EGb 761® Does Not Affect Blood Coagulation and Bleeding Time in Patients with Probable Alzheimer's Dementia-Secondary Analysis of a Randomized, Double-Blind Placebo-Controlled Trial.

Charlotte Kloft,Robert Hoerr

doi:10.3390/healthcare9121678

Abstract

Following reports of bleeding upon Ginkgo intake, we assessed whether Ginkgo extract EGb 761® affects coagulation or platelet function or increases the risk of bleeding. In a double-blind, placebo-controlled trial, prothrombin time, activated partial thromboplastin time, international normalized ratio and bleeding time were measured in patients with Alzheimer’s dementia at baseline, weeks 6 and 26. A total of 513 patients were randomized to 120 mg (n = 169) or 240 mg EGb 761® (n = 170) or placebo (n = 174). No relevant changes were found for coagulation parameters and bleeding time. Numbers of bleeding-related adverse events were similar in all groups. Concomitant intake of acetylsalicylic acid was documented for 68 patients in the placebo group and 105 in the EGb 761® groups. Within these groups, the means at baseline and week 26 differed by less than 1 unit for prothrombin time and bleeding time and less than 0.1 unit for international normalized ratio. Data on warfarin treatment in nine patients each taking placebo or EGb 761® did not indicate enhancement of warfarin effects by EGb 761®. No evidence was found that EGb 761® affects hemostasis or increases the bleeding risk. No pharmacodynamic interactions with warfarin or acetylsalicylic acid were found.

Highlights

Analyses of aggregate spontaneous reports from the US and Australia conclude that the intake of Ginkgo preparations may lead to an increased risk of bleeding due to interactions with warfarin [1,2]
The following reasons were documented in the treatment groups: withdrawal of informed consent (n = 13/9/10), adverse events (AEs) (n = 7/8/10), SAEs (n = 3/3/5), lack of efficacy (n = 3/8/2) and other reasons (n = 13/6/3)
The defined Ginkgo biloba leaf extract EGb 761® is approved in many countries for the treatment of dementia

Summary

Introduction

Analyses of aggregate spontaneous reports from the US and Australia conclude that the intake of Ginkgo preparations may lead to an increased risk of bleeding due to interactions with warfarin [1,2]. The results were interpreted as suggesting that taking Ginkgo preparations concomitantly with warfarin increases the patient’s risk of a bleeding-related adverse event [2]. A descriptive analysis of spontaneously reported adverse drug reactions (ADR) to Ginkgo biloba from 2000 to 2015 was performed in the electronic database of the Therapeutic Goods Administration in Australia [1]. The authors ascribed three adverse drug reactions to pharmacokinetic interactions with warfarin Their assumption is based on research on hepatocytes, showing that Ginkgo induced the cytochrome P450 3A4 enzyme which may affect the R enantiomer of warfarin [3]

Methods

Results

Conclusion