Dabigatran

Benjamin Clanner-Engelshofen is a freelance writer in the medical department. He studied biochemistry and pharmacy in Munich and Cambridge / Boston (USA) and noticed early on that he particularly enjoyed the interface between medicine and science. That is why he went on to study human medicine.

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The active ingredient dabigatran is a newer anticoagulant drug. Because of their mode of action and taking as a capsule, the newer anticoagulants such as dabigatran are also known as "direct oral anticoagulants" (DOAC). Here you can read everything interesting about the effects of dabigatran, its use and possible side effects.

This is how dabigatran works

The anticoagulant is taken in the form of a precursor (known as a “prodrug”) - called dabigatran etexilate - and only converted into the active form dabigatran in the body. In this form, the active ingredient inhibits blood clotting by blocking an important key protein (thrombin).

Blood clotting

Normally, in the case of an injured blood vessel, for example, blood coagulation proceeds like a cascade-like process (known as the “coagulation cascade”): the platelets (thrombocytes) circulating in the blood recognize the tissue damage and attach themselves to it, which activates them. When activated, the platelets release numerous messenger substances that attract additional platelets. The resulting blood clot constricts the blood vessel and thus reduces blood loss. This first part of hemostasis is known as primary hemostasis (primary hemostasis) and leads to rapid, if not very stable, vascular occlusion.

In the next step, “secondary hemostasis” sets in: the active coagulation factor thrombin is created from an inactive precursor protein (prothrombin). It converts individual proteins (fibrinogen) dissolved in the blood into long threads made of fibrin, which serve as a solid, cross-linked adhesive that makes the previously unstable vascular occlusion mechanically stable. This also includes other platelets and red blood cells (erythrocytes).

How dabigatran works

The active ingredient dabigatran specifically inhibits the coagulation factor thrombin, which means that no fibrin threads are formed.

When anticoagulant with dabigatran or other active ingredients, it is important to always find something mediocre - if the coagulation is inhibited too much, the patient can die from the smallest internal bleeding; if the ability to clot is too strong, blood clots form too quickly and block important vessels such as those in the heart or brain. This can lead to fatal heart attacks and strokes.

Benefits of the new oral anticoagulants

Older anticoagulants (heparins, coumarins) have been in use for a long time, but usually have significant disadvantages compared to the new oral anticoagulants:

Heparins, which also indirectly inhibit thrombin, are not ingested orally and must therefore be administered by injection. Coumarins, which inhibit the function of vitamin K (important for the formation of coagulation factors), can be taken orally. However, their indirect effect on coagulation can fluctuate widely (among other things depending on the vitamin K content of the food). Therefore, the coagulation value (INR value, formerly the Quick value) must be determined regularly and the dosage of the coumarins adjusted accordingly.

Orally taken dabigatran has an advantage here: the coagulation value does not have to be measured regularly in a well-adjusted patient because dabigatran has a direct effect depending on the dosage.

Dabigatran uptake, breakdown and excretion

After ingestion as a capsule, the prodrug dabigatran etexilate is absorbed into the blood in the intestine, where it is converted into dabigatran, the active ingredient. The highest blood levels are reached after half an hour to two hours. Ingestion with food delays but does not reduce absorption. Only small parts of the active ingredient are further metabolized in the body. For the most part, dabigatran is excreted unchanged via the kidneys with the urine. Half of the original amount of active ingredient left the body within half a day.

When is dabigatran used?

The anticoagulant dabigatran is used:

• for the preventive treatment of thrombosis in patients after a hip or knee replacement
• for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE)

The duration of use depends on the type of treatment. After surgery, dabigatran is taken for a few weeks for general prevention of blood clots in the long term.

This is how dabigatran is used

In general, the active ingredient dabigatran is taken once or twice a day with an interval of twelve hours and regardless of meals with a glass of water.

After knee replacement surgery, 220 milligrams of dabigatran are taken once a day in the morning for ten days. After hip replacement surgery, this period is extended to four to five weeks.

Patients who have to take dabigatran for the prevention of atrial fibrillation or for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) usually receive 150 milligrams of dabigatran twice a day, i.e. a total daily dose of 300 milligrams.

The dose may be reduced by the doctor if the patient is elderly (over 75 years of age), kidney function is impaired or there is otherwise an increased risk of bleeding. In such cases, 110 milligrams of dabigatran is usually used twice a day.

What are the side effects of dabigatran?

The active ingredient dabigatran can cause adverse drug effects such as anemia, nosebleeds, gastrointestinal bleeding, abdominal pain, diarrhea, nausea, changes in liver function values, skin bleeding and blood in the urine in one in ten to one hundred patients.

Furthermore, one in a hundred to a thousand people treated with dabigatran shows side effects such as hypersensitivity reactions, rash, itching, bruising of the skin, bleeding, coughing up blood, stomach ulcers, heartburn, vomiting and bleeding in the joints.

Note: Dabigatran can cause bleeding as a side effect, especially in the event of an overdose. In severe cases, the attending physician must then give the patient a specific antidote - the active ingredient idarucizumab. This blocks the anticoagulant effects of dabigatran.

What should be considered when taking dabigatran?

The combined use of dabigatran with other anticoagulants (such as heparins, coumarins and platelet aggregation inhibitors) should not take place, as otherwise the coagulation may be too strongly inhibited. A switch from one to another anticoagulant should only be done by an experienced doctor.

According to the manufacturer, non-steroidal anti-inflammatory drugs (NSAIDs) used as anticoagulants (acetylsalicylic acid - ASA) and pain relievers (ibuprofen, diclofenac) do not significantly increase the risk of bleeding when taken once. To be on the safe side, however, other pain relievers such as paracetamol should be used whenever possible.

Dabigatran is largely retained in the intestine by what are known as P-glycoproteins, which are responsible for the discharge of foreign substances such as medicinal substances. However, if other active ingredients that inhibit this protein are used at the same time, more dabigatran gets into the body and overdoses can occur. Examples of such substances are agents against cardiac arrhythmias (verapamil, amiodarone, quinidine), antibiotics (azithromycin, clarithromycin), the antihypertensive agent captopril and certain ingredients of food (piperine in black pepper, quinine in bitter lemon / tonic water).

As there are insufficient studies on the safety and effectiveness of its use during pregnancy and breastfeeding, dabigatran should not be taken during this time. The same applies to children and young people under the age of 18.

How to get medication with dabigatran

Dabigatran is only available on prescription in all doses and is therefore only available in pharmacies upon presentation of a doctor's prescription.

How long has dabigatran been known?

The anticoagulant was developed and clinically tested by the pharmaceutical company Boehringer-Ingelheim in the 1990s. Dabigatran was approved in the EU in 2008.

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