Pradaxa: instructions for use

Compound

Each capsule contains 86.48 mg or 126.83 mg of dabigatran etexilate mesylate, corresponding to 75 mg or 110 mg of dabigatran etexilate.

Excipients:

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

Composition of the capsule shell: hypromellose capsule overprinted with black ink Colorcon S-1-27797. The capsule consists of: 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, industrial methylated alcohol, butanol, isopropanol, black iron oxide dye (E172), purified water, propyl englycol.

Description

Capsules 75 mg

Oblong capsules of hypromellose (hydroxypropyl methylcellulose). The lid is opaque, light blue, the body is almost white with a yellowish-pink tint. The Boehringer Ingelheim company symbol is printed on the lid and “R 75” on the body. Overprint color is black.

Capsules 110 mg

Oblong capsules of hypromellose (hydroxypropyl methylcellulose). The lid is opaque light blue, the body is almost white with a yellowish-pink tint. The Boehringer Ingelheim company symbol is printed on the lid and “R 110” on the body. Overprint color is black.

The contents of the capsules of both dosages are yellowish pellets.

pharmachologic effect

Dabigatran etexilate is a low molecular weight prodrug that has no pharmacological activity.

Because coagulation fibrin6gen in thrombin activity prevents thrombus formation. Dabigatran inhibits free thrombin, fibrin-binding thrombin, and thrombin-induced platelet aggregation.

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

A close correlation was revealed between the concentration of dabigatran in the blood plasma and the severity of the anticoagulant effect. Dabigatran prolongs APTT, EVS and TV. Clinical confirmation of the effectiveness of dabigatran etexilate was obtained in the RE-LY study (Randomized Evaluation of Long-Term Anticoagulant Therapy), a multicenter, multinational, randomized parallel groups A study of two doses of dabigatran etexilate (110 mg twice daily and 150 mg twice daily) compared with warfarin in patients with atrial fibrillation and a moderate to high risk of stroke or systemic embolism.

The RE-LY study included 18,113 patients. average age was 71.5 years. Participants were 64% male, 70% Caucasian and 16% Asian. Average duration Treatment with dabigatran etexilate in RE-LY was 20 months. Dabigatran etexilate was prescribed as a fixed dose without monitoring coagulation.

This study demonstrated that dabigatran etexilate 110 mg twice daily is noninferior to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation, with a risk of intracranial bleeding and general bleeding With bottom compared to warfarin. More high dose 150 mg twice daily significantly reduces the risk of ischemic and hemorrhagic stroke, death from cardiovascular diseases, intracranial bleeding and general bleeding in comparison with warfarin. ;

IN clinical trial Phase II, which included a total of 252 patients, studied the use of dabigatran etexilate and warfarin in patients who had recently undergone surgery to replace a heart valve with a mechanical one (hospitalized after surgery), and in patients who had undergone similar surgery for more than three months back. In the group of patients taking dabigatran etexilate, there was a greater number of cases of thromboembolic complications (mainly strokes and thrombosis of the artificial heart valve, accompanied and unaccompanied clinical symptoms) and bleeding compared with the group of patients taking warfarin. In recently operated patients, major bleeding mainly manifested as postoperative hemorrhagic pericardial effusion, especially in those patients who underwent replacement surgery. heart valve started taking dabigatran etexilate early (i.e. on the 3rd day) after prosthetics.

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 of the drug was about 12-14 hours. T1/2 does not depend on the dose. However, in case of impaired renal function, T1/2 is prolonged.

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, however, the time to reach Cmax increases by 2 hours.

When using dabigatran etexilate without a special capsule shell made of hypromellose, oral bioavailability can increase by approximately 1.8 times (75%) compared to the capsule dosage form. Therefore, the integrity of capsules made from hypromellose should be maintained, given the risk of increasing the bioavailability of dabigatran etexilate, and it is not recommended to open capsules and use their contents in pure form(for example, added to food or drinks).

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. AUC is characterized by a gradual increase in amplitude without the appearance of a high peak in plasma concentration. 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 paresis and surgery may have a role in slowing absorption, regardless of dosage form drug. A decrease in the rate of absorption of the drug is usually observed only on the day of surgery. In the following days, absorption of dabigatran occurs rapidly, reaching Cmax 2 hours after oral administration.

Distribution

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

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.

Removal

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 the concentration of the drug.

Pharmacokinetics special groups patients

Elderly patients

In elderly people, the AUC value is higher than in young people by 1.4-1.6 times (by 40-60%), and Cmax 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 values ​​of AUCt,ss and Cmax,ss 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.

Renal dysfunction

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 severely impaired renal function (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 drug 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.

Liver dysfunction

In patients with moderate hepatic impairment (Child-Pugh score 7-9) there were no changes in plasma dabigatran concentrations compared to patients without hepatic impairment.

Body mass

In studies, basal dabigatran concentrations in patients weighing >100 kg were approximately 20% lower than in patients weighing 50–100 kg. Body weight in the majority (80.8%) of patients was ≥50-<100 кг, в пределах этого диапазона явных различий концентраций дабигатрана не установлено. Данные в отношении пациентов с массой тела ≤50 кг ограничены.

In the main studies on the prevention of VTE, it was found that the effect of the drug in female patients was approximately 1.4-1.5 times (40-50%) higher. In patients with atrial fibrillation, basal concentrations and concentrations after drug use were on average 1.3 (30%) higher. The differences found were not clinically significant.

Ethnic groups

In 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, no clinically significant differences were identified. Pharmacokinetic studies in black patients are limited, but available data indicate no significant differences.

Indications for use

Primary prevention of venous thromboembolism in adult patients after total arthroplasty surgery hip joint or total endoprosthetics knee joint.

PRADAXA capsules 110 mg:

Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more of the following risk factors:

Previous stroke, transient ischemic attack, or systemic embolism

Left ventricular ejection fraction<40%

Symptomatic heart failure, > New York Heart Association (NYHA) class 2

Age >75 years

Age > 65 years in combination with one of following states: diabetes, ischemic disease heart or hypertension.

Contraindications

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;

Age under 18 years (no clinical data);

Known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.

Pregnancy and lactation

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).

Directions for use and doses

Capsules should be taken orally, 1 or 2 times a day, regardless of meal time, with water. The capsule should not be opened.

Use in adults

For the prevention of venous thromboembolism (VTE) in patients after orthopedic surgery, the recommended dose is 220 mg 1 time / day (2 capsules of 110 mg).

In patients with moderate renal impairment due to the risk of bleeding, the recommended dose is 150 mg 1 time / day (2 capsules of 75 mg).

To prevent VTE after knee replacement, the use of Pradaxa should be started 1-4 hours after completion of the operation with 1 capsule. (110 mg) followed by increasing the dose to 2 caps. (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 begin with 2 caps. (220 mg)/day once.

Prevention of VTE after hip replacement, the use of Pradaxa should begin 1-4 hours after completion of the operation with a dose of 1 caps. (110 mg) followed by increasing the dose to 2 caps. (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 begin with 2 caps. (220 mg)/day once.

To prevent stroke, systemic thromboembolism and reduce cardiovascular mortality in patients with atrial fibrillation, it is recommended to use Pradaxa in a daily dose of 300 mg (1 capsule of 150 mg 2 times a day). Therapy should continue for life.

Use in children

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

Use in patients with impaired renal function

Before therapy, in order to avoid prescribing the drug to patients with severely impaired renal function (creatinine clearance less than 30 ml/min), it is necessary to first evaluate the plasmatic clearance. Due to the lack of data on the use of the drug in patients with severely impaired renal function (creatinine clearance less than 30 ml/min), the use of Pradaxa is not recommended.

Dabigatran is eliminated by hemodialysis; however clinical experience use in patients undergoing hemodialysis is limited.

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.

Prevention of venous thromboembolism after orthopedic surgery in elderly patients (over 75 years of age): experience is limited. The recommended dose is 150 mg (2 capsules of 75 mg once).

When using Pradaxa in elderly patients over 80 years of age to prevent stroke, systemic thromboembolism and reduce cardiovascular mortality in patients with atrial fibrillation, Pradaxa should be taken in a daily dose of 220 mg (1 capsule of 110 mg 2 times a day).

Effect of body weight

No dose adjustment is required depending on body weight.

Concomitant use of Pradaxa with active P-glycoprotein inhibitors (amiodarone, quinidine, verapamil) for the prevention of venous thromboembolism in patients after orthopedic surgery:

When used simultaneously with amiodarone, quinidine or verapamil, the dose of Pradaxa should be reduced to 150 mg 1 time / day (2 capsules of 75 mg). Patients taking Pradaxa after orthopedic surgery are not recommended to simultaneously start using verapamil and connect it to therapy in the future.

Use in patients with increased risk bleeding

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

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, it is possible to reduce daily dose Pradaxa drug up 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 Pradaxan is prescribed instead of a discontinued anticoagulant in the interval 0-2 hours before the next injection alternative therapy or simultaneously with discontinuation of a continuous infusion (eg, IV 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<2.0.

Switching from Pradaxa to Vitamin K Antagonists

With creatinine clearance ≥50 ml/min, the use of vitamin K antagonists is possible 3 days, and with creatinine clearance 30-50 ml/min - 2 days before discontinuation of Pradaxa.

Cardioversion

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

Missed dose

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.

Side effect

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.

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.

Additional specific side effects identified during the prevention of venous thromboembolism in patients undergoing orthopedic surgery:

Vascular disorders: bleeding from the surgical wound.

General disorders and disorders at the injection site: spotting.

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

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

Overdose

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

If bleeding occurs, stop using the drug. Symptomatic treatment is indicated. There is no specific antidote.

Treatment

Given the main route of elimination of dabigatran (renal), it is recommended to ensure adequate diuresis. Surgical hemostasis and blood volume replenishment are performed. It is possible to use fresh whole blood or transfuse fresh frozen plasma. Because dabigatran has low plasma protein binding, the drug can be eliminated by hemodialysis, but clinical experience with the use of dialysis in these situations is limited.

In case of an overdose of Pradaxa, it is possible to use concentrates of activated prothrombin complex or recombinant factor VIIa or concentrates of coagulation factors II, IX or X. There is experimental evidence to support the effectiveness of these agents in counteracting the anticoagulant effect of dabigatran, but no specific clinical studies have been conducted.

In the event of thrombocytopenia, or when using long-acting antiplatelet agents, the use of platelet mass may be considered.

Interaction with other drugs

Pharmacokinetic interactions

In vitro studies have not established an inducing or inhibitory effect of dabigatran on cytochrome P450. In in vivo 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.

Dronedarone. After simultaneous use of dabigatran etexilate and dronedarone at a single dose of 400 mg, the AUC0-∞ 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 1.9 times. 2.3 (by 136% and 125%), respectively. After single and multiple doses of dronedarone, 2 hours after administration of dabigatran etexilate, AUC0-∞ increased by 1.3 and 1.6 times, respectively. Dronedarone did not affect the final T1/2 and renal clearance of dabigatran.

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 interactions were 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 AUC0-∞ 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 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 / 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 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 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/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 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 / 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 when used simultaneously with dabigatran etexilate. Experience with long-term use of NSAIDs with a half-life of less than 12 hours with dabigatran etexilate is limited, and there is no evidence of an additional increase in the risk of bleeding.

Clopidogrel. 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 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-Flla), 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

Pantoprazole. 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.

Ranitidine. Ranitidine, when used concomitantly with dabigatran etexilate, did not have a significant effect on the degree of absorption of dabigatran. The changes in the pharmacokinetic parameters of dabigatran identified during the population analysis under the influence of proton pump inhibitors and antacid drugs 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 concomitant use of pantoprazole is probably not clinically significant.

Features of application

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 cases of severe renal impairment (KR<30 мл/мин).

If acute renal failure develops, Pradaxa 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 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 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.

Prevention of venous thromboembolism in patients after orthopedic surgery

It has been established that the use of NSAIDs for short-term anesthesia during surgery simultaneously with Pradaxa is not accompanied by 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 should only be considered if the patient's TT, EVS, or APTT values ​​do not exceed the upper limit of the local reference range.

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

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

This should be taken into account before any procedures are carried out.

Pradaxa is contraindicated in patients with severe renal impairment (CR<30 мл/мин), но если препарат все же применяют, отменять его следует не менее чем за 5 дней до операции.

If emergency surgery is necessary, Pradaxa should be temporarily discontinued. Surgical intervention, if possible, should be performed no earlier than 12 hours after the last dose of Pradaxa. If surgery cannot be delayed, the risk of bleeding may be increased (for cardioversion, see Dosage and Administration). In this case, the risk of bleeding should be assessed against the need for emergency intervention.

Spinal anesthesia/epidural anesthesia/lumbar puncture

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 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 that 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 engage in other potentially hazardous activities that require increased concentration and psychomotor speed has 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.

Use for renal impairment

Before therapy, in order to avoid prescribing the drug to patients with severely impaired renal function (creatinine clearance less than 30 ml/min), it is necessary to first evaluate the plasmatic clearance. Due to the lack of data on the use of the drug in patients with severely impaired renal function (creatinine clearance less than 30 ml/min), the use of Pradaxa is not recommended.

Renal function should be assessed during treatment when there is a suspicion of a possible decrease or deterioration in renal function (for example, with hypovolemia, dehydration, simultaneous use of certain medications, etc.).

When using Pradaxa for the prevention of venous thromboembolism in patients after orthopedic surgery with moderate renal dysfunction (creatinine clearance 30-50 ml/min), the daily dose of the drug should be reduced to 150 mg (2 capsules of 75 mg 1 time/day).

When using Pradaxa for the purpose of preventing stroke, systemic thromboembolism and reducing cardiovascular mortality in patients with atrial fibrillation with moderate renal impairment (creatinine clearance 30-50 ml/min), no dose adjustment is required. It is recommended to use the drug in a daily dose of 300 mg (1 capsule 150 mg 2 times a day). Renal function should be assessed at least once a year.

Dabigatran is eliminated by hemodialysis; however, clinical experience in patients undergoing hemodialysis is limited.

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.

Clexane

Self-medication can be harmful to your health.
You should consult your doctor and read the instructions before use.

When a loved one gets sick, you want to do everything to help him. Including finding a miracle remedy that can cure him in an instant. Unfortunately, such tablets have not yet been invented, and one has to be content with a fairly extensive arsenal of conventional medicines created to date. Many substances seem to be on the verge, when their beneficial effects can turn into mortal danger. These drugs also include the pharmacological group of anticoagulants, which, while preventing the formation of blood clots, at some point contribute to the occurrence of spontaneous bleeding, which, depending on the location, can be fatal. Such are the drugs Pradaxa and Warfarin, the side effects of which can manifest as hemorrhagic disorders.

Pharmacological group of the drug "Pradaxa"

This drug belongs to the group of anticoagulants. Its active substance, dabigatran etexilate, is a low-molecular, pharmacologically inactive precursor of dabigatran, a competitive, reversible direct thrombin inhibitor that manifests its effect primarily in blood plasma. Inhibition of thrombin activity prevents the process of thrombus formation. In addition to the direct effect on the factor, the active substance of the drug "Pradaxa", reviews of doctors about the action of which characterize it as a modern and effective drug, affects both fibrin clots and platelet aggregation.

Indications for use

This pharmacological group of drugs, which affects the body in the most serious way, requires very careful handling and strict adherence to the dosage. Only a doctor can prescribe such a remedy. This anticoagulant is used to prevent the occurrence of venous thromboembolism in patients with a history of any orthopedic surgery, as well as to prevent the development of stroke, systemic thromboembolism, and to reduce the rate of cardiovascular mortality in people suffering from atrial fibrillation. Patients who have experience using the drug Pradaxa leave mostly positive reviews, since its use involves a much smaller number of side effects compared to older generation drugs.

Contraindications for use

As already mentioned, drugs from this group have a serious effect on the body, so they are prescribed only for very strict indications.

Pradaxa tablets are not used for:

Hypersensitivity to substances such as dabigatran, abigatran etexilate or to the auxiliary components included in the composition;

Severe renal failure (creatinine clearance less than 30 ml/min);

Intense clinically significant bleeding, spontaneous or pharmacologically induced disruption of hemostasis;

Organ damage as a result of significant bleeding, including hemorrhagic stroke within 6 months before the start of treatment;

Simultaneous administration of "Ketoconazole" for systemic use;

Liver dysfunction or disease affecting survival;

The patient is under 18 years of age (since there are no clinical trial data).

Despite the significant list of contraindications for the drug Pradaxa, reviews from doctors still characterize it as safer compared to some of its analogues.

Directions for use and dosage

This medicine, produced by Boehringer Ingelheim in Austria and Germany, is available in the form of capsules containing the active substance 75 mg, 110 mg and 150 mg. Capsules are taken orally, without opening, regardless of meals. Frequency of administration - up to 2 times a day.

For the prevention of venous thromboembolism in those who have undergone orthopedic surgery, Pradaxa 110 mg is prescribed as a single dose of two capsules. Patients after knee replacement are recommended to start taking the medication no later than 4 hours after the end of the operation. The course of treatment is 10 days. When undergoing hip replacement, taking the drug should be continued for up to 28-35 days.

To prevent ischemic stroke in patients with non-valvular atrial fibrillation, a dosage of 150 mg 2 times a day of the drug Pradaxa is prescribed, reviews of the use of which indicate a good percentage of prevented pathological conditions.

Anticoagulants, by preventing the formation of blood clots, cause a decrease in blood clotting, which causes a general manifestation of undesirable effects. Thrombocytopenia and anemia may occur in the lymphatic and circulatory systems. Disturbances in the immune system can manifest as hypersensitivity reactions (urticaria, itching, rash, bronchospasm). Increased vascular permeability can cause hematomas and bleeding of various locations, including intracranial, nasal, gastrointestinal and others. The digestive organs may cause pain, dyspepsia, vomiting, dysphagia, gastroesophagitis, liver dysfunction and other abnormalities in the gastrointestinal tract. On the part of the skin, skin manifestations can be observed, and damage to connective and bone tissue can manifest as hemarthrosis.

The drug "Pradaxa". Analogues. Price

As mentioned above, this drug belongs to the group of anticoagulants, so substances of the same group can replace it. When selecting a suitable medicine, you need to clearly understand that you cannot be guided by criteria like: “it’s cheaper” or “it helped my neighbor a lot.” Anticoagulants are very serious substances that systemically affect the entire body, therefore only a doctor can prescribe both the dosage and the Pradaxa analogue.

Based on the structure of the active substance, there are no substitutes for this medicine. According to the pharmacological group, the drugs “Warfarin”, “Marcumar”, “Phenilin” and “Xarelto” may be suitable.

The price of this drug is quite high. Thus, a package containing 60 capsules costs about 3 thousand rubles, 30 capsules will cost approximately 2 thousand rubles. The cost of the medicine depends slightly on the content of the active substance. For Pradaxa 110 or Pradaxa 150, the price will differ quite a bit.

The drug "Warfarin"

This substance is the oldest of the anticoagulants presented above. Its use requires careful adherence to the dosage and monitoring of the blood condition, since exceeding the dose is very dangerous - the drug “Warfarin” becomes poisonous. It is used for the treatment and prevention of thrombosis and embolism of blood vessels. It is also prescribed for acute and recurrent venous thrombosis, pulmonary artery embolism, transient ischemic attacks and strokes, as well as for secondary prevention of myocardial infarction and accompanying thromboembolic complications. The medicine is also used to prevent thromboembolic complications in patients with atrial fibrillation, heart valve disease or with prosthetic heart valves, as well as in the postoperative period after orthopedic interventions to reduce the risk of blood clots.

Warfarin tablets should not be used in case of hypersensitivity to the constituent components of the drug, acute bleeding, pregnancy (especially during the first trimester and the last 4 weeks), as it affects the fetus, severe kidney and liver diseases, acute disseminated intravascular coagulation syndrome, deficiency of C and S proteins, thrombocytopenia. It is also not prescribed to patients who are expected to develop bleeding (including hemorrhagic disorders), suffering from esophageal varices, arterial aneurysms, gastric or duodenal ulcers, bacterial endocarditis, and malignant hypertension. Do not use in patients who have developed hemorrhagic stroke or intracranial hemorrhage, who have severe wounds (including surgical wounds), before

Anticoagulants, while preventing excessive clotting, can sometimes have a negative effect on the body, causing increased bleeding. The drug Warfarin also has this effect. Side effects are mainly limited to bleeding of various locations. In addition, disorders of the digestive system may occur.

Diet while taking Warfarin

The effectiveness of this product depends on the content of vitamin K. It enters the body with certain foods, especially leafy greens. But there is no need to sharply increase or decrease the proportion of these vegetables in the diet. When starting to take the medication, you should not make changes to your usual menu or take vitamins or dietary supplements without consulting your doctor. Once the dosage of the drug is established and established, a sharp increase in the consumption of foods rich in vitamin K can reduce its effectiveness and lead to increased blood clots. The largest amount of this vitamin is found in green tea, spinach, parsley, different types of cabbage, and lettuce. A sudden introduction of these products into the diet can lead to a weakening of the effect of the medicine, and regular consumption of berries or cranberry juice, on the contrary, can lead to an increase in its effectiveness. Drinking alcohol is absolutely unacceptable. That is, a diet when taking Warfarin is a necessary condition for successful and safe treatment.

Modern analogues of the drug "Warfarin"

At the moment, a number of medications are being produced that can replace this medication, but have a much smaller number of side effects, including those that do not require constant monitoring of INR (an indicator characterizing blood clotting). Substitutes for the drug Warfarin, the use of which is determined by the need to reduce the risk of thrombosis in the postoperative period, include the drugs Warfarex, Marevan, as well as Pradaxa and Xarelto, which have a similar mechanism of action and indications for use.

The drug "Warfarex" in the form of tablets containing warfarin sodium clarate as the active ingredient. It is used for diseases such as pulmonary embolism, deep vein thrombosis, heart attack, as well as for heart valve replacement surgery.

The drug "Marevan", containing the same active ingredient, is prescribed for the following diseases: thrombosis, heart attack (including for the prevention of complications after a heart attack), valve replacement and other heart diseases, strokes and ischemic attacks (including for their prevention).

The above products, differing only in the composition of the excipients, exhibit all the characteristic properties of the basis, and also require similar precautions and INR control.

The drug "Pradaxa" is an anticoagulant that is a direct thrombin inhibitor, by binding which prevents the formation of blood clots. It is prescribed for the treatment of limbs, for the prevention of strokes, systemic thromboembolism and to reduce the risk of complications in atrial fibrillation.

The drug "Xarelto" (rivaroxaban) is used for prophylactic purposes in case of thromboembolism after any orthopedic interventions on the lower extremities.

The drug "Xarelto". Peculiarities of purpose

These film-coated tablets contain micronized rivaroxaban as an active substance, which acts as a direct anticoagulant. It is a direct inhibitor of factor Xa (a blood clotting factor that is an activator of prothrombin), helping to suppress the formation of new thrombin molecules, but without affecting those already in the bloodstream. It is prescribed to prevent the development of venous thromboembolism in patients in the postoperative period after extensive orthopedic interventions.

You cannot use the drug "Xarelto" - an analogue of "Pradaxa" - in case of hypersensitivity to rivaroxaban and other components of the tablets, clinically significant active bleeding (for example, intracranial or gastrointestinal), liver diseases accompanied by coagulopathy, which significantly increases the risk of dangerous hemorrhages. This medicine is not prescribed during pregnancy and breastfeeding, as well as for children under 18 years of age. The use of the drug is not recommended for patients suffering from severe renal failure or hereditary intolerance to galactose or lactose. Xarelto tablets should be prescribed with caution to patients who have an increased risk of bleeding of any etiology: with congenital or acquired bleeding, with severe arterial hypertension, with exacerbation of ulcerative lesions of the stomach and duodenum, with a recent case of intracranial or intracerebral hemorrhage, with any pathologies of the blood vessels of the brain or spinal cord, with recent surgery on the spinal cord, brain or eyes. It is not recommended to use the medicine for people using systemic antifungals belonging to the azole group (for example, the drug "Ketoconazole") or receiving HIV protease inhibitors, since these substances increase the content of rivaroxaban (the active substance of the tablets) in the blood plasma, which increases the risk of bleeding .

The drug "Xarelto". Dosage and side effects

The tablets are taken orally, regardless of food intake, once a day (dose 10 mg). As a prophylaxis for venous thromboembolism after extensive surgical interventions, treatment is continued for 5 weeks, for the knee joint - up to 2 weeks.

The drug "Xarelto" is an analogue of "Pradaxa", therefore the negative consequences after taking them are similar to each other. The risk of obvious or hidden bleeding from any tissues and organs, leading to posthemorrhagic anemia, may increase. Such complications may include weakness, dizziness, pallor, headaches and shortness of breath.

Which drug should you prefer: Warfarin, Pradaxa or Xarelto?

It is necessary to clearly understand that systemic anticoagulants cannot be selected independently; the appropriate medicine, its dose and regimen of use are prescribed exclusively by a doctor. And these recommendations must be followed strictly. The information provided is for informational purposes only and cannot be a guide to action.

The main advantage of the drugs Pradaxa and Xarelto is that their use does not require INR control and is much less likely to cause side effects. But they can only be prescribed for non-valvular heart disease. Rheumatic damage to the valves or their replacement with artificial ones requires the use of the drug “Warfarin” exclusively.

The advantage of the drug "Xarelto" over others is that it is taken only once a day, and, according to some studies, it does not injure the organs of the gastrointestinal tract so much. But the range of indications for its use is very narrow, and this remedy is suitable mainly for patients after major surgery on the limbs to prevent the development of thromboembolism. In addition, this analogue of “Pradaxa” is categorically not suitable for women during pregnancy (any period) and lactation, since the active substance easily penetrates the placenta, having a negative effect on the fetus, as well as causing uterine bleeding, and is excreted in mother’s milk, therefore its administration is possible only with the complete abolition of breastfeeding.

As already mentioned, the drug “Warfarin” has a much wider range of applications, including, it is the only drug that is prescribed for lesions of the heart valves of any etiology (rheumatic or replaced artificial), in this it has no analogues. It can also be used during pregnancy (only if very necessary), except for the first trimester (as it has a teratogenic effect) and the last four weeks before childbirth (can cause spontaneous bleeding). The cost of the drug may also seem attractive, it will cost a couple of hundred rubles, while the price of Xarelto tablets or Pradaxa capsules is ten times higher. The disadvantage of Warfarin is the greater number of side effects and the need for constant monitoring of blood counts.

The drug "Pradaxa" has a wide range of indications for use, does not require monitoring of blood counts, and is much less likely to cause negative manifestations. Its use during pregnancy and breastfeeding is not recommended, although it is not a contraindication, since no studies have been conducted on its effects in these categories. Experiments on animals did not reveal any negative effects.

Thus, comparing analogues of the drug "Pradaxa", we can conclude that when choosing any of them, you need to take into account a significant number of criteria. All medications have their own characteristics of use, and each specific case must be considered separately. Therefore, only a doctor can prescribe adequate and safe treatment (using the drugs Warfarin, Xarelto or Pradaxa).

A modern pharmaceutical product from the subgroup of anticoagulants is the drug “Pradaxa”. The instructions for use indicate that these tablets or capsules have proven themselves to be an effective remedy in the fight against blood clots - as one of the components of treatment or disease prevention. The medication is widely used in the practice of surgeons and cardiologists. Why Pradaxa is prescribed, prices, reviews from patients and doctors, as well as analogues of the drug will also be discussed in the article.

What is the release form

On pharmacy shelves, Pradaxa 75 mg, 110 mg and 150 mg are presented as oblong opaque capsules with a cream-colored body and engraving. Inside there is a more active substance in the form of a pellet with a yellowish tint.

10 pcs are packaged in perforated blisters. Consumer pharmaceutical packs contain 1–6 blisters. In propylene bottles of 60 pcs.

Compound

The manufacturer, in the detailed instructions for use attached to each package of medication, indicates that the active substance of the Pradaxa anticoagulant is dabigatran ethoxylate mesylate. It has the ability to inhibit thrombin in the human body, thereby preventing the formation of blood clots.

Acacia gum and tartaric acid, hypromellose and dimethicone, as well as talc and hyprolose are auxiliary components of the drug that are responsible for maintaining the medicinal properties of the drug.

Pharmacological effects

Since dabigatran ethoxylate is a representative of a subgroup of direct anticoagulants, in the human body it, being converted into the active form of dabigatran, has the following pharmacological effects:

• inhibits free thrombin;
• prevents aggregation of blood platelets - platelets;
• prolongs APTT, ecarin clotting time, and thrombin time.

Clinical studies have convincingly proven that the anticoagulation effect of dabigatran is in no way inferior to that of warfarin.

Pradaxa tablets: what does the drug help with?

Experts recommend a medication with anticoagulant properties for both therapeutic and prophylactic purposes in conditions accompanied by a risk of blood clots.

The main indications for the use of the anticoagulant "Pradaxa":

• complex pharmacotherapy of strictly thrombosis - in the pulmonary arteries, as well as deep veins of the extremities;
• prevention of venous thromboembolism – after a person has undergone orthopedic surgery;
• preventive measures for people with cardiovascular pathologies - for example, atrial fibrillation;
• prevention of recurrence of thrombosis of deep vascular structures.

The decision that an anticoagulant should be present in a comprehensive treatment regimen for a particular pathology should be made exclusively by a specialist. Self-medication is absolutely unacceptable, since the risk of severe complications is high. For example, diffuse bleeding.

Instructions for use "Pradaxa"

Detailed instructions from the manufacturer indicate that capsules with an anticoagulant effect must be taken orally. There is no relationship with food intake, however, it is preferable to take after meals.

The frequency and duration of treatment with Pradaxa capsules is determined by a specialist on an individual basis. As a rule, 1–2 pieces/day are sufficient, accompanied by a moderate amount of water.

Optimal doses of medication:

• for the prevention of thrombosis – 2 pcs./day in the morning;
• after endoprosthetics - in the early stages of rehabilitation, 1 piece, then increased to 2 pieces/day;
• people with diagnosed atrial fibrillation - 2 pcs. /day.

For prophylactic purposes - to prevent the formation of blood clots, if there is a risk of their occurrence, it is recommended to take an anticoagulant in a minimum dose of 75 mg 1 r / s.

Contraindications

The subgroup of direct anticoagulants has many restrictions on their use. Therefore, its representative, the drug Pradaxa, is also not always allowed for complex treatment of certain diseases.

The detailed instructions supplied by the manufacturer indicate the following contraindications:

• severe functional failure of the renal glomeruli;
• clinically significant bleeding;
• hemorrhagic form of diathesis;
• spontaneous or pharmacologically caused violation of internal hemostasis;
• hemorrhagic stroke;
• high risk of acute bleeding, for example, with existing ulceration of the gastrointestinal tract structures;
• malignant neoplasms growing into large vessels - with the risk of bleeding;
• undergone replacement of heart valve structures;
• pediatric category of patients;
• an individual hyperreaction to the components of the Pradaxa medication, which can cause these tablets to cause side effects;
• recent TBI;
• surgical interventions in the recent past;
• suspicion of varicose veins of the esophagus, vascular aneurysms;
• simultaneous use of other coagulants;
• failure in the activity of hepatocytes.

With extreme caution, the drug is allowed to be taken by people over 75 years of age, with a low weight - less than 50 kg, as well as when taken simultaneously with NSAIDs, congenital disorders of the blood clotting system.

Undesirable effects

Since the active substance of the anticoagulant is Dabigatran ethoxylate, various undesirable effects may be observed while taking the drug:

• bleeding of any location, however, intestinal bleeding is more often recorded;
• anemia;
• thrombocytopenia;
• hematomas;
• prolonged bleeding of wounds;
• cutaneous hemorrhagic syndrome;
• functional failure of hepatocytes;
• increased activity of liver transaminases;
• hyperbilirubinemia.

In order for a specialist to promptly correct anticoagulant therapy, it is recommended to report every case of deteriorating health to the doctor immediately.

Analogues of the drug "Pradaxa"

The group of anticoagulants includes analogues:

Price and holiday conditions

The average price of Pradaxa, 150 mg tablets (Moscow), is 3185 rubles. You can buy medicine in Minsk for 20 - 165 Bel. rubles The price of the drug in Kyiv is 1150 hryvnia, in Kazakhstan – 3240 tenge. Sold according to prescription.

Instructions for the drug PRADAXA, contraindications and methods of use, side effects and reviews about this drug. Doctors' opinions and the opportunity to discuss on the forum.

Instructions for use

Directions for use and dosage of PRADAXA

The drug is prescribed orally.

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

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

For prevention of 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.

For prevention of VT after hip replacement Treatment should begin 1-4 hours after completion of the operation with a dose of 110 mg, followed by an increase in 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 liver dysfunction (Class B and C on the Child-Pugh scale) or diseases liver, which could have an impact on 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. U 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 Cockcroft formula:

For men

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

For women 0.85 x CC value 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 when dialysis. No clinical studies have been conducted in such patients.

Application experience elderly patients over 75 years of age 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.

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

Switching from parenteral anticoagulants to Pradaxa: There are no data, so it is not recommended to start therapy with Pradaxa before the planned administration of the next dose of a 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.

Side effects of PRADAX

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.

Possible bleeding of any location. Extensive bleeding is rare. The development of adverse reactions was similar to reactions in the case of enoxaparin sodium.

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 the 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 a wound, hematoma after procedures, bleeding after procedures, postoperative anemia, post-traumatic hematoma, bloody discharge after procedures, bleeding from the incision site, drainage after a 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.

Almost all medications cause side effects. As a rule, this occurs when taking drugs in maximum doses, when using a drug for a long time, or when taking several drugs at once. Individual intolerance to a particular substance is also possible. This can harm your body, so if the medicine causes side effects for you, you should stop taking it and consult a doctor.

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.

Clinical studies have not revealed the effect of the combination of pantoprazole or other proton pump inhibitors and Pradaxa on 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.

Very important information that is not always taken into account when taking medications. If you take two or more drugs, they can either weaken or strengthen each other's effects. In the first case, you will not get the expected result from the drug, and in the second, you risk getting an overdose or even poisoning.

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 used simultaneously 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 that increase the risk of developing hemorrhagic complications;

- a 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 a half-life of 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<30 мл/мин). При развитии острой почечной недостаточности прием препарата следует прекратить.

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.

Never use expired medications. At best, they will not help you, and at worst, they will harm you.

Storage conditions

The drug in bottles should be stored out of the reach of children, at a temperature not exceeding 25°C.

After an ischemic stroke, what is better to take - Xarelto or Pradaxa?

Both drugs can be used to prevent ischemic stroke in atrial fibrillation (atrial fibrillation) only in the case of a NON-VALVULAR form of the disease (that is, without severe rheumatic valve damage or without an artificial heart valve). In my opinion, Xarelto has some advantages at a similar price.

First, Xarelto 20mg is taken once daily, usually in the morning. This is simply more convenient and allows, if minor surgical interventions are necessary (for example, tooth extraction), to simply skip taking one tablet in the morning, remove the tooth and take the missed tablet in the evening.

In addition, Xarelto seems to have less damaging effects on the gastrointestinal tract.

Pradaxa (Dabigatran) for atrial fibrillation (atrial fibrillation):

(Quote from the 2010 ESC (European Society of Cardiology) guideline on atrial fibrillation, translated by the site author.)

Section 4.1.2.5: Research into new substances

Several new anticoagulant drugs developed for stroke prevention in AF come in two classes: oral direct thrombin inhibitors (eg, dabigatran etexilate and AZD0837), and oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban, YM150, etc. .).

In the Randomized Evaluation of Long-term anticoagulant therapy with dabigatran etexilate (RE-LY), dabigatran 110 mg twice daily was noninferior to VKAs (vitamin K antagonists) in preventing stroke and systemic embolism with a lower bleeding rate, and dabigatran at a dose of 150 mg twice daily showed lower rates of stroke and systemic embolism with similar rates of major bleeding compared with VKAs (vitamin K antagonists).

Pradaxa (Dabigatran) - official instructions for use. The drug is a prescription, the information is intended only for healthcare professionals!

Clinical and pharmacological group:

Anticoagulant. Direct thrombin inhibitor

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 higher compared to 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 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.

Indications for use of PRADAXA®

• prevention of venous thromboembolism in patients after orthopedic surgery.

Dosage regimen

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 per 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 per 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 increasing the dose to 220 mg per 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 begin with a dose of 220 mg per 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 an increase in the dose to 220 mg per 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 begin with a dose of 220 mg per 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 per day.

For men

Experience in elderly patients over 75 years of age is limited. The recommended dose is 150 mg per 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.

Side effect

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

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

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.

Contraindications to the use of PRADAXA®

• severe renal failure (creatinine clearance less than 30 ml/min);
• hemorrhagic disorders, hemorrhagic diathesis, spontaneous or pharmacologically induced disorder of hemostasis;
• active clinically significant bleeding;
• liver dysfunction and liver disease that 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 the start of therapy;
• age less than 18 years;
• known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients.

Use of PRADAXA® during pregnancy and breastfeeding

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.

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.

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 per day.

Creatinine clearance is determined using the Cockcroft 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.

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 that increase 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 per day. Pradaxa is contraindicated in patients with severe renal impairment (CK<30 мл/мин). При развитии острой почечной недостаточности прием препарата следует прекратить.

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.

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.

Clinical studies have not revealed the effect of the combination of pantoprazole or other proton pump inhibitors and Pradaxa on 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 per 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.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

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.