A Comprehensive Monograph on Phenprocoumon: Pharmacology, Clinical Application, and Safety Profile

Section 1: Executive Summary

Phenprocoumon is a long-acting, orally administered anticoagulant agent belonging to the 4-hydroxycoumarin class of medications.[1] It represents a cornerstone of antithrombotic therapy, particularly for the long-term prevention and treatment of thromboembolic disorders in several continental European nations, where it is marketed under brand names such as Marcoumar, Marcumar, and Falithrom.[2] As a Vitamin K Antagonist (VKA), its therapeutic effect is derived from the inhibition of the Vitamin K epoxide reductase complex subunit 1 (VKORC1). This molecular action disrupts the hepatic synthesis of biologically active, gamma-carboxylated forms of coagulation factors II (prothrombin), VII, IX, and X, as well as the endogenous anticoagulant proteins C and S, thereby impeding the coagulation cascade and preventing thrombus formation.[2]

The defining pharmacokinetic characteristic of phenprocoumon is its exceptionally long elimination half-life, which averages between 150 and 160 hours (approximately 6 to 7 days).[2] This property profoundly influences every aspect of its clinical management. It results in a slow onset of therapeutic effect, a prolonged anticoagulant state even after discontinuation, and a significant risk of "International Normalized Ratio (INR) rebound" in scenarios of overdose or acute reversal.[8] This extended duration of action, however, may also contribute to more stable plasma concentrations and INR values during maintenance therapy compared to shorter-acting VKAs.