Oral Anticoagulants

Phenprocoumon and Acenocoumarol. These agents are not generally available in the United States but are prescribed in Europe and elsewhere. Phenprocoumon (MARCUMAR) has a longer plasma half-life (5 days) than warfarin, as well as a somewhat slower onset of action and a longer duration of action (7 to 14 days). It is administered in daily maintenance doses of 0.75 to 6 mg. By contrast, acenocoumarol (SINTHROME) has a shorter half-life (10 to 24 hours), a more rapid effect on the PT, and a shorter duration of action (2 days). The maintenance dose is 1 to 8 mg daily.

Indandione Derivatives. Anisindione (MIRADON) is available for clinical use in some countries. It is similar to warfarin in its kinetics of action; however, it offers no clear advantages and may have a higher frequency of untoward effects. Phenindione (DINDEVAN) still is available in some countries. Serious hypersensitivity reactions, occasionally fatal, can occur within a few weeks of starting therapy with this drug, and its use can no longer be recommended.

Rodenticides. Bromadiolone, brodifacoum, diphenadione, chlorophacinone, and pindone are long-acting agents (prolongation of the PT may persist for weeks). They are of interest because they sometimes are agents of accidental or intentional poisoning. In this setting, reversal of the coagulopathy can require very large doses of vitamin K (i.e., >100 mg/day) for weeks or months.

Ximelagatran. Ximelagatran is a novel drug that is readily absorbed after oral administration and is rapidly metabolized to melagatran, a direct thrombin inhibitor. Therefore, its onset of action is much faster than that of warfarin. Ximelagatran is administered twice daily at a fixed dose and does not appear to require coagulation monitoring. Melagatran is excreted primarily by the kidney; therefore, dosage reduction may be necessary for patients with renal failure. Ximelagatran has been used successfully in clinical trials for prevention of venous thromboembolism (Francis et al., 2003; Schulman et al., 2003). Ximelagatran causes elevation of hepatic transaminases in about 6% of patients, but this side effect usually is asymptomatic and often is transient. The drug has not yet been approved for use in the United States.

Philip W. Majerus and Douglas M. Tollefsen
key words: blood, Oral Anticoagulants, Phenprocoumon and Acenocoumarol