Int
ern
at
i
onal
Journ
al of
P
u
bli
c Hea
lt
h S
c
ie
nce (IJPH
S)
Vo
l.
7
,
No.
1
,
Ma
rch
201
8
, pp.
59
~
6
4
IS
S
N:
22
52
-
8806
, DO
I: 10
.11
591/ij
phs.
v7
i
1.
1
14
38
59
Journ
al h
om
e
page
:
https:
//
ww
w.i
aesco
re
.c
om
/j
our
nals/
ind
ex.
php/IJP
H
S
Identific
atio
n
o
f
P
otential
Dr
u
g I
n
teracti
on
w
ith
C
omple
menta
ry
a
nd
Altern
ative Medicin
es
amon
g
Chroni
c Diseas
e Outp
atie
nts
Nu
rul
M
az
iyyah
1
, Apri
N
ur
dianto
2
,
A
rsi
t
an
ia
Nur K
un
Fajria
3
Facul
t
y
of
Med
i
ci
ne
and
Hea
l
th S
ci
ences
,
Univ
er
sita
s Muham
m
adiy
ah
Yog
y
ak
arta
,
Indon
esia
Art
ic
le
In
f
o
ABSTR
A
CT
Art
ic
le
history:
Re
cei
ved
J
a
n 1
2
, 2
01
8
Re
vised
Ma
r
8
,
201
8
Accepte
d
Ma
r
2
5
, 201
8
Chronic
dise
ase
s
such
as
conge
stive
h
ea
rt
f
ailure
(CHF
)
and
chr
onic
kid
n
e
y
disea
se
(CKD
)
a
re
re
la
t
ed
wi
th
m
ult
ipl
e
drug
pr
esc
ription
which
ca
n
lead
to
drug
int
eraction.
The
high
usage
of
complementa
r
y
and
al
t
ern
ative
m
edi
ci
nes
(CAM
)
in
Indo
nesia
ns
c
an
al
so
inc
r
ea
se
the
ris
k
for
drug
inter
ac
t
ion.
The
obje
c
ti
ve
of
thi
s
stud
y
is
to
d
es
cri
be
CAM
s
use
and
ide
n
ti
f
y
po
te
ntial
drug
int
er
ac
t
ion
with
CAM
s
in
CH
F
and
CKD
outpa
t
ie
nts.
The
stud
y
is
a
cro
ss
sec
ti
on
al
stud
y
.
Data
of
pre
scribe
d
drugs
and
CAM
s
consu
m
ed
by
t
h
e
pat
i
ent
s
was
col
le
c
te
d
b
y
using
m
edi
ca
t
ion
rec
o
nci
liati
on
pro
ce
s
s.
Data
of
routi
ne
CAM
s
and
pre
scribe
d
m
edi
c
ine
s
were
co
m
par
ed
to
ide
nt
i
f
y
pot
ent
i
al
drug
int
er
ac
t
ion
s
which
were
th
en
class
ifi
ed
bas
ed
on
their
m
echani
sm
and
signifi
c
anc
e
.
Th
e
result
show
e
d
tha
t
6,
90
%
o
f
CHF
pat
ie
nts
a
nd
25
%
of
CKD
pat
ie
nts
consum
ed
CAM
s.
Potent
ial
d
rug
int
er
action
bet
wee
n
th
e
CAM
s
and
the
pre
scribe
d
dr
ugs
was
ide
nti
fie
d
in
2.
74%
of
pat
ie
n
ts
consum
ing
CA
Ms
.
Based
on
the
m
ec
hani
sm
,
int
eract
ion
was
dom
ina
te
d
b
y
phar
m
ac
od
y
na
m
ic
s
int
er
ac
t
ion
(
69.
2%)
while
i
nte
ra
ct
ion
signif
ic
an
c
y
wa
s
var
ious.
It
c
an
be
conc
lud
ed
th
at
CAM
s
usage
was
m
ore
fami
li
ar
in
CKD
pat
i
ent
s
compar
ed
to
CHF
pat
i
ent
s.
Potentia
l
d
rug
int
er
ac
t
ion
with
CAMs
was
abl
e
to
be
ide
nti
fi
ed
thro
ugh
m
edi
ca
ti
on
rec
oncili
a
ti
on
proc
ess
and
should
be ta
k
en
i
nto
awa
r
ene
ss
b
y
the healt
h
ca
r
e te
am.
Ke
yw
or
d:
Alte
rn
at
ive
Chronic
diseas
e
Com
ple
m
entary
Drug interact
i
on
Copyright
©
201
8
Instit
ut
e
o
f Ad
vanc
ed
Engi
n
ee
r
ing
and
S
cienc
e
.
Al
l
rights re
serv
ed
.
Corres
pond
in
g
Aut
h
or
:
Nuru
l
Maz
iy
yah
,
Faculty
of Me
dicine a
nd H
e
a
lt
h
Scie
nces
,
Un
i
ver
sit
as M
uh
am
m
adiy
ah
Yogyaka
rta
,
Lingkar
Selat
a
n
R
oad, Tam
antirt
o,
Kasiha
n,
Ba
ntu
l,
Sp
eci
al
D
ist
rict
of
Y
ogya
ka
rta, In
donesia.
Em
a
il
:
m
azi
yy
ahnu
ru
l@y
a
hoo.
c
om
;
m
azi
yyahnu
ru
l@
um
y.
ac.id
1.
INTROD
U
CTION
Drug
I
nteracti
on
is
incl
uded
in
one
of
t
he
Drug
Re
la
te
d
Pr
oble
m
s
(D
R
Ps)
w
hich
is
st
il
l
of
te
n
seen
nowa
days
in
the
cl
inica
l
and
com
m
un
it
y
set
tin
gs.
O
ne
of
the
causes
for
the h
ig
h
incide
nce
of
dr
ug
inte
rac
ti
on
is
patie
nts
rec
ei
vin
g
m
ulti
ple
drug
pr
esc
ri
ption
s
uc
h
as
ger
ia
tric
patie
nts
or
patie
nts
with
chro
nic
diseases
nam
ely
Diabetes
Me
ll
i
tus,
hy
per
te
ns
i
on,
ki
dn
ey
fail
ur
e
,
and
hear
t
fail
ur
e
.
A
stu
dy
in
a
Ce
ntral
Publi
c
Ho
s
pital
in
Y
ogya
ka
rta,
I
ndonesi
a
re
veale
d
a
59%
of
dru
g
interact
io
n
oc
cur
e
nce
am
ong
in
patie
nts
a
nd
69
%
in
outpati
ents
[1
]
.
High
pe
rcen
ta
ge
of
drug
interact
io
n
shou
l
d
le
ad
to
a
war
e
ness
t
o
a
vo
i
d
sig
nif
ic
antly
hazar
dous i
nter
act
io
ns
.
The
us
e
of
co
m
ple
m
entary
and
al
te
rn
at
ive
m
edici
nes
(C
A
Ms)
s
uch
a
s
he
rb
s
an
d
s
uppl
e
m
ents
has
been
fam
i
li
ar
a
m
on
g
Ind
on
e
sia
n
pe
op
le
.
R
esult
from
a
n
at
ion
al
survey
no
ti
ced
a
n
in
crease
in
tra
diti
on
a
l
m
edici
ne
us
a
ge
for
sel
f
-
m
edicat
ion
f
r
om
15
.6
%
i
n
20
00
to
31.
7%
i
n
2001
[
2].
A
f
ollo
wing
s
urvey
in
2007
al
so
re
vealed
a
n
inc
rease
of
23.1%
in
CA
Ms
us
a
ge
sinc
e
2000
[
3].
T
he
relat
ion
s
hip
betwee
n
CAM
s
us
a
ge
and
dru
g
inte
racti
on
was
st
ud
ie
d
by
Tsai
et
al
.
wh
ic
h
descr
i
bed
88
2
dr
ug
i
nterac
ti
on
with
he
r
bs
a
nd
su
pple
m
e
nts,
of whic
h 240 w
ere classi
fie
d
a
s m
ajo
r
inte
rac
ti
on
[4
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
IS
S
N
:
2252
-
8806
IJPHS
V
ol.
7
, No
.
1
,
Ma
rch
20
1
8
:
59
–
6
4
60
High
inci
de
nc
e
of
dru
g
inter
act
ion
am
ong
chro
nic
diseas
e
patie
nts
a
nd
high
CAMs
usa
ge
am
ong
Ind
on
esi
a
ns
s
hould
le
a
d
to
a
pr
e
ven
ti
on
strat
egy
fro
m
healt
hcar
e
pro
vid
er
s.
P
ha
rm
aci
s
t
as
one
of
the
he
al
thcare
pro
vid
e
rs
co
nce
rni
ng
in
rati
onal
dru
g
thera
py
m
us
t
ta
ke
the
first
ste
p
f
or
t
his
pr
e
ve
ntion
strat
egy
.
Gathe
rin
g
im
p
or
ta
nt
inf
or
m
ation
of
dru
g
a
nd
CAMs
us
a
ge
thr
ough
m
edi
cat
ion
rec
onci
li
at
ion
proce
ss
can
be
cond
ucted
in
orde
r
to
ide
ntify
an
d
pr
e
ve
nt
dru
g
i
nteracti
on
in
t
hese
patie
nts
wh
ic
h
e
vent
ually
cou
l
d
preven
t
m
edicat
ion
error
s
ca
us
e
d
by
drug
inter
act
ion
[5
]
.
T
his
cou
l
d
be
a
be
ne
fici
al
su
pport
to
ph
ysi
ci
ans
who
us
ua
ll
y
m
eet
d
ifficult
y i
n scre
enin
g
a
nd d
et
e
ct
ion
process
of
drug interact
i
on
s
in
p
at
ie
nts
’
drug list
[6].
This stu
dy is ai
m
ed
to d
e
scrib
e CAMs u
se a
nd
i
de
ntify p
otentia
l drug inte
racti
on
betwe
e
n
presc
ribe
d
dru
gs
a
nd
between
CAMs
with
t
he
pr
esc
ribe
d
dru
gs
in
co
ngest
ive
he
art
fail
ure
(CH
F)
a
nd
c
hro
nic
kidne
y
disease
(CK
D)
outpati
ents
t
hro
ug
h
m
edicat
ion
rec
on
ci
li
at
ion
process
as
the
fi
rst
ste
p
in
pr
e
ven
ti
ng
dru
g
interact
ion.
2.
RESEA
R
CH MET
HO
D
This
stu
dy
was
cond
ucted
th
r
ough
a
cr
os
s
s
ect
ion
al
desi
gn
and
has
pa
ss
et
hical
cl
earan
ce.
Sub
j
ect
s
recr
uited
we
re
ou
t
patie
nts
visit
ing
one
of
a
pri
vate
hosp
it
al
in
Sp
eci
al
Distric
t
of
Yogya
ka
rta,
Ind
on
esi
a
fr
om
Aug
us
t
to
Oct
ob
e
r
20
14.
Pat
ie
nts
wer
e
e
nrolle
d
into
t
he
s
tud
y
if
they
w
ere
dia
gnos
e
d
with
ei
ther
c
ongestive
hear
t
fail
ure
or
chron
ic
ren
al
disease
an
d
we
re
will
ing
t
o
pa
rtic
ipate
,
ve
rified
by
sign
i
ng
the
inf
or
m
con
se
nt
pro
vid
e
d by th
e resea
rch
e
r.
Me
dicat
ion
rec
on
ci
li
at
ion
pr
oc
ess
was
then
cond
ucted
to
the
sel
ect
ed
pat
ie
nts.
Pati
ents
that
m
et
the
inclusio
n
crit
er
ia
wer
e
inter
vi
ewed
t
o
colle
c
t
and
gathe
r
up
data
of
m
edic
at
ion
an
d
C
A
Ms
us
age
(
def
i
ned
a
s
herbs
an
d
diet
ary
su
pple
m
ents)
wethe
r
pr
e
s
cribe
d
or
non
-
pr
esc
ribe
d
by
their
doct
or.
Pa
ti
ents
wer
e
re
quest
ed
to explai
n
t
he nam
e, d
os
e
, fre
qu
e
ncy,
how
, a
nd whe
n
they
c
on
s
um
e the m
e
dicat
ion
or CA
Ms.
Id
e
ntific
at
ion
of
pote
ntial
dr
ug
interact
io
n
was
done
by
c
om
par
ing
m
edicat
ion
an
d
C
AMs
us
ed
by
the
patie
nts
r
outi
nely
befor
e
their
visit
to
th
e
ho
s
pital
with
m
edicat
ion
ob
ta
ined
f
ro
m
the
do
ct
or
.
Lit
er
at
ur
e
stud
y
was
held
to
ve
rify
the
pote
ntial
interac
ti
on
s,
us
i
ng
m
ai
nly
Drug
I
nteracti
on
Fact
s
by
Tat
r
o
(
2010
)
an
d
Stock
le
y’s
Dr
ug
In
te
racti
on.
3.
RESU
LT
S
A
ND AN
ALYSIS
3.1.
Distribu
tio
n
of P
at
ie
n
ts
Pati
ents selec
te
d
f
or the st
ud
y
was divide
d
i
nto
tw
o
s
ubj
ect
s
base
d
on t
heir m
ai
n
diag
no
sis
wh
ic
h
a
r
e
Chronic
Ki
dn
e
y
Disease
(CK
D)
patie
nts
or
Congesti
ve
He
art
Fail
ur
e
(C
HF
)
patie
nts.
Seve
nty
three
patie
nts
m
et
the inclusi
on crite
ria
fro
m
b
oth
s
ubj
ect
s.
Distri
buti
on
of p
at
ie
nts
’ diagnosis ca
n be
s
een in Fig
ure
1.
Figure
1
.
Distri
bu
ti
on
of Pati
e
nt
s
Fr
om
73
patie
nts,
29
patie
nts
(
40
%
)
were
diag
nosed
wit
h
CH
F
wh
il
e
t
he
rest
of
44
pa
ti
ents
(60%
)
wer
e
dia
gnos
e
d
with
C
KD.
C
HF
a
nd
C
KD
patie
nts
a
re
e
xam
ples
of
chro
nic
disease
pat
ie
nts
with
a
relat
ively
high
pr
e
valen
ce
in
I
ndonesi
a,
especial
ly
in
T
he
S
pecial
Distric
t
of
Y
og
ya
kar
ta
.
Ba
sed
on
the
N
at
ion
al
Pr
im
ary
Health
Re
searc
h
(
Rise
t
Ke
seha
t
an
Da
s
ar
)
pu
blish
ed
in
2013
by
The
I
ndonesi
a
n
Mi
nistry
of
Healt
h,
Yogyaka
rta
ha
d
the
h
i
gh
est
prevale
nce
of
di
agnose
d
C
HF
patie
nts w
it
h
a
per
ce
ntage
of
0.25% com
pared
with
the
ot
her
pr
ov
i
nces
[7]
.
Me
an
wh
il
e,
t
he
pr
e
va
le
nce
of
C
K
D
patie
nts
i
n
Y
ogya
ka
rta
wa
s
a
lso
incl
ud
e
d
i
n
the
high
pr
e
valenc
e
gro
up
(
0.3%
)
with
East
N
usa
Ten
ggara,
S
outh
Su
la
wesi,
Lam
pu
ng,
We
st
Java,
Ce
ntra
l
Java
and East Ja
va
[
7]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
IJPHS
IS
S
N:
22
52
-
8806
Id
e
ntif
ic
ation
of
Po
te
ntial
Dr
ug
In
te
r
action w
it
h
Co
mp
le
ment
ar
y
and
Alt
er
nati
ve .... (N
urul
Ma
ziy
y
ah
)
61
3.2.
Dru
g Co
m
bin
at
i
on
an
d
CA
Ms
u
sage
Data
of
dru
g
com
bin
at
ion
a
nd
CAMs
usa
ge
i
n
patie
nts
’
es
pecial
ly
chro
nic
disease
patie
nts
is
essenti
al
to
obta
in
a
bri
ef
descr
i
ption
on
po
te
ntial
dru
g
interact
io
ns.
Table
1
li
st
the
num
ber
of
dru
g
com
bin
at
ion
i
n pati
ent
s
with
CHF a
nd CK
D
.
Table
1
.
Dru
g C
om
bin
at
ion
i
n
Pati
ents
Drug
co
m
b
in
atio
n
∑ CHF p
atien
ts
∑ CKD p
atien
ts
Total
Percentag
e
(%)
≤ 3 co
m
b
in
atio
n
8
-
8
11
4
–
6
co
m
b
in
atio
n
21
29
50
6
8
.5
> 6 co
m
b
in
atio
n
-
15
15
2
0
.5
Total
29
44
73
100
As
see
n
i
n
T
a
bl
e
1,
t
he
m
ajo
r
it
y
of
patie
nts
wer
e
bei
ng
pre
scribe
d
with
4
to
6
com
bin
at
ion
of
dru
gs
(68.5%
).
Wh
il
e
dr
ug
com
bin
at
ion
c
ou
l
d
hav
e
ben
e
fici
al
eff
ect
on
tre
at
ing
va
rio
us
diseases,
the
us
e
of
irrati
on
al
drug
com
bin
at
ion
(
includi
ng
C
A
Ms)
h
as
be
en
known
to
i
ncrea
se
the
risk
of
pote
ntial
haz
ardo
us
eff
ect
su
c
h
as
detrim
ental
dr
ug
inte
racti
ons
[8
]
.
The
refo
re
rati
on
al
dru
g
com
bin
at
ion
s
hould
be
a
co
nc
ern
i
n
healt
hcar
e
pr
ovide
rs
in
or
der
to g
i
ve
the
patie
nt the o
ptim
u
m
d
ru
g t
her
a
py
.
Chronic
kidne
y
disease
patie
nts
we
re
ide
ntifie
d
with
m
ore
drug
c
om
bin
at
ion
s
tha
n
C
HF
patie
nts.
This
m
igh
t
oc
cur
beca
us
e
of
var
i
ou
s
com
plica
ti
on
s
seen
in
patie
nts
with
CK
D
s
uc
h
a
s
anem
ia
,
el
ec
trolyt
e
i
m
balance,
os
t
eod
yst
r
ophy,
e
tc
wh
erea
s
each
com
plica
ti
on
has
it
s
own
t
her
a
py
[9
]
.
T
hi
s
is
diff
ere
nt
from
CHF
patie
nts
wh
ic
h
usual
ly
are
not
accom
pan
ie
d
with
m
any
com
plica
tio
ns.
As
for
CAMs
us
a
ge,
F
i
gure
2
descr
i
bes
t
he d
iffer
e
nce
betw
een th
e
CH
F a
nd CK
D pati
en
ts.
Figure
2
.
CAM
s u
sa
ge
i
n
C
HF an
d
C
KD
pati
ents
Ba
sed
on
F
i
gure
2,
C
KD
pa
ti
ents
we
re
m
or
e
fam
i
li
ar
with
CAMs
us
a
ge
c
om
par
ed
with
C
HF
patie
nts
(
25% v
ers
us
6
.
9%
).
Th
e h
ig
h
us
age
of
C
AMs
in
C
KD
p
at
ie
nts
i
n
this
stu
dy
is
sim
il
ar
with
the r
esults
seen
f
ro
m
a
st
ud
y
in
T
haila
nd
w
her
e
half
of
the
CK
D
pati
ents
inclu
de
d
in
the
stu
dy
use
d
he
rb
s
an
d
di
et
ary
su
pple
m
ents.
These
patie
nts
we
re
m
os
tl
y
us
in
g
herbs
an
d
s
upplem
ents
with
a
pur
po
s
e
of
m
ai
ntaining
their
well
-
bei
ng.
F
riends
a
nd
fam
ily
reco
m
m
end
at
ion
w
as
t
he
m
ai
n
reas
on
to
tr
y
,
w
hile
pe
rceived
be
ne
fi
ts
of
us
i
ng
the CAMs
w
as
m
os
tl
y t
he
reaso
n t
o co
ntin
ue
cons
um
ing
the
m
[10
]
,
[
11]
.
3.3.
Pot
e
nt
i
al D
r
u
g
In
ter
act
i
on
Po
te
ntial
drug
interact
ions
w
ere
ide
ntifie
d
by
c
om
par
ing
dru
gs
a
nd/
or
CAMs
c
on
s
um
ed
r
ou
ti
nely
with
the
new
dru
gs
prescri
be
d
by
the
doct
or
at
the
ti
m
e
of
ho
s
pital
visit
.
Drug
intera
ct
io
n
was
t
hen
cl
assifi
ed
as
pharm
acoki
netic
and
ph
arm
acod
ynam
i
c
interact
io
n
base
d
on
t
he
m
echan
is
m
of
t
he
inter
ac
ti
on
s.
Evaluation Warning : The document was created with Spire.PDF for Python.
IS
S
N
:
2252
-
8806
IJPHS
V
ol.
7
, No
.
1
,
Ma
rch
20
1
8
:
59
–
6
4
62
Sign
i
ficancy
of
inte
racti
on
as
one
of
the
im
po
rta
nt
pa
ram
eter
s
i
n
m
aking
f
ollow
up
decis
ion
s
was
det
er
m
ined
by classi
ficat
io
n from
Tatro
’s Dr
ug Interact
io
n
Fact
s
(20
10)
.
Th
e
r
es
ult can
b
e
seen
in
T
a
bl
e
2
.
Table
2
.
Po
te
ntial
D
r
ug Intera
ct
ion
s i
n
CH
F
and CK
D pati
ents
Drug
A
Drug
B
Interaction
M
echa
n
is
m
Sig
n
if
ican
cy
Ph
.
Kin
etic
Ph
.
d
y
n
a
m
i
c
A.
CHF p
atien
ts
Acetos
al
Bis
o
p
rolo
l
1
4
Dig
o
x
in
Cap
to
p
ril
2
4
Dig
o
x
in
Lisin
o
p
ril
5
4
Dig
o
x
in
Sp
iron
o
lak
to
n
7
2
Fu
ros
e
m
id
Dig
o
x
in
13
1
Fu
ros
e
m
id
Cap
to
p
ril
2
3
W
arfarin
Tur
m
e
ric
Acid
1
5
Clo
p
id
o
g
rel
Fish
Oil
1
2
B.
CKD p
atien
ts
Acetos
al
Vita
m
in
B1
2
2
3
Aceta
m
in
o
p
h
en
Fu
ros
e
m
id
2
5
Nif
ed
ip
in
e
Diltiaze
m
1
3
O
m
ep
ra
zo
le
Vita
m
in
B1
2
2
5
Bis
o
p
rolo
l
Diltiaze
m
2
2
Bis
o
p
rolo
l
Clo
n
id
in
e
6
1
Fu
ros
e
m
id
Cap
to
p
ril
5
3
Bis
o
p
rolo
l
Nif
ed
ip
in
e
7
4
Acetos
al
Cap
to
p
ril
1
2
Acetos
al
Clo
p
id
o
g
rel
1
1
Cap
to
p
ril
Epo
etin
Alph
a
15
Un
k
n
o
wn
Cap
to
p
ril
Po
tass
iu
m
1
Un
k
n
o
wn
Cap
to
p
ril
Ir
b
esartan
1
Un
k
n
o
wn
Total o
f
patien
ts
24
54
Percentag
e
(%)
3
0
.8
6
9
.2
Ph
.
kin
et
ic
: P
ha
rm
acok
ineti
c,
Ph
.
dynam
ic
: Phar
m
acod
yna
m
ic
As
sho
wn
in
T
able
2,
po
te
nt
ia
l
dr
ug
inte
ra
ct
ion
s
ide
ntifie
d
in
CHF
a
nd
CKD
pa
ti
ents
m
os
tly
had
ph
a
rm
acod
yna
m
ic
m
echan
ism
.
This
ty
pe
of
interact
i
on
re
fer
s
t
o
dru
gs
or
s
ub
sta
nces
t
ha
t
interact
in
t
he
sam
e
recept
or
syst
e
m
,
ta
rg
et
of
ac
ti
on
or
physi
ol
og
y
syst
em
wh
ic
h
the
n
c
on
t
rib
utes
to
an
a
dd
it
ive
(sine
rgi
sti
c)
or
antag
on
ist
ic
eff
ect
w
hile
ph
arm
acok
ineti
c
interact
ion
s
us
ually
caus
e
an
increase
or
dec
rease
of
dr
ug
con
ce
ntrati
on
in
the
blood
even
t
ually
le
a
ding
to
tox
ic
or
s
ub
t
her
a
pe
utic
eff
ect
[12
]
.
If
com
par
ed
with
ph
a
rm
aco
kin
et
ic
interact
ion
s,
ph
a
rm
acod
yn
a
m
ic
interact
ion
s
usual
ly
nee
ds
a
m
uch
dee
per
c
om
pr
ehe
nsi
on
on
the
m
echan
is
m
of
act
io
n
f
or
t
he
dru
gs
or
s
ubsta
nce
t
o
inter
act
[13].
The
re
fore
predict
in
g
eff
ect
of
this
t
ype
of
interact
ions m
a
y req
uire se
ve
r
al
co
nsi
der
at
i
ons
.
Wh
e
n
an
al
yz
ing
po
te
ntial
dr
ug
interact
io
ns
in
patie
nts,
consi
der
at
io
n
sh
oul
d
be
gi
ve
n
m
os
tl
y
on
ty
pes
of
i
ntera
ct
ion
s
t
hat
are
cl
inica
ll
y
sign
ific
ant
wh
ic
h
w
il
l
po
ssi
bly
ha
ve
si
gn
i
ficant
eff
ect
on
the
pa
ti
ents.
In
t
his
stu
dy,
s
ign
ific
a
nce
of
the
interact
io
n
can
be
see
n
by
the
nu
m
ber
of
sign
i
ficance
l
evel
(last
c
olum
n
in
Table
2),
w
here
the
s
m
al
le
r
t
he
num
ber
,
the
m
or
e
sign
ific
a
nt.
This
sho
uld
be
the
basis
for
healt
hcar
e p
r
ov
i
de
r
(esp
eci
al
ly
the
ph
a
rm
aci
st)
t
o
determ
ine
the
best
interve
nt
ion
in
ord
e
r
to
preve
nt
detri
m
ental
eff
ect
on
th
e
patie
nts
du
e
t
o
dru
g
i
nterac
ti
on
s.
T
he
si
gnific
ance
le
vel
of
1
i
nd
ic
at
es
an
interact
io
n
w
hich
is
ca
pa
ble
in
causin
g
pe
rm
a
nen
t
dam
age
a
nd
death
to
pa
ti
ents
[14].
P
otentia
l
intera
ct
ion
s
ide
ntifie
d
in
this
le
ve
l
wer
e
fu
ro
s
em
ide
wi
th
digox
i
n,
bis
opr
olo
l
with
c
lon
idi
ne,
an
d
acet
os
al
(asp
i
r
in)
with
cl
opi
dogrel
.
Give
n
a
hig
h
nu
m
ber
of
cas
es
(13
cases
),
co
-
a
dm
inist
ratio
n
of
f
urosem
i
de
with
digo
xi
n
is
a
com
m
on
pr
esc
riptio
n
i
n
CH
F
patie
nts.
B
oth
dru
gs
a
re
es
se
ntial
to
m
ai
nta
in
CHF
patie
nt
sta
bili
ty
and
has
bee
n
rec
omm
end
ed
f
or
hea
rt
fail
ur
e
patie
nts
with
re
du
ce
d
ejecti
on
fr
act
i
on
[
15]
.
T
he
i
nteracti
on
bet
ween
the
tw
o
dru
gs
is
ca
pa
bl
e
on
increasin
g
the
risk
of
digox
i
n
to
xicit
y
du
e
to
hypo
kalem
ia
wh
ic
h
ca
n
l
ead
to
ef
fects
su
c
h
as
ar
rh
yt
hm
ia.
Ma
ny
stu
dies
hav
e
s
hown
di
goxin
to
xicit
y
le
ading
to
hos
pital
iz
at
ion
am
ong
C
HF
patie
nts
presc
ribe
d
with
bo
t
h
digox
i
n
a
nd
di
ur
et
ic
ag
ents.
A
high
incide
nce
of
ho
sp
it
al
iz
at
ion
is
m
os
tly
seen
in
CH
F
patie
nts
w
ho
receive
m
or
e
than
one
di
ur
et
i
c
agen
t
in
c
ombinati
on
with
di
goxin
.
The
refor
e
c
om
bin
ing
digox
i
n
with
s
ever
a
l
diuret
ic
agen
t
s
m
us
t
be
avo
ide
d,
w
hile
co
-
a
dm
inist
ratio
n
of
digox
i
n
with
on
e
diu
reti
c
age
nt
su
ch
a
s
furo
s
em
ide
ca
n
be
ha
nd
le
d
by
pota
ssiu
m
m
on
it
or
in
g
(to
dete
rm
in
e
risk
of
hypokalem
ia
)
and
add
i
ng
po
ta
ssi
um
su
pple
m
ent (
to pre
ven
t
hypo
kale
m
ia
)
[14
]
,
[
16
]
.
Re
la
te
d
to
CA
Ms
co
ns
um
ption
in
C
HF
a
nd
CK
D
patie
nt
s,
the
re
we
re
2
cases
(
2.7
4%)
of
patie
nts
consum
ing
tu
r
m
eric
aci
d
an
d
fis
h
oil
were
identifie
d
w
it
h
pharm
acody
nam
ic
s
interact
ion
with
the
oth
e
r
pr
esc
ribe
d
dru
gs
.
Tu
rm
eric
aci
d
ha
s
a
pote
ntial
interact
io
n
wi
th
warfari
n
wh
ic
h
is
a
n
antic
oa
gula
nt
age
nt
Evaluation Warning : The document was created with Spire.PDF for Python.
IJPHS
IS
S
N:
22
52
-
8806
Id
e
ntif
ic
ation
of
Po
te
ntial
Dr
ug
In
te
r
action w
it
h
Co
mp
le
ment
ar
y
and
Alt
er
nati
ve .... (N
urul
Ma
ziy
y
ah
)
63
us
ua
ll
y
pr
esc
ribed
in
CH
F
patie
nts
with
diag
nose
of
a
tria
l
fibr
il
la
ti
on
in
orde
r
to
reduce
t
he
ri
sk
f
or
thr
om
bo
em
bo
li
c
even
t
[17].
Tur
m
eric
aci
d
is
kn
ow
n
to
ha
ve
an
in
vitr
o
eff
ect
in
the
inh
i
biti
on
of
pl
at
el
et
a
ct
ivati
ng
fact
or
(PAF
)
a
nd
plate
le
t
ag
gregati
on
the
refor
e
inc
reasin
g
the
risk
of
bleedin
g
in
pa
ti
ents
consum
ing
ant
ic
oagulant.
Docum
entat
ion
for
this
ty
pe
of
i
nteracti
on
has
no
t
ye
t
been
well
est
ablishe
d
an
d
there
c
ou
l
d
be
var
ia
ti
on
in
ph
arm
acolog
ic
al
eff
e
ct
du
e
to
in
consi
ste
ncy
of
the
he
rb
pote
nc
y
it
sel
f
[18
]
-
[
20
]
.
A
sign
ific
a
nce
le
vel
of
5
f
or
thi
s
pote
ntial
interact
ion
i
ndic
at
es
a
m
ino
r
cl
in
ic
al
sign
ific
anc
e;
hen
ce
,
the
pa
ti
ent
m
us
t
still
be
m
on
it
or
ed
f
or
risk
of
bleedin
g
wh
ic
h
is
t
he
m
os
t
com
m
o
n
si
de
e
f
fect
of
warfarin
.
Awarenes
s
m
us
t
be
raised
since
warfari
n
is
include
d
in
dru
gs
with
a
nar
r
ow
thera
pe
utic
ind
e
x
w
her
e
ris
k
of
to
xicit
y
cou
l
d
inc
rease
or co
uld bec
om
e less effecti
ve
if
cons
um
ed
with
he
rb
s
[2
1]
.
Wh
il
e
the
pot
entia
l
interact
ion
betwee
n
tu
rm
eri
c
aci
d
and
wa
rf
a
rin
wa
s
sta
te
d
as
m
i
nor,
a
no
t
her
interact
ion
wit
h
CAMs
i
den
t
ifie
d
in
t
his
stud
y
had
a
sig
nificance
le
vel
of
2.
O
ne
patie
nt
pr
e
scribe
d
with
cl
op
id
ogrel
al
s
o
c
on
s
um
ed
fis
h
oil
w
hich
(b
a
sed
on
li
te
rature)
co
uld
le
ad
t
o
a
n
interact
i
on
betwee
n
b
ot
h.
Fish
oil
is
known
to
pote
ntiat
e
ph
arm
acolog
ic
a
l
eff
ect
of
a
nticoag
ulant
a
nd
oth
e
r
drug
s
wh
ic
h
hav
e
e
f
fect
on
plate
le
ts
and
t
hrom
bin
su
c
h
as
cl
op
i
dogr
el
.
Ther
e
f
or
e
this
su
pple
m
ent
has
bee
n
wi
dely
us
e
d
(a
nd
c
om
m
on
ly
pr
esc
ribe
d
by
do
ct
or
s
)
for
patie
nts
w
it
h
or
at
risk
f
or
ca
r
diovasc
ular
diseases.
A
stu
dy
of
fish
oil
su
pple
m
entat
ion
i
n
diabetes
pa
ti
ents
us
i
ng
low
dose
as
piri
n
s
how
n
t
hat
c
o
-
a
dm
inist
rati
on
rev
eal
e
d
a
gr
eat
er
reducti
on
of
ag
gr
e
gatio
n
of
pl
at
el
et
com
par
ed
to
as
pirin
al
one.
Des
pite
the
be
nef
it
of
fis
h
oil
s
upplem
entat
ion
in
patie
nts
al
so
receivi
ng
anti
plate
le
ts
or
a
nt
ic
oagulants,
co
ns
ide
rati
on
m
us
t
be
giv
e
n
s
pe
ci
fical
ly
to
patie
nts
with h
i
gh
risk of
bleedin
g
s
uc
h
as p
at
ie
nts in
p
la
n
f
or
s
urge
ry o
r pati
ents w
ho a
pp
ea
rs
w
it
h
sign
s
of
e
ve
n
m
i
ld
ble
edin
g [
22
]
-
[
24
]
.
4.
CONCL
US
I
O
N
C
om
ple
m
entary
and
al
te
rn
at
ive
m
edici
nes
(
CAMs
)
us
a
ge
was
m
or
e
fam
il
ia
r
in
CKD
patie
nts
com
par
ed
to
CHF
patie
nts.
Po
te
ntial
dr
ug
interact
io
ns
with
CAMs
w
ere
identifie
d
(alt
hough
in
a
s
m
al
l
nu
m
ber
;
2.7
4%
)
as
pharm
acod
y
nam
ic
m
ec
han
ism
throu
gh
m
edicat
ion
r
econ
ci
li
at
ion
proces
s
an
d
s
ho
uld
be
ta
ken
i
nto
a
wa
ren
es
s
by
t
he
healt
hcar
e
te
am
accord
in
g
t
o
the
sig
nifica
nce
le
vel
of
in
te
racti
on
besi
de
s
ot
her
pr
esc
ribe
d dru
g
inte
racti
ons
wh
ic
h
a
re c
omm
on
ly
seen
in
chro
nic d
ise
ase
p
at
ie
nts.
ACKN
OWLE
DGE
MENTS
We
w
ould
li
ke
to
than
k
Un
i
ve
rsita
s
Muh
am
m
adiy
ah
Yogy
akar
ta
,
Ind
on
e
sia
fo
r
t
he
res
earch
gr
a
nt
giv
e
n
to
co
m
plete
this stu
dy.
REFERE
NCE
S
[1]
F.
Rahmawat
i
,
et
al
.
,
“
Retros
pec
t
ive
stud
y
of
drug
int
er
ac
t
ion
s
in
Dr.
Sardjit
o
hospita
l
Yog
yaka
rt
a,
”
Majal
a
h
Farmas
i
Indone
sia,
vo
l
/i
ss
ue:
17
(
4
)
,
pp
.
177
–
183
,
2006.
[2]
S.
Supardi,
et
al
.
,
“
Us
e
of
m
anuf
ac
tur
ed
tr
adi
t
ion
al
m
edicine
for
s
el
f
m
edica
t
ion
i
n
Indone
sia
,
”
Ju
rnal
Bahan
A
la
m
Indone
sia
,
vo
l
/i
s
sue:
2
(
4
)
,
pp
.
13
6
-
41,
2003
.
[3]
S.
Supardi
and
A.
L.
Sus
y
an
ti
,
“
Tra
dit
ion
al
m
e
dic
in
e
usage
for
self
m
edi
c
ation
purpose
in
I
ndo
nesia
:
anal
y
s
is
of
SU
SENAS
dat
a y
e
ar
2007
,
”
Bu
letin Pe
ne
li
t
ian
K
e
sehatan
;
vo
l
/i
ss
ue:
38
(
2
)
,
pp
.
80
-
89,
2010
.
[4]
H.
H.
Tsai
,
e
t
a
l.
,
“
Evaluation
o
f
documente
d
dr
ug
int
eract
ions
and
cont
ra
indica
ti
ons
associa
t
ed
with
her
bs
and
die
t
ar
y
supplem
ent
s:
a
s
y
s
te
m
ati
c
l
it
er
at
ur
e
r
evi
e
w
,”
Int
J
Cl
in
Pr
act
,
vol
/
issue:
66
(
11
)
,
pp
.
1056
-
1
078,
2012
.
[5]
J.
H.
Barnst
ei
ne
r,
“
Medic
a
ti
on
r
ec
onc
il
i
at
ion
”
in
R.
G.
Hughes
,
“
Pati
ent
saf
ety
and
qua
li
t
y
:
an
evi
den
ce
-
b
ase
d
handbook
for
nu
rses
,
Rockvill
e,
MD
,
AH
RQ Pub
li
c
at
ion
,
vol
.
2,
2
008.
[6]
B.
H.
Vaidhun
and
S.
Am
irt
hal
ing
am,
“
Phy
si
ci
ans
expect
at
io
ns
to
pre
vent
t
he
drug
int
er
actions
in
cl
in
ical
pra
ctice,
”
Int
J
P
harm
acy
and
Ph
arm
Sci
,
vol
/
issue:
2
(
3
)
,
pp
.
172-
173,
2010
.
[7]
Indone
sian
Mini
str
y
of
Hea
lt
h
,
“
Nati
ona
l
primar
y
he
al
th
r
ese
ar
c
h
,
”
Jaka
r
ta,
Bad
an
Penel
i
tian
da
n
Pengembanga
n
Keseha
ta
n
Indon
esia
n
Min
istr
y
o
f
Hea
l
th, 2013.
[8]
H.
C.
Kort
ing
a
nd
M.
S
.
Kort
in
g,
“
The
b
ene
f
it
/r
isk
rat
io
:
a
hand
book
for
th
e
ra
tional
use
of
pot
e
nti
all
y
h
az
ard
ou
s
drugs
,
”
Florid
a,
CRC Press,
200
8.
[9]
J.
T.
DiPiro,
et
al.
,
“
Pharm
ac
ot
her
ap
y
:
a
pat
ho
ph
y
siolog
ic
app
r
oac
h,
six
th
editi
on
,”
Unit
ed
States,
The
McGr
a
w
-
Hill
Com
panies,
2005
.
[10]
M.
Ta
ngki
at
ku
m
ja
i
,
e
t
al
.
,
“
Preva
l
enc
e
of
her
bal
and
d
ie
t
ar
y
supplement
usag
e
in
Th
ai
outp
atient
s
with
chr
on
ic
kidney
d
isea
se:
a
cro
ss
-
sec
ti
ona
l
surve
y
,
”
BMC
Compleme
nt Al
t
ern
Me
d
,
vol
.
13
,
pp
.
153,
2013.
[11]
M.
Ta
ngk
ia
tkum
ja
i
,
e
t
a
l.
,
“
Rea
s
ons
wh
y
Tha
i
p
at
i
ent
s
with
chr
onic
k
idney
d
ise
ase
use
or
do
no
t
use
h
erb
al
and
die
star
y
supp
le
m
ent
s,
”
BMC
Compleme
nt
Altern
Me
d
,
vo
l
.
14,
pp.
473,
20
1
4.
[12]
R.
A.
He
lms
and
D.
J.
Quan
,
“
Te
xtbooks
of
th
era
peu
ti
cs
drug
and
dise
ase
m
an
age
m
ent
,
”
Phil
a
del
phi
a,
Li
ppin
c
ott
W
il
li
ams
and
W
il
kins,
2006.
[13]
Cascor
bi
I.,
“
Dr
ug
int
eract
ions
—
princ
iples,
ex
amples
and
cl
in
ic
a
l
conse
quences,
”
Dtsch
Arztebl
Int
,
vol
/i
ss
ue
:
109
(
33
–
34
)
,
pp
.
546
–
56,
2012
.
Evaluation Warning : The document was created with Spire.PDF for Python.
IS
S
N
:
2252
-
8806
IJPHS
V
ol.
7
, No
.
1
,
Ma
rch
20
1
8
:
59
–
6
4
64
[14]
D.
S.
Ta
tro
,
“
Dr
ug
intera
c
ti
on
fa
ct
s
,
”
Phila
d
el
ph
i
a,
Li
ppin
cot Wil
li
am a
nd
W
il
kin
s,
2006.
[15]
C.
W
.
Yan
c
y
,
et
al
.
,
“
ACCF
/AH
A
guide
l
ine
for
t
he
m
ana
gemen
t
of
hea
r
t
f
ai
lur
e:
a
rep
or
t
of
the
Am
eri
ca
n
Co
lle
g
e
of
Cardi
olog
y
F
oundat
ion/
Am
e
r
ic
an
He
art
As
sociation
T
ask
Force
on
Prac
ti
c
e
Guidel
in
es,
”
J
Am
Coll
Cardiol
,
v
ol
.
62,
pp
.
e147
–
23
9,
2013
.
[16]
M.
T.
W
ang,
e
t
al.
,
“
Risk of
dig
oxin
int
oxi
ca
t
ion
in
hea
rt
fa
il
ur
e
pat
i
ent
s e
xposed
to
digoxi
n
–
diur
et
i
c
int
er
actions:
a
popula
ti
on
-
b
ase
d
stud
y
,
”
Br
J
C
l
in
Pharmacol
,
v
ol
/i
ss
ue:
70
(
2
)
,
p
p.
258
–
267
,
201
0.
[17]
R.
O.
e
t
al
.
,
“
ACC/AH
A
cl
ini
c
al
per
form
an
ce
m
ea
sures
for
ad
ult
s
with
s
y
sto
lic
hea
r
t
fa
il
ure
:
A
rep
ort
of
th
e
Am
eri
ca
n
Coll
e
ge
of
Cardi
olog
y
/Am
erica
n
Hea
rt
As
socia
ti
on
Ta
sk
Force
on
Perform
anc
e
Mea
sures
(W
rit
in
g
Com
m
it
te
e
to
Deve
lop
He
art
Fai
lure
Cli
n
ical
Per
form
anc
e
Mea
su
res),
”
J
Am
Coll
Cardiol,
vol
.
46
,
pp.
1144
–
1178
,
2005.
[18]
W
.
Abebe
,
“
Herba
l
m
edica
t
ion:
pote
ntial
for
adv
erse
in
te
ra
ctions
with
ana
lg
esic
drugs,
”
J
Cli
n
P
harm
Ther
,
vo
l
.
27
,
pp
.
391
–
401
,
2
002.
[19]
A.
M.
Hec
k,
et
al.
,
“
Potential
in
te
ra
ct
ions
be
twe
en
al
t
ern
a
ti
ve
th
era
pi
es
and
warf
ari
n
,”
Am
J
Hea
lt
h
Syst
Pharm
,
vol
.
57
,
pp
.
1221
-
1227,
2000
.
[20]
X.
Yang,
e
t
al
.
,
“
Curcumin
inhi
bit
s
platelet
-
de
riv
ed
growth
fa
ct
or
-
stim
ula
te
d
v
asc
ula
r
sm
ooth
m
us
cl
e
ce
l
l
func
ti
o
n
and
in
jur
y
-
induced
neo
int
ima
for
m
at
ion,
”
Art
erio
scle
r Thr
omb V
a
sc
Bi
o
l
,
vol
.
26
,
pp.
85
–
90,
2006.
[21]
M.
Y.
M.
Ism
ai
l,
“
Herb
-
drug
int
e
rac
t
ions
and
pat
i
ent
counse
l
li
ng
,
”
Int
J
Pharm
Pharm
Sci
,
vol
/i
ss
u
e:
7
(
2
)
,
pp
.
1
-
7
,
2009.
[22]
R.
C.
Bloc
k
,
et
al
.
,
“
Eff
ects
of
low
-
dose
aspiri
n
and
fish
oil
on
pla
te
l
et
func
tion
and
nf
-
kappab
in
adul
ts
with
dia
be
te
s m
el
l
it
us
,
”
Prostaglandi
n
s Leuk
ot Ess
ent
Fat
ty Acids
,
vol
/
issue:
89
(
1
)
,
pp.
9
–
18
,
2013
.
[23]
P.
M.
K
.
Et
her
ton
,
et
al.
,
“
Fis
h
c
onsum
pti
on,
fish
oil
,
om
ega
-
3
fatt
y
a
ci
ds,
and
c
ar
diova
scul
ar
dise
ase
,
”
Circu
lat
io
n
,
vol
.
106
,
pp
.
274
7
-
2757
,
2002
.
[24]
C.
Alder
m
an
,
“
Antipl
atel
et
eff
e
ct
s of
f
ish oil
su
pple
m
ent
s
,
”
RG
H P
harm
acy
E
-
Bul
letin
,
vol
/i
ss
ue:
41
(
8
)
,
2011
.
Evaluation Warning : The document was created with Spire.PDF for Python.