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Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Antiretroviral Pharmacokinetic Characteristics (summary):
Metabolism
Protease Inhibitors (PIs)
Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
Integrase Inhibitors
atazanavir (Reyataz®)1, darunavir
(Prezista®)2, fosamprenavir (Telzir®)3,
indinavir (Crixivan®)4, lopinavir/ritonavir
(Kaletra)5, nelfinavir (Viracept®)6, ritonavir
(Norvir®)7, saquinavir (Invirase®)8, tipranavir
(Aptivus)9
efavirenz (Sustiva®)10, etravirine
(Intelence)11, nevirapine (Viramune®)12,
rilpivirine (Edurant®)13
dolutegravir (Tivicay®),14, elvitegravir/cobicistat
(Stribild®, single-tablet regimen with
tenofovir/emtricitabine)15, raltegravir
(Isentress®)16
Mainly CYP3A4
Efavirenz, nevirapine: CYP3A4, 2B6
(minor)
Dolutegravir: UGT1A1, CYP3A4 (10-15%).
Elvitegravir: CYP3A, UGT1A1/3
Etravirine: CYP3A4, CYP2C9, and
CYP2C19.
Hepatic Inhibitor
Cobicistat: CYP3A, 2D6 (minor)
Rilpivirine: CYP3A4 (major), as well as
CYP2C19, 1A2, 2C8/9/10 (minor).
Raltegravir: UGT1A1
Mainly CYP3A4 (darunavir, indinavir,
nelfinavir, amprenavir >> saquinavir)
Efavirenz: 2C9, 2C1910 (? Clinical
significance).
Atazanavir: 3A4, UGT1A1 >>2C8 (weak)
Etravirine11: CYP2C9 (weak), CYP2C19
(moderate), p-glycoprotein (weak)
Cobicistat: CYP3A, CYP2D6; also pglycoprotein (P-gp), BCRP, OATP1B1 and
OATP1B3.
Caution when unboosted atazanavir is
coadministered with drugs that are 2C8
substrates with narrow therapeutic indices
(e.g., paclitaxel, repaglinide); clinically
significant interactions with 2C8 substrates
are not expected when atazanavir is
boosted with ritonavir.
Delavirdine (Rescriptor®):20 3A4 (potent)
Dolutegravir inhibits the renal organic cation
transporter, OCT2.14
Raltegravir has no inhibitory or inductive
potential in vitro.16
Nelfinavir: 2B6 in vitro.
Ritonavir: CYP3A4 (potent)> >2D6 >2C9
>2C19 >2A6 >1A2>2E1.
At low boosting doses, ritonavir has a
negligible effect in CYP2D6 inhibition.5
Ritonavir inhibits CYP2B6 in vitro,17 but
induces 2B6 in vivo.18
Tipranavir: 2D619
Hepatic Inducer
Nelfinavir: UGT, 2B6, 2C8, 2C9/1921
Efavirenz: 3A4 (potent), 2B622 and
UGT1A123
Dolutegravir does not induce CYP1A2,
CYP2B6, or CYP3A4 in vitro.14
Ritonavir: UGT, CYP1A2, CYP2C9/19, 2B6
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 1 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Protease Inhibitors (PIs)
Tipranavir: mixed induction/inhibition
effects; often acts as inducer of CYP3A4
(potent) and UGT, even when boosted with
ritonavir9
Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
Integrase Inhibitors
Etravirine11: 3A4 (weak)
Elvitegravir: CYP2C9 (modest)
Nevirapine12: 3A4, 2B6 (potent)
Raltegravir has no inhibitory or inductive
potential in vitro.16
Rilpivirine: 2C19 (moderate), CYP1A2, 2B6
and 3A4 (weak).24 A clinically relevant
effect on CYP enzyme activity is considered
unlikely with the 25 mg dose.13
Sedative Route of
25, 26
Metabolism
Alprazolam
(APZ)
Xanax®
Bromazepam
Parent: CYP3A
Metabolite: UGT (4
&alpha hydroxy)
Parent: Hydroxylation
Protease Inhibitors
27
atazanavir (Reyataz®) , darunavir
2
3
(Prezista®) , fosamprenavir (Telzir®) ,
4
indinavir (Crixivan®) ,
5
lopinavir/ritonavir (Kaletra) , nelfinavir
6
7
(Viracept®) , ritonavir (Norvir®) ,
8
saquinavir (Invirase®) , tipranavir
9
(Aptivus)
Possible ↑ alprazolam concentrations.
NNRTIs
10
efavirenz (Sustiva®) , etravirine
11
(Intelence) , nevirapine
12
(Viramune®) , rilpivirine
13
(Edurant®)
possible ↓ alprazolam
concentrations and withdrawal
Elvitegravir/cobicistat:
possible ↑ alprazolam
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
possible ↓ bromazepam
Elvitegravir/cobicistat:
Alprazolam is no longer
contraindicated in the Norvir®
7
product monograph.
Short-term study of 1mg alprazolam
with 4 doses of ritonavir 200 mg
resulted in 148% ↑ alprazoma AUC
28
and ↑ t ½ from 13 to 30 hours.
Steady-state study of 1 mg alprazolam
with 12 days of ritonavir resulted in a
29
12% ↓ alprazolam AUC. This likely
reflects early inhibitory and chronic
induction effects of ritonavir. Based on
this, therapy can likely be initiated
using very low alprazolam doses,
and monitoring for tolerability and
efficacy. After 2-3 weeks,
alprazolam dosage may need to be
increased.
Possible ↑ bromazepam
Integrase Inhibitor
dolutegravir (Tivicay®),14,
elvitegravir/cobicistat
(Stribild®, single-tablet
regimen with
tenofovir/emtricitabine)15,
raltegravir (Isentress®)16
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 2 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Protease Inhibitors
27
atazanavir (Reyataz®) , darunavir
2
3
(Prezista®) , fosamprenavir (Telzir®) ,
4
indinavir (Crixivan®) ,
5
lopinavir/ritonavir (Kaletra) , nelfinavir
6
7
(Viracept®) , ritonavir (Norvir®) ,
8
saquinavir (Invirase®) , tipranavir
9
(Aptivus)
concentrations
Sedative Route of
25, 26
Metabolism
Lectopam®
Buspirone
Buspar®
Chloral hydrate
(Novo, PMS)
Clonazepam
Rivotril®
Clorazepate
Tranxene®
Diazepam
Valium®
Parent: CYP3A4
Buspirone has
immunomodulating
properties. A significant
↑ in CD4/CD8 ratio, and
a ↓ in CD8+ T-cell
counts was observed in
HIV patients who were
30
not on antiretrovirals.
Parent: AD
Metabolite: UGT
(trichloroethanol)
Parent: CYP3A4
possible ↑ buspirone concentrations
Parent: Acid hydrolysis
Metabolites (active):
nordiazepam, 2C19desmethyldiazepam
Parent: CYP2C19>3A
Metabolites (active):
nordiazepam, Ndesmethyldiazepam,
temazepam
32
Estazolam
Prosom®
Parent: CYP3A4
Eszopiclone
Parent: CYP3A4, 2E1
33
Case report of patient with Parkinsonlike symptoms (ataxia, shuffling gait,
cogwheel rigidity, resting tremor, and
sad affect) 6 weeks after
ritonavir/indinavir (400mg/400mg
BID) were added to buspirone 40mg
31
am/30mg pm.
no predicted effect
NNRTIs
10
efavirenz (Sustiva®) , etravirine
11
(Intelence) , nevirapine
12
(Viramune®) , rilpivirine
13
(Edurant®)
concentrations and withdrawal
possible ↓ buspirone
concentrations and withdrawal
Integrase Inhibitor
dolutegravir (Tivicay®),14,
elvitegravir/cobicistat
(Stribild®, single-tablet
regimen with
tenofovir/emtricitabine)15,
raltegravir (Isentress®)16
possible ↑ bromazepam
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
Elvitegravir/cobicistat:
possible ↑ buspirone
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
no predicted effect
No predicted effect
possible ↑ clonazepam concentrations
possible ↓ clonazepam
concentrations and withdrawal
possible ↑ metabolite concentrations
possible ↓ metabolite
concentrations and withdrawal
Elvitegravir/cobicistat:
potential for ↑ clonazepam
15
concentrations.
Possible ↑ metabolite
concentrations with
elvitegravir/cobicstat.
Clorazepate is no longer
contraindicated in the Norvir®
7
product monograph; use with caution.
possible ↑ diazepam and nordiazepam
concentrations
Diazepam is no longer
contraindicated in the Norvir®
7
product monograph; ; use with caution.
possible ↑ estazolam concentrations
possible ↑ eszopiclone concentrations
possible ↓ diazepam and
nordiazepam concentrations and
withdrawal
Elvitegravir/cobicistat:
possible ↑ diazepam
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
possible ↓ estazolam
concentrations and withdrawal
Elvitegravir/cobicistat:
possible ↑ estazolam
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
Elvitegravir/cobicistat:
possible ↓ eszopiclone
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 3 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Sedative Route of
25, 26
Metabolism
Protease Inhibitors
27
atazanavir (Reyataz®) , darunavir
2
3
(Prezista®) , fosamprenavir (Telzir®) ,
4
indinavir (Crixivan®) ,
5
lopinavir/ritonavir (Kaletra) , nelfinavir
6
7
(Viracept®) , ritonavir (Norvir®) ,
8
saquinavir (Invirase®) , tipranavir
9
(Aptivus)
concentrations and withdrawal
Lunesta®
Flurazepam
Dalmane®
Parent: liver
Metabolites (active):
desalkyl, hydroxyethyl
Lorazepam
Ativan®
Parent: UGT
Midazolam
(MDZ)
Versed®
Parent: CYP3A
Metabolite: UGT
(hydroxy)
Nitrazepam
NNRTIs
10
efavirenz (Sustiva®) , etravirine
11
(Intelence) , nevirapine
12
(Viramune®) , rilpivirine
13
(Edurant®)
Parent: nitro-reduction,
possible ↑ flurazepam concentrations
Flurazepam is no longer
contraindicated in the Norvir®
7
product monograph; use with caution.
Nelfinavir, ritonavir and tipranavir
may ↓ lorazepam concentrations via
UGT induction.
Contraindicated in product
monographs. Possible ↑↑ midazolam
concentrations.
Saquinavir: case report of prolonged
sedation requiring flumazenil with
34
combination.
Kinetic study showing
5-fold ↑ PO MDZ AUC and 2.4-fold ↑
35
IV MDZ AUC.
In a retrospective cohort study, 51
patients were exposed to midazolam
and PIs while undergoing
bronchoscopy. The relative risk of
severe prolonged sedation was 6.21
(9.80% in PI exposed vs. 1.58% in PI
non-exposed). The length of
hospitalization was 3 days longer in the
PI exposed group. Coadministration of
these agents should be avoided and
alternate sedatives used for
procedures. If the combination is used,
36
intensive monitoring is required.
possible ↑ nitrazepam concentrations
possible ↓ flurazepam
concentrations and withdrawal
Tipranavir may ↓ lorazepam
concentrations (via UGT
induction); no predicted effect with
the NNRTIs.
possible ↓ midazolam
concentrations and efficacy
Integrase Inhibitor
dolutegravir (Tivicay®),14,
elvitegravir/cobicistat
(Stribild®, single-tablet
regimen with
tenofovir/emtricitabine)15,
raltegravir (Isentress®)16
possible ↑ eszopiclone
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
Elvitegravir/cobicistat:
possible ↑ flurazepam
concentrations. Monitor and
reduce benzodiazepine dose
15
if necessary.
No predicted effect.
Oral midazolam is
contraindicated with
15
elvitegravir/cobicistat.
Parenteral midazolam:
potential for ↑ midazolam
concentrations with
elvitegravir/cobicistat.
Coadministration should be
done in a setting that ensures
close clinical monitoring and
appropriate medical
management in case of
respiratory depression and/or
prolonged sedation.
Dosage reduction for
midazolam should be
considered, especially if more
than a single dose of
15
midazolam is administered.
possible ↓ nitrazepam
Possible ↑ nitrazepam
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 4 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Protease Inhibitors
27
atazanavir (Reyataz®) , darunavir
2
3
(Prezista®) , fosamprenavir (Telzir®) ,
4
indinavir (Crixivan®) ,
5
lopinavir/ritonavir (Kaletra) , nelfinavir
6
7
(Viracept®) , ritonavir (Norvir®) ,
8
saquinavir (Invirase®) , tipranavir
9
(Aptivus)
Sedative Route of
25, 26
Metabolism
Mogadon®
acetylation
Oxazepam
Serax®
Parent: UGT
Nelfinavir, ritonavir and tipranavir
may ↓ oxazepam concentrations via
UGT induction.
Propofol
Diprivan®
Parent: CYP2B6 >UGT
Possible ↓ propofol concentrations
with ritonavir-boosted regimens.
Ramelteon
Rozerem®
Parent: CYP1A2 >2C,
37
3A4
Temazepam
Restoril®
Parent: UGT>>CYP
38
(2B6, 2C, 3A)
Triazolam (TZL)
Halcion®
Parent: CYP3A
Metabolite: GT (4 &
alpha hydroxy)
Possible ↓ ramelteon concentrations
with ritonavir-boosted regimens via
1A2, 2C9 induction; clinical
significance unknown since ritonavir is
also a potent CYP3A4 inhibitor. Use
with caution and monitor for efficacy/
toxicity.
Nelfinavir, ritonavir and tipranavir
may ↓ temazepam concentrations via
UGT induction.
Contraindicated in product
monographs; possible ↑ triazolam
concentrations.
May inhibit CYP3A4.
In vitro study showed ritonavir is a
39
strong inhibitor of triazolam.
Shortterm study of 0.125mg triazolam with 4
doses of ritonavir 200 mg resulted in ↑
triazolam half-life from 3.7 to 50
40, 41
hours.
This likely reflects early
inhibitory effects of ritonavir, but does
not account for chronic induction.
A significant interaction is unlikely.
Valerian Root
Zaleplon
Starnoc
concentrations and withdrawal
42,
43
Aldehyde oxidase >
44
CYP3A4
NNRTIs
10
efavirenz (Sustiva®) , etravirine
11
(Intelence) , nevirapine
12
(Viramune®) , rilpivirine
13
(Edurant®)
Possible ↑ zaleplon concentrations.
Tipranavir may ↓ oxazepam
concentrations (via UGT
induction); no predicted effect with
the NNRTIs.
Possible ↓ propofol concentrations
with efavirenz or nevirapine-based
regimens.
no major predicted effect
Integrase Inhibitor
dolutegravir (Tivicay®),14,
elvitegravir/cobicistat
(Stribild®, single-tablet
regimen with
tenofovir/emtricitabine)15,
raltegravir (Isentress®)16
concentrations with
elvitegravir/cobicstat.
No predicted effect.
Possible ↑ ramelteon
concentrations with
elvitegravir/cobicstat. Use
with caution and monitor for
efficacy/toxicity.
no predicted effect
No predicted effect.
possible ↓ triazolam
concentrations and withdrawal
Triazolam is
contraindicated with
15
elvitegravir/cobicistat.
A significant interaction is unlikely.
Potential for additive CNS toxicity
when starting EFV.
Possible ↓ zaleplon
concentrations.
A significant interaction is
unlikely.
Possible ↑ zaleplon
concentrations with
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 5 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
Sedative Route of
25, 26
Metabolism
Zolpidem
Ambien

Parent: CYP3A (61%)
>> 2C9 (22%), 1A2
(14%) >> 2D6, 2C19
(<3%)
Zopiclone
Imovane®
Parent: CYP3A4> 2C8,
38
2C9
Protease Inhibitors
27
atazanavir (Reyataz®) , darunavir
2
3
(Prezista®) , fosamprenavir (Telzir®) ,
4
indinavir (Crixivan®) ,
5
lopinavir/ritonavir (Kaletra) , nelfinavir
6
7
(Viracept®) , ritonavir (Norvir®) ,
8
saquinavir (Invirase®) , tipranavir
9
(Aptivus)
possible ↑ in zolpidem concentrations
No longer contraindicated in Norvir®
7
product monograph. In vitro study
showed RTV is a less potent inhibitor
of zolpidem than triazolam. In addition,
short-term study of zolpidem 5.0 mg
with 4 doses of RTV 200mg resulted in
an insignificant increase in t ½ from 2
to 2.4 hours. There were no clinical
41
sequelae seen. A 50% zolpidem
dosage reduction may be warranted
when used with potent enzyme
38
inhibitors.
possible ↑ zopiclone concentrations.
NNRTIs
10
efavirenz (Sustiva®) , etravirine
11
(Intelence) , nevirapine
12
(Viramune®) , rilpivirine
13
(Edurant®)
Possible decrease in zolpidem
concentrations and withdrawal
possible ↓ zopiclone
concentrations and withdrawal
A 50% zopiclone dosage reduction
may be warranted when used with
38
potent enzyme inhibitors.
Integrase Inhibitor
dolutegravir (Tivicay®),14,
elvitegravir/cobicistat
(Stribild®, single-tablet
regimen with
tenofovir/emtricitabine)15,
raltegravir (Isentress®)16
elvitegravir/cobicstat. Use
with caution and monitor for
efficacy/toxicity.
Elvitegravir/cobicistat:
possible ↑ zolpidem
concentrations. Monitor and
reduce zolpidem dose if
15
necessary.
Elvitegravir/cobicistat:
possible ↑ zopiclone
concentrations. Monitor and
reduce zopiclone dose if
15
necessary.
Key: CYP= Hepatic Cytochrome P450 isoenzyme; AD= Alcohol dehydrogenase; substrate= route of hepatic elimination of that specific drug (specified by a specific
cytochrome P450 isoenzyme); inducer= leads to more rapid clearance of substrates of a specific hepatic isoenzyme (lowers levels of the respective drug and may lead to
decreased efficacy); inhibitor= leads to decreased clearance of substrates of a specific hepatic isoenzyme (increases levels of a respective drug and may lead to toxicity).
UGT= Uridine diphosphate glucuronyltransferase
Please note: This chart summarizes some of the major drug interactions identified to date, based on current available data; other drug interactions may
exist. Please use caution whenever adding/modifying therapy. The information in this table is intended for use by experienced physicians and pharmacists.
It is not intended to replace sound professional judgment in individual situations, and should be used in conjunction with other reliable sources of
information. Due to the rapidly changing nature of information about HIV treatment and therapies, users are advised to recheck the information contained
herein with the original source before applying it to patient care.
References:
1.
Bristol-Myers Squibb Canada. Reyataz (atazanavir) Product Monograph. Montreal, QC May 11, 2012.
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 6 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
2.
Janssen Inc. Prezista (darunavir) Product Monograph. Toronto, Ontario September 21, 2011.
3.
ViiV Healthcare ULC. Telzir (fosamprenavir) Prescribing Information. Montreal, QC January 24, 2011.
4.
Merck Frosst Canada Ltd. Crixivan (indinavir) Product Monograph. Kirkland, QC April 17, 2012.
5.
AbbVie Corporation. Kaletra (lopinavir/ritonavir) Prescribing Information. Saint Laurent, Canada November 1, 2012.
6.
Pfizer Canada Inc. Viracept (nelfinavir) Product Monograph. Kirkland, QC March 4, 2011.
7.
AbbVie Corporation. Norvir (ritonavir) Prescribing Information. Saint-Laurent, QC December 18, 2012.
8.
Hoffmann-La Roche Ltd. Invirase (saquinavir) Product Monograph. Mississauga, ON May 11, 2012.
9.
Boehringer Ingelheim. Aptivus (tipranavir) Product Monograph. Burlington, ON March 11, 2011.
10.
Bristol-Myers Squibb Canada. Sustiva (efavirenz) Prescribing Information. Montreal, QC June 11, 2012.
11.
Janssen Inc. Intelence (etravirine) Product Monograph. Toronto, ON November 9, 2011.
12.
Boehringer Ingelheim (Canada) Ltd. Viramune and Viramune XR (nevirapine) Product Monograph. Burlington, ON May 30, 2011.
13.
Janssen Inc. Edurant (rilpivirine) Product Monograph. Toronto, ON July 20, 2011.
14.
ViiV Healthcare ULC. Tivicay (dolutegravir) Prescribing Information. Research Triangle Park, NC August, 2013.
15.
Gilead Sciences Inc. Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Prescribing Information. Foster City, CA August, 2012.
16.
Merck Frosst Canada Ltd. Isentress (raltegravir) Prescribing Information. Kirkland, QC February 10, 2012.
17.
Hesse LM, von Moltke LL, Shader RI, et al. Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.
Drug Metabolism & Disposition 2001;29:100-02.
18.
Kharasch ED, Mitchell D, Coles R, et al. Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir. Antimicrob Agents Chemother
2008;52(5):1663-9.
19.
Vourvahis M, Dumond J, Patterson K, et al. Effects of tipranavir/ritonavir on the activity of cytochrome p450 enzymes 1A2, 2C9 and 2D6 in healthy
volunteers [abstract 52]. 8th International Workshop on Clinical Pharmacology of HIV Therapy, April 16-18, 2007, Budapest, Hungary.
20.
ViiV Healthcare ULC. Rescriptor (delavirdine) Product Monograph. Montreal, QC December 15, 2009.
21.
Dixit V, Hariparsad N, Li F, et al. Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human
hepatocytes: implications for predicting clinical drug interactions. Drug Metab Dispos 2007;35(10):1853-9.
22.
Robertson SM, Maldarelli F, Natarajan V, et al. Efavirenz induces CYP2B6-mediated hydroxylation of bupropion in healthy subjects. J Acquir Immune Defic
Syndr 2008;49(5):513-9.
Prepared by: Michelle Foisy, Pharm.D., Northern Alberta Program, Edmonton, Alberta. Updated by Michelle Foisy, Pharm.D. & Alice Tseng, Pharm.D., Toronto General Hospital
August 2013
www.hivclinic.ca
Page 7 o f 9
Interactions Between Sedatives/Hypnotics/Anxiolytics and Antiretrovirals
23.
Lee L, Soon GH, Shen P, et al. Effect of efavirenz and darunavir/ritonavir on bilirubin levels in healthy adult volunteers: role of induction of UGT1A1 and
bile efflux transporters [abstract 27]. 11th International Workshop on Clinical Pharmacology of HIV Therapy, April 5-7, 2010, Sorrento, Italy.
24.
Crauwels HM, Van Heeswijk R, Stevens T, et al. The effect of TMC278, a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) on
CYP3A activity in vivo [abstract P_28]. 10th International Workshop on Clinical Pharmacology of HIV Therapy, April 15-17, 2009, Amsterdam.
25.
Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clinical Pharmacokinetics
1997;32(3):210-58.
26.
[internet database] [database on the Internet]. Thomson Reuters (Healthcare) Inc. 2009 [cited June 10].
27.
Bristol-Myers Squibb Canada. Reyataz (atazanavir) Product Monograph. Montreal, QC January, 2011.
28.
Greenblatt D, Motlke L, Harmatz J, et al. Alprazolam-ritonavir interaction: Implications for product labeling. Clinical Pharmacology and Therapeutics
2000;67:335-41.
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