-
Handbook ofHIV Drug Therapy
Alice Tseng, Pharm.D., FCSHP, AAHIVPImmunodeficiency
ClinicToronto General HospitalToronto, ON
Michelle Foisy, Pharm.D., FCSHP, AAHIVPNorthern Alberta
ProgramEdmonton, AB
VOLUME TWODrug Interactions
-
Sing
leTa
blet
Reg
imen
s
Nuc
leos
(t)id
e R
ever
se
Tran
scri
ptas
e In
hibi
tors
Non
-Nuc
leos
ide
Rev
erse
Tran
scri
ptas
e In
hibi
tors
Prot
ease
Inhi
bito
rsIn
tegr
ase
Inhi
bito
r
Atri
pla
(efa
viren
z 60
0 m
g,
teno
fovir
300
mg,
em
tric
itabi
ne 2
00 m
g)
Truv
ada
(teno
fovir
300
mg,
emtr
icita
bine
200
mg)
3TC
(lam
ivudi
ne 1
50 m
g,30
0 m
g)
Retr
ovir
(zid
ovud
ine
100
mg)
Edur
ant
(rilp
ivirin
e 25
mg)
Sust
iva
(efa
viren
z 20
0 m
g,
600
mg)
Aptiv
us(ti
pran
avir
250
mg)
Prez
ista
(dar
unav
ir 40
0 m
g,
600
mg)
Nor
vir
(rito
navir
100
mg)
Fuze
on(e
nfuv
irtid
e 10
8 m
g/via
l))
Com
pler
a(r
ilpivi
rine
25 m
g,
emtr
icita
bine
200
mg,
te
nofo
vir 3
00 m
g)
Kive
xa(a
baca
vir 6
00 m
g,la
mid
uvin
e 30
0 m
g)
Com
bivi
r(la
mivu
dine
150
mg,
zido
vudi
ne 3
00 m
g)
Triz
ivir
(aba
cavir
300
mg,
lam
ivudi
ne 1
50 m
g,zi
dovu
dine
300
mg)
Vire
ad(te
nofo
vir 3
00 m
g)
Ziag
en(a
baca
vir 3
00 m
g)
Vide
x EC
(did
anos
ine
400
mg)
Zeri
t(s
tavu
dine
30
mg,
40 m
g)
Inte
lenc
e(e
trav
irine
200
mg)
Resc
ript
or(d
elav
irdin
e 10
0 m
g)
Vira
mun
e(n
evira
pine
200
mg)
Vira
mun
e XR
(nev
irapi
ne 4
00 m
g)
Crix
ivan
(indi
navir
400
mg)
Invi
rase
(saq
uina
vir 5
00 m
g)
Kale
tra
(lopi
navir
100
mg,
riton
avir
25 m
g,)
(lopi
navir
200
mg,
riton
avir
50 m
g)
Vira
cept
(nel
fi nav
ir 62
5 m
g)Ce
lsen
tri
(mar
aviro
c 15
0 m
g,30
0 m
g))
Reya
taz
(ata
zana
vir 1
50 m
g,20
0 m
g, 3
00 m
g)
Telz
ir(fo
sam
pren
avir
700
mg)
Fusi
on In
hibi
tor
CCR
5In
hibi
tor
200
mg,
300
mg)
vial))
(nev
irapi
ne 2
00 m
g)(n
evira
pine
200
mg)
Isen
tres
s(r
alte
grav
ir 40
0 m
g)
riton
avir
50 m
g)
Stri
bild
(Elvi
tegr
avir
150
mg,
co
bici
stat
150
mg,
te
nofo
vir 3
00 m
g,
emtr
icita
bine
200
mg)
(nev
irapi
ne 4
00 m
g)
HIV
MED
ICAT
ION
S AT
A G
LAN
CE
-
Handbook ofHIV Drug Therapy
Copyright 2013, Alice Tseng, Pharm.D. All rights reserved.
All material in this handbook is copyrighted by the author and
may be reprinted only withwritten permission of the author.
Requests to reprint or reproduce material may be sent byfax or
e-mail to Alice Tseng, Pharm.D., Immunodeficiency Clinic, Toronto
General Hospital,416-340-4890, [email protected].
Additional information and updates may be found at:
www.hivclinic.ca
Editor In Chief
Alice Tseng, Pharm.D., FCSHP, AAHIVPImmunodeficiency Clinic,
Toronto General HospitalFaculty of Pharmacy, University of
TorontoToronto, ON
Associate Editor
Michelle Foisy, Pharm.D., FCSHP, AAHIVPNorthern Alberta Program,
Alberta Health ServicesEdmonton, AB
VOLUME TWODrug Interactions
-
TABLE OF CONTENTS FORHIV DRUG THERAPY HANDBOOK 2013
ACKNOWLEDGEMENTS. . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . i
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . iii
I. ANTIRETROVIRAL INTERACTIONS CCR5 Inhibitors . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 1 Integrase Inhibitors. . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . 17
Non-Nucleoside Reverse Transcriptase Inhibitors . . . . . . . . . .
. . . . . . . . 43 Protease Inhibitors . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Protease Inhibitors-Secondary Agents . . . . . . . . . . . . . . .
. . . . . . . . . . . . 167 Reverse Transcriptase Inhibitors. . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Tenofovir. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . 225
II. INTERACTIONS WITH OTHER DRUG CLASSES Anticonvulsant Drugs of
Choice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 242 Anticonvulsants . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . 245
Antihyperglycemic Comparison Chart. . . . . . . . . . . . . . . . .
. . . . . . . . . . . 267 Antihyperglycemics . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Antihypertensives . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . 285 Antimalarials . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . 301 Antineoplastic Agents . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 Azole
Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . 358 Hepatitis C Directly Acting
Antivirals . . . . . . . . . . . . . . . . . . . . . . . . . . . .
377 Antiretroviral Treatment Options for Patients on DAAs - Summary
. . . 392 Lipid-Lowering Drugs. . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . 394 Methadone . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 409 Narcotics . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 425 Oral Contraceptives. . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . 441 Psychotropics. . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 453 Pulmonary Arterial Hypertension Drugs . .
. . . . . . . . . . . . . . . . . . . . . . . 479 Recreational
Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . 484 Sedatives/Hypnotics . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492
Smoking Cessation Products . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . 500 Transplant Drugs. . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 504
III. GLOSSARY . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . 518
Tom Tranmer
-
285ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
1 o
f 16
Ant
iretr
ovira
l Pha
rmac
okin
etic
Cha
ract
eris
tics
(sum
mar
y):
Pr
otea
se In
hibi
tors
(PIs
) N
on-N
ucle
osid
e R
ever
se T
rans
crip
tase
In
hibi
tors
(NN
RTI
s)
Inte
gras
e In
hibi
tors
at
azan
avir
(Rey
ataz
)1
, dar
unav
ir (P
rezi
sta
)2, f
osam
pren
avir
(Tel
zir
)3,
indi
navi
r (C
rixiv
an
)4, l
opin
avir/
riton
avir
(Kal
etra
)5, n
elfin
avir
(Vira
cept
)6
, rito
navi
r (N
orvi
r)7
, saq
uina
vir (
Invi
rase
)8
, tip
rana
vir (
Apt
ivus
)9
efav
irenz
(Sus
tiva
)10 ,
etra
virin
e (In
tele
nce
)11 ,
nevi
rapi
ne (V
iram
une
)12 ,
rilpi
virin
e (E
dura
nt
)13
elvi
tegr
avir/
cobi
cist
at (S
tribi
ld
, sin
gle-
tabl
et re
gim
en w
ith
teno
fovi
r/em
trici
tabi
ne)1
4 , ra
ltegr
avir
(Isen
tress
)1
5
Met
abol
ism
M
ainl
y C
YP
3A4
Efa
vire
nz, n
evira
pine
: C
YP
3A4,
2B
6 (m
inor
)
Etra
virin
e: C
YP
3A4,
CY
P2C
9, a
nd
CY
P2C
19.
Rilp
iviri
ne:
CY
P3A
4 (m
ajor
), as
wel
l as
CY
P2C
19, 1
A2,
2C
8/9/
10 (m
inor
).
Elv
itegr
avir:
CY
P3A
, UG
T1A
1/3
Cob
icis
tat:
CY
P3A
, 2D
6 (m
inor
)
Ral
tegr
avir:
UG
T1A
1
Hep
atic
Inhi
bito
r M
ainl
y C
YP
3A4
(dar
unav
ir, in
dina
vir,
nelfi
navi
r, am
pren
avir
>> s
aqui
navi
r)
Rito
navi
r: C
YP
3A4
(pot
ent)>
>2D
6 >2
C9
>2C
19 >
2A6
>1A
2>2E
1
At l
ow b
oost
ing
dose
s, ri
tona
vir h
as a
ne
glig
ible
effe
ct in
CY
P2D
6 in
hibi
tion.
5 R
itona
vir i
nhib
its C
YP
2B6
in v
itro,
16 b
ut
indu
ces
2B6
in v
ivo.
17
Nel
finav
ir: 2
B6
in v
itro.
Efa
vire
nz:
2C9,
2C
1910
(? C
linic
al
sign
ifica
nce)
.
Etra
virin
e11 :
CY
P2C
9 (w
eak)
, CY
P2C
19
(mod
erat
e), p
-gly
copr
otei
n (w
eak)
Del
avird
ine
(Res
crip
tor
)18 ;
3A4
(pot
ent)
Cob
icis
tat:
CY
P3A
, CY
P2D
6; a
lso
p-gl
ycop
rote
in (P
-gp)
, BC
RP
, OA
TP1B
1 an
d O
ATP
1B3.
Ral
tegr
avir
has
no in
hibi
tory
or
indu
ctiv
e po
tent
ial i
n vi
tro.15
Hep
atic
Indu
cer
Nel
finav
ir: U
GT,
2C
9/19
Rito
navi
r: U
GT,
CY
P1A
2, C
YP
2C9/
19, 2
B6
Tipr
anav
ir: m
ixed
indu
ctio
n/in
hibi
tion
effe
cts;
ofte
n ac
ts a
s in
duce
r of C
YP
3A4
(pot
ent)
and
UG
T, e
ven
whe
n bo
oste
d w
ith
riton
avir9
Efa
vire
nz:
3A4
(pot
ent),
2B
619 a
nd
UG
T1A
120
Etra
virin
e11 :
3A
4 (w
eak)
Nev
irapi
ne12
: 3A
4, 2
B6
(pot
ent)
Rilp
iviri
ne:
2C19
(mod
erat
e), C
YP
1A2,
2B
6 an
d 3A
4 (w
eak)
.21 A
clin
ical
ly re
leva
nt
effe
ct o
n C
YP
enz
yme
activ
ity is
con
side
red
unlik
ely
with
the
25 m
g do
se.13
Elv
itegr
avir:
CY
P2C
9 (m
odes
t)
Ral
tegr
avir
has
no in
hibi
tory
or
indu
ctiv
e po
tent
ial i
n vi
tro.15
-
286 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
2 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
AN
GIO
TEN
SIN
-CO
NVE
RTI
NG
EN
ZYM
E (A
CE)
INH
IBIT
OR
S
Ben
azep
ril (L
oten
sin
)
Cap
topr
il (C
apot
en
)
Cila
zapr
il (In
hiba
ce
)
Ena
lapr
il (V
asot
ec
) Fo
sino
pril
(Mon
opril
)
Lisi
nopr
il (P
rinvi
l, Z
estri
l)
Per
indo
pril
(Cov
ersy
l)
Qui
napr
il (A
ccup
ril
) R
amip
ril (A
ltace
)
Tran
dola
pril
(Mav
ik
, Tar
ka
)
Oth
er th
an
capt
opril
and
lis
inop
ril, A
CE
in
hibi
tors
are
pr
odru
g es
ters
th
at m
ust b
e co
nver
ted
in th
e liv
er a
nd/o
r GI
tract
to a
ctiv
e m
etab
olite
s.
Elim
inat
ion
of
unch
ange
d dr
ug
or m
etab
olite
s m
ay b
e re
nal o
r fe
cal.
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
AN
GIO
TEN
SIN
II R
ECEP
TOR
BLO
CK
ERS
(AR
Bs)
Can
desa
rtan
(Ata
cand
)
8-32
mg
once
da
ily
2C9
(min
or),
bilia
ry e
xcre
tion
Pos
sibl
e
AR
B (n
elfin
avir,
rit
onav
ir), m
ay n
ot b
e cl
inic
ally
si
gnifi
cant
.
Pos
sibl
e
AR
B (e
favi
renz
, et
ravi
rine)
, may
not
be
clin
ical
ly s
igni
fican
t.
Pos
sibl
e
AR
V, m
ay n
ot b
e cl
inic
ally
sig
nific
ant.
Epr
osar
tan
(Tev
eten
)
600
mg
once
dai
ly
(max
800
mg
once
da
ily o
r 400
mg
BID
)
Bili
ary
excr
etio
n no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
Irbes
arta
n (A
vapr
o)
150
mg
once
dai
ly
(max
300
mg)
2C
9, b
iliar
y ex
cret
ion
Pos
sibl
e
AR
B (n
elfin
avir,
rit
onav
ir), m
ay n
ot b
e cl
inic
ally
si
gnifi
cant
.
Pos
sibl
e
AR
B (e
favi
renz
, et
ravi
rine)
, may
not
be
clin
ical
ly s
igni
fican
t.
Pos
sibl
e
AR
V, m
ay n
ot b
e cl
inic
ally
sig
nific
ant.
Losa
rtan
50-1
00 m
g on
ce
2C9>
>3A
4 to
P
ossi
ble
in a
ctiv
e m
etab
olite
P
ossi
ble
in a
ctiv
e m
etab
olite
N
et e
ffect
diff
icul
t to
pred
ict.
-
287ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
3 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
(Coz
aar
) da
ily
activ
e m
etab
olite
, E
-317
4 fo
rmat
ion
and
effi
cacy
fo
rmat
ion
and
effe
ct
Olm
esar
tan
(Olm
etec
)
20-4
0 m
g on
ce
daily
B
iliar
y ex
cret
ion
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
Telm
isar
tan
(Mic
ardi
s)
80 m
g on
ce d
aily
(4
0 m
g in
hep
atic
im
pairm
ent)
Bili
ary
excr
etio
n no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
Val
sarta
n (D
iova
n)
Sta
rting
dos
e 80
m
g, m
ax 3
20 m
g on
ce d
aily
Bili
ary
excr
etio
n no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
BET
A-B
LOC
KER
S
Ace
buto
lol
(Mon
itan
) 10
0 m
g B
ID (m
ax
400
mg
BID
) 2D
6 P
ossi
ble
bet
a-bl
ocke
r with
rit
onav
ir no
pre
dict
ed e
ffect
P
ossi
ble
bet
a-bl
ocke
r; m
onito
r for
effe
ct a
nd
decr
ease
bet
a-bl
ocke
r dos
e if
nece
ssar
y.14
Ate
nolo
l (T
enor
min
,
Teno
retic
-
aten
olol
-ch
lorth
alid
one)
50 m
g on
ce d
aily
(m
ax 1
00 m
g)
Ren
al
no p
redi
cted
effe
ct
Ata
zana
vir 4
00 m
g da
ily p
lus
aten
olol
50
mg
daily
for 5
day
s di
d no
t cau
se a
sub
stan
tial
incr
ease
in th
e P
R in
terv
al.
Als
o, m
inim
al c
hang
es in
at
enol
ol (3
4%
Cm
ax, 2
5%
A
UC
, 2%
C
min) a
nd
ataz
anav
ir le
vels
(7%
A
UC
an
d 26
%
Cm
in).
No
dose
ad
just
men
t nee
ded.
1
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
-
288 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
4 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
been
stu
died
. C
autio
n is
w
arra
nted
as
ther
e ar
e po
st-
mar
ketin
g re
ports
of s
econ
d an
d th
ird d
egre
e he
art b
lock
in
patie
nts
rece
ivin
g dr
ugs
that
pr
olon
g P
R in
terv
al (s
uch
as
beta
-blo
cker
s).23
Car
diac
eve
nts,
hav
e be
en
repo
rted
with
pat
ient
s on
rit
onav
ir an
d be
ta b
lock
ers.
7 P
R p
rolo
ngat
ion
may
occ
ur
and
caut
ion
is w
arra
nted
.
Car
vedi
lol
(Cor
eg
) 6.
25 m
g B
ID (m
ax
25 m
g B
ID)
2D6,
2C
9>1A
2,
2E1,
3A
4 P
ossi
ble
bet
a-bl
ocke
r
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t be
en s
tudi
ed.
Cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
(suc
h as
be
ta-b
lock
ers)
.23
Car
diac
eve
nts,
hav
e be
en
repo
rted
with
pat
ient
s on
rit
onav
ir an
d be
ta b
lock
ers.
7 P
R p
rolo
ngat
ion
may
occ
ur
and
caut
ion
is w
arra
nted
.
Pos
sibl
e
bet
a-bl
ocke
r P
ossi
ble
/ b
eta-
bloc
ker;
mon
itor f
or e
ffect
and
adj
ust
beta
-blo
cker
dos
e if
nece
ssar
y.14
Labe
talo
l (T
rand
ate
) S
tarti
ng d
ose
100
mg
BID
afte
r foo
d,
rang
e 20
0-40
0 m
g B
ID (m
ax 6
00 m
g B
ID)
2D6
Pos
sibl
e
bet
a-bl
ocke
r with
rit
onav
ir. C
ardi
ac e
vent
s, h
ave
been
repo
rted
with
pat
ient
s on
rit
onav
ir an
d be
ta b
lock
ers.
7 P
R p
rolo
ngat
ion
may
occ
ur
no p
redi
cted
effe
ct
Pos
sibl
e
bet
a-bl
ocke
r; m
onito
r for
effe
ct a
nd
decr
ease
bet
a-bl
ocke
r dos
e if
nece
ssar
y.14
-
289ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
5 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
and
caut
ion
is w
arra
nted
.
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t be
en s
tudi
ed.
Cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
(suc
h as
be
ta-b
lock
ers)
.23
Met
opro
lol
(Bet
aloc
,
Lopr
esor
)
50-1
00 m
g B
ID
(max
200
mg
BID
) 2D
6 P
ossi
ble
bet
a-bl
ocke
r with
rit
onav
ir. C
ardi
ac e
vent
s,
have
bee
n re
porte
d w
ith
patie
nts
on ri
tona
vir a
nd b
eta
bloc
kers
.7 P
R p
rolo
ngat
ion
may
occ
ur a
nd c
autio
n is
w
arra
nted
.
Ext
rem
e br
adyc
ardi
a (2
0-25
bp
m) w
ith c
ompl
ete
AV
blo
ck
and
seve
re h
ypot
ensi
on (B
P
50/2
0 m
mH
g) o
ccur
red
in a
pa
tient
on
stab
le th
erap
y in
clud
ing
laci
dipi
ne a
nd
met
opro
lol;
sym
ptom
s de
velo
ped
48 h
ours
afte
r st
artin
g te
nofo
vir,
emtri
cita
bine
, and
lo
pina
vir/r
itona
vir f
or p
ost-
expo
sure
pro
phyl
axis
. A
n in
tera
ctio
n be
twee
n lo
pina
vir/r
itona
vir a
nd
met
opro
lol a
nd la
cidi
pine
was
hy
poth
esiz
ed to
be
the
caus
e
no p
redi
cted
effe
ct
Pos
sibl
e
bet
a-bl
ocke
r; m
onito
r for
effe
ct a
nd
decr
ease
bet
a-bl
ocke
r dos
e if
nece
ssar
y.14
-
290 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
6 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
of th
is a
dver
se e
vent
.24
Nad
olol
(C
orga
rd
) S
tarti
ng d
ose
40-
80 m
g on
ce d
aily
, us
ual d
ose
320
mg
daily
(max
640
m
g pe
r day
)
Ren
al
no p
redi
cted
effe
ct
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t be
en s
tudi
ed.
Cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
(suc
h as
be
ta-b
lock
ers)
.23
Car
diac
eve
nts,
hav
e be
en
repo
rted
with
pat
ient
s on
rit
onav
ir an
d be
ta b
lock
ers.
7 P
R p
rolo
ngat
ion
may
occ
ur
and
caut
ion
is w
arra
nted
.
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
Pin
dolo
l (V
iske
n)
Sta
rting
dos
e 5
mg
BID
with
m
eals
, usu
al d
ose
15-4
5 m
g da
ily
2D6
Pos
sibl
e
bet
a-bl
ocke
r with
rit
onav
ir. C
ardi
ac e
vent
s,
have
bee
n re
porte
d w
ith
patie
nts
on ri
tona
vir a
nd b
eta
bloc
kers
.7 P
R p
rolo
ngat
ion
may
occ
ur a
nd c
autio
n is
w
arra
nted
.
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t be
en s
tudi
ed.
Cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
(suc
h as
no p
redi
cted
effe
ct
Pos
sibl
e
bet
a-bl
ocke
r; m
onito
r for
effe
ct a
nd
decr
ease
bet
a-bl
ocke
r dos
e if
nece
ssar
y.14
-
291ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
7 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
beta
-blo
cker
s).23
Pro
pran
olol
(In
dera
l LA
)
Sta
rting
dos
e 80
m
g on
ce d
aily
, us
ual d
ose
160-
320
mg
once
dai
ly
2D6,
3A
4, 2
C19
P
ossi
ble
bet
a-bl
ocke
r.
Lopi
navi
r/rito
navi
r and
dru
gs
that
pro
long
the
PR
hav
e no
t be
en s
tudi
ed.
Cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
(suc
h as
be
ta-b
lock
ers)
.23
Car
diac
eve
nts,
hav
e be
en
repo
rted
with
pat
ient
s on
rit
onav
ir an
d be
ta b
lock
ers.
7 P
R p
rolo
ngat
ion
may
occ
ur
and
caut
ion
is w
arra
nted
.
Pos
sibl
e
bet
a-bl
ocke
r P
ossi
ble
bet
a-bl
ocke
r; m
onito
r for
effe
ct a
nd
decr
ease
bet
a-bl
ocke
r dos
e if
nece
ssar
y.14
CA
LCIU
M C
HA
NN
EL B
LOC
KER
S (C
CB
)
Am
lodi
pine
(N
orva
sc
) 5
mg
once
dai
ly
(max
10
mg)
C
YP
3A
In h
ealth
y su
bjec
ts o
n in
dina
vir 8
00/ri
tona
vir 1
00
mg
BID
, ste
ady-
stat
e
amlo
dipi
ne A
UC
9
0%.25
If
coad
min
istra
tion
is n
eces
sary
, in
itiat
e ca
lciu
m b
lock
er th
erap
y at
low
dos
es, w
ith c
aref
ul
titra
tion
to re
spon
se a
nd s
ide
effe
cts.
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
292 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
8 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
mar
ketin
g re
ports
of s
econ
d an
d th
ird d
egre
e he
art b
lock
in
patie
nts
rece
ivin
g dr
ugs
that
pr
olon
g P
R in
terv
al s
uch
as
CC
Bs.
7
Dilt
iaze
m
(Car
dize
m
CD
, T
iaza
c)
180-
240
mg
once
da
ily (m
ax 3
60
mg)
CY
P3A
, pla
sma
and
tissu
e es
tera
ses,
su
lfatio
n an
d gl
ucur
idon
atio
n.
Act
ive
met
abol
ite
25 to
50%
as
pote
nt a
s di
ltiaz
em.
2 to
4%
unc
hang
ed in
th
e ur
ine2
6
In h
ealth
y su
bjec
ts o
n in
dina
vir 8
00/ri
tona
vir 1
00
mg
BID
, ste
ady-
stat
e
dilti
azem
AU
C
27%
(NB
: 2/
13 s
ubje
cts
(15%
) had
>4-
fold
d
iltia
zem
AU
C).2
5 If
coad
min
istra
tion
is n
eces
sary
, in
itiat
e ca
lciu
m b
lock
er th
erap
y at
low
dos
es, w
ith c
aref
ul
titra
tion
to re
spon
se a
nd s
ide
effe
cts.
Ata
zana
vir 4
00 m
g da
ily w
ith
dilti
azem
180
mg
daily
in
crea
sed
dilti
azem
pla
sma
conc
entra
tions
, Cm
in, a
nd A
UC
by
app
rox.
2-fo
ld (n
=28)
. Th
ere
was
als
o an
add
itive
PR
ef
fect
. Th
ere
was
no
sign
ifica
nt c
hang
e in
the
phar
mac
okin
etic
s of
at
azan
avir
(n=3
0).
A d
ose
redu
ctio
n of
dilt
iaze
m b
y 50
%
shou
ld b
e co
nsid
ered
. C
oadm
inis
tratio
n of
at
azan
avir/
riton
avir
with
di
ltiaz
em h
as n
ot b
een
stud
ied,
how
ever
sim
ilar
reco
mm
enda
tions
wou
ld
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring.
C
oadm
inis
tratio
n of
efa
vire
nz
(600
mg
for 1
4 da
ys) r
esul
ted
in
60%
Cm
ax,
69%
AU
C
and
63%
Cm
in o
f dilt
iaze
m.
Hig
her d
oses
of d
iltia
zem
may
be
requ
ired.
No
dose
ad
just
men
t of e
favi
renz
is
nece
ssar
y.28
P
oten
tial d
rug
inte
ract
ion
betw
een
nevi
rapi
ne a
nd
dilti
azem
, whi
ch m
ay c
ause
de
crea
sed
dilti
azem
pla
sma
conc
entra
tions
.29 H
ighe
r dos
es
of d
iltia
zem
may
be
requ
ired.
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
293ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
9 o
f 16
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
appl
y.1
Coa
dmin
istra
tion
with
tip
rana
vir/r
itona
vir h
as n
ot
been
stu
died
; the
net
effe
ct o
n di
litia
zem
is d
iffic
ult t
o pr
edic
t gi
ven
the
conf
lictin
g ef
fect
of
tipra
navi
r and
rito
navi
r on
su
bstra
tes
of b
oth
CY
P3A
and
P
-gp.
Cau
tion
is w
arra
nted
.27
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
suc
h as
C
CB
s.7
Felo
dipi
ne
(Ple
ndil
, R
ened
il)
5 m
g on
ce d
aily
(r
ange
2.5
-10
mg
daily
)
CY
P3A
CC
B c
once
ntra
tions
; ini
tiate
th
erap
y at
low
dos
es, w
ith
care
ful t
itrat
ion
to re
spon
se
and
side
effe
cts.
Cas
e re
port
of p
atie
nt o
n st
able
fixe
d do
se c
ombi
natio
n of
fel
odip
ine
5 m
g an
d m
etop
rolo
l 50
mg
daily
who
w
as s
tarte
d on
nel
finav
ir 20
00
mg
daily
, with
zid
ovud
ine
and
lam
ivud
ine
for p
ost-e
xpos
ure
prop
hyla
xis
(PE
P).
Afte
r 3
days
, the
pat
ient
exp
erie
nced
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
294 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
10
of 1
6
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
edem
a, d
izzi
ness
, fat
igue
and
or
thos
tatic
hyp
oten
sion
. Th
e au
thor
s co
nclu
ded
that
the
patie
nt d
evel
oped
sid
e ef
fect
s du
e to
an
incr
ease
in
felo
dipi
ne c
once
ntra
tions
m
edia
ted
due
to n
elfin
avir-
med
iate
d C
YP
3A4
inhi
bitio
n.30
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
suc
h as
C
CB
s.7
Ladi
cipi
ne (n
ot
curr
ently
av
aila
ble
in
Can
ada)
2 m
g on
ce d
aily
(m
ax 6
mg)
C
YP
3A4,
po
ssib
le P
-gp
C
CB
con
cent
ratio
ns; i
nitia
te
ther
apy
at lo
w d
oses
, with
ca
refu
l titr
atio
n to
resp
onse
an
d si
de e
ffect
s.
Ext
rem
e br
adyc
ardi
a (2
0-25
bp
m) w
ith c
ompl
ete
AV
blo
ck
and
seve
re h
ypot
ensi
on (B
P
50/2
0 m
mH
g) o
ccur
red
in a
pa
tient
on
stab
le th
erap
y in
clud
ing
laci
dipi
ne a
nd
met
opro
lol;
sym
ptom
s de
velo
ped
48 h
ours
afte
r st
artin
g te
nofo
vir,
emtri
cita
bine
, and
lo
pina
vir/r
itona
vir f
or p
ost-
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
295ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
11
of 1
6
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
expo
sure
pro
phyl
axis
. A
n in
tera
ctio
n be
twee
n lo
pina
vir/r
itona
vir a
nd
met
opro
lol a
nd la
cidi
pine
was
hy
poth
esiz
ed to
be
the
caus
e of
this
adv
erse
eve
nt.24
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
suc
h as
C
CB
s.7
Nife
dipi
ne
(Ada
lat X
L)
20-3
0 m
g on
ce
daily
(max
90
mg)
C
YP
3A (m
ajor
), 1A
2, 2
A6
C
CB
con
cent
ratio
ns; i
nitia
te
ther
apy
at lo
w d
oses
, with
ca
refu
l titr
atio
n to
resp
onse
an
d si
de e
ffect
s.
A s
ever
e in
tera
ctio
n re
sulti
ng
in a
cute
rena
l ins
uffic
ienc
y,
hypo
tens
ion
and
edem
a w
as
note
d w
hen
a re
gim
en
cont
aini
ng lo
pina
vir/r
itona
vir
was
sta
rted
in a
pat
ient
re
ceiv
ing
nife
dipi
ne 3
0 m
g tw
ice
a da
y; t
he s
ympt
oms
reso
lved
upo
n di
scon
tinua
tion
of th
e H
AA
RT
regi
men
, and
re
-em
erge
d af
ter
lopi
navi
r/rito
navi
r was
re-
intro
duce
d.31
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
296 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
12
of 1
6
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
A 5
1-ye
ar-o
ld m
an w
ith H
IV
infe
ctio
n w
ho w
as re
ceiv
ing
exte
nded
-rel
ease
nife
dipi
ne
(60
mg/
day)
dev
elop
ed
sym
ptom
atic
orth
osta
sis
and
hear
t blo
ck a
fter s
tarti
ng
antir
etro
vira
l the
rapy
that
in
clud
ed n
elfin
avir
1250
mg
twic
e da
ily. M
edic
atio
n w
as
chan
ged,
how
ever
, the
pat
ient
de
velo
ped
orth
osta
tic
sym
ptom
s af
ter r
esta
rting
ne
lfina
vir.
Sub
sequ
ent
adm
inis
tratio
n of
ant
iretro
vira
l th
erap
y co
ntai
ning
in
dina
vir/r
itona
vir w
ith
exte
nded
-rel
ease
nife
dipi
ne
resu
lted
in re
curr
ence
of h
is
orth
osta
tic s
ympt
oms.
32
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
suc
h as
C
CB
s.7
Ver
apam
il (Is
optin
SR
,
Love
ra-H
S
)
180-
240
mg
once
da
ily (m
ax 4
80
mg)
CY
P3A
(maj
or),
1A2,
2C
9, 2
C19
. A
ctiv
e m
etab
olite
no
rver
apam
il ha
s
C
CB
con
cent
ratio
ns; i
nitia
te
ther
apy
at lo
w d
oses
, with
ca
refu
l titr
atio
n to
resp
onse
an
d si
de e
ffect
s.
Pos
sibl
e
CC
B
conc
entra
tions
; titr
ate
to
resp
onse
with
car
eful
m
onito
ring
Pos
sibl
e
CC
B; m
onito
r for
ef
fect
and
dec
reas
e C
CB
dos
e if
nece
ssar
y.14
-
297ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
13
of 1
6
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
20%
act
ivity
of
vera
pam
il.
PR
pro
long
atio
n m
ay o
ccur
w
ith th
e co
mbi
natio
n of
CC
Bs
and
riton
avir-
base
d re
gim
ens;
cau
tion
is
war
rant
ed a
s th
ere
are
post
-m
arke
ting
repo
rts o
f sec
ond
and
third
deg
ree
hear
t blo
ck in
pa
tient
s re
ceiv
ing
drug
s th
at
prol
ong
PR
inte
rval
suc
h as
C
CB
s.7
DIU
RET
ICS
Chl
orth
alid
one
(Hyg
roto
n;
Teno
retic
-
aten
olol
-ch
lorth
alid
one)
12.5
-50
mg
once
da
ily
Neg
ligib
le h
epat
ic
met
abol
ism
30-6
5% re
nal
excr
etio
n as
un
chan
ged
drug
33
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
Furo
sem
ide
(Las
ix
) 20
-40
mg
BID
R
enal
(90%
); he
patic
m
etab
olis
m
mai
nly
gluc
uron
idat
ion.
P
ropo
rtion
of
hepa
tic c
lear
ance
in
crea
ses
subs
tant
ially
(4x)
in
sev
ere
rena
l fa
ilure
.34
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
Hyd
roch
loro
-th
iazi
de
12.5
-50
mg
once
da
ily
Ren
al
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
-
298 ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
14
of 1
6
Dru
g U
sual
Dos
e (e
ssen
tial
hype
rten
sion
)
Met
abol
ism
22
Prot
ease
Inhi
bito
rs (P
Is)
Non
-Nuc
leos
ide
Rev
erse
Tr
ansc
ripta
se In
hibi
tors
(N
NR
TIs)
Inte
gras
e In
hibi
tor
(i.e.
,elv
itegr
avir/
cobi
cist
at;
gene
rally
no
pred
icte
d in
tera
ctio
ns w
ith ra
ltegr
avir
base
d on
pha
rmac
okin
etic
pr
oper
ties)
Inda
pam
ide
(Loz
ide
) 1.
25 m
g on
ce
daily
in th
e m
orni
ng (m
ax 2
.5
mg
once
dai
ly)
2C9,
2D
6, 3
A4
Pos
sibl
e
inda
pam
ide
P
ossi
ble
inda
pam
ide
Pos
sibl
e
/ in
dapa
mid
e co
ncen
tratio
ns; m
onito
r for
ef
fect
and
adj
ust i
ndap
amid
e do
se if
nec
essa
ry.
Met
olaz
one
(Z
arox
olyn
)
2.5-
5 m
g on
ce
daily
(max
10
mg)
R
enal
no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
no
pre
dict
ed e
ffect
Spi
rono
lact
one
(A
ldac
tone
)
50-1
00 m
g da
ily
(max
200
mg
daily
)
Ren
al
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
no p
redi
cted
effe
ct
P
leas
e no
te:
This
cha
rt su
mm
ariz
es s
ome
of th
e m
ajor
dru
g in
tera
ctio
ns id
entif
ied
to d
ate,
bas
ed o
n cu
rren
t ava
ilabl
e da
ta; o
ther
dru
g in
tera
ctio
ns m
ay
exis
t. P
leas
e us
e ca
utio
n w
hene
ver a
ddin
g/m
odify
ing
ther
apy.
The
info
rmat
ion
in th
is ta
ble
is in
tend
ed fo
r use
by
expe
rienc
ed p
hysi
cian
s an
d ph
arm
acis
ts.
It is
not
inte
nded
to re
plac
e so
und
prof
essi
onal
judg
men
t in
indi
vidu
al s
ituat
ions
, and
sho
uld
be u
sed
in c
onju
nctio
n w
ith o
ther
relia
ble
sour
ces
of
info
rmat
ion.
Due
to th
e ra
pidl
y ch
angi
ng n
atur
e of
info
rmat
ion
abou
t HIV
trea
tmen
t and
ther
apie
s, u
sers
are
adv
ised
to re
chec
k th
e in
form
atio
n co
ntai
ned
here
in w
ith th
e or
igin
al s
ourc
e be
fore
app
lyin
g it
to p
atie
nt c
are.
Re
fere
nces
: 1.
B
risto
l-Mye
rs S
quib
b C
anad
a. R
eyat
az (a
taza
navi
r) P
rodu
ct M
onog
raph
. Mon
treal
, QC
Jan
uary
, 201
1.
2.
Jans
sen
Inc.
Pre
zist
a (d
arun
avir)
Pro
duct
Mon
ogra
ph. T
oron
to, O
ntar
io S
epte
mbe
r 21,
201
1.
3.
ViiV
Hea
lthca
re U
LC. T
elzi
r (fo
sam
pren
avir)
Pre
scrib
ing
Info
rmat
ion.
Mon
treal
, QC
Jan
uary
24,
201
1.
4.
Mer
ck F
ross
t Can
ada
Ltd.
Crix
ivan
(ind
inav
ir) P
rodu
ct M
onog
raph
. Kirk
land
, QC
Apr
il 17
, 201
2.
5.
Abb
ott L
abor
ator
ies
Lim
ited
Can
ada.
Kal
etra
(lop
inav
ir/rit
onav
ir) P
resc
ribin
g In
form
atio
n. S
aint
Lau
rent
, Can
ada
Dec
embe
r 9, 2
011.
6.
P
fizer
Can
ada
Inc.
Vira
cept
(nel
finav
ir) P
rodu
ct M
onog
raph
. Kirk
land
, QC
Mar
ch 4
, 201
1.
7.
Abb
ott L
abor
ator
ies
Lim
ited
Can
ada.
Nor
vir (
riton
avir)
Pre
scrib
ing
Info
rmat
ion.
Sai
nt-L
aure
nt, Q
C N
ovem
ber 2
8, 2
011.
8.
H
offm
ann-
La R
oche
Ltd
. Inv
irase
(saq
uina
vir)
Pro
duct
Mon
ogra
ph. M
issi
ssau
ga, O
N M
ay 1
1, 2
012.
9.
B
oehr
inge
r Ing
elhe
im. A
ptiv
us (t
ipra
navi
r) P
rodu
ct M
onog
raph
. Bur
lingt
on, O
N M
arch
11,
201
1.
-
299ANTIHYPERTENSIVE INTERACTIONS
Act
ual a
nd P
redi
cted
Pha
rmac
okin
etic
Inte
ract
ions
Bet
wee
n A
ntih
yper
tens
ives
and
Ant
iretr
ovira
ls
Prep
ared
by
Car
a H
ills-
Nie
min
en, S
t. P
auls
Hos
pita
l, V
anco
uver
, BC
and
Mic
helle
Foi
sy, N
orth
ern
Alb
erta
Pro
gram
, Edm
onto
n, A
B, S
epte
mbe
r 201
1.
Upd
ated
by
A. T
seng
, Pha
rm.D
.FC
SH
P, A
AH
IVP
, Tor
onto
Gen
eral
Hos
pita
l A
ugus
t 29,
201
2
ww
w.h
ivcl
inic
.ca
page
15
of 1
6
10.
Bris
tol-M
yers
Squ
ibb
Can
ada.
Sus
tiva
(efa
vire
nz) P
resc
ribin
g In
form
atio
n. M
ontre
al, Q
C J
une
11, 2
012.
11
. Ja
nsse
n In
c. In
tele
nce
(etra
virin
e) P
rodu
ct M
onog
raph
. Tor
onto
, ON
Nov
embe
r 9, 2
011.
12
. B
oehr
inge
r Ing
elhe
im (C
anad
a) L
td. V
iram
une
and
Vira
mun
e X
R (n
evira
pine
) Pro
duct
Mon
ogra
ph. B
urlin
gton
, ON
May
30,
201
1.
13.
Jans
sen
Inc.
Edu
rant
(rilp
iviri
ne) P
rodu
ct M
onog
raph
. Tor
onto
, ON
Jul
y 20
, 201
1.
14.
Gile
ad S
cien
ces
Inc.
Stri
bild
(elv
itegr
avir,
cob
icis
tat,
emtri
cita
bine
, ten
ofov
ir di
sopr
oxil
fum
arat
e) P
resc
ribin
g In
form
atio
n. F
oste
r City
, CA
Aug
ust,
2012
. 15
. M
erck
Fro
sst C
anad
a Lt
d. Is
entre
ss (r
alte
grav
ir) P
resc
ribin
g In
form
atio
n. K
irkla
nd, Q
C F
ebru
ary
10, 2
012.
16
. H
esse
LM
, von
Mol
tke
LL, S
hade
r RI,
et a
l. R
itona
vir,
efav
irenz
, and
nel
finav
ir in
hibi
t CY
P2B
6 ac
tivity
in v
itro:
pot
entia
l dru
g in
tera
ctio
ns w
ith b
upro
pion
. Dru
g M
etab
olis
m &
D
ispo
sitio
n 20
01;2
9:10
0-02
. 17
. K
hara
sch
ED
, Mitc
hell
D, C
oles
R, e
t al.
Rap
id c
linic
al in
duct
ion
of h
epat
ic c
ytoc
hrom
e P
4502
B6
activ
ity b
y rit
onav
ir. A
ntim
icro
b A
gent
s C
hem
othe
r 200
8;52
(5):1
663-
9.
18.
ViiV
Hea
lthca
re U
LC. R
escr
ipto
r (de
lavi
rdin
e) P
rodu
ct M
onog
raph
. Mon
treal
, QC
Dec
embe
r 15,
200
9.
19.
Rob
erts
on S
M, M
alda
relli
F, N
atar
ajan
V, e
t al.
Efa
vire
nz in
duce
s C
YP
2B6-
med
iate
d hy
drox
ylat
ion
of b
upro
pion
in h
ealth
y su
bjec
ts. J
Acq
uir I
mm
une
Def
ic S
yndr
200
8;49
(5):5
13-
9.
20.
Lee
L, S
oon
GH
, She
n P
, et a
l. E
ffect
of e
favi
renz
and
dar
unav
i/rito
navi
r on
bilir
ubin
leve
ls in
hea
lthy
adul
t vol
unte
ers:
rol
e of
indu
ctio
n of
UG
T1A
1 an
d bi
le e
fflux
tran
spor
ters
[a
bstra
ct 2
7]. 1
1th
Inte
rnat
iona
l Wor
ksho
p on
Clin
ical
Pha
rmac
olog
y of
HIV
The
rapy
, Apr
il 5-
7, 2
010,
Sor
rent
o, It
aly.
21
. C
rauw
els
HM
, Van
Hee
swijk
R, S
teve
ns T
, et a
l. Th
e ef
fect
of T
MC
278,
a n
ext-g
ener
atio
n no
n-nu
cleo
side
reve
rse
trans
crip
tase
inhi
bito
r (N
NR
TI) o
n C
YP
3A a
ctiv
ity in
viv
o [a
bstra
ct P
_28]
. 10
th In
tern
atio
nal W
orks
hop
on C
linic
al P
harm
acol
ogy
of H
IV T
hera
py,
Apr
il 15
