Pradaxa - 18 reviews, instructions for use

Compound

The composition of 1 capsule of the drug includes dabigatran etexilate mesylate 172.95 mg (150 mg in terms of dabigatran etexilate ) and additional substances: tartaric acid, dimethicone , acacia gum, hypromellose, talc, hydroxypropylcellulose, potassium chloride, E407, E171, E132, E110 , water, butanol, ethanol, isopropanol , shellac, pylene glycol, E172.
There is also a dosage form containing dabigatran etexilate 75 mg and 110 mg.

Pharmacodynamics and pharmacokinetics

The active substance of the tablet, after conversion to dabigatran , inhibits the activity of the enzyme thrombin , which in turn is responsible for the process of converting fibrinogen into fibrin and the formation of a blood clot . Dabigatran also has the ability to reduce the activity of already formed blood clots, free thrombin, fibrin-bound thrombin , subsequent platelet aggregation does not occur.

The active component effectively reduces the prothrombin index , in direct proportion to its concentration in the blood plasma achieved while taking the drug.

Almost immediately after taking the drug, a hydrolysis , converting dabigatran etexilate into dabigatran. The bioavailability of dabigatran is about 6%, the maximum concentration of the active substance will be observed within an hour or two after administration. Regardless of the dose taken, the half-life is from 11 to 14 hours. In patients with renal failure, changes in some pharmacokinetic parameters occur.

Contraindications

Pradaxa is contraindicated:

Indications for use

Acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) - for the treatment and prevention of deaths associated with these diseases;
Stroke, systemic thromboembolism - for the prevention and reduction of cardiovascular mortality in patients with atrial fibrillation;
Venous thromboembolism (VTE) – for prevention after operations on the musculoskeletal system;
Recurrent DVT and/or PE – prevention of disease and deaths associated with these diseases.

Side effects

Possible:

thrombocytopenia and anemia , intracranial bleeding ;
formation of hematomas , the occurrence of bleeding of various origins and locations, including from postoperative wounds, nose, stomach and intestines;
bronchospasm hypersensitivity reactions such as urticaria , itching and rash ;
diarrhea , abdominal pain, indigestion , nausea , dysphagia , liver dysfunction;
hemarthrosis , hematuria;
bleeding , poor healing, formation of hematomas and discharge from wounds, drainage from wounds.

Interaction

Do not combine with drugs that affect hemostasis, vitamin K antagonists , P-glycoprotein inhibitors ( Verapamil , Ketoconazole , Clarithromycin , Amiodarone , Quinidine ).

Use with caution in combination with dronedarone , St. John's wort , Carbamazepine and Pantoprazole .

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

Pradaxa®

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

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 inhibitors/inducers of P-

glycoprotein:

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

Ketoconazole.

Ketoconazole for systemic use after a single dose of 400 mg increases the 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 FIIa), 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 increased 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.

Analogues of Pradaxa

There are practically no analogues of Pradaxa, the closest in effect to the medicine are Warfarin and Xarelto .

Which is better: Pradaxa or Warfarin?

Warfarin is the most used vitamin K antagonist , and has many restrictions on its use. Constant monitoring of the INR is required; the drug is not compatible with all foods and medications. Not everyone is able to maintain the required INR level, which leads to unwanted side effects or a decrease in the effectiveness of the drug. Unlike Warfarin, Pradaxa is a new generation drug, the risk of bleeding is lower with the drug, and there are fewer restrictions on its use.

In any case, which drug should be used, Pradaxa or Warfarin, must be decided by the attending physician.

special instructions

Prescribing Pradaxa requires caution in conditions that are characterized by an increased risk of bleeding. The basis for searching for the source of bleeding is a decrease in hematocrit and/or hemoglobin in the blood, accompanied by a decrease in blood pressure.

In order to detect excessive anticoagulant activity of dabigatran, it is necessary to use tests to determine the ecarin or thrombin clotting time, or, if they are not available, a test to determine the aPTT.

With reduced renal function (including in elderly patients), an increase in drug exposure may be observed. If acute renal failure develops, therapy is discontinued.

The likelihood of bleeding increases when Pradaxa is used in combination with ticagrelor, unfractionated heparin (except for doses required to maintain the patency of an arterial or venous catheter) and heparin derivatives, low molecular weight heparins, fondaparinux sodium, thrombolytic drugs, blockers of glycoprotein GP IIb/IIIa platelet receptors, ticlopidine , dextran, rivaroxaban, vitamin K antagonists and P-glycoprotein inhibitors (itraconazole, tacrolimus, cyclosporine, ritonavir, nelfinavir and saquinavir). Also, the risk of bleeding may be increased due to pharmacological interactions with selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors, antiplatelet agents and other anticoagulants.

Concomitant use with dronedarone is contraindicated.

When preventing VTE after surgery on the musculoskeletal system, short-term use of non-steroidal anti-inflammatory drugs for anesthesia during surgical interventions is not accompanied by an increased risk of bleeding.

If there is an increased risk of bleeding (for example, with bacterial endocarditis, after recent major trauma or a biopsy), the patient's condition must be monitored to detect signs of bleeding in a timely manner.

Due to the high probability of bleeding, the drug is discontinued before surgery or invasive procedures (at least 24 hours, in some cases 2-5 days). If emergency surgery is necessary, Pradaxa should be temporarily interrupted, and the operation should be performed no earlier than 12 hours after taking the last dose of the drug. If this is not possible, due to the high risk of bleeding, the benefit-risk ratio needs to be assessed.

After a spinal puncture (repeated or traumatic) and prolonged use of an epidural catheter, the first dose of Pradaxa can be taken no earlier than 120 minutes after removal of the catheter, while monitoring the patient's condition (to exclude neurological symptoms that may be associated with epidural hematoma or spinal bleeding) .

Since taking Pradaxa may increase the risk of bleeding, it is recommended to exercise caution when driving or performing potentially hazardous activities.

Pradaxa price (where to buy)

The price of Pradaxa 110 mg is about 3,200 rubles for 60 pieces.

You can buy Pradaxa in Moscow for 2000 rubles for 30 capsules of 75 mg.

The price of Pradaxa 150 mg is within 2000 rubles for 30 pieces.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine

ZdravCity

Pradaxa capsules 150 mg 60 pcs. Boehringer Ingelheim
RUB 3,526 order
Pradaxa capsules 150 mg 60 pcs. Boehringer IngelheimBoehringer Ingelheim Pharma GmbH & Co.KG
RUR 3,526 order
Pradaxa capsules 150 mg 30 pcs.Boehringer Ingelheim
RUB 1,942 order
Pradaxa capsules 110 mg 30 pcs.Boehringer Ingelheim
RUB 1,941 order
Pradaxa capsules 110 mg 60 pcs.Boehringer Ingelheim
RUR 3,526 order

Pharmacy Dialogue

Pradaxa (caps. 150 mg No. 30)Boehringer Ingelheim
RUB 1,770 order
Pradaxa (caps. 110 mg No. 180) Boehringer Ingelheim
9565 rub. order
Pradaxa (caps. 150 mg No. 60) Boehringer Ingelheim
RUB 3,417 order
Pradaxa (caps. 110 mg No. 60) Boehringer Ingelheim
RUR 3,491 order
Pradaxa (caps. 150 mg No. 180) Boehringer Ingelheim
RUB 10,371 order

Pharmacy24

Pradaxa 110 mg No. 60 capsules Boehringer Ingelheim Pharma GmbH & Co.
KG, Nimechchina 2148 UAH. order
Pradaxa 110 mg No. 60 capsules Promotion Boehringer Ingelheim Pharma GmbH & Co. KG, Nimechchina
1030 UAH. order
Pradaxa 150 mg No. 60 capsules Boehringer Ingelheim Pharma GmbH & Co. KG, Nimechchina
2148 UAH order
Pradaxa 150 mg No. 60 capsules Promotion Boehringer Ingelheim Pharma GmbH & Co. KG, Nimechchina
1030 UAH. order

Directions for use and dosage

Pradaxa is taken orally with water. The capsule should not be opened. Eating does not affect the effectiveness of the drug.

Do not squeeze capsules through the foil.

The daily dose is taken in 1 or 2 doses.

Recommended dosage regimen:

VTE after operations on the musculoskeletal system: 2 capsules of 110 mg once a day, for moderate functional impairment of the kidneys - 2 capsules of 75 mg. After knee and hip replacement (1-4 hours after completion of the operation): initial dose – 1 capsule 110 mg once a day, then the single dose is increased by 2 times, without increasing the frequency of administration. Duration of treatment: knee joint – 10 days, hip joint – 28-35 days. If hemostasis is not achieved, therapy is postponed. If the drug is started later, the daily initial dose is 220 mg;
Stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation: 2 times a day, 1 capsule 150 mg. It is recommended to take the drug for life;
Acute DVT and/or PE: 2 times a day, 1 capsule 150 mg after parenteral treatment with an anticoagulant (duration: at least 5 days). Duration of the course – up to six months;
Recurrent DVT and/or PE: 1 capsule 150 mg 2 times a day. The duration of the course is determined by individual risk factors (lifelong use of the drug is possible).

Before prescribing therapy, patients with functional renal impairment need to evaluate creatinine clearance (with creatinine clearance less than 30 ml/min, the use of the drug is not recommended).

When carrying out prophylaxis of VTE after operations on the musculoskeletal system in patients with a creatinine clearance of 30-50 ml/min, the daily dose should be reduced to 150 mg. When prescribing the drug for other indications when creatinine clearance is more than 30 ml/min, no correction is required.

Before prescribing therapy, elderly patients need to assess renal function. In the future, it is assessed at least once a year. Correction of the drug dosage regimen depends on the severity of renal functional disorders.

Patients whose weight is less than 50 kg require medical monitoring of their health status.

When carrying out the prevention of VTE after surgery on the musculoskeletal system when combined with active P-glycoprotein inhibitors (amiodarone, verapamil or quinidine), the dose of Pradaxa is reduced to 2 capsules of 75 mg per day. It is not recommended to start treatment simultaneously with verapamil and to connect it to therapy in the future. In other cases, no dose adjustment is required.

The increased risk of bleeding is determined by several factors: age over 75 years, combined use with P-glycoprotein inhibitors, moderate functional renal impairment (creatinine clearance - 30-50 ml/min), anamnestic data on gastrointestinal bleeding. Depending on their presence, adjustment of the drug dosage regimen may be necessary:

Prevention of stroke, systemic thromboembolism and reduction of cardiovascular mortality in patients with atrial fibrillation: one or more factors - 2 times a day, 1 capsule 110 mg;
Treatment of acute and prevention of recurrent DVT and/or PE and prevention of deaths associated with these diseases: several factors - therapy is carried out only after assessing the benefit/risk ratio (due to lack of clinical data).

When switching from Pradaxa to parenteral use of anticoagulants during VTE prophylaxis after surgery on the musculoskeletal system, anticoagulants are administered 24 hours after taking the last dose of Pradaxa, in other cases - after 12 hours.

When switching back, instead of the anticoagulant being discontinued, the first dose of Pradaxa is prescribed within 2 hours before the next injection of alternative therapy or simultaneously with the cessation of the constant infusion.

If you miss a single dose, do not double the next dose.