Dabigatran

BRAND NAME:

Pradaxa – These are available in the form of Pradaxa dabigatran etexilate capsules 75mg, 110mg and 150mg. It helps in reducing strokes and blood clots in adults.

MECHANISM OF ACTION:

Dabigatran inhibits thrombin-mediated coagulation factor activation by reversibly binding to the thrombin molecule's active site. It might have less antagonistic impact on platelet aggregation mediated by thrombin. Even when thrombin is coupled to fibrin, dabigatran can inactivate it, decreasing thrombin-mediated inhibition of fibrinolysis and possibly even enhancing it. Warfarin functions by blocking vitamin K-dependent thrombin and coagulation factor synthesis farther up the cascade, in contrast to direct thrombin inhibitors. Heparin often needs to be given concurrently because of the prothrombotic action that occurs first and the delayed beginning of the antithrombotic effect.

PHARMACOKINETICS:

Absorption: When taking dabigatran, one should eat or not eat at all. Dabigatran has an accumulation factor of two in both adult and pediatric patients, and in healthy individuals and adult patients, its pharmacokinetics are essentially linear over a 10-400 mg range. Oral dabigatran has a bioavailability of 3 to 7%, while dabigatran pellets have a 37% higher bioavailability than capsules. 75% of the bioavailability is achieved when the capsule shell is removed. It is crucial to refrain from tampering with the dabigatran capsules before ingestion. The Cmax for an oral dosage is reached in one hour; if a high-fat meal is taken simultaneously, this period may increase to two hours.

Distribution: The distribution volume of dabigatran is 50–70 liters.

Metabolism: Dabigatran is administered orally as a prodrug called dabigatran etexilate, which is then metabolized into the active form. The oral bioavailability and plasma prodrug levels, as well as in vitro assays, show a considerable first-pass metabolism by carboxylesterases, namely intestinal CES2 for M2 and hepatic CES1 for dabigatran. Dabigatran etexilate can also be hydrolyzed by CES1 to M1, followed by CES2 to dabigatran, albeit the former route is assumed to account for most of the active form in plasma.

Dabigatran can be 1-O-acyl glucuronidated by UGT1A9, UGT2B7, and UGT2B15, followed by acetyl migration to produce the equivalent 2-O-, 3-O-, and 4-O acyl glucuronides, all of which show comparable activity to dabigatran but account for a minor proportion of recovered metabolites.

Elimination: Dabigatran is mostly eliminated in the urine. Following the oral dose of radiolabelled dabigatran, 7% of the radioactivity is recovered in urine and 86% in feces.

PHARMACODYNAMICS:

Dabigatran is a P-gp transporter substrate; hence, it should not be used with P-gp inhibitors or inducers, especially in patients with compromised renal function. Dabigatran and other direct-acting oral anticoagulants should be avoided in triple-positive antiphospholipid syndrome patients because they increase the risk of recurrent thrombosis. Idarucizumab is approved for emergency reversal in adult patients; however, its safety and efficacy in young children have yet to be established. Hemodialysis, prothrombin complex concentrates, and recombinant FVIIA can all be used to treat the disorder.

DOSAGE AND ADMINISTRATION:

Swallow the capsule whole; do not open the capsule and empty the pellets from the capsule. Dabigatran comes in two strengths: 75 mg and 150 mg.

The dosage of this medication will differ for each patient. The amount of medicine you take is determined by its potency. Furthermore, the number of doses you take per day, the interval between doses, and the duration of pharmaceutical administration are determined by the specific medical problems for which the medication is being taken.

Oral dosage form (capsule): The adult dose is 75 to 150 mg twice daily to prevent blood clots and strokes in adults with non-valvular atrial fibrillation.

Children's doses should be administered as prescribed by a physician.

CONTRAINDICTIONS:

Absolute contraindications to anticoagulant treatment include the following:

• Major trauma

• Intracranial haemorrhage

• Coagulopathy

Anticoagulation may be advised for persons with relative contraindications, such as the following:

• Gastrointestinal bleed

• Low-risk operations.

Anticoagulant therapy should be used with caution in these patients.

• Geriatrics

• Pregnant Patients

DRUG INTERACTIONS:

Dabigatran may interact with other drugs, altering how they work or increasing the likelihood of serious adverse effects. Medicines that may interact with dabigatran include mifepristone, cobicistat, cyclosporine, dronedarone, ketoconazole, and rifampin. Avoid taking aspirin, nonsteroidal anti-inflammatory drugs, or other blood thinners without visiting your doctor.

FOOD INTERACTIONS:

Avoid herbs and substances that have anticoagulant or antiplatelet effects. Garlic, ginger, and bilberries are among the examples.

SIDE EFECTS:

• Acid or sour stomach

• Belching

• Constipation

• Bloody stools

• Heartburn

• Heartburn

• Nausea

• Vomiting

• Pain or burning in the throat

• Stomach discomfort, upset, burning pain

• In digestion.

OVERDOSE:

Symptoms of overdose may include the following:

• Unusual brushing or bleeding

• Pink or brown urine

• Red or black, tarry stools

• Coughing up blood.

TOXICITY:

Overall, older persons have a superior risk-benefit ratio, even though they are more likely than younger adults to experience negative effects. Patients who have a creatinine clearance of less than 15 ml/minute do not appear to benefit from dabigatran etexilate, and those whose clearance is between 15 and 30 ml/min should have their doses lowered.

In animal trials, dabigatran causes vaginal and uterine hemorrhage close to delivery and increases the number of dead offspring. Dabigatran may or may not be eliminated in breast milk; thus, it is important to weigh the advantages and disadvantages of stopping the drug or breastfeeding.

STORAGE:

Store at 20-25°C (68-77°F), with excursions to 15-30°C (59-86°F).

Capsules: Once the bottle is opened, keep the capsules in their original container; they are only stable for 4 months.

Pellets: Keep in original packaging to avoid moisture; do not open the packets until ready to use; and use within 6 months of opening the aluminum bag containing the packets.