Does Ginseng Affect Warfarin Response?

Much has been written about theeffect of herbal supplements onprescription medications, particularlythose with a narrow therapeutic indexsuch as oral anticoagulants. Nonetheless,considerable confusion remains,because much of the datacomes from isolated case reports orsmall studies in healthy individuals.

A recent well-controlled study assessedthe effect of ginseng on the anticoagulantresponse to warfarin, and it provides?for the first time?credible evidencethat ginseng does interact withwarfarin in a way that may be clinicallyimportant in some patients.

What Did the Recent StudyReveal?

Twenty healthy people took warfarinfor 3 days with and without pretreatmentwith American ginseng for 2weeks. Ginseng was associated with amodest reduction in both the internationalnormalized ratio (INR) and thewarfarin area under the plasma concentration-time curve.¹

Although the mean reduction in warfarineffect and plasma concentrationswas modest, it did occur in most of thepeople. The effect also was quite variablefrom person to person, with some individualshaving a substantial change.

This study was performed in healthypeople, and it seems likely that theeffect on warfarin could result inadverse outcomes in at least somepatients who receive the combination.

How Does This Result Comparewith Results of Previous Studies?

In a previous case report, a 47-year-oldman who had been stabilized onwarfarin with an INR of about 3 had areduction in his INR to about 1.5 afterhe took ginseng for 2 weeks.² Afterstopping the ginseng for 2 weeks, hisINR returned to about 3 again. Inanother case of possible reduction inwarfarin effect with ginseng, thrombosisoccurred in a prosthetic aorticvalve.³ Both of these cases are consistentwith the findings of the controlledstudy cited above?namely, that ginsengcan reduce the effect of warfarin.

Another study in healthy individualsfailed to find any effect of ginseng on asingle oral dose of warfarin.⁴ Althoughthis study appears to conflict with thestudies cited above, the ginseng wasgiven for only 7 days, which may havebeen an insufficient period to see theinteraction. Also, the dose and type ofginseng were different from those inthe studies that found a reduced warfarineffect with ginseng.

What Is the Mechanism forThis Interaction?

The mechanism for the effect is notestablished. Available evidence suggeststhat ginseng administration doesnot result in enzyme induction, at leastfor CYP1A2 and CYP3A4.^5,6 Little evidenceexists, however, on whether ornot ginseng affects CYP2C9, which isthe cytochrome P-450 isozyme primarilyresponsible for S-warfarin metabolism.So it is possible that ginseng modestlyinduces CYP2C9, but otherpotential mechanisms have not beenrigorously ruled out.

What Are the Limitations ofthe Available Data?

Numerous ginseng products areavailable, with different sources of theginseng root, different methods ofpreparation, and different recommendeddoses. Indeed, some ginsengproducts have been found to have noginseng at all. It is difficult, therefore,to compare one study of a ginsengdrug interaction with any other study.For the same reasons, it is difficult toapply the results of published studiesto a specific patient, because it wouldbe rare for the patient under considerationto be taking the same brand as inthe study. Moreover, even if the sameginseng brand is used, different lots ofthe product are likely to have differentamounts of active constituents.

How Should This InteractionBe Handled?

To reduce the likelihood of an adversedrug interaction between warfarin andginseng, pharmacists should considerthe following recommendations:

• Ideally, patients on warfarinshould avoid taking any ginsengproducts, and it would be prudentto warn patients accordingly.Indeed patients on warfarinwould be well advised to avoid allherbal medications.
• If a warfarin-treated patient insistson taking ginseng, the patientshould be advised not to switchfrom one brand to another, andnot to vary the dose of ginseng.This course of action will not guaranteea stable interaction, ofcourse, because the same brandcan vary from lot to lot, but it isprobably a sensible precaution.
• If a patient on warfarin has anychange in his or her ginsengintake (eg, starting, stopping,change in dose, change in brand),it would be prudent to monitorfor any change in the anticoagulanteffect of warfarin.

Drs. Horn and Hansten are both professorsof pharmacy at the University of WashingtonSchool of Pharmacy. For an electronic versionof this article, including references ifany, visit www.hanstenandhorn.com.

For a list of references, send a stamped,self-addressed envelope to: ReferencesDepartment, Attn. A. Stahl,Pharmacy Times, 241 Forsgate Drive,Jamesburg, NJ 08831; or send ane-mail request to: astahl@mwc.com.