dabigatran

Action and Spectrum

Actions and Spectrum: 

The action of dabigatran is to bind to and inhibit the activity of thrombin, which prevents the formation of fibrin clots. dabigatran is a direct thrombin inhibitor, which means that it targets thrombin specifically, rather than inhibiting other factors in the blood clotting cascade. 

dabigatran has a broad spectrum of activity, which means that it can prevent a wide range of blood clots. It is used to prevent blood clots in patients with atrial fibrillation, deep vein thrombosis (DVT), and pulmonary embolism (PE). It is also used for the prevention of stroke in patients with non-valvular atrial fibrillation. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Adults 

Dyspepsia and gastritis. 

Pediatrics 

Minor bleeding 

GI adverse effects 

1-10% 

Adults 

GI bleed. 

Major bleed. 

Pediatrics 

Major bleeding. 

Clinically relevant nonmajor bleeding. 

Major and clinically relevant nonmajor bleeding. 

<1% 

Adults 

Hypersensitivity, including urticaria, rash, pruritus (<0.1%) 

Intracranial hemorrhage. 

Frequency not defined. 

Adults 

Alopecia 

Vomiting 

Thrombocytopenia 

Neutropenia 

Nausea 

Angioedema 

Esophageal ulcers 

Agranulocytosis 

Diarrhea 

Black Box Warning

Black Box Warning: 

dabigatran has a black box warning for the risk of serious or fatal bleeding. The risk of bleeding is increased in patients like renal impairment, and in patients who are taking medications that also increase the risk of bleeding.

Other conditions which may increase the risk of bleeding include age over 75, concomitant use of antiplatelet agents or nonsteroidal anti-inflammatory drugs (NSAIDs), and a history of bleeding disorders or gastrointestinal bleeding. 

Patients taking dabigatran should be monitored closely for signs of bleeding, and any bleeding should be promptly evaluated and treated. In the event of a bleeding emergency, the effects of dabigatran can be reversed with a medication called idarucizumab. 

It’s important for patients taking dabigatran to communicate their health status or medications to their healthcare provider to ensure the medication remains safe and effective for them. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Active bleeding: dabigatran should not be used in individuals who are currently experiencing active bleeding, as it may increase the risk of bleeding. 
• Severe liver disease: dabigatran should not be used in individuals with severe liver disease, as it may increase the risk of bleeding. 
• Mechanical heart valves: dabigatran is not recommended for individuals with mechanical heart valves, as it may increase the risk of blood clots. 
• Hypersensitivity: dabigatran should not be used in individuals who are allergic to the medication or any of its components. 
• Pregnancy: dabigatran is not recommended for use during pregnancy, as it may harm the fetus. 

Caution 

• Renal Impairment: dabigatran is primarily excreted through the kidneys, and therefore caution should be exercised in individuals with renal impairment. A dose adjustment may be necessary in these individuals. 
• Elderly Patients: Elderly patients may be more susceptible to bleeding events when taking dabigatran. Therefore, caution should be exercised in elderly patients when starting or adjusting the dose of dabigatran. 
• Other Medications: dabigatran can interact with other medications, including antiplatelet drugs and other anticoagulants. Therefore, caution should be exercised when taking dabigatran with other medications, and it is important to discuss all medications with your healthcare provider. 
• Spinal/Epidural Anesthesia or Puncture: If you are taking dabigatran and are scheduled for spinal or epidural anesthesia or puncture, your healthcare provider should be informed. This is because taking dabigatran increases the risk of developing a blood clot in the spinal or epidural area, which can lead to paralysis. 
• Bleeding: dabigatran increases the risk of bleeding, and caution should be exercised when taking dabigatran in individuals with bleeding disorders or a history of bleeding. 

Pregnancy / Lactation

Pregnancy consideration:   

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

Pharmacodynamics: 

This compound hinders the development of thrombus by competitively inhibiting thrombin, which is responsible for converting fibrinogen to fibrin during the coagulation cascade. Additionally, it blocks both free and clot-bound thrombin as well as thrombin-induced platelet aggregation. 

Pharmacokinetics: 

Absorption 

The peak plasma time for this compound is approximately 1 hour when taken on an empty stomach, and about 2 hours when consumed with a high-fat meal.  

The intact oral capsule exhibits a low bioavailability of 3-7%. However, taking the pellets without the capsule shell increases the oral bioavailability by 75%. In healthy adults, oral pellets have 37% higher relative bioavailability than dabigatran capsules.

It’s important to note that the relative bioavailability between the two dosage forms is age-dependent, and the observed relative bioavailability in adults cannot be applied to pediatric patients. 

Distribution 

This compound is protein-bound to 35% and has a volume of distribution (Vd) ranging from 50-70 L. 

Metabolism 

dabigatran etexilate which is prodrug that is converted to dabigatran. It is a substrate of the efflux transporter P-gp. This compound is not a substrate, inhibitor, or inducer of CYP450 enzymes. 

Elimination and Excretion 

The half-life of this compound varies depending on the formulation and renal function. For pellets, the half-life is between 9-11 hours. When taken in capsule form, the half-life ranges from 12-17 hours in individuals with normal renal function, 14-17 hours in those with mild to moderate renal impairment, and 28 hours in individuals with severe renal impairment.

Renal clearance accounts for 80% of the total clearance after intravenous administration. The compound is primarily excreted through feces (86%), with a smaller amount excreted in the urine (7%). 

Adminstartion

Administration: 

Oral administration 

• dabigatran is usually taken orally two times a day with/without food, as directed by a healthcare professional. 
• The dose of dabigatran can vary depending on patient medical condition being treated, as well as other individual factors such as age, weight, and kidney function. It is important to follow the specific dosing instructions provided by a healthcare professional. 
• dabigatran should be swallowed whole with a glass of water. The medication should not be crushed, chewed, or opened. 
• If a dose of dabigatran is missed, it should be taken as soon as possible, unless it is within 6 hours of the next scheduled dose. If a dose is missed, it is recommended to take it as soon as possible, unless it is almost time for the next scheduled dose, in which case it is advisable to skip the missed dose and resume with the regular dosing schedule. 
• dabigatran can increase the risk of bleeding, so it is important to monitor for signs of bleeding such as easy bruising, nosebleeds, or prolonged bleeding from cuts. In the case of significant bleeding, a healthcare professional should be consulted immediately. 
• dabigatran can interact with certain other medications, so it is important to inform a healthcare professional of all medications being taken, including over-the-counter medications, herbal supplements, and vitamins. 
• dabigatran should be stored at room temperature,dry place and away from direct sunlight. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dabigatran 

Pronounced: [ da-BIG-a-tran ]  

Why do we use dabigatran? 

dabigatran is a medication class of drugs called direct oral anticoagulants . It is primarily used to stop blood clots and reduce the risk of stroke in people with atrial fibrillation. 

Some other uses of dabigatran include: 

• Treating and preventing blood clots in deep vein thrombosis and pulmonary embolism. 
• Preventing blood clots in people who have undergone hip/knee replacement surgery. 
• Treating and preventing blood clots in people with venous thromboembolism. 
• Reducing the risk of repeated VTE in people who have previous history episode of VTE.