Angioedema and hypersensitivity reactions (eg, anaphylaxis): Discontinue therapy immediately with anaphylaxis or angioedema involving the tongue, hypopharynx, or larynx; initiate supportive care.
Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Dabigatran etexilate is an Anticoagulant Agent belonging to pharmacology class of Direct thrombin inhibitors.
Dabigatran etexilate can be used in the treatment of deep venous thrombosis and pulmonary embolism treatment and prevention, nonvalvular atrial fibrillation, venous thromboembolism prophylaxis in total hip arthroplasty. It is also used to treat Venous thromboembolism prophylaxis in total knee arthroplasty.
Dabigatran etexilate is Rapidly absorbed from the gastrointestinal tract; initially slow (postoperative). Food delays time to peak plasma concentration. Bioavailability: Approx 3-7%, may be increased by up to 75% (without cap shell). Time to peak plasma concentration: 0.5-2 hours; approx 6 hours (postoperative) and enters breast milk with Volume of distribution of 50-70 L and Plasma protein binding of approx 35%. Dabigatran etexilate is rapidly and completely metabolised in the liver by plasma and hepatic esterases via hydrolysis to its active metabolite, dabigatran, which then undergoes hepatic glucuronidation to form its active acylglucuronide isomers and get excreted mainly via urine (approx 80-85%, as unchanged drug). Elimination half-life: Approx 12-17 hours.
The common side effects of Dabigatran etexilate includes: Thromboembolic events (premature discontinuation), bleeding, spinal or epidural haematoma resulting to long term or permanent paralysis. Blood and lymphatic system disorders: Anemia.
Dabigatran etexilate is available in the form of Capsule.
The molecule is available in India, Japan, Germany, China
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.
Tmax of Dabigatran etexilate was 3-8 hours (tablet); 4-12 hours (oral suspension).
Dabigatran etexilate is available in Capsule.
Oral capsule: Administer capsules with a full glass of water without regard to meals; however, if dyspepsia occurs, consider administration with meals. Do not break, chew, or open capsules, as this will lead to 75% increase in absorption and potentially serious adverse reactions.
Dabigatran etexilate can be used in the treatment of deep venous thrombosis and pulmonary embolism treatment and prevention, nonvalvular atrial fibrillation, venous thromboembolism prophylaxis in total hip arthroplasty. It is also used to treat Venous thromboembolism prophylaxis in total knee arthroplasty.
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 etexilate is approved for use in the following clinical indications
Deep venous thrombosis and pulmonary embolism treatment and prevention: Treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in pediatric patients ≥3 months to <12 years of age (oral pellets), pediatric patients ≥8 to <18 years of age (capsules), and adults (capsules) who have been treated with a parenteral anticoagulant for ≥5 days; to reduce the risk of recurrence of DVT and PE in pediatric patients ≥3 months of age to <12 years of age (oral pellets), pediatric patients ≥8 to <18 years of age (capsules), and adults (capsules) who have been previously treated.
Nonvalvular atrial fibrillation: Prevention of stroke and systemic embolism in adult patients (capsules) with nonvalvular atrial fibrillation.
Venous thromboembolism prophylaxis in total hip arthroplasty: Prophylaxis of DVT and PE in adult patients (capsules) who have undergone total hip arthroplasty.
Although not approved there have been certain off labeled uses documented for Dabigatran etexilate which includes:
Venous thromboembolism prophylaxis in total knee arthroplasty.
Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism):
Oral capsule: 150 mg twice daily. Note: Patients who are particularly concerned about the risk of bleeding or those assessed to be at increased risk of bleeding, may be considered candidates for an alternative lower dose regimen of 110 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.
Venous thromboembolism:
Deep vein thrombosis and/or pulmonary embolism (treatment): Note: Dabigatran has not been studied in patients with active cancer; another anticoagulant is likely more appropriate.
After at least 5 days of initial therapy with a parenteral anticoagulant, transition to dabigatran in hemodynamically stable patients:
Oral capsule: 150 mg twice daily.
Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and is dependent on many factors, such as presence of provoking events, patient risk factors for recurrence and bleeding, and individual preferences.
Provoked venous thromboembolism: 3 months (provided provoking risk factor is no longer present).
Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of venous thromboembolism (VTE) recurrence and bleeding .
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals.
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 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. 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) :
oOral capsule: Initial: 110 mg given 1 to 4 hours after completion of surgery and establishment of hemostasis or when dabigatran is not initiated on day of surgery, give an initial dose of 220 mg after hemostasis has been achieved; then continue maintenance dose of 220 mg once daily (Eriksson 2007a) 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
75 mg, 110 mg, 150 mg.
Capsule
Dose Adjustment in Kidney Patient:
Deep vein thrombosis and/or pulmonary embolism (treatment): Note: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance, specifically when CrCl <50 mL/minute; consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: Avoid use. No clinical data as patients with CrCl ≤30 mL/minute were excluded from clinical trials.
Hemodialysis/peritoneal dialysis: Avoid use .
Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism): Note: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance, specifically when CrCl <50 mL/minute; consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl 15 to ≤30 mL/minute: Oral capsule: 75 mg twice daily. Note: Patients with CrCl <30 mL/minute were excluded from the RE-LY trial . Recommended dose is based on pharmacokinetic data suggesting that this dose provides similar exposure to the recommended dose in patients with CrCl >30 mL/minute ; safety and efficacy have not been established. Some experts consider dabigatran contraindicated in patients with severe kidney impairment (CrCl ≤30 mL/minute).
CrCl <15 mL/minute: Avoid use .
Hemodialysis, intermittent (thrice weekly): Avoid use. Dialyzable (49% to 59% over 4 hours ). Use in hemodialysis patients has been associated with increased risk of major bleeding .
Peritoneal dialysis: Avoid use.
Venous thromboembolism prophylaxis: Note: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance, specifically when CrCl <50 mL/minute; consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: Avoid use. Patients with CrCl <30 mL/minute were excluded from clinical trials.
Hemodialysis/peritoneal dialysis: Avoid use
- Dose Adjustment in Pediatric Patient:
Venous thromboembolic event (VTE), treatment and prevention: Note: For treatment, initiate dabigatran after 5 days of treatment with a parenteral anticoagulant; for prevention, initiate dabigatran after treatment is complete. Adjust dose during treatment according to age and actual weight:
Oral pellets:
Note: Dosing is based on weight AND age; use caution when selecting dose. Twice-daily dosing should be as close to a 12-hour dosing interval as is possible.
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.
Transitioning between anticoagulants:
Infants ≥3 months, Children, and Adolescents <18 years:
Note: This provides general guidance on transitioning between anticoagulants; also refer to institutional protocol for additional detail:
Transitioning from oral or parenteral anticoagulant to dabigatran: Capsules and oral pellets:
Transitioning from low molecular weight heparin or fondaparinux (therapeutic dose) to dabigatran: Initiate dabigatran 0 to 2 hours prior to the time of the next scheduled dose of the parenteral anticoagulant.
Transitioning from continuously administered parenteral anticoagulant (eg, IV unfractionated heparin) to dabigatran: Start dabigatran when continuously administered parenteral anticoagulant is discontinued.
Transitioning from warfarin to dabigatran: Discontinue warfarin and initiate dabigatran when the INR is <2.
Transitioning from dabigatran to another anticoagulant: Capsules and oral pellets:
Transitioning from dabigatran to parenteral anticoagulant: After the last dose of dabigatran, wait 12 hours before starting a parenteral anticoagulant.
Transitioning from dabigatran to warfarin: Note: Dabigatran can elevate the INR, complicating interpretation if overlapped with warfarin. To minimize interference, check INR near the end of dabigatran dosing interval. Warfarin's effect on the INR will be better reflected only after dabigatran has been stopped for ≥2 days. Calculate eGFR using the Schwartz formula:
eGFR ≥50 mL/minute/1.73 m2: Initiate warfarin 3 days before discontinuing dabigatran.
eGFR <50 mL/minute/1.73 m2: Dabigatran should not be used (has not been studied).
Transitioning from dabigatran in the perioperative setting: Note: Calculate eGFR using the Schwartz formula: Capsules and oral pellets:
eGFR >80 mL/minute/1.73 m2: Discontinue dabigatran 24 hours before elective surgery.
eGFR 50 to 80 mL/minute/1.73 m2: Discontinue dabigatran 2 days before elective surgery.
eGFR <50 mL/minute/1.73 m2: Dabigatran should not be used.
Dabigatran etexilate may be contraindicated in the following conditions:
Myasthenia gravis, uncontrolled narrow-angle glaucoma , severe gastrointestinal condition (e.g. toxic megacolon, gastric retention); urinary retention (when used for overactive bladder). Patient undergoing haemodialysis. Severe hepatic impairment (Child-Pugh class C). Concomitant use with strong CYP3A4 inhibitors in patients with severe renal or moderate hepatic impairment.
Concerns related to adverse effects:
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), kidney impairment, and older 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 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: 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).
Alcohol Warning
There is no sufficient scientific evidence traceable regarding use and safety of Dabigatran etexilate in concurrent use with alcohol.
Breast Feeding Warning
Dabigatran etexilate is present in breast milk.
Information is available from 2 women given dabigatran etexilate 220 mg orally 2 to 7 days postpartum. Breast milk was sampled up to 10 hours following a single dose. Maximum concentrations occurred ~2 hours (maternal plasma) and ~7 hours (breast milk) after the dose. Dabigatran peak concentrations were 204.6 ng/mL (maternal plasma) and 8 ng/mL (breast milk) in subject 1 and 414.9 ng/mL (maternal plasma) and 53 ng/mL (breast milk) in subject 2. The women in this study had chosen not to breastfeed.
Food Warning
Food has no effect on the bioavailability of dabigatran, but delays the time to peak plasma concentrations by 2 hours.
Management: Administer without regard to meals.
The adverse reactions related to Dabigatran etexilate can be categorized as
Common Adverse effects:
Thromboembolic events (premature discontinuation), bleeding, spinal or epidural hematoma resulting to long term or permanent paralysis. Blood and lymphatic system disorders: Anemia.
Less Common Adverse effects:
Dyspepsia, gastritis, nausea, diarrhea, abdominal pain, gastrointestinal, hemorrhage.
Rare Adverse effects:
The clinically relevant drug interactions of Dabigatran etexilate is briefly summarized here:
- Increased plasma concentration with verapamil, amiodarone, quinidine, clarithromycin, ticagrelor, posaconazole.
- May increase the risk of spinal or epidural haematomas with neuraxial anaesthesia.
- May either increase or decrease serum concentration with ritonavir. May decrease plasma levels with pantoprazole.
- Decreased plasma concentrations with P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin).
The most common side effects of Dabigatran etexilate includes:
Thromboembolic events (premature discontinuation), bleeding, spinal or epidural hematoma resulting to long term or permanent paralysis. Blood and lymphatic system disorders: Anemia.
Pregnancy Category (FDA): C
Pregnancy Category (AUS): Dabigatran is not included in Australian Drug Evaluation Committee (ADEC) Pregnancy Categories.
Labor and Delivery
Safety and effectiveness of PRADAXA during labor and delivery have not been studied in clinical trials. Consider the risks of bleeding and of stroke in using PRADAXA in this setting.
Death of offspring and mother rats during labor in association with uterine bleeding occurred during treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21) with dabigatran at a dose of 70 mg/kg (about 2.6 times the human exposure at MRHD of 300 mg/day based on AUC comparisons).
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 PRADAXA is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of PRADAXA in pediatric patients have 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.
Use In Renal Impair=No dose adjustment of PRADAXA is recommended in patients with mild or moderate renal impairment. Reduce the dose of PRADAXA in patients with severe renal impairment (CrCl 15-30 mL/min). Dosing recommendations for patients with CrCl <15 mL/min or on dialysis cannot be provided.
Adjust dose appropriately in patients with renal impairment receiving concomitant P-gp inhibitors.
Gender
FDA Package Insert for Dabigatran contains no information regarding Gender.
Race
FDA Package Insert for Dabigatran contains no information regarding Race.
Renal Impairment
FDA Package Insert for Dabigatran contains no information regarding Renal Impairment.
Hepatic Impairment
FDA Package Insert for Dabigatran contains no information regarding Hepatic Impairment.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Dabigatran was not carcinogenic when administered by oral gavage to mice and rats for up to 2 years. The highest doses tested (200 mg/kg/day) in mice and rats were approximately 3.6 and 6 times, respectively, the human exposure at MRHD of 300 mg/day based on AUC comparisons.
Dabigatran was not mutagenic in in vitro tests, including bacterial reversion tests, mouse lymphoma assay and chromosomal aberration assay in human lymphocytes, and thein vivo micronucleus assay in rats.
In the rat fertility study with oral gavage doses of 15, 70, and 200 mg/kg, males were treated for 29 days prior to mating, during mating up to scheduled termination, and females were treated 15 days prior to mating through gestation Day 6. No adverse effects on male or female fertility were observed at 200 mg/kg or 9 to 12 times the human exposure at MRHD of 300 mg/day based on AUC comparisons. However, the number of implantations decreased in females receiving 70 mg/kg, or 3 times the human exposure at MRHD based on AUC comparisons.
Immunocompromised Patients
FDA Package Insert for Dabigatran contains no information regarding Immunocompromised Patients.
Miscellaneous
FDA Package Insert for Dabigatran contains no information regarding Miscellaneous.
Symptoms: Hemorrhagic complications.
Management: Symptomatic and supportive treatment. Individualized based on the severity and location of hemorrhage. May give activated charcoal if ingestion occurred within 1-2 hours of presentation; consider surgical haemostasias and blood volume replacement. Administer idarucizumab as an antidote for situations when rapid reversal of anticoagulant effect is required. May consider administration of coagulation factor concentrates (activated or non-activated) or recombinant Factor VIIa; platelet concentrates in case of thrombocytopenia or concomitant use of long-acting antiplatelet agents.
Pharmacodynamics:
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
Rapidly absorbed from the gastrointestinal tract; initially slow (postoperative). Food delays time to peak plasma concentration. Bioavailability: Approx 3-7%, may be increased by up to 75% (without cap shell). Time to peak plasma concentration: 0.5-2 hours; approx 6 hours (postoperative).
Distribution:
Enters breast milk. Volume of distribution: 50-70 L. Plasma protein binding: Approx 35%.
Metabolism:
Dabigatran etexilate is rapidly and completely metabolised in the liver by plasma and hepatic esterases via hydrolysis to its active metabolite, dabigatran, which then undergoes hepatic glucuronidation to form its active acylglucuronide isomers.
Excretion:
Mainly via urine (approx 80-85%, as unchanged drug). Elimination half-life: Approx 12-17 hours.
- https://www.uptodate.com/contents/ Dabigatran etexilate -drug-information?search= Dabigatran etexilate &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F154338
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf
- https://www.medicaid.nv.gov/Downloads/provider/ Dabigatran etexilate _2015-1215.pdf
- https://www.mims.com/india/drug/info/ Dabigatran etexilate ?type=full&mtype=generic#mechanism-of-action
