Mechanism of Action
- Local fibrinolysis by binding to fibrin, converts entrapped plasminogen to plasmin
Pharmacokinetics
- Half-Life: 12-14 hours
- Metabolism: Lower gastric region and duodenum
- Time to peak: 2 to 3 hours
- Oral availability: ~3-7%
- Excretion: 85% primarily Renal elimination of unchanged drug
- Protein binding: ~35%
Dosing – Pediatric
- For VTE treatment and prophylaxis for Pediatric patients. Do NOT use in patients with mechanical prosthetic heart valves (contraindicated due to increased risk of thromboembolic events). Dabigatran isn’t recommended in patients with antiphospholipid syndrome. Dabigatran is indicated for pediatric VTE treatment after 5-10 days of parenteral anticoagulation
- VTE treatment and thromboprophylaxis for pediatric patients at least 3 months of age and 3 kg or greater after at least 5 days of initial parenteral anticoagulant treatment, as well as nonvalvular atrial fibrillation prophylaxis for patients at least 8 years of age and 50 kg or greater.
Initiating Therapy
Minimum Monitoring Requirements: Prior to initiation of therapy or continuation of home therapy, but no longer than 48 hours before, the following labs should be checked: CBC, coagulation profile (PT, PTT, fibrinogen activity), hepatic function panel, creatinine, urine pregnancy if applicable
| Administration | |
| Oral Pellets | Administer if able to swallow soft, solid foods by mixing with only the following: apple juice, applesauce, baby rice cereal (prepared with water), mashed carrots, or mashed bananas. The pellets should NOT be administered with any milk products, should NOT be administered via a syringe or feeding tube, and should be administered within 30 min. of mixing with juice or food Soft food amount (applesauce, baby rice cereal, mashed carrots/bananas): ~2 teaspoons Apple juice amount: 1-2 oz. |
| Capsule | Administer with a full glass of water without regard to meals; however, if upset stomach 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. |
Pediatric Dosing for VTE treatment and prevention
**Initiate after ≥5 days of parenteral anticoagulation for treatment. For prevention, initiate after treatment complete. Dosing is based on patient WEIGHT and AGE.
Oral Pellets
| Infants 3 to <4 months | |
| 3 to <4 kg | 30 mg q12h |
| 4 to <7 kg | 40 mg q12h |
| 7 to <9 kg | 50 mg q12h |
| Infants 4 to <5 months | |
| 3 to <4 kg | 30 mg q12h |
| 4 to <7 kg | 40 mg q12h |
| 7 to <9 kg | 60 mg q12h |
| Infants 5 to <6 months | |
| 3 to <4 kg | 30 mg q12h |
| 4 to <5 kg | 40 mg q12h |
| 5 to <7 kg | 50 mg q12h |
| 7 to <11 kg | 60 mg q12h |
| Infants 6 to <8 months | |
| 4 to <5 kg | 40 mg q12h |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 60 mg q12h |
| 9 to <11k g | 80 mg 12h |
| Infants 8 to <9 months | |
| 4 to <5 kg | 40 mg q12h |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 60 mg q12h |
| 9 to <11 kg | 80 mg 12h |
| 11 to <13 kg | 100 mg q12h |
| Infants 9 to <10 months | |
| 4 to <5 kg | 40 mg q12h |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 80 mg 12h |
| 11 to <13 kg | 100 mg q12h |
| Infants 10 to <11 months | |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 80 mg 12h |
| 11 to <16 kg | 100 mg q12h |
| Infants 11 to <12 months | |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 90 mg q12h |
| 11 to <13 kg | 100 mg q12h |
| 13 to <16kg | 140 mg q12h |
| Children <1.5 years | |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 90 mg q12h |
| 11 to <13 kg | 100 mg q12h |
| 13 to <21kg | 140 mg q12h |
| Children 1.5 to <2 years | |
| 5 to <7 kg | 50 mg q12h |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 90 mg q12h |
| 11 to <13 kg | 110 mg q12h |
| 13 to <21 kg | 140 mg q12h |
| 21 to <26 kg | 180 mg q12h |
| Children 2 to <12 years | |
| 7 to <9 kg | 70 mg q12h |
| 9 to <11 kg | 90 mg q12h |
| 11 to <13 kg | 110 mg q12h |
| 13 to <16 kg | 140 mg q12h |
| 16 to <21 kg | 170 mg q12h |
| 21 to <41 kg | 220 mg q12h |
| ≥41 kg | 260 mg q12h |
Oral Capsules
| Children ≥8 years and adolescents | |
| 11 to <16 kg | 75 mg q12h |
| 16 to <26 kg | 110 mg q12h |
| 26 to <41 kg | 150 mg q12h |
| 41 to <61 kg | 185 mg q12h |
| 61 to <81 kg | 220 mg q12h |
| ≥81 kg | 260 mg q12h |
**It is important to note that in the pediatric clinical trials for dabigatran that continued treatment dosing for secondary prevention of VTE in children beyond the 3-month acute treatment phase, the dosing regimen was NOT changed.
Monitoring
Anticoagulation Monitoring Parameter and Reference Range
Routine coagulation testing is not required for monitoring of dabigatran. There is currently no FDA-approved assay or calibration reagent available. Observed peak and trough concentrations of dabigatran in patients exposed to therapeutic dosing have been reported. If monitoring is indicated, ecarin clotting time (ECT) and diluted thrombin time (dTT) are the preferred tests, but these assays aren’t available at PMCH/Special Coag Lab; additionally, therapeutic ranges haven’t been established.
Dosage Forms
- Dabigatran is available as capsules or oral pellets. The dosage forms are NOT interchangeable on a mg:mg basis due to PK differences (e.g., bioavailability). Combining dosage forms to achieve total dose is NOT recommended.
- Pellet dosage forms – 20 mg (60 each); 30 mg (60 each); 40 mg (60 each); 50 mg (60 each); 110 mg (60 each); 150 mg (60 each)
- Capsule dosage forms – 75 mg, 150 mg, 110 mg
Oral Pellets≥3 months to <12 years of age Capsules≥8 years of age - Patient assistance program for drug: Boehringer-Ingelheim
Safety Precautions
- Renal impairment: Consider on individual basis in consultation with IHTC, nephrology, and pharmacy for patients with CrCl <50 mL/minute. In general, for eGFR <50 mL/minute/1.73m2, avoid use.
- Hepatic impairment: There are no dosage adjustments provided in prescriber information. A small fraction of absorbed dabigatran is metabolized to glucuronides in the liver; however, this conjugation doesn’t change the activity of dabigatran. Therefore, a decrease in liver function isn’t expected to affect the activity of dabigatran significantly. Dabigatran undergoes elimination predominantly (~80%) through the kidney.
Drug-Drug interactions:
- Substrate of p-glycoprotein
- P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of dabigatran. Avoid concurrent use of dabigatran with P-glycoprotein inducers whenever possible.
- Drug interactions that increase drug levels: amiodarone, quinidine, azole antifungals (e.g., ketoconazole), ritonavir
- Drug interactions that decrease drug levels: rifampin, phenytoin, carbamazepine, St. John’s wort
- P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolites of dabigatran.
- Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) may enhance the anticoagulant effect of Anticoagulants.
- Drug-Food Interactions – Food delays the time to peak plasma concentration by 2 hours, administer without regard to meals for capsules.
