Much has been written about the
effect of herbal supplements on
prescription medications, particularly
those with a narrow therapeutic index
such as oral anticoagulants. Nonetheless,
considerable confusion remains,
because much of the data
comes from isolated case reports or
small studies in healthy individuals.
A recent well-controlled study assessed
the effect of ginseng on the anticoagulant
response to warfarin, and it provides?
for the first time?credible evidence
that ginseng does interact with
warfarin in a way that may be clinically
important in some patients.
What Did the Recent Study
Twenty healthy people took warfarin
for 3 days with and without pretreatment
with American ginseng for 2
weeks. Ginseng was associated with a
modest reduction in both the international
normalized ratio (INR) and the
warfarin area under the plasma concentration-
Although the mean reduction in warfarin
effect and plasma concentrations
was modest, it did occur in most of the
people. The effect also was quite variable
from person to person, with some individuals
having a substantial change.
This study was performed in healthy
people, and it seems likely that the
effect on warfarin could result in
adverse outcomes in at least some
patients who receive the combination.
How Does This Result Compare
with Results of Previous Studies?
In a previous case report, a 47-year-old
man who had been stabilized on
warfarin with an INR of about 3 had a
reduction in his INR to about 1.5 after
he took ginseng for 2 weeks.2 After
stopping the ginseng for 2 weeks, his
INR returned to about 3 again. In
another case of possible reduction in
warfarin effect with ginseng, thrombosis
occurred in a prosthetic aortic
valve.3 Both of these cases are consistent
with the findings of the controlled
study cited above?namely, that ginseng
can reduce the effect of warfarin.
Another study in healthy individuals
failed to find any effect of ginseng on a
single oral dose of warfarin.4 Although
this study appears to conflict with the
studies cited above, the ginseng was
given for only 7 days, which may have
been an insufficient period to see the
interaction. Also, the dose and type of
ginseng were different from those in
the studies that found a reduced warfarin
effect with ginseng.
What Is the Mechanism for
The mechanism for the effect is not
established. Available evidence suggests
that ginseng administration does
not result in enzyme induction, at least
for CYP1A2 and CYP3A4.5,6 Little evidence
exists, however, on whether or
not ginseng affects CYP2C9, which is
the cytochrome P-450 isozyme primarily
responsible for S-warfarin metabolism.
So it is possible that ginseng modestly
induces CYP2C9, but other
potential mechanisms have not been
rigorously ruled out.
What Are the Limitations of
the Available Data?
Numerous ginseng products are
available, with different sources of the
ginseng root, different methods of
preparation, and different recommended
doses. Indeed, some ginseng
products have been found to have no
ginseng at all. It is difficult, therefore,
to compare one study of a ginseng
drug interaction with any other study.
For the same reasons, it is difficult to
apply the results of published studies
to a specific patient, because it would
be rare for the patient under consideration
to be taking the same brand as in
the study. Moreover, even if the same
ginseng brand is used, different lots of
the product are likely to have different
amounts of active constituents.
How Should This Interaction
To reduce the likelihood of an adverse
drug interaction between warfarin and
ginseng, pharmacists should consider
the following recommendations:
- Ideally, patients on warfarin
should avoid taking any ginseng
products, and it would be prudent
to warn patients accordingly.
Indeed patients on warfarin
would be well advised to avoid all
- If a warfarin-treated patient insists
on taking ginseng, the patient
should be advised not to switch
from one brand to another, and
not to vary the dose of ginseng.
This course of action will not guarantee
a stable interaction, of
course, because the same brand
can vary from lot to lot, but it is
probably a sensible precaution.
- If a patient on warfarin has any
change in his or her ginseng
intake (eg, starting, stopping,
change in dose, change in brand),
it would be prudent to monitor
for any change in the anticoagulant
effect of warfarin.
Drs. Horn and Hansten are both professors
of pharmacy at the University of Washington
School of Pharmacy. For an electronic version
of this article, including references if
any, visit www.hanstenandhorn.com.
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