Phenprocoumon

Phenprocoumon is a long-acting oral anticoagulant and a derivative of coumarin. It is a vitamin K antagonist that inhibits coagulation by blocking the synthesis of clotting factors II, VII, IX, and X. It is used for prophylaxis and treatment of thromboembolic diseases (thrombosis/pulmonary embolism) and for prophylaxis of myocardial infarction in ventricular fibrillation. It is the standard coumarin used in Germany. It is administered in the form of peroral and parenteral preparations.

Pharmacodynamics

Phenprocoumon inhibits the enzyme vitamin K reductase, resulting in a deficiency of the reduced form of vitamin K (vitamin K2). Because vitamin K is a cofactor for the carboxylation of vitamin K-dependent proteins, this limits the gamma carboxylation and subsequent activation of vitamin K-dependent coagulation proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, is inhibited. This leads to a decreased prothrombin level which in turn leads to a decrease in thrombin. Thrombin is instrumental in the cross-linking of platelets. This significantly reduces the likelihood of thromboembolic events.

Pharmacokinetics

Bioavailability is close to 100%. Protein binding is 99%. Phenprocoumon is metabolized by hepatic microsomal enzymes (mainly CYP2C9 ) to inactive hydroxylated metabolites and by reductases to reduced metabolites. The elimination half-life is between 5 and 6 days.

Drug Interactions

In general, combination with other anticoagulants should be avoided as this may result in a severe bleeding tendency.

Side effects

Common side effects:

• Hematomas after injuries
• blood in urine
• Nosebleeds
• Bleeding gums

In rare cases, liver inflammation and dangerous brain bleeding may also occur.

Other less common side effects:

• Hair loss
• decrease in bone density
• gray discoloration of the skin
• urticaria
• skin necrosis

Toxicological data

LD50 (rat, oral): 200 mg-kg-1