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Database of Antiretroviral Drug Interactions

Interactions between Antidepressants and Antiretrovirals

Interactions with Amitriptyline
Antiretroviral (ARV)Dose of ARVDose of AmitriptylineEffect on ARV LevelsEffect on Amitriptyline LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat
(Genvoya, Stribild)
--- Not studied; Increased levels of amitriptyline expected Possible increased risk of amitriptyline adverse effects-

Initiate amitriptyline low dose and titrate according to response, adverse effects, and/or drug levels

Elvitegravir/ritonavir-boosted protease inhibitor
--- Not studied; expected increase in amitriptyline levels Possible increased risk of amitriptyline adverse effects-

Initiate amitriptyline low dose and titrate according to response, adverse effects, and/or drug levels

Ritonavir55
(RTV)(Norvir)
- - - Increased amitriptyline levelsIncreased amitriptyline effects (eg, dry mouth, hypotension, confusion)Inhibition of CYP450 3A4 and 2D6 by ritonavir

Monitor and adjust amitriptyline as indicated

"-" indicates that there are no data available
Interactions with Bupropion
Antiretroviral (ARV)Dose of ARVDose of BupropionEffect on ARV LevelsEffect on Bupropion LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz165
(EFV)(Sustiva)
600 mg QHS150 mg SR x 1-Bupropion AUC: decreased 55%; Cmax: decreased 34%; half-life: decreased 46%Decreased bupropion effectsInduction of CYP 2B6 by efavirenz

Monitor for signs and symptoms of depression and titrate bupropion to effect

Elvitegravir/cobicistat705
(Genvoya, Stribild)
--- Not studied; potential decrease in bupropion levels Potential decreased bupropion effectiveness-

Monitor bupropion response and adverse effects, titrate dose.

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease bupropion levelsPotential decreased bupropion effectiveness-

Monitor bupropion response and adverse effects, titrate dose.

Lopinavir/ritonavir533
(LPV/r)(Kaletra)
400/100 mg BID100 mg x 1Ritonavir AUC: decreased 15%Bupropion AUC: decreased 57%; Cmax: decreased 57%Decreased bupropion effectsPossible induction of CYP450 2B6 and UGT enzymes

Titrate dose of bupropion based on response

Tipranavir168
(TPV)(Aptivus)
500 mg BID with 200 mg BID150 mg BID-Bupropion AUC: decreased 46%; Cmax: decreased 42%; Cmin: decreased 55%Decreased bupropion effectsInduction of CYP450 3A4 by tipranavir

Monitor for symptoms of depression and titrate bupropion to effect

"-" indicates that there are no data available
Interactions with Buspirone
Antiretroviral (ARV)Dose of ARVDose of BuspironeEffect on ARV LevelsEffect on Buspirone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat707
(Genvoya, Stribild)
--- Not studied; possible increased buspirone levels Potential increased risk of buspirone adverse effects-

Start with low dose buspirone and titrate accordingly. Monitor for side effects.

Elvitegravir/ritonavir-boosted protease inhibitor707
--- Not studied; possible increased levels of buspirone Possible increased risk of buspirone adverse effects-

Start with low dose buspirone and titrate accordingly. Monitor for side effects.

"-" indicates that there are no data available
Interactions with Citalopram
Antiretroviral (ARV)Dose of ARVDose of CitalopramEffect on ARV LevelsEffect on Citalopram LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat705
(Genvoya, Stribild)
---Not studied; may increase citalopram levelsPossible increased SSRI adverse effects-

Initiate therapy with lowest citalopram dose. Monitor citalopram response and titrate dose according to efficacy and adverse effects.

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease citalopram levels Potential decreased antidepressant effectiveness-

Monitor citalopram response and titrate dose

"-" indicates that there are no data available
Interactions with Desipramine
Antiretroviral (ARV)Dose of ARVDose of DesipramineEffect on ARV LevelsEffect on Desipramine LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat623
(Genvoya, Stribild)
150 mg cobicistat50 mg-Desipramine AUC: increased 65%Increased desipramine effects-

Initiate low dose desipramine and titrate dose according to efficacy and adverse effects.

Elvitegravir/ritonavir-boosted protease inhibitor
---Expected increase in desipramine levelsIncreased risk of desipramine adverse effects-

Initiate lowest dose of desipramine and titrate according to efficacy, adverse effects and/or levels

Nelfinavir260
(NFV)(Viracept)
- - - May increase desipramine levelsIncreased desipramine effects (eg, dry mouth, dizziness, urinary retention)Inhibition of CYP450 2D6 by nelfinavir

Monitor and adjust desipramine as indicated

Ritonavir260
(RTV)(Norvir)
- - - Desipramine clearance: decreased 59%Increased desipramine effects (eg, dry mouth, dizziness, urinary retention)Inhibition of CYP450 2D6 by ritonavir

Monitor and adjust desipramine as indicated

"-" indicates that there are no data available
Interactions with Doxepin
Antiretroviral (ARV)Dose of ARVDose of DoxepinEffect on ARV LevelsEffect on Doxepin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may increase doxepin levelsPotential increase in doxepin-related adverse effects (e.g. sedation, dry mouth, etc.)-

Start with lowest possible dose of doxepin. Monitor response and titrate dose.

"-" indicates that there are no data available
Interactions with Escitalopram
Antiretroviral (ARV)Dose of ARVDose of EscitalopramEffect on ARV LevelsEffect on Escitalopram LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat705
(Genvoya, Stribild)
--- Not studied; potential increased SSRI levels Possible increase in SSRI adverse effects-

Initiate escitalopram therapy with lowest dose. Monitor escitalopram response and titrate according to efficacy and adverse effects

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease escitalopram levelsPotential decreased antidepressant effectiveness-

Monitor escitalopram response and titrate dose

Ritonavir387
(RTV)(Norvir)
600 mg x 1 dose20 mg x 1 doseNo significant changeNo significant change--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Fluoxetine
Antiretroviral (ARV)Dose of ARVDose of FluoxetineEffect on ARV LevelsEffect on Fluoxetine LevelsPotential Clinical EffectsMechanism of InteractionManagement
Delavirdine88
(DLV)(Rescriptor)
--Delavirdine Cmin: increased 50%-Increased delavirdine effectsInhibition of CYP450 3A4 by fluoxetine

No dose adjustment necessary

Elvitegravir/cobicistat705
(Genvoya, Stribild)
---Not studied; potential for increased fluoxetine levelsPossible increased risk of fluoxetine adverse effects-

Start with lowest fluoxetine dose. Monitor response and titrate dose according to efficacy and adverse effects

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease fluoxetine levelsPotential decreased antidepressant effectiveness-

Monitor fluoxetine response and titrate dose

Ritonavir262, 55
(RTV)(Norvir)
600 mg x 1 dose days 1 and 1030 mg Q12HAUC: increased 19%; Cmax: no significant change-Increased ritonavir effects; possibly increased fluoxetine effectsInhibition of CYP450 2D6 by both drugs

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Fluvoxamine
Antiretroviral (ARV)Dose of ARVDose of FluvoxamineEffect on ARV LevelsEffect on Fluvoxamine LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat705
(Genvoya, Stribild)
--Not studied; possible increase or decreased levels of elvitegravir-Potential decreased elvitegravir effects-

Consider alternative antidepressant

Elvitegravir/ritonavir-boosted protease inhibitor705
--Not studied; may increase or decrease elvitegravir levels-Potential decreased elvitegravir effectiveness-

Consider alternative antidepressant

"-" indicates that there are no data available
Interactions with Imipramine
Antiretroviral (ARV)Dose of ARVDose of ImipramineEffect on ARV LevelsEffect on Imipramine LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/ritonavir-boosted protease inhibitor
--- Expected increased imipramine levels Possible increased risk of imipramine adverse effects-

Initiate imipramine at lowest dose. Monitor response and titrate according to efficacy, adverse effects, and/or drug levels.

"-" indicates that there are no data available
Interactions with Nortriptyline
Antiretroviral (ARV)Dose of ARVDose of NortriptylineEffect on ARV LevelsEffect on Nortriptyline LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/ritonavir-boosted protease inhibitor
--- Expected increased nortriptyline levels Possible increased risk of nortriptyline adverse effects-

Initiate nortriptyline at lowest dose. Monitor response and titrate according to efficacy, adverse effects, and/or drug levels.

"-" indicates that there are no data available
Interactions with Paroxetine
Antiretroviral (ARV)Dose of ARVDose of ParoxetineEffect on ARV LevelsEffect on Paroxetine LevelsPotential Clinical EffectsMechanism of InteractionManagement
Darunavir161
(DRV)(Prezista)
400 mg BID with ritonavir 100 mg BID20 mg QDNo significant changeParoxetine AUC: decreased 39%; Cmax: decreased 36%; Cmin: decreased 37%Decreased paroxetine effects-

Titrate paroxetine to effect; monitor for continued response if darunavir/ritonavir initiated

Elvitegravir/cobicistat705
(Genvoya, Stribild)
--- Not studied; may increase paroxetine levels Possible increased risk of paroxetine adverse effects-

Initiate paroxetine at lowest dose. Monitor response and titrate dose according to efficacy and adverse effects

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease paroxetine levelsPotential decreased antidepressant effectiveness-

Monitor paroxetine response and titrate dose

Etravirine169, 405
(ETR)(Intelence)
125 mg BID20 mg QDNo significant changeNo significant change- -

No dose adjustment necessary

Fosamprenavir394
(FPV)(Lexiva)
700 mg BID with 100 mg ritonavir BID20 mg QD x 10 daysAmprenavir: no significant change; Ritonavir: no significant changeParoxetine AUC: decreased 55%; Cmax: decreased 60%Decreased paroxetine effects-

Titrate paroxetine to effect

"-" indicates that there are no data available
Interactions with Sertraline
Antiretroviral (ARV)Dose of ARVDose of SertralineEffect on ARV LevelsEffect on Sertraline LevelsPotential Clinical EffectsMechanism of InteractionManagement
Darunavir161
(DRV)(Prezista)
400 mg BID with ritonavir 100 mg BID50 mg QDNo significant changeSertraline AUC: decreased 49%; Cmax: decreased 44%; Cmin: decreased 49%Decreased sertraline effects-

Titrate sertraline to effect; monitor to ensure continued response if darunavir/ritonavir initiated

Elvitegravir/cobicistat705
(Genvoya, Stribild)
---Not studied; may increase sertraline levels Possible increased risk of sertraline adverse effects-

Initiate sertraline at lowest dose. Monitor response and titrate according to efficacy and adverse effects

Elvitegravir/ritonavir-boosted protease inhibitor705
---Not studied; may decrease sertraline levelsPotential decreased antidepressant effectiveness-

Monitor sertraline response and titrate dose

"-" indicates that there are no data available
Interactions with Trazodone
Antiretroviral (ARV)Dose of ARVDose of TrazodoneEffect on ARV LevelsEffect on Trazodone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Darunavir161
(DRV)(Prezista)
---Increased trazodone concentrationsIncreased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Possible inhibition of trazodone metabolism

Use with caution; if benefit outweighs risk, initiate trazodone at lower dose. Monitor for CNS and cardiovascular effects.

Elvitegravir/cobicistat699
(Genvoya, Stribild)
--- Not studied; may increase trazodone levels Possible increased trazodone adverse effects-

Initiate trazodone lowest dose. Monitor response and titrate according to efficacy and adverse effects.

Elvitegravir/ritonavir-boosted protease inhibitor699
---Not studied; may increase trazodone levelsPotential increase in trazodone effects (e.g. sedation)-

Start with lowest dose of trazodone and titrate to response.

Indinavir259
(IDV)(Crixivan)
----Increased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Inibition of CYP450 3A4 by indinavir

Decrease trazodone dose or start low and titrate to effect

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
---Increased trazodone concentrationsIncreased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Possible inhibition of trazodone metabolism

Use with caution; if benefit outweighs risk, initiate trazodone at lower dose

Ritonavir55
(RTV)(Norvir)
---Trazodone AUC: increased 2.4-fold; Cmax: increased 34%Increased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Possible inhibition of trazodone metabolism

Use with caution; if benefits outweigh risk, initiate trazodone at lower dose

Ritonavir259
(RTV)(Norvir)
200 mg BID for 2 days50 mg x 1 doseNot studiedTrazodone AUC: increased 240%; Cmax: increased 34%; half-life: increased 220%Increased trazodone effects (eg, nausea, hypotension, syncope)Inhibition of CYP450 3A4 by ritonavir

Decrease trazodone dose or start low and titrate to effect

"-" indicates that there are no data available
 55:Norvir [package insert]. North Chicago, IL: Abbott Laboratories, 2008.
 78:Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; Oct 2005.
 88:Rescriptor [package insert]. La Jolla, California: Agouron Pharmaceuticals, Inc; June 2001.
 161:Prezista [package insert]. Raritan, NJ: Tibotec Therapeutics Inc.; April 2010.
 165:Robertson S, Maldarelli F, Natarajan V, et al. Efavirenz induces CYP450 2B6 activity as measured by bupropion hydroxylation in healthy subjects [poster #761]. 13th Conference on Retroviruses and Opportunistic Infections; 2008 February 3-6; Boston, Massachusetts.
 168:Lavrut T, Garraffo R, Ferrando S, et al. Effect of tipranavir/ritonavir treatment on the steady-state pharmacokinetics of bupropion in healthy volunteers [abstract P4.3/03]. 11th European AIDS Conference; 2007 October 24-27; Madrid, Spain.
 169:Scholler-Gyure M, Kakuda TN, Bollen S, et al. No pharmacokinetic interaction between TMC125 and paroxetine in HIV-negative volunteers [abstract P4.3/01]. 11th European AIDS Conference; 2007 October 24-27; Madrid, Spain.
 259:Desyrel [package insert]. Princeton: NJ, Bristol-Myers Squibb Company, 2003.
 260:von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci 1998;87:1184-9.
 262:Ouellet D, Hsu A, Qian J, et al. Effect of fluoxetine on pharmacokinetics of ritonavir. Antimicrob Agents Chemother 1998;42:3107-12.
 387:Gutierrez MM, Rosenberg J, Abramowitz W. An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome P450 3A4 inhibitor ritonavir. Clin Ther 2003;25:1200-10.
 394:van der Lee MJ, Blenke AAM, Rongen GA, et al. Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Antimicrob Ag Chemother 2007; 51: 4098-4104.
 405:Intelence [package insert]. Raritan, NJ: Tibotec Therapeutics; 2010.
 533:Hogeland GW, Swindells S, McNabb JC, et al. Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects. Nature 2007; 81: 69-75.
 623:Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; August 2012.
 699:Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.
 705:Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.
 707:Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.