Acenocoumarol

Acenocoumarol is an oral anticoagulant in the vitamin K antagonist class. It is used to prevent and treat thromboembolic disorders in adults, including nonvalvular atrial fibrillation, venous thromboembolism, and prophylaxis after certain orthopedic surgeries, as well as to prevent thrombosis in patients with prosthetic heart valves in some regions.

Mechanism and pharmacokinetics: Acenocoumarol inhibits vitamin K epoxide reductase, reducing the production of vitamin K–dependent clotting factors II, VII, IX, and X, along with proteins C and S. The anticoagulant effect is monitored by the international normalized ratio (INR). It has a relatively short half-life, approximately 8–11 hours, and is metabolized in the liver by cytochrome P450 enzymes, allowing relatively rapid adjustments in dose compared with some other anticoagulants.

Dosing and monitoring: Dosing is individualized and adjusted to achieve a therapeutic INR, typically in the range of 2.0–3.0 for many indications, with higher targets (for example 2.5–3.5) for certain mechanical valve scenarios according to local guidelines. Regular INR testing is required to maintain the desired anticoagulant effect. Doses may change with illnesses, drug interactions, or dietary vitamin K intake.

Interactions and cautions: Acenocoumarol interacts with many drugs and with dietary vitamin K. Antibiotics, antifungals, anticonvulsants, NSAIDs, and antiplatelet agents can alter INR and increase bleeding risk. Consistent vitamin K intake is advised. Contraindications include active major bleeding, pregnancy, significant hepatic impairment, and known hypersensitivity. In pregnancy, vitamin K antagonists are generally avoided in favor of safer alternatives.

Adverse effects and reversal: The principal adverse effect is bleeding, which can be serious. Rare reactions include skin necrosis and purple toe syndrome. Reversal in cases of major bleeding involves withholding the drug and administering vitamin K, with additional measures such as fresh frozen plasma or prothrombin complex concentrates as clinically indicated.