Vol 2, Issue 2, 2020 (69-76)
http://journal.unpad.ac.id/idjp
*Corresponding author,
e-mail : t.rusdiana@unpad.ac.id (T. Rusdiana)
https://doi.org/10.24198/idjp.v2i2.27289
2020 T. Rusdiana et al
Interaction of Warfarin with Herbs Based on Pharmacokinetic and
Pharmacodynamic Parameters
Amelia Soyata
1
, Aliya Nur Hasanah
2
, Taofik Rusdiana
1,*
1
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas
Padjadjaran, Sumedang, Indonesia
2
Department of Analysis of Pharmaceutical and Medical Chemistry, Faculty of Pharmacy, Universitas
Padjadjaran, Sumedang, Indonesia
Received : 15 May 2020/Revised : 17 May 2020/Accepted : 5 Jun 2020/ Published:23 Jun 2020
ABSTRACT
Warfarin is an oral anticoagulant that has been widely used and has strong efficacy, but the
use of warfarin is still a concern because of its narrow therapeutic index which cause
interactions when co-administration with drugs, herbs or food. This interaction can affect the
pharmacokinetics and pharmacodynamics of warfarin and the most fatal effect from warfarin
interactions is bleeding. In this review article data on warfarin-herbs interactions were
collected based on pharmacokinetic parameters (AUC
0-∞,
C
max
, T
1/2
, Cl/F, and V/F), while
pharmacodynamic parameters (International normalized ratio (INR), platelet aggregation,
AUC INR and Protombine Time). As a result some herbs had significant interactions with
warfarin. Herbs that affect warfarin pharmacokinetic were Danshen gegen, echinacea, St.
John's wort and caffeine and herbs that affect pharmacodynamic were policosanol, Ginkgo
biloba, cranberry, St. John's wort, ginseng, pomegranate, Psidium guajava and curcumin, so
co-administration warfarin with herbs need to be considered.
Keywords: Warfarin, Interactions, Herbs, Pharmacokinetics, Pharmacodynamics
1. Introduction
Warfarin is an oral anticoagulant that had been
widely used since 1954 and prescribed for decades
(1). Warfarin is used to prevent thromboembolic
complications in a patient with various
cardiovascular diseases including atrial fibrillation
and thrombosis (2). The anticoagulation effect of
warfarin is achieved by inhibit the formation cycle
of vitamin K in the liver. It inhibits vitamin K
epoxide reductase (VKOR) that very important in
the formation of factors VII and IX in blood
clotting (3). Although warfarin has strong efficacy,
the use of warfarin is still a concern because of its
narrow therapeutic window, it cause an interaction
when co-administration with drugs, herbs, or foods.
Drug-drug interaction occurs every time the
effects of the drug are modified by the presence of
other drugs which causes therapeutic failure,
toxicity, or serious complication (4). Warfarin is
included in the top ten of drugs with severe side
effects in 2019 (5). Based on a report in the United
States, about 58% patients who take warfarin, they
also take herbal medicines to improve their health
condition (6,7). While there is 34 warfarin
interaction from 133 cases of herb-drug interaction
(8), because of that warfarin is one of the most
frequently studied drug-related to its interactions.
This interaction can affect the pharmacokinetic and
pharmacodynamic of warfarin, and the most fatal
effect by warfarin interaction is bleeding (9).
Warfarin is metabolized by CYP450 in the liver.
Warfarin has R and S enantiomer. R-warfarin is
metabolized by CYP3A4, CYP1A2, and
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
70
CYP2C19, while S-warfarin mainly metabolized
by CYP2C9 (10,11). Many studies have shown that
warfarin interactions are mediated by CYP
enzymes and protein plasma binding (12). The
herbs can influence the enzymes and affect
pharmacokinetic and pharmacodynamic of
warfarin.
The herbs influence the metabolism enzyme of
warfarin by inhibition or induction. A few herbs
have been reported inhibit CYP2C9 enzyme
including Harpagophytum procumbens, Trifolium
pratense (13), Citrus paradise (14), Serenoa
repens (15), Glycine max (16), Angelica sinensis
(17) while Allium sativum (18), Cannabis sativa
(19) are reported induction CYP2C9.
Therefore it is necessary to gather
information related to the interaction of warfarin
with herbs based on pharmacokinetic and
pharmacodynamics parameters, so the
administration of warfarin therapy to patients who
take certain herbal medicines can be more
controlled, and reduce the side effects. This article
will gather the information related to the
interaction of warfarin with herbs based on its
pharmacokinetic and pharmacodynamics
parameters.
2. Methodology
In this review article, literature was collected
from the internet through google scholar, Elsevier,
Pubmed, using the keywords “warfarin”, “herb-
drug interaction”, “interaction of warfarin”, “the
pharmacokinetics of warfarin”, “pharmacokinetic
drug interaction”, “pharmacodynamics
interaction”, “pharmacodynamics of warfarin”. The
data of warfarin interaction with some herbs were
obtained based on the result of previous studies and
we do further searches from the relevant
references. Inclusion criteria are articles which
have pharmacokinetic parameters,
pharmacodynamic parameters, publication year >
2000, and articles that have references on warfarin,
herbs, and drug interactions. The number of
literature that has been collected was 145 articles,
but only 65 articles included based on the inclusion
criteria. It is illustrated by Figure 1.
Figure 1. Flow Chart Of the Literature Review
Initial selected Article
(n= 145 )
80 articles exluded , that is :
Articles not in English (n=4)
Case Report (n=3)
Articles< 2000 (n=12)
Unrelated articles (n= 61)
65 articles selected after
initial screening
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
71
3. Discussion
There are two classifications of drug
interactions: pharmacokinetic interactions and
pharmacodynamic interactions. Pharmacokinetic
interaction is associated with absorption,
distribution, metabolism, and excretion. It can
change drug concentration in blood.
Pharmacodynamic interaction is related to drug
effects, it is classified into three groups such as
direct effect at receptor function, interference with
a biological or physiological control process and
additive/opposed pharmacological effect (20).
Pharmacokinetic and pharmacodynamic
interactions occur due to the presence of other
substances that affect the drug, for example when
using herbs simultaneously, the active ingredients
of these herbs cause the interactions. This
interaction can be seen from changes in
pharmacokinetic parameters and pharmacodynamic
parameters.
The pharmacokinetic parameters are area under
curve
0
-
∞
(AUC
0
-
∞)
is area under the plasma
concentration time in zero to infinity. C
max
is the
maximum concentration of drug in plasma. T
max
is
the maximum time to reach maximum plasma
concentration. T
1/2
is time required for drug to
decline by half. Clearance (Cl/F) is the total
clearance of drug after oral administration. Volume
distribution (V/F) is the volume of distribution of
drug after non-intravenous administration. Mean
residence time (MRT). Fu is fraction of unbound
drug in plasma (21). The parmacodynamic
parameters for warfarin are international
normalized ratio (INR), AUC of INR, platelet
aggregation, and protombine time (PT). PT is the
time for blood to clot (22). This article has
summarized the pharmacokinetic interaction of
warfarin with herbs based on pharmacokinetic
parameters in Table 1 and pharmacodynamic
parameters in Table 2.
3.1 Danshen gegen
Based on of Zhou et al (23) extract of Danshen
gegen (DG) was given to rats after warfarin
administration for 5 days show influence on the
pharmacokinetic parameters, such as C
max,
AUC
0-∞
and T
max
. For R-warfarin, there was a decrease in
the C
max
from 1.03 mg/ml to 0.52 mg/ml, a
decrease in the AUC from 13.09 mg/ml to 6.56
mg/ml, also decrease in T
1/2
from 19.74 minutes to
10.98 minutes. For S-warfarin, there was a
decrease in C
max
from 1.44 mg/ml to 0.93 mg/ml,
whereas for AUC
0-∞
and T
1/2
was not significantly
different (Table 1).
In conclusion based on Table 1 (23) co-
administration of DG extract with warfarin
influence the pharmacokinetic parameters of
warfarin in rats. It is caused by DG extract's active
substances, such as puerarin (1986.0mg/100mg),
salvianolic acid B (2048.3mg/100mg), daidzein
(122.5 mg/100 mg), daidzin (190.9 mg /100 mg),
protocatechuic aldehyde (117.3 mg/100 mg), and
the hydrophobic components such as tanshinones
(31).
The interaction between DG extract and
warfarin is caused by the interaction of DG
extract's active substance with cytochrome P450
(CYP450) (32). Tanshinones inhibit CYP3A4 (33).
The results of studies on rats, Danshen gegen
extract induces CYP1A2 activity around 60% (34),
while on the other side according to Lin (34)
tanshinone II A inhibits CYP1A2 (35). Component
of Danshen gegen has been analyzed by clinical
studies, a sequential studies on this enzyme show
that CYP3A and CYP1A1 are inducted by
Danshen gegen (8). These findings indicate that
there are potential interactions for drugs that are
substrates for CYP3A4 or CYP1A2 when given
together with Danshen gegen. As we know that the
main metabolism of warfarin occurs in the liver by
CYP2C9, CYP1A2, and CYP3A4, so the use of
warfarin and Danshen gegen simultaneously needs
to be reconsidered.
3.2 Policosanol and Echinacea
Echinacea is one of the herbal medicines that
used as immunostimulants from Echinacea
purpurea and Echinacea angustifolia (36).
Policosanol is a complex mixture of alcohol
obtained by extracting the Saccharum officinarum
(37). Policosanol has been reported to reduce
cholesterol levels (38), and can be used in patients
with cardiovascular disease who receive warfarin
therapy.
Administration of 25 mg warfarin to healthy
volunteers simultaneously with echinacea (a
mixture of 600 mg Echinacea angustifolia and 675
mg of Echinacea purpurea which is standardized
with 5.75 mg alkamide per tablet), and policosanol
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
72
Table 1. Pharmacokinetic Interaction of Warfarin with Herbs
No
Herb
Phase
Pharmacokinetic Parameters
Ref
AUC
0
-
∞
(µg mL/h)
Cmax
(µg/mL)
Tmax
(h)
T
1/2
(h)
Cl/F
(mL/h)
V/F
(L/kg)
MRT
(h)
Fu
1
Danshen
R-warfarin
13.09
1.03
2.92
19.74
(23)
gegen
R-warfarin + S.miltiorrhiza
6.56
0.52
1.71
10.98
(Silvia
S-warfarin
13.09
1.03
2.92
19.74
Miltiorrhiza)
S-warfarin + S.miltiorrhiza
19.90
0.93
1.96
25.18
2
Policosanol
S-warfarin
53.9
1.3
1.7
38.6
267.3
0.21
0.01
(24)
and
S-warfarin + Policosanol
51.9
1.3
1.2
38.6
278
0.23
0.01
Echinacea
S-warfarin + Echinacea
49
1.3
1.9
36.5
289.7
0.23
0.01
R-warfarin
79.4
1.3
2
50.6
178.3
0.19
0.01
R-warfarin +Policosanol
77.8
1.4
1.2
38.6
278
0.20
0.01
R-warfarin + Echinacea
49
1.2
2
49.2
186.4
0.20
0.01
3
Ginkgo
S-warfarin
68
1.7
2.1
35.8
189
0.12
0.48
(25)
and
S-warfarin + Ginkgo
65.8
1.8
1.4
35.1
200
0.12
0.47
Ginger
S-warfarin + Ginger
66
1.7
1.6
35.7
201
0.12
0.48
R-warfarin
104
1.7
2.1
50.3
127
0.12
1.8
R-warfarin + Ginkgo
102.2
1.8
1.6
48.6
126
0.11
1.7
R-warfarin + Ginger
102.6
1.7
1.6
47.7
131
0.11
1.8
4
Cranberry
R-warfarin
108.7
1.8
1.4
55.6
123
0.01
(26)
R-warfarin + Cranberry
105.8
1.7
1.9
47.7
124
0.01
S-warfarin
60.3
1.8
1.4
38.6
213
0.006
S-warfarin + Cranberry
63
1.7
1.9
34.9
204
0.005
5
St John’s wort
S-warfarin
65.4
1.89
1.29
31.7
198
0.12
0.34
(27)
R-warfarin
120.9
1.92
1.34
51.7
110
0.10
0.48
And
S-warfarin + St John’s wort
47.7
1.82
1.26
25.1
270
0.13
0.36
Ginseng
R-warfarin + St John’s wort
91.1
1.84
1.34
40.3
142
0.10
0.47
S-warfarin + Ginseng
57.8
1.93
1.30
29.2
220
0.13
0.39
R-warfarin + Ginseng
108.1
1.89
1.30
47.9
119
0.10
0.46
6
Pomegranate
Peel
Warfarin
106.61
3.67
6
17
1.45
25
(28)
and
Warfarin + Pomegranate
99.45
4.22
3
21
1.54
25
Guava
Warfarin + Elegic Acid
131.66
4.98
3
16
1.17
23
Leaves
Warfarin + Guava Leaves
252.56
6.97
11
17
0.61
30
Warfarin + Quercetin
115.90
5.43
5
18
1.14
22
7
Curcumin
Warfarin
16.68
1.14
3.17
19.47
(29)
Warfarin + Curcumin 25
mg/kg
21.93
1.49
1.33
13.28
Warfarin + Curcumin 50
mg/kg
16.34
1.15
1.67
19.29
Warfarin + Curcumin 100
mg/kg
26.64
1.71
2.67
17.39
8
Caffeine
Warfarin
109.3
1.9
8.1
34
0.2
(30)
Warfarin + Caffeine
147.2
1.9
7.6
49,1
0.2
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70
tablet 10 mg 2 times a day for 2 weeks show that
echinacea increase the total clearance of S-warfarin
but has no effect on R-warfarin. Administration of
policosanol has no significant effect on the
pharmacokinetic and pharmacodynamic parameters
of warfarin (Table 1) (24).
Echinacea tablets contain more than 1%
phenolic compound (caftaric acid, chlorogenic
acid, echinacoside, and chichoric acid) as well as
alkamides (2-ena and 2.4 dienes) (39). In Abdul
study (24) tablets were used with the same content
as the formulation in the study of Gorski et al (39).
There was no effect of policosanol in
pharmacokinetic of warfarin (39), so it could be
linked to the cause of the absence of
pharmacokinetic changes. Policosanol has been
reported reduce blood cholesterol levels at a dose
of 20 mg per day (40), but the results of Abdul (24)
did not show any significant changes in platelet
aggregation after being given policosanol 20 mg
for 2 weeks (24). Other study reported no blood
clotting factors after 8 weeks of treatment with
policosanol 10 mg per day in cholesterolemia
patients (41). Also, there is no significant
relationship between the CYP2C9 or VKORC1
gene (40,41). The relatively small number of
samples can influence the interpretation of the
results. Although the results of Abdul et al (24)
show that the use of warfarin together with
policosanol and echinacea did not provide a
significant interaction, the use of this substance
needs to be maintained continuously.
3.3 Ginkgo and Ginger
Jiang et al (25) show there was no significant
changes on pharmacokinetic and
pharmacodynamics parameters of S-warfarin and
R-warfarin in healthy volunteers (Table 1 and
Table 2). It similar with Kumar (43) on
administration of ginkgo with warfarin from
international normalized ratio (INR) in patients
consuming 100 mg of ginkgo extract daily for 4
weeks, it showed that ginkgo did not affect the
warfarin (44).
Table 1 showed the level of urine excretion was
not change after administration of ginkgo and
ginger which means that these two herbs did not
affect CYP2C9 activity. When 60 mg of ginkgo
extract was given 4 times daily for 28 days to
healthy volunteers, there was no activity in
CYP3A4, CYP1A2, CYP2E1, or CYP2D6.
Although there are no interactions, the content of
ginkgo has been reported to inhibit and induce
cytochrome P450(43,44). In vitro studies the use of
different doses of ginkgo, for example, Egb 761
extract contain less than 5ppm ginkgolide acid
affect the activity of CYP (47).
Table 2. Pharmacodynamics Interaction of Warfarin with Herbs
No
Herb
Phase
INR
Value
Platelet
Aggregation
AUC of
INR
PT (s)
References
1
Policosanol
and Echinacea
Warfarin
1.7
52.7
(24)
Warfarin + Policosanol
1.9
55.2
Warfarin + Echinacea
1.8
55.2
2
Ginkgo and
Ginger
Warfarin
1.12
7.5
124
(25)
Warfarin + Ginkgo
1.14
8.4
121
Warfarin + Ginger
1.12
8.1
125
3
Cranberry
Warfarin
1.2
96
(26)
Warfarin + Cranberry
1.2
119.2
4
St John’s wort
and Ginseng
Warfarin
1.14
7.7
111
(27)
Warfarin + St John’s wort
1.12
7.5
88.3
Warfarin + Ginseng
1.13
7.1
111.1
5
Pomegranate
Peel and Guava
Leaves Extract
Warfarin
19
191
(28)
Warfarin + Pomegranate
Peel
42
360
Warfarin + Elegic Acid
51
414
Warfarin + Guava Leaves
52
425
Warfarin + Quercetin
55
448
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
71
Ginkgolides from ginkgo can inhibit platelet
activating factor (48). However, there is also
evidence that ginkgo did not affect adenosine
diphosphate or platelet aggregation (49). Ginkgo
also did not provide platelet or coagulation activity
at doses of 120, 240 and 480 mg per day given for
14 days in healthy volunteers (46) which is in line
with the results of Jiang et al (25).
3.4 Cranberry
Based on the results of Abdul et al (26) find that
cranberry did not have a significant effect on
warfarin (Table 1). Based on the pharmacodynamic
parameters of warfarin after cranberry juice
administration, there was a significant increase in
the average value of AUC INR by 30% (Table 2)
and it influences the platelet aggregation. It also
supported by the results of Greenblatt et al (50) the
activity of CYP2C9 did not affected by cranberry.
Lilja et al (51) also examined the administration of
cranberry juice for 5 days with warfarin, there was
no significant change from AUC of S-warfarin.
However, the results of pharmacodynamic
interactions of cranberry is different from Li et al
(52) and Ansell et al (53), they found no significant
changes in the warfarin response, but the volunteer
by Li et al only 7 patients and Ansell (53) only 14
patients. Lilja et al (51) concluded the absence of
pharmacodynamic interactions because of the dose
of 10 mg with cranberry juice administration for
only 7 days. According to Hamann et al (54) based
on case reports, there is a change in the INR after
administration of cranberry juice, it can be detected
with a longer period and use a high dose of
warfarin like 56 mg per week. From Abdul (26) we
can conclude that the administration of cranberry
for 2 weeks increased warfarin sensitivity to
healthy volunteers, but did not have a
pharmacokinetic effect, so the monitoring is
needed regarding the use of warfarin with
cranberry.
3.5 St John’s wort and Ginseng
12 healthy volunteers were given 25 mg of
warfarin together with St. John's wort for 14 days
and 7 days of ginseng (27). Co-administration of
St. John's wort with warfarin at the recommended
dose can increase the clearance of warfarin
enantiomers and decrease the pharmacodynamic
effects of warfarin. The administration of ginseng
did not provide a significant difference to the
pharmacokinetic parameters of warfarin (27).
There were significant differences of the AUC,
T
1/2
, and Cl/F of R-warfarin and S-warfarin by St.
John's wort. While pharmacodynamic parameters
show significant differences after the
administration of warfarin with St. John's wort
(Table 2). However, when warfarin was given with
ginseng there is no significant differences, there
was still a change in the value of INR and platelet
aggregation (27).
St John’s wort inhibits the activity of CYP2C9,
CYP2D6, and CYP3A4 (55), but St John’s wort
also induction CYP1A2, CYP2E1, and CYP3A4
(56). The test of healthy volunteers for 14 days St.
John's wort induce CYP3A4 activity in the liver
(56). This effect due to the existence of the
pregnane X receptor (PXR) (57). The influence of
St. John's wort in the activity of the CYP450
enzyme is the cause of the pharmacokinetic
changes from warfarin because these enzymes play
a role in warfarin metabolism (27).
It can be concluded that St. John’s wort has
potential action with drugs whose metabolism is
influenced by CYP2C9 and CYP3A4 substrates.
The result of Jiang (27) can be evidence to support
recommendations for monitoring the INR on
patients when warfarin co-administration with
drugs.
3.6 Pomegranate Peel Extract and Guava
Leaves Extract
The results of Alnaqeeb et al (28) on
administration of warfarin 0.5 mg/kg with 250
mg/kg guava leaf extract and 100 mg/kg
pomegranate peel extract for 5 days showed that it
increased the value of protombine time (PT) and
INR warfarin (Table 2). Elagitanins and elagic acid
in pomegranate peel has a strong action in
decreasing platelet aggregation in human plasma
(58). It causes an increase in PT after pomegranate
peel extract is given. While the effect of guava leaf
extract on the PT and INR was also related to the
antiplatelet activity of the flavonoids contained in
it, especially quercetin which potentially increase
the risk of bleeding (59).
The study pharmacokinetic interaction of
warfarin showed that there was no significant
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
72
effect of pomegranate peel extract on plasma
warfarin concentration, this could be related to the
low of elagitanin content in the extract. Although
there was an increase in C
max
because the elagic
acid and elagitanin could inhibit CYP3A and P-
glycoprotein (60).
Pharmacokinetic interactions between warfarin
and guava leaf extract significantly increase C
max
(Table 1), and significantly change AUC and Cl. It
is caused by quercetin which can inhibit the
activity of CYP2C9, CYP2C8 and CYP3A4
(61,62). It can be concluded that the administration
of warfarin simultaneously with pomegranate peel
extract and guava leaf extract have
pharmacokinetic and pharmacodynamic
interaction.
3.7 Curcumin
Curcumin is an active ingredient of Curcuma
longa that has been widely used as a food
ingredient, has antioxidant activity, and anticancer
activity (63,64). Some studies report that curcumin
has drug interactions. Liu et al.,(29) conducted
warfarin 0.2 mg/kg with oral administration of 25
mg/kg curcumin, 50 mg/kg, and 100 mg/kg to rats
for 7 days show that curcumin had no effect on
pharmacodynamics of warfarin. However
administration of 100 mg/kg of curcumin
significantly increased AUC
0-∞
and C
max
. When
compared to the control group, 100 mg/kg of
curcumin increased 1.6 times higher AUC
0-∞
value
and 1.5 times higher of C
max
, whereas plasma
clearance decreased by 57.14% and there is no
change in T
1/2
. Interaction of warfarin and curcumin
is achieved by inhibit P-glycoprotein and increase
warfarin absorption.
In conclusion, the administration of curcumin at
a dose of 100 mg/kg affects pharmacokinetics but
does not affect the pharmacodynamics of warfarin
(29). However, the co-administration of curcumin
and warfarin must still be monitored to minimize
the side effects.
3.8 Caffeine
Caffeine is widely consumed in the community
so that it allows interactions with drugs. Coffee and
tea are the main sources of caffeine. Zafar et al (30)
showed that administration of 0.5 mg/kg warfarin
and caffeine 5 mg/kg to rabbits has no significant
effect on the C
max
, T
max,
and Vd (Table 1), but there
were changes of warfarin T
1/2
when compared with
the control group. This result indicates that
multiple doses of caffeine increase T
1/2
of warfarin.
Furthermore, the total clearance of warfarin when
it was given together with caffeine was lower than
control, caffeine reduced the elimination of
warfarin from the body. Also, AUC has a
significant increased (Table 1) after the
administration of caffeine with warfarin, it means
that caffeine inhibits warfarin metabolism. The
inhibition is due to blocking CYP1A2 and
CYP3A4 (30). In conclusion, caffeine can affect
the pharmacokinetic profile of warfarin, so the co-
administration of caffeine and warfarin needs to be
reconsidered.
3.9 Challenge and Future Perspective
The co-administration of warfarin with herbs
needs to be considered because they cause
interactions. It is better to consume these herbs 1-2
hours after consuming warfarin to prevent their
adverse effects. The effect of the pharmacokinetic
interactions is an increase in drug levels in the
blood, this can be dangerous, whereas the effects of
this pharmacodynamic warfarin interaction are
bleeding, bruising, fatigue, gastrointestinal effects,
hemorrhage and thrombosis (65). In the future,
more extensive research needs to be done to find
out interactions with other herbs, in addition it is
also necessary to do in depth research to study the
mechanism of the interaction.
4. Conclusion
It can be concluded that some herbal medicines
have significant interactions with warfarin based
on pharmacokinetic and pharmacodynamic
parameters. The herbs that affect the
pharmacokinetics of warfarin are Danshen gegen,
echinacea, St. John's wort and caffeine. While
herbs those affect the pharmacodynamics of
warfarin are policosanol, Ginkgo biloba,
Cranberry, St. John's wort, ginseng, pomegranate
peel, guava leaves and curcumin, so the
administration of warfarin with those herbs need
more concerned.
T. Rusdiana et al / Indo J Pharm 1 (2020) 69-76
73
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