Dabigatran
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Direct Thrombin Inhibitor, Therapy Class:
Anticoagulant, Dabigatran is an anticoagulant agent belonging to Direct thrombin Inhibitor.
Dabigatran is an anticoagulant used for the prevention of venous thromboembolic events or stroke in patients with recent elective hip or knee replacement surgery and atrial fibrillation.
The absolute bioavailability of dabigatran following oral administration of dabigatran etexilate is approximately 3 to 7%. The oral bioavailability of dabigatran etexilate increases by 75% when the pellets are taken without the capsule shell compared to the intact capsule formulation. Dabigatran capsules should therefore not be broken, chewed, or opened before administration. Dabigatran is approximately 35% bound to human plasma proteins. The red blood cell to plasma partitioning of dabigatran measured as total radioactivity is less than 0.3. The volume of distribution of dabigatran is 50 to 70 L. Dabigatran is eliminated primarily in the urine. After oral administration of radiolabeled dabigatran, 7% of radioactivity is recovered in urine and 86% in feces. The half-life of dabigatran in healthy subjects is 12 to 17 hours.
Dabigatran shows common side effects like Stomach pain, upset stomach, heartburn, and nausea.
Dabigatran is available in the form of Oral capsule.
Dabigatran is available in India, US, UK, Singapore, Canada, China, Japan, Russia and Australia.
Dabigatran belonging to the Direct thrombin Inhibitor, acts as an anticoagulant agent.
Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties.
The Data of onset of action and duration of action of Dabigatran is about 1-2 hours.
The Tmax was found to be approximately 1-2 hours of following the administration of Dabigatran.
Dabigatran is available in the form of Oral capsule.
Dabigatran capsule is taken orally twice daily.
Dabigatran is an anticoagulant used for the prevention of venous thromboembolic events or stroke in patients with recent elective hip or knee replacement surgery and atrial fibrillation.
Dabigatran is an anticoagulant agent belonging to Direct thrombin inhibitor.
Dabigatran is a competitive, selective, reversible direct inhibitor of free and fibrin-bound thrombin. It also prevents thrombin-mediated effects including cleavage of fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII, and inhibition of thrombin-induced platelet aggregation.
Dabigatran is approved for use in the following clinical indications
- Venous thromboembolism
Dabigatran is an anticoagulant used for the prevention of venous thromboembolic event.
- Nonvalvular atrial fibrillation
Dabigatran is used for the treatment of Nonvalvular atrial fibrillation.
Although not approved, there have been certain off-label indications. These include
- Pediatric Venous thromboembolic event (VTE), treatment and prevention (off label)
- Venous thromboembolism
- Deep vein thrombosis and/or pulmonary embolism (treatment) Oral capsule: 150 mg twice daily.
- Venous thromboembolism prophylaxis in total hip arthroplasty or total knee arthroplasty (alternative agent)
- Total hip arthroplasty
Oral capsule: Initial: 110 mg given 1 to 4 hours after completion of surgery and establishment of hemostasis or when dabigatran is not initiated on the day of surgery, give an initial dose of 220 mg after hemostasis has been achieved; then continue maintenance dose of 220 mg once daily for a minimum of 10 to 14 days. The optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days; some experts suggest a duration in the higher end of range (30 days) for total hip arthroplasty.
- Total knee arthroplasty (off-label use)
Oral capsule: Initial: 110 mg given 1 to 4 hours after completion of surgery and establishment of hemostasis or when dabigatran is not initiated on the day of surgery, give an initial dose of 220 mg after hemostasis has been achieved; then continue maintenance dose of 220 mg once daily for a minimum of 10 to 14 days; may be extended up to 35 days. Optimal duration of prophylaxis is unknown. Some experts suggest a duration in the lower end of the range (10 to 14 days) for total knee arthroplasty.
- Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism)
Oral capsule: 150 mg twice daily.
- Post-percutaneous coronary intervention with stent placement and nonvalvular atrial fibrillation (off label)
Oral capsule: 110 mg or 150 mg twice daily; dabigatran dose depends on patient-specific thrombotic and bleeding risk factors; administer with an appropriate antithrombotic regimen including clopidogrel (preferred P2Y12 inhibitor in this situation) with or without aspirin, depending on the risks for thrombosis and bleeding, and time since percutaneous coronary intervention (PCI). It is recommended to discontinue aspirin 1 to 4 weeks after PCI and continue dabigatran and clopidogrel.
- Pediatric Venous thromboembolic event (VTE), treatment and prevention (off-label use)
Oral pellets:
Infants 3 to <4 months
Weight 3 to <4 kg: Oral pellets: Oral: 30 mg twice daily.
Weight 4 to <7 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 50 mg twice daily.
Infants 4 to <5 months
Weight 3 to <4 kg: Oral pellets: Oral: 30 mg twice daily.
Weight 4 to <7 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 60 mg twice daily.
Infants 5 to <6 months
Weight 3 to <4 kg: Oral pellets: Oral: 30 mg twice daily.
Weight 4 to <5 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <11 kg: Oral pellets: Oral: 60 mg twice daily.
Infants 6 to <7 months
Weight 4 to <5 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 60 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 80 mg twice daily.
Infants 7 to <8 months
Weight 4 to <5 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 60 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 80 mg twice daily.
Infants 8 to <9 months
Weight 4 to <5 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 60 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 80 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 100 mg twice daily.
Infants 9 to <10 months
Weight 4 to <5 kg: Oral pellets: Oral: 40 mg twice daily.
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 80 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 100 mg twice daily.
Infants 10 to <11 months
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 80 mg twice daily.
Weight 11 to <16 kg: Oral pellets: Oral: 100 mg twice daily.
Infants 11 to <12 months
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 90 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 100 mg twice daily.
Weight 13 to <16 kg: Oral pellets: Oral: 140 mg twice daily.
Children <1.5 years
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 90 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 100 mg twice daily.
Weight 13 to <21 kg: Oral pellets: Oral: 140 mg twice daily.
Children 1.5 to <2 years
Weight 5 to <7 kg: Oral pellets: Oral: 50 mg twice daily.
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 90 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 110 mg twice daily.
Weight 13 to <21 kg: Oral pellets: Oral: 140 mg twice daily.
Weight 21 to <26 kg: Oral pellets: Oral: 180 mg twice daily.
Children 2 to <12 years
Weight 7 to <9 kg: Oral pellets: Oral: 70 mg twice daily.
Weight 9 to <11 kg: Oral pellets: Oral: 90 mg twice daily.
Weight 11 to <13 kg: Oral pellets: Oral: 110 mg twice daily.
Weight 13 to <16 kg: Oral pellets: Oral: 140 mg twice daily.
Weight 16 to <21 kg: Oral pellets: Oral: 170 mg twice daily.
Weight 21 to <41 kg: Oral pellets: Oral: 220 mg twice daily.
Weight ≥41 kg: Oral pellets: Oral: 260 mg twice daily.
Capsules:
Children ≥8 years and Adolescents <18 years
Weight 11 to <16 kg: Capsules: Oral: 75 mg twice daily.
Weight 16 to <26 kg: Capsules: Oral: 110 mg twice daily.
Weight 26 to <41 kg: Capsules: Oral: 150 mg twice daily.
Weight 41 to <61 kg: Capsules: Oral: 185 mg twice daily.
Weight 61 to <81 kg: Capsules: Oral: 220 mg twice daily.
Weight ≥81 kg: Capsules: Oral: 260 mg twice daily.
Dabigatran is available in various strengths as 75mg, 110mg and 150mg.
Dabigatran is available in the form of Oral capsule.
Dosage Adjustment in Kidney Patient
- Deep vein thrombosis and/or pulmonary embolism (treatment)
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: Avoid use.
- Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism)
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl 15 to ≤30 mL/minute: Oral capsule: 75 mg twice daily.
CrCl <15 mL/minute: Avoid use.
- Venous thromboembolism prophylaxis
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: Avoid use (expert opinion).
Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo Biloba. Avoid St. John's Wort this herb induces PGP which may reduce the serum levels of Dabigatran.
Dabigatran is contraindicated in patients with
- Active pathological bleeding.
- History of a serious hypersensitivity reaction to Dabigatran (e.g., anaphylactic reaction or anaphylactic shock).
- Mechanical prosthetic heart valve.
- Bleeding
The most common complication is bleeding, including severe and potentially fatal bleeding. Risk factors for bleeding include concurrent use of drugs that increase the risk of bleeding (eg, antiplatelet agents, heparin), renal impairment, and elderly patients (especially if low body weight). Discontinue in patients with active pathological bleeding. Important: Idarucizumab is the most effective agent for dabigatran reversal; efficacy and safety of idarucizumab have not been established in pediatric patients. Protamine and vitamin K do not reverse or impact the anticoagulant effects of dabigatran. Dabigatran is dialyzable (~57% removed over 4 hours); however, supporting data are limited for utilizing this method. Depending on the bleeding severity, activated oral charcoal should be considered if ingestion occurred within 1 to 2 hours of presentation. The following alternative options may also be considered depending on the clinical scenario and availability of idarucizumab: 4-factor unactivated prothrombin concentrate (PCC) (eg, Kcentra) or 4-factor activated prothrombin complex concentrate (aPCC) (eg, FEIBA). Some studies and case reports have shown moderate success in correcting coagulation tests with some of these agents; however, correction of coagulation tests does not imply reversal of the anticoagulation effect of the medication. Platelet concentrates should be considered when thrombocytopenia is present or long-acting antiplatelet drugs have been used.
- Thromboembolic events
[US Boxed Warning]: Upon premature discontinuation, the risk of thrombotic events is increased. If dabigatran must be discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant during the time of interruption. In patients with non-valvular atrial fibrillation who had an acute ischemic stroke while receiving a direct oral anticoagulant (DOAC) (eg, dabigatran), guidelines generally support withholding oral anticoagulation until 1 to 2 weeks after the ischemic stroke (time frame may vary with shorter times for transient ischemic attack or small, non-disabling stroke and longer times for moderate to severe stroke).
- Antiphospholipid syndrome
Use is not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome; safety and efficacy have not been established. Patients positive for all three antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-beta-2 glycoprotein I) may have increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.
- GI/Bariatric surgery
Altered absorption: Evaluate the risk versus benefit of possible decreased drug absorption. Dabigatran capsules are designed to release in the stomach, which is dependent on an acidic environment. Absorption primarily occurs in the proximal small intestine. Surgeries that increase the pH (more alkaline) of the stomach (eg, Roux-en-Y gastric bypass) or decrease small intestine sites may decrease absorption of dabigatran. The available data are conflicting for absorption alterations, derived from small populations, and underrepresent individual DOACs and distinct surgeries.
Breast Feeding Warning
It is not known whether dabigatran is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Dabigatran is administered to a nursing woman.
Pregnancy Warning
Use of direct-acting oral anticoagulants increases the risk of bleeding in all patients. When used in pregnancy, there is also the potential for fetal bleeding or subclinical placental bleeding which may increase the risk of miscarriage, preterm delivery, fetal compromise, or stillbirth. Direct-acting oral anticoagulants during pregnancy and use in pregnant patients is not recommended.
Food Warning
Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo Biloba. Avoid St. John's Wort this herb induces PGP which may reduce the serum levels of Dabigatran.
- Common Adverse effects
Abdominal discomfort, abdominal pain, dyspepsia, epigastric discomfort, esophagitis, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, hemorrhagic gastritis, upper abdominal pain, acute myocardial infarction, hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, genitourinary tract hemorrhage (major), retroperitoneal hemorrhage (major), allergic angioedema, anaphylactic shock, anaphylaxis, hypersensitivity reaction, intracranial hemorrhage.
- Rare Adverse effects
Gastrointestinal ulcer, Spinal hematoma (with spinal puncture or spinal/epidural anesthesia), Epidural intracranial hemorrhage (with spinal puncture or spinal/epidural anesthesia), Alopecia, Esophageal ulcer, Agranulocytosis, neutropenia, thrombocytopenia, angioedema.
- Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
- Antacids: May decrease the serum concentration of Dabigatran Etexilate. Management: Dabigatran etexilate Canadian product labeling recommends avoiding concomitant use with antacids for 24 hours after surgery. In other situations, administer dabigatran etexilate 2 hours prior to antacids. Monitor clinical response to dabigatran therapy.
- Anticoagulants: Dabigatran Etexilate may enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.
- Antiplatelet Agents (P2Y12 Inhibitors): May enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Antiplatelet Agents (P2Y12 Inhibitors) may increase the serum concentration of Dabigatran Etexilate. Specifically, clopidogrel may increase dabigatran serum concentrations. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
- Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.
- Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
- Aspirin: May enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling states that low dose aspirin could be considered, but the use of antiplatelets are not recommended for stroke prevention in patients with atrial fibrillation.
- Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
- Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
- Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
- Dronedarone: May increase the serum concentration of Dabigatran Etexilate. Management: Dose reductions and/or avoidance of this combination may be necessary. Specific recommendations vary by renal function and indication for dabigatran. Refer to full interaction monograph for details.
- Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment.
- Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-GP substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-GP substrates.
- Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Coadministration may enhance the anticoagulant effect of Anticoagulants.
- Nonsteroidal Anti-Inflammatory Agents (Nonselective): Coadministration may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
- Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL.
- Oritavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses.
- Pacritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors).
- Salicylates: May enhance the anticoagulant effect of Anticoagulants.
- Thrombolytic Agents: May enhance the anticoagulant effect of Dabigatran Etexilate. Management: Carefully monitor for bleeding. Dabigatran Canadian labeling recommends avoiding use with thrombolytic agents. Consider avoiding alteplase treatment of acute ischemic stroke in patients receiving dabigatran.
The common side effects of Dabigatran include the following
- Common
Stomach pain, upset stomach, heartburn, nausea.
- Rare
Unusual bruising or bleeding, pink or brown urine, red or black, tarry stools, coughing up blood, vomiting material that is bloody or looks like coffee grounds, bleeding from the gums, frequent nosebleeds, heavy menstrual bleeding, bleeding from a cut that lasts longer than normal, joint pain or swelling, headache, dizziness or feeling faint, weakness, hives, rash, itching, difficulty breathing or swallowing, chest pain or tightness, swelling of the face, throat, tongue, lips, eyes, arms, hands, feet, ankles, or lower legs.
Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Dabigatran has been shown to decrease the number of implantations when male and female rats were treated at a dosage of 70 mg/kg (about 2.6 to 3.0 times the human exposure at the maximum recommended human dose [MRHD] of 300 mg/day based on area under the curve [AUC] comparisons) prior to mating and up to implantation (gestation Day 6). Treatment of pregnant rats after implantation with dabigatran at the same dose increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. Although dabigatran increased the incidence of delayed or irregular ossification of fetal skull bones and vertebrae in the rat, it did not induce major malformations in rats or rabbits.
- Nursing Mothers
It is not known whether dabigatran is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Dabigatran is administered to a nursing woman.
- Pediatric Use
As per FDA, safety and effectiveness of Dabigatran in pediatric patients has not been established.
- Geriatric Use
Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups.
Accidental overdose may lead to hemorrhagic complications. There is no antidote to dabigatran etexilate or dabigatran. In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with Dabigatran, and investigate the source of bleeding. Dabigatran is primarily excreted in the urine and shows low plasma protein binding. Therefore, dabigatran can be dialyzed with the removal of about 60% of drug over 2 to 3 hours; however, data supporting this approach are limited. Consider surgical hemostasis or the transfusion of fresh frozen plasma or red blood cells. There is some experimental evidence to support the role of activated prothrombin complex concentrates (e.g., FEIBA), or recombinant Factor VIIa, or concentrates of coagulation factors II, IX or X; however, their usefulness in clinical settings has not been established. Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used. Measurement of aPTT or ECT may help guide therapy.
Pharmacodynamic
Dabigatran etexilate is a double prodrug that is hydrolyzed to the active dabigatran by intestinal and hepatic carboxylesterases. Dabigatran is a reversible competitive thrombin inhibitor that directly inhibits the conversion by thrombin of fibrinogen to fibrin, impairing the clotting process and acting as an anticoagulant. Dabigatran use prolongs coagulation markers such as the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT), and dilute thrombin time (DTT), but not the international normalized ratio (INR), which cannot be used in this context as it can in warfarin monitoring.
Pharmacokinetics
- Absorption
The absolute bioavailability of dabigatran following oral administration of dabigatran etexilate is approximately 3 to 7%. Dabigatran etexilate is a substrate of the efflux transporter P-gp. After oral administration of dabigatran etexilate in healthy volunteers, Cmax occurs at 1-hour post-administration in the fasted state. Coadministration of Dabigatran with a high-fat meal delays the time to Cmax by approximately 2 hours but has no effect on the bioavailability of dabigatran; Dabigatran may be administered with or without food. The oral bioavailability of dabigatran etexilate increases by 75% when the pellets are taken without the capsule shell compared to the intact capsule formulation. Dabigatran capsules should therefore not be broken, chewed, or opened before administration.
- Distribution
Dabigatran is approximately 35% bound to human plasma proteins. The red blood cell to plasma partitioning of dabigatran measured as total radioactivity is less than 0.3. The volume of distribution of dabigatran is 50 to 70 L. Dabigatran pharmacokinetics are dose-proportional after single doses of 10 to 400 mg. Given twice daily, dabigatran's accumulation factor is approximately two.
- Metabolism
After oral administration, dabigatran etexilate is converted to dabigatran. The cleavage of the dabigatran etexilate by esterase-catalyzed hydrolysis to the active principle dabigatran is the predominant metabolic reaction. Dabigatran is not a substrate, inhibitor, or inducer of CYP450 enzymes. Dabigatran is subject to conjugation forming pharmacologically active acyl glucuronides. Four positional isomers, 1-O, 2-O, 3-O, and 4-O-acyl glucuronide exist, and each account for less than 10% of total dabigatran in plasma.
- Excretion
Dabigatran is eliminated primarily in the urine. Renal clearance of dabigatran is 80% of total clearance after intravenous administration. After oral administration of radiolabeled dabigatran, 7% of radioactivity is recovered in urine and 86% in feces. The half-life of dabigatran in healthy subjects is 12 to 17 hours.
There are some clinical studies of the drug Dabigatran mentioned below:
- Grottke O, Aisenberg J, Bernstein R, Goldstein P, Huisman MV, Jamieson DG, Levy JH, Pollack CV, Spyropoulos AC, Steiner T, Del Zoppo GJ. Efficacy of prothrombin complex concentrates for the emergency reversal of dabigatran-induced anticoagulation. Critical Care. 2016 Dec;20(1):1-5.
- Moj D, Maas H, Schaeftlein A, Hanke N, Gómez-Mantilla JD, Lehr T. A comprehensive whole-body physiologically based pharmacokinetic model of dabigatran etexilate, dabigatran and dabigatran glucuronide in healthy adults and renally impaired patients. Clinical pharmacokinetics. 2019 Dec;58(12):1577-93.
- Nagarakanti R, Ellis CR. Dabigatran in clinical practice. Clinical therapeutics. 2012 Oct 1;34(10):2051-60.
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf
- https://www.uptodate.com/contents/dabigatran-drug-information#F6211464
- https://www.rxlist.com/pradaxa-drug.htm#warnings
- https://reference.medscape.com/drug/pradaxa-dabigatran-342135
- https://medlineplus.gov/druginfo/meds/a610024.html#special-dietary
- https://www.mims.com/india/drug/info/dabigatran?type=full&mtype=generic
- https://go.drugbank.com/drugs/DB06695
- https://www.drugs.com/dosage/dabigatran.html
Published on: 25 Oct 2022 6:07 AM GMT
