Direct oral anticoagulant (thrombin inhibitor)
Dabigatran is an anticoagulant (blood thinner) used to prevent stroke in people with atrial fibrillation and to treat and prevent blood clots. The capsules must not be opened or chewed. Like all anticoagulants, it increases the risk of bleeding.
Also known as: Pradaxa, dabigatran etexilate
Dabigatran with aspirin increases bleeding risk, especially gastrointestinal.
Aspirin inhibits platelets and injures the gastric mucosa, and dabigatran directly inhibits thrombin; the combination increases the risk of gastrointestinal and other bleeding in an additive way. The risk is higher in the elderly (over 75 years), renal impairment (dabigatran is eliminated renally), low body weight and a history of bleeding or ulcer. Anticoagulant plus antiplatelet combinations are reserved for specific indications (AF + recent coronary disease); outside them, avoid. If unavoidable, consider the lowest dabigatran dose, gastroprotection and monitoring for bleeding signs.
Aspirin + dabigatran: additive bleeding risk (antiplatelet + antithrombin + gastrointestinal injury). Assess the indication and dose.
Dabigatran inhibits thrombin and aspirin inhibits platelet COX-1; additive bleeding effect.
Monitor bleeding and dyspeptic symptoms.
GI bleeding, anaemia, haematuria.
Assess risk-benefit; the combination is used in selected AF + coronary artery disease.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen increases the bleeding risk with dabigatran.
Dabigatran is a direct thrombin inhibitor; ibuprofen reversibly inhibits platelet COX-1 and injures the gastric mucosa. The sum of these effects increases the risk of gastrointestinal and other bleeding. Aggravating factors: advanced age, renal impairment (dabigatran is eliminated renally), low body weight, history of bleeding or ulcer. Prefer, when needed, an analgesic without antiplatelet effect (paracetamol) and, if the NSAID is unavoidable, use the lowest dose for the shortest possible time, with monitoring of bleeding and renal function.
Dabigatran + ibuprofen: additive bleeding risk (antiplatelet effect + gastrointestinal injury). Avoid in high-risk patients and monitor for signs of bleeding.
Dabigatran and ibuprofen have additive anti-haemostatic effects; the NSAID also damages the gastric mucosa.
Monitor blood count and GI symptoms.
GI bleeding, acute anaemia.
Prefer alternative analgesia; if an NSAID is unavoidable, monitor closely.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Dabigatran plus clopidogrel increases bleeding risk.
Clopidogrel inhibits platelet aggregation and dabigatran directly inhibits thrombin; the combination adds up the anticoagulant effects and increases the risk of major bleeding, including intracranial and gastrointestinal bleeding. The dabigatran label states that the bleeding risk increases with the concomitant use of "other drugs affecting haemostasis, including antiplatelet agents" and warns about the added risk in elderly patients, with renal impairment or low body weight; the clopidogrel label states that the bleeding risk increases with "the concomitant use of other drugs that increase the risk of bleeding". The combination is avoided in practice (dual/triple therapy in atrial fibrillation is used for short periods and with restricted criteria — e.g. after stenting). If used, monitor for bleeding signs, renal function (dabigatran is renally eliminated) and consider a dabigatran dose reduction.
Clopidogrel + dabigatran: additive bleeding (antiplatelet + anticoagulant). Watch bleeding and renal function.
Combined thrombin and P2Y12 inhibition, with an additive bleeding effect.
Monitor blood count and bleeding signs.
Severe bleeding, melaena, haematemesis.
Use only with a clear indication; adjust the dabigatran dose to renal function.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Clopidogrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55731d95-0c99-ff61-e063-6394a90a1ab5 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Dabigatran-warfarin transition should follow a protocol to avoid under- or over-anticoagulation.
The combination of warfarin and dabigatran (two anticoagulants with different mechanisms — vitamin K antagonism and direct thrombin inhibition) has no therapeutic indication and multiplies the risk of major bleeding, including intracranial haemorrhage. Switching between the two drugs must follow a protocol: when changing from warfarin to dabigatran, stop warfarin and start dabigatran when the INR is below the threshold; conversely, start warfarin a few days before stopping dabigatran, monitoring the INR. Dual anticoagulation can occur transiently in poorly managed switches or by medication error — alert the patient to bleeding signs.
Two anticoagulants at the same time: additive bleeding risk. Do not combine; switching between warfarin and dabigatran requires a protocol (stop one, start the other with controlled INR/coagulation).
Switching requires coordination between dabigatran's immediate effect and warfarin's delayed onset.
Monitor INR and bleeding signs during the transition.
Supratherapeutic INR or bleeding during transition.
Follow the SmPC transition schedule; adjust with the INR.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Dabigatran should be taken with water, with or without food; taking it with a meal does not significantly change absorption.
Swallow the capsules whole with water, without opening them.
EMC-UK (MHRA) — approved Dabigatran SmPC: https://www.medicines.org.uk/emc/product/100715/smpc
Alcohol may potentiate the bleeding risk of dabigatran.
Limit alcohol intake during treatment.
EMC-UK (MHRA) — approved Dabigatran SmPC: https://www.medicines.org.uk/emc/product/100715/smpc
Dabigatran is predominantly renally eliminated; in severe renal impairment exposure increases markedly and bleeding risk is high.
Do not use with CrCl < 30 ml/min; assess renal function before starting.
EMC-UK (MHRA) — approved Dabigatran SmPC: https://www.medicines.org.uk/emc/product/100715/smpc
Dabigatran is contraindicated in clinically significant active bleeding.
Do not use in patients with active bleeding.
EMC-UK (MHRA) — approved Dabigatran SmPC: https://www.medicines.org.uk/emc/product/100715/smpc
Dabigatran is contraindicated in pregnancy because of the bleeding risk and lack of safety data.
Do not use in pregnancy; use LMWH when anticoagulation is needed.
Contraindicated during breastfeeding.
Women of childbearing age must use effective contraception during treatment.
EMC-UK (MHRA) — approved Dabigatran SmPC: https://www.medicines.org.uk/emc/product/100715/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Direct-acting oral anticoagulant, reversible inhibitor of thrombin (factor IIa). By inhibiting thrombin, it blocks the conversion of fibrinogen to fibrin and the activation of factors V, VIII and XIII and of platelets — the last step of the coagulation cascade. No routine coagulation monitoring is required.
Dabigatran binds to the active site of thrombin (factor IIa), both free and clot-bound, preventing fibrin formation and thrombin-dependent platelet activation. Pharmacodynamics are reflected in prolongation of aPTT, thrombin time and ECT.
Absolute bioavailability of oral dabigatran etexilate is only 3–7%; Cmax occurs ~1 hour after administration in the fasted state. A high-fat meal delays Cmax by ~2 hours without affecting bioavailability. Dabigatran is ~35% bound to plasma proteins and the volume of distribution is 50–70 L. Capsules must not be opened (bioavailability +75% without the capsule shell).
Dabigatran etexilate is converted to dabigatran by esterase-catalysed hydrolysis; dabigatran is then conjugated to four active acyl glucuronides (each <10% of plasma dabigatran). It is not a substrate, inhibitor or inducer of CYP450.
The half-life of dabigatran in healthy adults is 12–17 hours. Elimination is predominantly renal — renal clearance represents ~80% of total clearance after intravenous administration; exposure increases with the severity of renal impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
