BACKGROUND: People using prescription medication often concurrently take herbal supplements. In a case report, the anticoagulant effect of warfarin decreased after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General Clinical Research Center, University of Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4. Beginning in week 2, patients were assigned to receive either American ginseng or placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin level. RESULTS: The peak INR statistically significantly decreased after 2 weeks of ginseng administration compared with placebo (difference between ginseng and placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically significantly reduced in the ginseng group as compared with the placebo group. Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS: The study sample consisted of young, healthy volunteers in a research setting rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin, physicians should ask patients about ginseng use

Coumarin derivatives combine 3 unfavorable properties which make them prone to potentially life threatening drug-drug interactions: (i) high protein binding; (ii) cytochrome P450 dependent metabolism; and (iii) a narrow therapeutic range. An entire list of drugs which are supposed to interact with coumarins (mostly with warfarin) comprises about 250 different compounds. Noteworthy are the interactions with cardiovascular or antilipidaemic drugs which are often coadministered with coumarins: amiodarone, propafenone and fibrates. Cardiovascular drugs which are obviously devoid or proven to be devoid of an interaction are angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers and cardiac glycosides. There are several other drugs which enhance the hypoprothrombinaemic response to coumarins by various mechanisms: inhibitors of the elimination of the eutomer S-(-)-warfarin (e.g. miconazole, phenylbutazone), combined with protein binding displacement (e.g., sulfinpyrazone, phenylbutazone), synergistic hypoprothrombinaemia (e.g. cefazoline). Furthermore, bleeding complications may occur with drugs affecting platelet function [aspirin (acetylsalicylic acid) and several nonsteroidal anti- inflammatories (NSAIDs)]. Strong inducers of coumarin metabolism are rifampicin (rifampin) and carbamazepine. Biphasic interactions may occur where a drug first enhances the hypoprothrombinaemic response to a coumarin but has a sustained inducing effect on coumarin metabolism (e.g. phenytoin or sulfinpyrazone). The complex response of coumarins to concomitant drug therapy makes it difficult to predict the occurrence and degree of a deterioration of anticoagulant control in individual patients. For clinical practice, it seems advisable that one should monitor for changes in prothrombin time when adding or deleting any newly approved drug or any drug suspected (e.g. on the basis of this review) to cause an interaction to patients on coumarin therapy. The onset of the adverse prothrombin time response might be from between 1 to 2 days up to 3 weeks (in case of phenprocoumon) after starting a concomitant drug regimen. With amiodarone, an adverse prothrombin time response might occur up to 2 months after initiating therapy. For heparins, only a drug interaction with aspirin or nitroglycerin seems clinically relevant due to the possibility of coadministration during acute cardiac events. Both drugs are shown to enhance the activated partial thromboplastin time response to heparin

AIM: The aim of this study was to investigate the effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin. METHODS: This was an open-label, three-way crossover randomized study in 12 healthy male subjects, who received a single 25-mg dose of warfarin alone or after 14 days' pretreatment with St John's wort, or 7 days' pretreatment with ginseng. Dosing with St John's wort or ginseng was continued for 7 days after administration of the warfarin dose. Platelet aggregation, international normalized ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured. Statistical comparisons were made using anova and 90% confidence intervals are reported. RESULTS: INR and platelet aggregation were not affected by treatment with St John's wort or ginseng. The apparent clearances of S-warfarin after warfarin alone or with St John's wort or ginseng were, respectively, 198 +/- 38 ml min(-1), 270 +/- 44 ml min(-1) and 220 +/- 29 ml min(-1). The respective apparent clearances of R-warfarin were 110 +/- 25 ml min(-1), 142 +/- 29 ml min(-1) and 119 +/- 20 ml min(-1). The mean ratio and 90% confidence interval (CI) of apparent clearance for S-warfarin was 1.29 (1.16, 1.46) and for R-warfarin it was 1.23 (1.11, 1.37) when St John's wort was coadministered. The mean ratio and 90% CI of AUC(0-168) of INR was 0.79 (0.70, 0.95) when St John's wort was coadministered. St John's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers. CONCLUSIONS: St John's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac-warfarin. Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin

BACKGROUND: The objective of this study was to determine whether an interaction exists between warfarin and Korean red ginseng. METHODS: A prospective, double-blind, randomized, two-period crossover study was conducted on 25 patients with cardiac valve replacement under warfarin therapy. Either Korean red ginseng 1 g or placebo (hop extract 0.25 g, caramel color 0.05 g, and red ginseng flavor 0.03 g) was concomitantly administered with warfarin. INR and warfarin concentrations were analyzed on the 3rd and 6th weeks of each study period. RESULTS: The INR changes on the 3rd and 6th weeks of Korean red ginseng administration were -0.16+/-0.95 and -0.14+/-0.94 whereas those of placebo were -0.03+/-0.65 and 0.25+/-0.95; there were no statistically significant differences in mean INR changes. CONCLUSION: Korean red ginseng could be used with close monitoring and under appropriate education in patients who take warfarin

Background: Today, the combined use of Oriental herbal medicines and Western biomedical medicines has been a prevalent yet controversial practice. Case reports and healthy volunteer trials have had conflicting results on the effect Panax ginseng has on warfarin's pharmacologic action, some reporting a reductive and others a potentiating influence. Objective: This study investigated the interaction between warfarin and P. ginseng by observing the prothrombin time (PT) and the international normalized ratio (INR) in ischemic stroke patients who did not have a history of taking warfarin. Design: Randomized, open-label, controlled study. Subjects: Twenty-five (25) patients newly diagnosed with ischemic stroke by brain computed tomography or magnetic resonance imaging in the Korean Medical Hospital, Kyung Hee University (Seoul, Republic of Korea). Intervention: Ischemic stroke patients were randomized into 2 groups: the ginseng group (n = 12), given both P. ginseng and warfarin, and the control group (n = 13), given only warfarin, both for 2 weeks. The warfarin dose was restricted to 2 mg in the first week and 5 mg in the second week. Results: The peak values and the international normalized ratio (INR) and prothrombin time (PT) areas under the curve (AUC) in both groups significantly increased compared to those at baseline. However, there was no statistically significant difference in peak values and INR and PT AUC between groups in both the first and second weeks. Conclusions: This study suggests that coadministration of P. ginseng and warfarin in ischemic stroke patients does not influence the pharmacologic action of warfarin. copyright 2008 Mary Ann Liebert, Inc

OBJECTIVE: To review and characterize the evidence describing potential interactions between warfarin and garlic, ginger, ginkgo, or ginseng. DATA SOURCES: Searches of MEDLINE (1966-1999), other bibliographic databases, several abstracting services, and tertiary references were conducted. STUDY SELECTION AND DATA EXTRACTION: Articles were examined by each author, and additional citations were obtained from the references of these articles. Preference was given to Englishlanguage articles of human studies. DATA SYNTHESIS: Evidence is lacking for an interaction of warfarin wth galic or ginger. One case report associates ginseng use with decreased warfarin-maintained anticoagulation effect. Another case report links concomitant use of ginkgo and warfarin with the development of intracerebral hemorrhage. Hemorrhage and tendencies were noted in four cases with ginkgo use and in three cases with garlic; in none of these cases were patients receiving warfarin. CONCLUSIONS: The true risks of these interactions and effects are difficult to characterize due to the limited number and nature of existing reports

A 47-year-old man with a St. Jude-type mechanical heart valve in the aortic position had received anticoagulation therapy with warfarin since 1990 to prevent embolic events. He had a history of hypertension, angina and osteoarthritis.Other medications included diltiazem hydrochlorid 30 mg three times daily, nitroglycerin and salsalate 500 mg three times daily. The dosage of warfarin sodium had remained 5 mg/day. INR had ranged from 3,0 to 4,0 (goal 2,5-3,5) for the past nine months. INR was measured every two to seven weeks. The patient started taking ginseng capsules (Ginsana) three times daily in an effort to boost his ´energy level´. His INR was 3,1 four weeks before he started taking ginseng.To weeks after his INR declined to 1,5. Ginseng was discontinued, and the INR returned to 3,3 in two weeks.

Summary af artiklen American Ginseng Reduces Warfarins effect in Healthy Patients

We report a case of thrombosis on a mechanical bileaflet aortic valve prosthesis (MBAVP) caused by inadequate anticoagulation levels that occurred after a period of self-medication with a ginseng procuct.