion

After oral administration of dabigatran etexilate is quickly and completely converted to dabigatran, which is the active form in plasma. The main route of metabolism of dabigatran etexilate is hydrolysis catalyzed by esterases, which converts it to the active metabolite dabigatran.

When dabigatran is conjugated, 4 isomers of pharmacologically active acyl glucuronides are formed: 1-O, 2-O, 3-O, 4-O, each of which constitutes less than 10% of the total dabigatran content in plasma. Traces of other metabolites were detected only using highly sensitive analytical methods.

The metabolism and elimination of dabigatran were studied in healthy volunteers (men) after a single intravenous administration of radiolabeled dabigatran. The drug was excreted mainly through the kidneys (85%) unchanged. Excretion in feces was about 6% of the administered dose. Within 168 hours after administration of the drug, the removal of total radioactivity was 88-94% of the dose used.

Pharmacokinetics in special clinical situations

In volunteers with moderate renal impairment (creatinine clearance 30-50 ml/min), the AUC value of dabigatran after oral administration was 2.7 times greater than in subjects with normal renal function. In severe renal failure (creatinine clearance 10-30 ml/min), the AUC value of dabigatran and T1/2 increased by 6 and 2 times, respectively, compared with patients without renal failure.

Compared with young people, in elderly patients the AUC and Cmax values ​​increased by 40-60% and 25%, respectively. In population pharmacokinetic studies involving elderly patients up to 88 years of age, it was found that with repeated doses of dabigatran its content in the body increased. The observed changes correlated with an age-related decrease in creatinine clearance.

In 12 patients with moderate hepatic impairment (Child-Pugh class B), there were no changes in dabigatran levels compared to controls.

Population pharmacokinetic studies assessed pharmacokinetic parameters in patients weighing from 48 to 120 kg. Body weight had little effect on plasma clearance of dabigatran. Its content in the body was higher in patients with low body weight. In patients weighing more than 120 kg, there was a decrease in the effectiveness of the drug by approximately 20%, and with a body weight of 48 kg, an increase of approximately 25% compared to patients with average body weight.

In phase 3 clinical studies, there were no differences in the effectiveness and safety of Pradaxa® in men and women. In women, exposure to the drug was 40-50% higher than in men, but no dose adjustment was required.

A comparative study of the pharmacokinetics of dabigatran in Europeans and Japanese after a single and repeated dose of the drug in the studied ethnic groups did not reveal clinically significant changes. Pharmacokinetic studies have not been conducted in blacks.

PRADAXA: DOSAGE

The drug is prescribed orally.

For adults, for the prevention of venous thromboembolism (VT) in patients after orthopedic surgery, the recommended dose is 220 mg/day once (2 capsules of 110 mg).

In patients with moderate renal impairment, the risk of bleeding is increased; the recommended dose is 150 mg/day once (2 capsules of 75 mg).

To prevent VT after knee replacement, treatment should begin 1-4 hours after completion of the operation with a dose of 110 mg, followed by an increase in the dose to 220 mg/day once over 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.

To prevent VT after hip replacement, treatment should begin 1-4 hours after completion of the operation with a dose of 110 mg, followed by increasing the dose to 220 mg/day once over 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 disease that could affect survival, or with an increase of more than 2 times the ULN of liver enzymes were excluded from clinical studies. In this regard, the use of Pradaxa in this category of patients is not recommended.

After intravenous administration, 85% of dabigatran 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/day.

For men

Experience in elderly patients over 75 years of age is limited. The recommended dose is 150 mg/day once. When conducting pharmacokinetic studies in elderly patients who experience a decrease in kidney function with age, an increase in the content of the drug in the body was found. The dose of the drug should be calculated in the same way as for patients with impaired renal function.

The transition from treatment with dabigatran etexilate to parenteral administration of anticoagulants should be carried out 24 hours after the last dose of Pradaxa.

Switching from parenteral anticoagulants to Pradaxa: no data available, therefore it is not recommended to initiate therapy with Pradaxa before the scheduled administration of the next dose of parenteral anticoagulant.

Rules for using the drug

1. Remove the capsules from the blister, peeling off the foil.

2.Do not squeeze capsules through the foil.

3.Remove the foil so much that it is convenient to remove the capsules.

Capsules should be washed down with water and taken with meals or on an empty stomach.

Overdose

There is no antidote for dabigatran etexilate or dabigatran.

Using doses of the drug higher than recommended leads to an increased risk of bleeding. If bleeding develops, treatment should be suspended to determine the cause of the 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 by dialysis, but clinical experience with this method is lacking.

Drug interactions

Concomitant use 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 cytochrome P450 system and do not affect cytochrome P450 enzymes in humans in vitro. Therefore, when used together with Pradaxa, drug interactions are not expected.

When used together with atorvastatin, no interaction is observed.

When used together, the pharmacokinetics of diclofenac and dabigatran etexilate do not change, indicating little interaction. Short-term use of NSAIDs to reduce pain after surgery did not increase the risk of bleeding.

There is limited experience with the use of Pradaxa in combination with long-term systematic use of NSAIDs, and therefore careful monitoring of the patient's condition is required.

No pharmacokinetic interaction with digoxin has been identified.

In clinical studies, the combination or other proton pump inhibitors and Pradaxa did not influence the development of bleeding or pharmacological effects.

When used together with ranitidine, the extent of absorption of dabigatran does not change.

When Pradaxa and amiodarone are used together, the rate and degree of absorption of the latter and the formation of its active metabolite desethylamiodarone do not change. AUC and Cmax increase by 60% and 50%, respectively. When using dabigatran etexilate and amiodarone together, the dose of Pradaxa should be reduced to 150 mg/day. Due to the long half-life of amiodarone, potential drug interactions may persist for several weeks after discontinuation of amiodarone.

Caution should be exercised when using Pradaxa together with active P-glycoprotein inhibitors (verapamil, clarithromycin).

Repeated administration of verapamil over several days increased dabigatran concentrations by 50-60%. This effect may be reduced if dabigatran is administered at least 2 hours before verapamil.

Concomitant use of Pradaxa with quinidine is contraindicated.

Potential inducers such as rifampicin and St. John's wort extract may reduce the effect of dabigatran. Caution should be exercised when using dabigatran with similar drugs.

When dabigatran is used concomitantly with antacids and gastric secretagogues, no change in the dose of dabigatran is required.

There was no interaction of dabigatran with opioid analgesics, diuretics, paracetamol, NSAIDs (including COX-2 inhibitors), HMC-CoA reductase inhibitors, cholesterol/triglyceride lowering drugs (not related to statins), angiotensin II receptor blockers , ACE inhibitors, beta-blockers, calcium channel blockers, prokinetics, benzodiazepine derivatives.

Pregnancy and lactation

Reproductive toxicity has been demonstrated in experimental animal studies. There are no clinical data on the use of dabigatran etexilate during pregnancy. The potential risk to humans is unknown.

Women of reproductive age should avoid pregnancy while being treated with Pradaxa. During pregnancy, the use of dabigatran etexilate is not recommended, unless the expected benefit outweighs the possible risk.

If dabigatran etexilate is used, breastfeeding should be discontinued. There are no clinical data on the use of the drug during breastfeeding.

PRADAXA SIDE EFFECTS

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

Bleeding from any location is possible. Extensive bleeding is rare. The development of adverse reactions was similar to reactions in the case of sodium use.

From the hematopoietic system: anemia, thrombocytopenia.

From the blood coagulation system: hematoma, wound bleeding, nosebleeds, gastrointestinal bleeding, rectal bleeding, hemorrhoidal bleeding, cutaneous hemorrhagic syndrome, hemarthrosis, hematuria.

From the digestive system: liver dysfunction, increased activity of liver transaminases, hyperbilirubinemia.

From laboratory parameters: decrease in hemoglobin and hematocrit levels

Local reactions: bleeding from the injection site, bleeding from the catheter insertion site.

Complications associated with procedures and surgical interventions: bloody discharge from the wound, hematoma after procedures, bleeding after procedures, postoperative anemia, post-traumatic hematoma, bloody discharge after procedures, bleeding from the incision site, drainage after the procedure, wound drainage.

The frequency of observed adverse reactions when taking dabigatran etexilate did not exceed the frequency range of adverse reactions developing when using enoxaparin sodium.

Storage conditions and periods

The drug in bottles should be stored out of the reach of children, 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 must be used within 30 days.

The drug in blisters should be stored out of the reach of children, in a dry place, at a temperature not exceeding 25°C. Shelf life - 3 years.

Indications

• prevention of venous thromboembolism in patients after orthopedic surgery.

Contraindications

• severe renal failure (creatinine clearance less than 30 ml/min);
• hemorrhagic disorders,
• hemorrhagic diathesis,
• spontaneous or pharmacologically induced disturbance of hemostasis;
• active clinically significant bleeding;
• liver dysfunction and liver diseases,
• which may affect survival;
• simultaneous use of quinidine;
• organ damage as a result of clinically significant bleeding,
• including hemorrhagic stroke within the previous 6 months before starting therapy;
• age less than 18 years;
• known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.

special instructions

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

Unfractionated heparins or their derivatives, low molecular weight heparins, fondaparinux sodium, desirudin, thrombolytic agents, GPIIb/IIIa receptor antagonists, clopidogrel, ticlopidine, dextran, sulfinpyrazone and vitamin K antagonists should not be co-administered with Pradaxa®.

The combined use of Pradaxa in doses recommended for the treatment of deep vein thrombosis and acetylsalicylic acid in doses of 75-320 mg increases the risk of bleeding. There are no data demonstrating an increased risk of bleeding associated with dabigatran when taking Pradaxa at the recommended dose in patients receiving low doses of acetylsalicylic acid for the prevention of cardiovascular disease. However, the available information is limited, therefore, when using low-dose acetylsalicylic acid and Pradaxa together, it is necessary to monitor the condition of patients in order to timely diagnose bleeding.

Careful monitoring (for symptoms of bleeding or anemia) should be carried out in cases in which there may be an increased risk of developing hemorrhagic complications:

• recent biopsy or trauma;
• use of drugs,
• increasing the risk of developing hemorrhagic complications;
• combination of Pradaxa with drugs,
• that affect hemostasis or coagulation processes;
• bacterial endocarditis.

Prescription of NSAIDs for a short time when combined with Pradaxa with an analgesic chain after surgery does not increase the risk of bleeding. There is limited data regarding the systematic use of NSAIDs with T1/2 less than 12 hours in combination with Pradaxa, there is no evidence of an increased risk of bleeding.

Pharmacokinetic studies have shown that in patients with decreased renal function, incl. associated with age, there was an increase in the effectiveness of the drug. In patients with moderately reduced renal function (creatinine clearance 30-50 ml/min), it is recommended to reduce the daily dose to 150 mg/day. Pradaxa is contraindicated in patients with severe renal impairment (CK

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 removal of the catheter. Such patients should be monitored for possible detection of neurological symptoms.

Impact on the ability to drive vehicles and operate machinery

The effect of dabigatran etexilate on the ability to drive vehicles and operate machinery has not been studied.

Use for renal impairment

After intravenous administration, 85% of dabigatran 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/day.

Creatinine clearance is determined using the Cockroft formula:

For men

CC (ml/min)=(140-age) X body weight (kg)/72 x serum creatinine (mg/dl)

For women 0.85 x CC values ​​for men.

There is no data on the use of the drug in patients with severe renal impairment (creatinine clearance less than 30 ml/min). The use of Pradaxa® in this category of patients is not recommended.

Dabigatran is eliminated by dialysis. No clinical studies have been conducted in such patients.

Use for liver dysfunction

Patients with severe liver dysfunction (Child-Pugh class B and C) or liver disease that could affect survival, or with an increase of more than 2 times the ULN of liver enzymes were excluded from clinical studies. In this regard, the use of Pradaxa in these patients is not recommended.

In this medical article you can familiarize yourself with the drug Pradaxa. The instructions for use will explain in what cases the tablets can be taken, what the medicine helps with, what are the indications for use, contraindications and side effects. The annotation presents the forms of release of the drug and its composition.

In the article, doctors and consumers can only leave real reviews about Pradaxa, from which one can find out whether the medicine has helped in the treatment of thrombosis, embolism and stroke prevention in adults and children, for which it is also prescribed. The instructions list analogues of Pradaxa, prices of the drug in pharmacies, as well as its use during pregnancy.

A medicine with antithrombotic and anticoagulant effects is Pradaxa. The instructions for use indicate that capsules or tablets of 75 mg, 110 mg and 150 mg are prescribed in traumatology and orthopedics for the purpose of preventing venous thromboembolism after surgery.

Release form and composition

Pradaxa is available in capsule dosage form for oral administration. They have an oblong shape, a relatively soft consistency, and a cream-colored shell. The capsule contains small yellow pellets. The main active ingredient of the drug is dabigatran etexilate.

Several dosages of Pradaxa capsules are available containing the main component 75 mg (the capsule is engraved R75), 110 mg (engraved R110) and 150 mg (engraved R150). The capsule also contains auxiliary components.

Pradaxa capsules are packaged in foil blisters of 10 pieces or in a polyethylene bottle of 60 pieces. One package may contain 1, 3 or 6 blisters, as well as 1 polyethylene bottle with capsules. It must contain instructions for using the drug.

pharmachologic effect

The effect of the drug is manifested in the suppression of thrombin activity. Dabigatran etexilate is a low molecular weight substance that does not have any pharmacological activity. Only after ingestion and absorption it turns into dabigatran. Dabigatra is an active, competitive, reversible direct thrombin inhibitor.

The substance not only effectively inhibits the activity of thrombin, which binds fibrin, but also free thrombin. It inhibits platelet aggregation, which is caused by thrombin. With high body weight, over 120 kg, the effectiveness of the drug is reduced by 20%, and with low body weight, less than 48 kg, it increases by 20%.

Indications for use

What does Pradaxa help with? Tablets are prescribed for prevention:

• stroke;
• venous and systemic thromboembolism.

Also indicated for use is atrial fibrillation (to reduce the mortality rate after fibrillation).

Instructions for use

Pradaxa capsules, depending on the indications, are prescribed in a daily dose of 110-300 mg. The frequency of administration is 1-2 times a day. The treatment regimen and duration of use depend on the indications and clinical situation.

Use in patients at increased risk of bleeding

The presence of factors such as age 75 years or older, moderate reduction in renal function (creatinine clearance 30-50 ml/min), concomitant use of P-glycoprotein inhibitors, or a history of gastrointestinal bleeding may increase the risk of bleeding. In patients with one or more of these risk factors, at the discretion of the physician, the daily dose of Pradaxa may be reduced to 220 mg (take 1 capsule 110 mg 2 times a day).

Transition from the use of Pradaxa to parenteral use of anticoagulants

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation: parenteral anticoagulants should be started 12 hours after the last dose of Pradaxa.

Prevention of venous thromboembolism in patients after orthopedic surgery: parenteral administration of anticoagulants should begin 24 hours after taking the last dose of Pradaxa.

Transition from parenteral anticoagulants to Pradaxa

The first dose of Pradaxa is prescribed instead of the discontinued anticoagulant in the interval 0-2 hours before the next injection of alternative therapy or simultaneously with the cessation of a continuous infusion (for example, intravenous use of unfractionated heparin (UFH)).

Switching from vitamin K antagonists to Pradaxa

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

The use of vitamin K antagonists is discontinued; the use of Pradaxa is possible with MHO less than 2.0.

Switching from Pradaxa to Vitamin K Antagonists

With a CC of more than 50 ml/min, the use of vitamin K antagonists is possible 3 days, and with a CC of 30-50 ml/min - 2 days before discontinuation of the Pradaxa drug.

Cardioversion

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

Planned or emergency cardioversion does not require discontinuation of Pradaxa therapy.

Missed dose

Prevention of recurrent DVT and/or PE and deaths caused by these diseases: a missed dose of Pradaxa can be taken if 6 hours or more remain before the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Prevention of venous thromboembolism in patients after orthopedic surgery: It is recommended to take the usual daily dose of Pradaxa at the usual time the next day. If you miss individual doses, you should not take a double dose of the drug.

Treatment of acute DVT and/or PE and prevention of deaths caused by these diseases: a missed dose of Pradaxa can be taken if 6 hours or more remain before the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation

A missed dose of Pradaxa can be taken if there are 6 hours or more left before taking the next dose of the drug; If the period is less than 6 hours, the missed dose should not be taken. If you miss individual doses, you should not take a double dose of the drug.

Contraindications

According to the instructions, Pradaxa and drug analogues should not be taken if:

• active clinically significant bleeding, pharmacologically induced or spontaneous disruption of homeostasis;
• varicose veins of the esophagus;
• liver dysfunction;
• history of intracranial hemorrhage;
• history of spinal injuries or brain injuries;
• intracerebral or intraspinal vascular disorders;
• gastrointestinal ulcer;
• severe renal failure;
• known hypersensitivity to any of the components of the product;
• malignant neoplasms.

The simultaneous use of Pradaxa and antiplatelet agents increases the risk of bleeding three times. The use of this medication in combination with other anticoagulants is contraindicated. There are no clinical data on the effects of taking this medication in patients under 18 years of age.

Side effects

Many reviews of Pradaxa claim that long-term use of the drug for preventive purposes can cause: urticaria, rash, itching, bronchospasm, diarrhea, abdominal pain, dyspepsia.

In some cases, while taking this drug, thrombocytopenia, anemia, gastroesophageal reflux disease, gastroesophagitis, hyperbilirubinemia, hematuria, urogenital bleeding, and cutaneous hemorrhagic syndrome may develop.

Children, pregnancy and breastfeeding

Use during pregnancy is contraindicated. If it is necessary to use during lactation, due to the lack of clinical data, it is recommended to stop breastfeeding (as a precaution).

In childhood

For people under 18 years of age, the effectiveness and safety of Pradaxa have not been studied, so treatment with the drug in childhood is not recommended.

special instructions

The drug is prescribed by the doctor individually for each patient in accordance with medical indications. He always pays attention to the specific instructions for using Pradaxa capsules, which include:

• For elderly patients, in most cases the dosage of the drug must be reduced.
• If you are using medications other than anticoagulants, it is important to notify your doctor about this.
• Before starting to use Pradaxa capsules, a study of the functional activity of the liver and kidneys is required.
• There is no reliable data on the negative effect of the drug on the fetus during pregnancy, however, it is prescribed to pregnant and breastfeeding women only for strict medical reasons.
• The drug is not prescribed to children and adolescents under 18 years of age, as there is no reliable data regarding its safety.
• Concomitant use with other direct or indirect anticoagulants significantly increases the risk of bleeding.

Drug interactions

Acetylsalicylic acid, in combination with Pradaxa, can significantly increase the risk of bleeding.

Do not combine with drugs that affect hemostasis, vitamin K antagonists, P-glycoprotein inhibitors (verapamil, ketoconazole, clarithromycin, amiodarone, quinidine). Use with caution in combination with dronedarone, St. John's wort, carbamazepine and Pantoprazole.

Analogues of the drug Pradaxa

The group of anticoagulants includes:

1. Thrombophobe.
2. Angiox.
3. Heparin.
4. Fraxiparine Forte.
5. Trombless.
6. Heparoid.
7. Calciparin.
8. Fenilin.
9. Skinlight.
10. Viatromb.
11. Klivarin.
12. Eliquis.
13. Troparin.
14. Exanta.
15. Acenocoumarol.
16. Hemapaxan.
17. Fluxum.
18. Enoxaparin sodium.
19. Lyoton 1000.
20. Enixum.
21. Venabos.
22. Troxevasin Neo.
23. Leeching.
24. Warfarex.
25. Emeran.
26. Clexane.
27. Ellon gel.
28. Venolife.
29. Trombless Plus.
30. Sinkumar.
31. Pelentan.
32. Thrombogel.
33. Fraxiparine.
34. Essaven.
35. Seprotin.
36. Hepatrombin.
37. Anfiber.
38. Fragmin.
39. Marevan.
40. Gepalpan.
41. Angioflux.
42. Nigepan.
43. Tsibor.
44. Warfarin.
45. Lavenum.

Vacation conditions and price

The average cost of Pradaxa (75 mg tablets No. 30) in Moscow is 1980 rubles. In the pharmacy chain, capsules are sold only with a doctor's prescription. It is not recommended to use them independently or on the advice of a non-specialist.

After opening the bottle of capsules, they should be used within 4 months. The shelf life of the medicine is 3 years. The instructions for use for Pradaxa capsules require that they be stored in the original original packaging, protected from light and humidity, and out of the reach of children, at an air temperature not exceeding +25° C.