Description of the drug PRADAXA® (PRADAXA)

Description of the drug PRADAXA® (PRADAXA)

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

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

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

After simultaneous use of dabigatran etexilate and dronedarone at a 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.

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.

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 combination of dabigatran etexilate and ketoconazole for systemic use is contraindicated.

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

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

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

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

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

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%.

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.

Composition and indications for use

This medicine is an anticoagulant that affects blood clotting and reduces the risk of blood clots. The main active ingredient of the drug is dabigatran etexilate. The product is available in capsule form.

The main indications for use are:

• prevention of stroke, systemic and venous thromboembolism;
• recovery after orthopedic surgery;
• reducing the number of deaths from cardiovascular diseases;
• decreased libido in men.

It is extremely rare that the medicine is prescribed to pregnant women. Its use is permitted only in cases where the benefits to the health and life of the expectant mother outweigh the risks to the unborn child. It is also worth stopping treatment with Pradaxa while breastfeeding, because... the substances of the drug penetrate into breast milk and, therefore, enter the baby’s body.

How to take the medicine?

The dosage and duration of treatment is determined only by the attending physician. The instructions indicate that the maximum permissible daily dose of the substance can be up to 300 mg. Usually the drug is prescribed only to adults. Drink it twice a day with plenty of water, regardless of meals.

The maximum amount of active substance in the blood is observed 30-120 minutes after taking the medicine. Then the concentration begins to gradually decrease. The half-life of the drug from the body is 14-17 hours, and if taken with food, this time will increase by two hours.

Permissible dose

Despite all the warnings of doctors and the high risk of side effects, reviews indicate that many patients are confident that a “drop” of wine or cognac will not harm their health. When using Pradaxa, it is permissible to drink a maximum of 0.5 liters of beer, 0.3 liters of unfortified wine or 50 ml of strong drink. This amount of alcohol can be consumed 2 times a week. However, you should not drink 2 days in a row. After taking the drug, at least 24 hours must pass.

You cannot mix different types of alcohol and at the same time drink juices such as pomegranate, cranberry and grapefruit, because they also affect blood clotting.

Signs that ethyl alcohol has reacted with the medication are the following symptoms:

• blood or fluid from the nose;
• sudden bleeding of the gums;
• change in color of stool (to dark) and urine (to brown);
• presence of blood in urine;
• prolonged headache and abdominal pain.

Brief characteristics of the drug

The medicine is available in capsules, each of which contains dabigatran etexilate mexilate.

Upon entry into the body, the following pharmacological action occurs:

• suppression of thrombin formation;
• elimination of thrombosis;
• prolongation of APTT and thrombin time;
• anticoagulant activity.

The drug is absorbed through the gastrointestinal mucosa and slightly binds to blood plasma proteins. Metabolism also occurs in the blood. Administration is carried out through the kidneys and gastrointestinal tract.

Indications for use:

• prevention of venous thromboembolism in patients who have undergone joint surgery;
• prevention of stroke, thromboembolism due to atrial fibrillation;
• treatment and prevention of deep vein thrombosis, pulmonary embolism.

The dosage depends on the patient’s age, body weight, the presence of systemic diseases, and the underlying disease that requires adjustment with the drug.

Side effects:

• anemia, thrombocytopenia;
• skin and systemic allergic reactions;
• bleeding in the brain;
• minor and significant bleeding from peripheral vessels;
• the appearance of blood from the nose and during coughing;
• gastrointestinal bleeding, abdominal pain, dyspeptic disorders, encephalitis, vomiting;
• liver inflammation with increased enzymes and bilirubin in the blood;
• complications as a result of the injection in the form of hematoma, infection, local pain;
• bleeding from the wound after surgery.

Contraindications for use:

• hypersensitivity to one of the components of the product;
• liver and kidney diseases;
• damage to internal organs during serious hemorrhage or bleeding, for example, after a stroke or heart attack;
• serious defects of the gastrointestinal mucosa;
• use of an anticoagulant;
• heart valve prosthesis;
• minor age, patients over 75 years of age.

The drug is prescribed with caution to patients weighing less than 50 kg, using non-steroidal anti-inflammatory drugs and having a history of bacterial endocarditis, thrombocytopenia, esophagitis, gastritis.

Possible consequences

By consuming alcoholic beverages and Pradaxa at the same time, a person may experience:

• intoxication of the body;
• tachycardia;
• nausea and vomiting;
• heavy, labored breathing;
• Strong headache;
• limb spasms;
• bronchospasms;
• anemia.

One of the serious consequences is intracranial and intracerebral hemorrhages. As a result, the patient may experience speech impairment, paralysis, and cessation of the cardiovascular system. In addition, hemorrhages can be fatal.

In cases where alcohol and the drug are combined by a person who constantly drinks alcohol and suffers from a disease such as alcoholism, the consequences can be even more serious. In such cases, the work of the liver is disrupted by the constant use of ethyl alcohol, and the organ cannot neutralize the breakdown products of the drug and toxins. As a result, the patient experiences liver failure.

Pradaxa and beer

Pradaxa and beer don't mix. The medicine reduces the level of thrombin and fibrinogen, so the process of thrombosis slows down. But a large amount of ethyl alcohol can lead to activation of substances and the appearance of blood clots.

During treatment with the drug, it is forbidden to drink alcohol or beer. This leads to dilation of the walls of blood vessels, increasing the risk of hemorrhage into organs.

There is an increased load on the liver, it becomes inflamed, and function decreases. Intoxication of the body occurs.

If ethanol reduces the function of the drug, there is a risk of thrombosis with necrosis of internal organs due to clogged vessels. A heart attack or stroke may occur if the patient is predisposed to diseases.

The most dangerous combinations and consequences

The combination of alcohol and chemical-based drugs can lead to serious disorders in the body, and in some cases to fatal consequences.

List of medications and their side effects in combination with alcohol:

Compatibility of Pradaxa and alcohol

? Pradaxa and alcohol can have negative effects on the body, starting with the digestive tract. The patient has an increased risk of bleeding of the mucous membrane, which is aggravated by simultaneous use with ethanol. Dyspeptic reactions occur, vomiting occurs, removing part of the drug.

Metabolism and metabolism takes place in the liver. At high doses, the hepatocyte wall is damaged, and inflammation gradually develops.

Both substances are perceived by the immune system as a foreign toxic object. The patient experiences local allergic reactions as a result of inflammation. An anaphylactic reaction, bronchospasm, and angioedema may occur.

The drugs spread across the blood-brain barrier into the brain. They cause damage to the vessel wall, which can lead to intracranial hemorrhage.

The person becomes weak, sick, and faints. The concentration of red blood cells decreases, hypoxia and anemia occur.

Compatibility of the drug with alcohol

Most doctors are unshakable in their opinion that it is impossible to combine Pradaxa with alcohol-containing drinks. Such a combination is impossible and dangerous for human life. It is an indisputable fact that alcohol negatively affects the body, and its combination with medications is a colossal blow to all vital organs. No one can predict how even a minimal amount of alcohol taken will affect the patient’s condition.

Under no circumstances should pregnant women combine medications and alcoholic beverages. Even a minimal amount of wine in this case can lead to consequences such as collapse, loss of a child, future infertility and even death.