Safety aspects of a coumarin-troxerutin combination regarding liver function in a double-blind placebo-controlled study

Abstract

Objective: Coumarin is reported to elevate liver function tests (LFT) values. In a prospective, placebo-controlled, clinical trial, efficacy and safety of a coumarin-containing combination (SB-LOT) were evaluated in the treatment of chronic venous insufficiency. Here, we report on the drug safety of coumarin with special respect to liver reaction.

Methods: 114 patients were treated with SB-LOT (30 mg coumarin and 180 mg troxerutin t.i.d.) and 117 with placebo during a period of 16 weeks. LFT values (ALT, AST, AP and gamma-GT) were monitored at baseline, 4, 6, 8, 12 and 16 weeks of therapy. Adverse drug reactions were assessed regarding causality. Additionally, lymphocyte proliferation test was used to identify allergic reactions. Logistic regression analysis was performed to identify possible risk factors.

Results: No serious adverse drug reactions occurred. Elevations of LFT were assessed as biochemical abnormality. Specific clinical symptoms such as jaundice did not occur. Only 1 patient reported fatigue and exhaustion. Logistic regression estimated a basic risk for elevation of LFT of 4.9% under SB-LOT and 2.1% under placebo. Hepatitis in the history and diseases of the liver were identified as risk factors.

Conclusion: This evaluation contributes to safety data of SB-LOT in man. LFT elevation is transient and the low risk of the SB-LOT therapy to increase LFT value can be limited when risk factors are considered.