Drug Experience Warfarin and ginseng

RUG
EXPERIENCE

Straightforward reports of unusual drug experiences are included in this section. While selected references may be cited,
the purpose of a Drug Experience report is not to present an
extensive review of the literature.
A related section, Grand Rounds, includes papers that are
well-documented patient case reports with a thorough review of
the important literature to help put the case in perspective.
Authors should report serious adverse drug reactions to the
FDA medical products reporting program (MedWatch). A
MedWatch form appears in the January 1 and July 1 issues of
AJHP. Such reporting will not jeopardize the chances that
AJHP will publish manuscripts on the same drug reactions.

Probable interaction
between warfarin and ginseng
KATHERINE JANETZKY AND ANTHONY P. MORREALE
Am J Health-Syst Pharm. 1997; 54:692-3

he use of nontraditional medicine to treat

diseases or symptoms is rapidly expanding in
the Western world, but the safety of combining
these remedies and treatments with more traditional
therapy has not been well studied. Ginseng (the dried
root of Panax ginseng) has been used for several thousand years in Asia as a tonic, prophylactic agent, and
restorative.1 Ginseng is purported to provide energy
and strength2 and has been used to treat nervous disorders, shortness of breath, lack of sexual desire, chronic
fatigue, pain, and nausea. However, its efficacy is primarily anecdotal; there is little scientific verification of
its pharmacologic effects. In addition, little is known
about possible adverse effects and drug interactions
involving ginseng.
Commercial ginseng products vary widely in their
ginsenoside content, and this variability may lead to
differences in biological activity. In one study, 6 of 50
ginseng products contained no specific ginsenosides.3

KATHERINE JANETZKY, PHARM.D., BCPS, is Anticoagulation Pharmacist Specialist and ANTHONY P. MORREALE, PHARM.D., M.B.A., BCPS,
is Assistant Chief, Pharmacy Service, Veterans Affairs Medical
Center, San Diego, CA.
Address reprint requests to Dr. Janetzky at the Pharmacy Service (119), Veterans Affairs Medical Center, 3350 La Jolla Village
Drive, San Diego, CA 92161-0155.

692 Am J Health-Syst Pharm Vol 54 Mar 15 1997

The ginsenoside content of the remaining 44 products

ranged from 1.9% to 9.0% (w/w). A popular brand of
ginseng in the United States is marketed under the
name Ginsana (Pharmaton, Ridgefield, CT). The manufacturer claims that each capsule contains 100 mg of
standardized, concentrated ginseng; this would ensure
consistent levels of the eight most potent ginsenosides.
Unlike ginseng, warfarin has been extensively studied in controlled clinical trials. Drug interactions with
warfarin can occur secondary to plasma protein displacement, interactions with the cytochrome P-450
enzyme system, or interference with drug metabolism
or hematopoiesis.
This report describes a probable interaction between
warfarin and a ginseng product (Ginsana).
Case report. 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 hydrochloride 30 mg three
times daily, nitroglycerin as needed for chest pain, and
salsalate 500 mg three times daily as needed. He had
taken diltiazem since July 1988, nitroglycerin as needed
since 1990, and salsalate as needed since 1992. The
dosage of warfarin sodium had remained 5 mg/day (7.5
mg each Tuesday). The International Normalized Ratio
(INR) had ranged from 3.0 to 4.0 (goal, 2.53.5) for the
past nine months; INR was measured every two to
seven weeks (Figure 1). In February 1995 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.
Two weeks after the patient started taking ginseng,
his INR declined to 1.5. Ginseng was discontinued, and
the INR returned to 3.3 in two weeks. The patient
denied changing his drug regimen during this period
and said his dietary vitamin K content had been consistent and his compliance with all of his medications
good. The patient said he had not used any vitamins or
other nutritional or health-food supplements. He also
denied any changes in his overall health status, including any significant changes in weight, smoking, or
drinking. He had no known thyroid problems.
Discussion. No thrombotic episodes resulted from
the subtherapeutic INR. Because of the risk of thrombosis, the patient was not rechallenged with another
course of ginseng. Other medications, dietary factors,

Warfarin and ginseng Drug Experience

Figure 1. International Normalized Ratios (INRs) between August 1994 and May 1995. Ginseng was started on February 2 and stopped
on March 8. No other medication changes were made.

INR

4
3.5
3
2.5
2
1.5
1
0.5
0
8/9/94

8/23/94 10/19/94 12/7/94 1/25/95

3/8/95

3/28/95 4/19/95 5/10/95

Date

and changing health status were ruled out as possible

causes of the subtherapeutic INR; the ginseng was the
only change in the patients regimen. The interaction
was rated as probable by the Naranjo assessment method.4
The mechanism of this probable drug interaction is
unknown. It is unclear whether ginseng contains vitamin K, antagonizes clotting factor production by the
liver, interacts with the cytochrome P-450 enzyme system, or affects the metabolism of warfarin by another
mechanism.
Conclusion. The case report presented here sug-

gests an interaction between ginseng and warfarin;

studies are needed to verify that the interaction exists
and, if so, to determine the mechanism involved.
References
1. Court WE. Ginsenga Chinese folk medicine of current interest. Pharm J. 1975; 214:180-1.
2. Bahrke M, Morgan W. Evaluation of the ergogenic properties
of ginseng. Sports Med. 1994; 18:229-48.
3. Cui J, Garle M, Eneroth P et al. What do commercial ginseng
preparations contain? Lancet. 1994; 344:134. Letter.
4. Naranjo CA, Busto U, Sellers M et al. Method for estimating the
probability of adverse drug reactions. Clin Pharmacol Ther.
1981; 30:239-45.

Vol 54 Mar 15 1997 Am J Health-Syst Pharm 693