Oral Anticoagulants – Rivaroxaban and Dabigatran
- October 1, 2019
Rivaroxaban (Factor Xa inhibitor), dabigatran etexilate (direct thrombin inhibitor), or warfarin (vitamin K epoxide reductase inhibitor) can be used as oral anticoagulants for most indications. Warfarin remains first line for patients with mechanical heart valves or severe chronic kidney disease.
Rivaroxaban and dabigatran are licensed for:
Rivaroxaban and dabigatran have not been trialed head-to-head or with other new anticoagulants.
Rivaroxaban is available as 10 mg, 15 mg, and 20 mg tablets.
Dabigatran is available as 75 mg, 110 mg, and 150 mg capsules.
Mechanism of action
Rivaroxaban inhibits Factor Xa, a key enzyme in the coagulation system that converts prothrombin to thrombin, while dabigatran inhibits thrombin. These actions of rivaroxaban and dabigatran reduce clot formation and consequent thrombo-occlusive events.
Rivaroxaban has high oral bioavailability (F >80%).Rivaroxaban is partially renally cleared (~30%), with the remainder hepatically cleared (~30%, via cytochrome (CYP) enzymes, such as CYP 3A). Rivaroxaban is also a substrate of the efflux transporter P-glycoprotein (P-gp). Rivaroxaban has an average half-life of approximately 7 hours.
Dabigatran etexilate has low oral bioavailability (F 0.07). Following absorption dabigatran etexilate is rapidly and completely metabolised to dabigatran (active form). Dabigatran is renally cleared (> 80%), and has an average half-life of approximately 15 hours.
Factors affecting pharmacokinetics
Rivaroxaban serum concentrations are altered by drugs that inhibit/ induce liver enzymes or P-gp, and in renal impairment. Avoid drugs that are major inhibitors/ inducers of both CYP 3A enzymes and P-gp (see the Pink Book) or call Medicines Information Service.
Dabigatran is affected by drugs that inhibit/ induce P-gp. P-gp inhibitors (e.g. ketoconazole) can increase fractional oral bioavailability and consequently serum concentrations of dabigatran. Avoid major P-gp inhibitors, else seek guidance from Medicines Information Service. Reduce doses in patients with creatinine clearance less than 80 mL/min and avoid in patients with creatinine clearance less than 30 mL/min.
For both drugs periodically monitor renal function. Coagulation tests and drug concentrations can be monitored, but seek guidance from haematology or Medicines Information Service.
The most common non-bleeding adverse effects of rivaroxaban and dabigatran are gastrointestinal disorders (e.g. nausea, vomiting, diarrhoea, dyspepsia and abdominal pain).
Management of bleeding
For both standard treatment measures should be instituted (e.g. compression, surgery, fluid replacement, blood products (e.g. packed red cells, fresh frozen plasma or platelets)). Phytomenadione (vitamin K) is not useful.
Repacking into compliance packaging
Due to limited information available on the stability of medicines repacked into compliance packaging, only repack medicines if the benefits of compliance packaging outweigh the risk of the medicine being less stable in compliance packaging.
For further information, please see repackaging dabigatran bulletin.