University of California, San Francisco Logo

University of California, San Francisco | About UCSF | Search UCSF | UCSF Medical Center

Home > Treatment > Interactions
Database of Antiretroviral Drug Interactions

Interactions between Sedative-hypnotics and Antiretrovirals

Interactions with Alprazolam
Antiretroviral (ARV)Dose of ARVDose of AlprazolamEffect on ARV LevelsEffect on Alprazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
---Not studied; may increase alprazolam levelsIncreased alprazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

Delavirdine88
(DLV)(Rescriptor)
---Not studied; may increase alprazolam levelsIncreased alprazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 and 2C9 by delavirdine

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

Ritonavir55, 178, 255
(RTV)(Norvir)
200 mg BID1 mg x 1 dose- Alprazolam clearance: decreased 59%; half-life: increased 122%Increased alprazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

Ritonavir55
(RTV)(Norvir)
500 mg BID x 10 d1 mg x 1- Alprazolam AUC: no significant change; Cmax: decreased 16%- -

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

"-" indicates that there are no data available
Interactions with Clonazepam
Antiretroviral (ARV)Dose of ARVDose of ClonazepamEffect on ARV LevelsEffect on Clonazepam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat623
(Genvoya, Stribild)
----Potentially increased clonazepam effects-

More frequent clinical monitoring is recommended

"-" indicates that there are no data available
Interactions with Clorazepate
Antiretroviral (ARV)Dose of ARVDose of ClorazepateEffect on ARV LevelsEffect on Clorazepate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
---Not studied; may increase clorazepate levelsIncreased clorazepate effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Avoid combination; consider alternative agents

"-" indicates that there are no data available
Interactions with Diazepam
Antiretroviral (ARV)Dose of ARVDose of DiazepamEffect on ARV LevelsEffect on Diazepam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
- - - Not studied; may increase diazepam levelsIncreased diazepam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Do not coadminister

Alternative Agents:
Lorazepam Oxazepam Temazepam

Ritonavir178, 55
(RTV)(Norvir)
---Increased diazepam levelsIncreased diazepam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A by ritonavir

Do not coadminister

Alternative Agents:
Lorazepam Oxazepam Temazepam

"-" indicates that there are no data available
Interactions with Flurazepam
Antiretroviral (ARV)Dose of ARVDose of FlurazepamEffect on ARV LevelsEffect on Flurazepam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
---Not studied; may increase flurazepam levelsIncreased flurazepam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

"-" indicates that there are no data available
Interactions with Lorazepam
Antiretroviral (ARV)Dose of ARVDose of LorazepamEffect on ARV LevelsEffect on Lorazepam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz90
(EFV)(Sustiva)
600 mg x 10 days2 mg x 1 dose- Lorazepam AUC: no significant change; Cmax: increased 16%- -

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Midazolam
Antiretroviral (ARV)Dose of ARVDose of MidazolamEffect on ARV LevelsEffect on Midazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Atazanavir
(ATV)(Reyataz)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by atazanavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Bictegravir759
(Biktarvy)
50 mg daily2 mg x 1Not studied Cmax increased 3%; AUC increased 15%Potential increased sedation -

No dose adjustment necessary

Darunavir161
(DRV)(Prezista)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by darunavir/ritonavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Delavirdine88
(DLV)(Rescriptor)
---Not studied; may increase midazolam levelsIncreased midazolam effects (increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 and 2C9 by delavirdine

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Antiretroviral (ARV)Dose of ARVDose of MidazolamEffect on ARV LevelsEffect on Midazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Dolutegravir641
(Tivicay)
25 mg QD3 mg-No significant change --

No dose adjustment necessary

Efavirenz90
(EFV)(Sustiva)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by efavirenz

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Elvitegravir/cobicistat623
(Genvoya, Stribild)
----Potentially increased midazolam effects (e.g. prolonged sedation, altered mental status, respiratory depression)-

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided.

Indinavir16, 257
(IDV)(Crixivan)
---No significant change in procedure time or oxygenationIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by indinavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Nelfinavir24
(NFV)(Viracept)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by nelfinavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Antiretroviral (ARV)Dose of ARVDose of MidazolamEffect on ARV LevelsEffect on Midazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Raltegravir408
(RAL)(Isentress)
400 mg BID2 mg x 1- No significant change- -

No dose adjustment necessary

Ritonavir178
(RTV)(Norvir)
---Increased midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Saquinavir75
(SQV)(Fortovase, Invirase)
1000 mg BID with 100 mg ritonavir BID7.5 mg PO x 1-Midazolam AUC: increased 1144%; Cmax: increased 327%Increased midazolam effectsInhibition of CYP450 3A4 by saquinavir/ritonavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Saquinavir254, 258
(SQV)(Fortovase, Invirase)
600 mg TID x 8 weeks5 mg IV x 1 dose-Increased midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by saquinavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Tipranavir154
(TPV)(Aptivus)
---Not studied; may increase midazolam levelsIncreased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by tipranavir/ritonavir

Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

"-" indicates that there are no data available
Interactions with Triazolam
Antiretroviral (ARV)Dose of ARVDose of TriazolamEffect on ARV LevelsEffect on Triazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by amprenavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Atazanavir
(ATV)(Reyataz)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by atazanavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam; Oxazepam; Temazepam; Trazodone

Darunavir161
(DRV)(Prezista)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by darunavir/ritonavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Delavirdine88
(DLV)(Rescriptor)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 and 2C9 by delavirdine

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Efavirenz90
(EFV)(Sustiva)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by efavirenz

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Antiretroviral (ARV)Dose of ARVDose of TriazolamEffect on ARV LevelsEffect on Triazolam LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat623
(Genvoya, Stribild)
----Potentially increased triazolam effects (e.g. prolonged sedation, altered mental status, respiratory depression)-

Do not coadminister

Indinavir16
(IDV)(Crixivan)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by indinavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Nelfinavir24
(NFV)(Viracept)
---Not studied; may increase triazolam levelsInceased triazolam effects (increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by nelfinavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Ritonavir55, 256
(RTV)(Norvir)
200 mg BID x 2 days0.125 mg x 1 dose-Triazolam AUC: increased 1939%; half-life: increased 1267%; Cmax: increased 87%Increased triazolam effects (eg, increased confusion, sedation, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam, Oxazepam, Temazepam, Trazodone

Saquinavir254
(SQV)(Fortovase, Invirase)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by saquinavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Tipranavir154
(TPV)(Aptivus)
---Not studied; may increase triazolam levelsIncreased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by tipranavir/ritonavir

Do not coadminister; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

"-" indicates that there are no data available
Interactions with Zolpidem
Antiretroviral (ARV)Dose of ARVDose of ZolpidemEffect on ARV LevelsEffect on Zolpidem LevelsPotential Clinical EffectsMechanism of InteractionManagement
Ritonavir256
(RTV)(Norvir)
200 mg BID x 2 days5 mg x 1 dose-Zolpidem AUC: increased 28%; Cmax: increased 22%Increased zolpidem effects (eg, increased sedation, confusion)Inhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

"-" indicates that there are no data available
 16:Crixivan [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; Oct 2005.
 24:Viracept [package insert]. La Jolla, CA: Agouron Pharmaceuticals, Inc.; Sept 2004.
 55:Norvir [package insert]. North Chicago, IL: Abbott Laboratories, 2008.
 60:Agenerase [package insert]. Research Triangle Park, NC: Glaxo Wellcome Inc; 2004.
 75:Invirase [package insert]. Roche Laboratories Inc, Nutley, NJ, 2007.
 78:Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; Oct 2005.
 88:Rescriptor [package insert]. La Jolla, California: Agouron Pharmaceuticals, Inc; June 2001.
 90:Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; Dec 2011.
 154:Aptivus [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; Nov 2005.
 161:Prezista [package insert]. Raritan, NJ: Tibotec Therapeutics Inc.; April 2010.
 178:Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000;38:41-57.
 254:CDC. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Jan 28, 2000. [AIDS Treatment Information Service: Current Treatment] Available at: http://www.hivatis.org/trtgdlns.html.
 255:Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Alprazolam-ritonavir interaction: implications for product labeling. Clin Pharmacol Ther 2000;67:335-41.
 256:Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Differential impairment of triazolam and zolpidem clearance by ritonavir. J Acquir Immune Defic Syndr 2000;24:129-36.
 257:Gastaldo JM, Neidig JL, Para MF, et al. The clinical significance of the drug interaction between protease inhibitors and midazolam [abstract #422]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sept 17-20; Toronto, Canada.
 258:Merry C, Mulcahy F, Barry M, et al. Saquinavir interaction with midazolam: pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease. AIDS 1997;11:268-69.
 408:Iwamoto M, Wenning, LA, Troyer MD, et al. lack of a pharmacokinetic interaction of MK-0518 on midazolam [abstract P300]. 8th International Congress on Drug Therapy in HIV Infection. 2006 12-16 November; Glasgow, Scotland.
 623:Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; August 2012.
 641:Tivicay [package insert]. Research Triangle Park, NC: Viiv Healthcare; Sept 2013.
 759:Biktarvy [package insert]. Foster City, CA: Gilead Sciences, 2018