dicoumarol

B01AA01

Forms & Strengths

Adult Dosing

Initial dose: 25 to 200 mg on the first day, followed by 25 to 100 mg daily based on daily prothrombin time/INR determinations
Maintenance dose: Typically 25 to 75 mg daily adjusted to target INR (usually 2.0 to 3.0)

Pediatric Dosing

Safety and efficacy in pediatric patients have not been established; use is generally avoided

Indications

Prophylaxis and treatment of venous thrombosis and its extension
Prophylaxis and treatment of pulmonary embolism
Thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement

Mechanism of Action

Vitamin K antagonist that inhibits the synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X) and anticoagulant proteins C and S
Blocks the gamma-carboxylation of glutamic acid residues on precursor proteins via inhibition of vitamin K epoxide reductase

Contraindications

Hypersensitivity to dicoumarol or any component of the formulation
Hemorrhagic tendencies or blood dyscrasias
Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces
Bleeding tendencies associated with active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tracts
Severe hepatic or renal impairment
Aneurysms, severe uncontrolled hypertension, pericarditis, and pericardial effusions
Pregnancy

Adverse Reactions

Drug Interactions

Significantly increased bleeding risk with antiplatelet agents (aspirin, clopidogrel) and NSAIDs
Potentiation of anticoagulant effect by CYP2C9 and CYP3A4 inhibitors (e.g., amiodarone, fluconazole, metronidazole)
Diminished anticoagulant effect by CYP inducers (e.g., rifampin, barbiturates, carbamazepine)
Decreased absorption and efficacy with concurrent administration of bile acid sequestrants (cholestyramine)
Altered response with dietary or supplemental vitamin K intake

Curated Content: Needs Vetting Before Put to Clinical Use