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Database of Antiretroviral Drug Interactions

Interactions between Antifungals and Antiretrovirals

Interactions with Caspofungin
Antiretroviral (ARV)Dose of ARVDose of CaspofunginEffect on ARV LevelsEffect on Caspofungin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nelfinavir384
(NFV)(Viracept)
1250 mg BID x 14 days50 mg IV x 14 daysNot studiedNo significant change--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Fluconazole
Antiretroviral (ARV)Dose of ARVDose of FluconazoleEffect on ARV LevelsEffect on Fluconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Atazanavir268
(ATV)(Reyataz)
300 mg QD with ritonavir 100 mg QD x 10 days200 mg QD x 10 daysNo significant changeNo significant change--

No dose adjustment necessary

Delavirdine88
(DLV)(Rescriptor)
300 mg TID400 mg x 1 doseNo significant changeNo significant changeNot studied-

No dose adjustment necessary

Efavirenz90
(EFV)(Sustiva)
400 mg x 7 days200 mg x 7 daysAUC: increased 16%; Cmax: no significant changeNo significant change- Inhibition of CYP450 3A4 by fluconazole

No dose adjustment necessary

Etravirine405, 435
(ETR)(Intelence)
200 mg BID200 mg QAMEtravirine AUC: increased 86%; Cmax: increased 75%; Cmin: increased 109%No significant changeIncreased etravirine effectsInhibition of CYP450 3A4 by fluconazole

Dose adjustment not established

Indinavir271, 272, 16
(IDV)(Crixivan)
1000 mg Q8H400 mg QDIndinavir AUC: decreased 19-24%; Cmax: no significant change; Cmin: no significant changeNo significant change--

No dose adjustment necessary

Antiretroviral (ARV)Dose of ARVDose of FluconazoleEffect on ARV LevelsEffect on Fluconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nevirapine427
(NVP)(Viramune)
200 mg BID200 mg three times weeklyNevirapine AUC: increased 33%; Cmin: increased 38%; Cmax: increased 26%- Possibly increased nevirapine effectsInhibition of CYP450 3A4 by fluconazole

No dose adjustment necessary

Nevirapine269
(NVP)(Viramune)
200 mg QD x 14 days then 200 mg BID200 mg QD x 40 daysNevirapine AUC: increased 110%; Cmax: increased 115%; Cmin: increased 135%; half-live: decreased 52% (data compared to historical controls)No significant changeIncreased nevirapine effectsPossible inhibition of CYP450 3A4 by fluconazole

Dose adjustment not established

Ritonavir273
(RTV)(Norvir)
200 mg Q6H x 4 days400 mg x 1 day, then 200 mg days 2-5Cmax: increased 14.5%; AUC: increased 12%; Cmin: increased 14%- - Inhibition of CYP450 3A4 by fluconazole

No dose adjustment necessary

Saquinavir270
(SQV)(Fortovase, Invirase)
1200 mg TID400 mg QD on day 2, then 200 mg QD on days 3-8Saquinavir AUC: increased 50%; Cmax: increased 56%Not reportedIncreased saquinavir effectsInhibition of CYP450 3A4 by fluconazole

Dose adjustment not established

Stavudine275
(d4T)(Zerit)
40 mg BID200 mg QDStavudine AUC: no significant change; Cmax: no significant change; Cmin: increased 25%---

No dose adjustment necessary

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 200 mg ritonavir BID100 mg QD x 12 daysTipranavir AUC: increased 50%; Cmax: increased 32%; Cmin: increased 69%No significant changeIncreased tipranavir effectsInhibition of CYP450 3A4 by fluconazole

Dose adjustment not necessary. Fluconazole doses greater than 200 mg/day not recommended

Zidovudine81
(AZT, ZDV)(Retrovir)
200 mg Q8H400 mg QDZidovudine AUC: increased 74%; Half-life: increased 128%-Increased zidovudine effects-

No dose adjustment necessary

Zidovudine274
(AZT, ZDV)(Retrovir)
500 mg QD, 250 mg QID400 mg QD, 200 mg QDZidovudine half-life: increasedFluconazole half-life: no significant changeIncreased zidovudine effects-

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Itraconazole
Antiretroviral (ARV)Dose of ARVDose of ItraconazoleEffect on ARV LevelsEffect on Itraconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
--Not studied; may increase amprenavir levelsNot studied; may increase itraconazole levels-Inhibition of CYP450 3A4 by either drug

Dose adjustment not established

Atazanavir/cobicistat727
(others)(Evotaz)
-- Not studied; may increase atazanavir levels Not studied; may increase itraconzazole levels- Inhibition of CYP3A4

Unless guided by therapeutic drug monitoring, limit doses of itraconazole to less than 200 mg daily when used with atazanavir/cobicistat.

Darunavir161
(DRV)(Prezista)
----Increased darunavir and itraconazole effectsInhibition of CYP450 3A4 by darunavir and itraconazole

Dose adjustment not established; if co-administration needed, itraconazole dose should not exceed 200 mg daily

Didanosine280, 19
(ddI)(Videx)
300 mg (buffered formulation) x 1 dose200 mg (capsule) x 1 doseNot studiedItraconaxole Cmax: undetectableDecreased itraconazole effectsDecreased itraconazole absorption due to decreased gastric acidity resulting from antacid buffer contained within didanosine tablets/suspension

Administer itraconazole capsules at least 2 hours after didanosine tablets/suspension

Alternative Agents:
Itraconazole solution

Efavirenz90
(EFV)(Sustiva)
600 mg x 14 days200 mg Q12H x 28 days-Itraconazole AUC: decreased 39%; Cmax: decreased 37%; Cmin: decreased 44%; Hydroxyitraconazole AUC: decreased 37%; Cmax: decreased 35%; Cmin: decreased 43%Decreased itraconazole effectsInduction of CYP450 3A4 by efavirenz

Do not coadminister

Antiretroviral (ARV)Dose of ARVDose of ItraconazoleEffect on ARV LevelsEffect on Itraconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat623
(Genvoya, Stribild)
--Potentially increased effectsPotentially increased effects--

Avoid itraconazole > 200 mg daily and monitor itraconazole concentrations with coadministration.

Elvitegravir/ritonavir-boosted protease inhibitor699
--Not studied; potential increased elvitegravir levelsNot studied; may increase itraconazole levelsPotential increased adverse effects from both elvitegravir and itraconazoleInhibition of CYP3A4

Consider keeping doses of itraconazole less than 200 mg/day when elvitegravir is boosted with ritonavir or cobicistat.

Etravirine405
(ETR)(Intelence)
--Possibly increased etravirine effectsPossibly decreased itraconazole levelsDecreased itraconazole effects-

-

Indinavir16
(IDV)(Crixivan)
600 mg Q8H200 mg BIDIndinavir AUC: similar to AUC of 800 mg Q8H alone-Increased indinavir effectsInhibition of CYP450 3A4 by itraconazole

Decrease indinavir to 600 mg Q8; do not exceed itraconazole 200 mg BID

Lopinavir/ritonavir78, 279
(LPV/r)(Kaletra)
--Not studied; may increase ritonavir levelsNot studied; may increase itraconazole levelsIncreased lopinavir/ritonavir effects; increased itraconazole effectsInhibition of CYP450 3A4 by both drugs

Manufacturer recommends against using high doses of itraconazole (e.g. 200 mg daily)

Alternative Agents:
Fluconazole

Ritonavir278
(RTV)(Norvir)
--Increased ritonavir levels-Increased ritonavir effectsInhibition of CYP450 3A4 by itraconazole

Dose adjustment not established

Saquinavir277
(SQV)(Fortovase, Invirase)
400 mg BID (with ritonavir 600 mg BID)200 mg BID-Itraconazole half-life: increased 414%Increased itraconazole effects; increased saquinavir effectsInhibition of CYP450 3A4 by itraconazole and saquinavir and ritonavir

Consider reducing itraconazole to 100 mg BID

Saquinavir276
(SQV)(Fortovase, Invirase)
800 mg or 1200 mg saquinavir soft gel caps BID with 100 mg itraconazole QD x 14 days100 mg QD x 14 daysNo significant changes (compared to 1400 mg saquinavir soft gel caps BID with no itraconazole)Not studied-Inhibition of CYP450 3A4 by itraconazole

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Ketoconazole
Antiretroviral (ARV)Dose of ARVDose of KetoconazoleEffect on ARV LevelsEffect on Ketoconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir284, 63, 60
(APV)(Agenerase)
1200 mg x 1 dose400 mg x 1 doseAmprenavir AUC: increased 31%; Cmax: decreased 16%Ketoconazole AUC: increased 44%; Cmax: increased 19%No significant changeInhibition of gastrointestinal and hepatic CYP450 3A4 by amprenavir; inhibition of P-glycoprotein by amprenavir; inhibition of CYP 3A4 by ketoconazole

Dose adjustment not established

Atazanavir283,
(ATV)(Reyataz)
400 mg QD on days 1-13200 mg QD on days 7-13No significant changeNot studied--

No dose adjustment necessary

Darunavir414, 161
(DRV)(Prezista)
400 mg BID with ritonavir 100 mg BID200 mg BIDDarunavir AUC: increased 42%; Cmax: increased 21%; Cmin: increased 73%Ketoconazole AUC: increased 212%; Cmax: increased 111%; Cmin: increased 868%Increased darunavir effects; increased ketoconazole effectsInhibition of CYP450 3A4 by darunavir and ketoconazole

Dose adjustment not established; if co-administration needed, ketoconazole dose should not exceed 200 mg daily

Delavirdine88
(DLV)(Rescriptor)
--Delavirdine Cmin: increased 50%-Increased delavirdine effectsInhibition of CYP450 3A4 by ketoconazole

No dose adjustment necessary

Didanosine285, 19
(ddI)(Videx)
375 mg (buffered formulation) BID x 4 days200 mg QD x 4 daysNo significant changeNo significant changePossibly decreased didanosine effectsDecreased ketoconazole absorption due to decreased gastric acidity resulting from antacid buffer contained within didanosine tablets/suspension

Consider didanosine EC or administer ketoconazole at least 2 hours prior to didanosine tablets/suspension

Antiretroviral (ARV)Dose of ARVDose of KetoconazoleEffect on ARV LevelsEffect on Ketoconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Didanosine84
(ddI)(Videx)
400 mg (enteric coated capsule) x 1 dose200 mg x 1 doseNot studiedNo significant change--

No dose adjustment necessary

Doravirine761
(Pifeltro, Delstrigo)
100 mg x 1400 mg dailyAUC increased to 306%; Cmax increased by 25%; C24 increased to 275%Not studiedPotentially increased doravirine adverse effectsInhibition of CYP3A4

No dose adjustment necessary. Monitor for doravirine adverse effects.

Efavirenz90
(EFV)(Sustiva)
- - - Not studied; may decrease ketoconazole levelsDecreased ketoconazole effectsInduction of CYP450 3A4 by efavirenz

Do not coadminister

Elvitegravir/cobicistat623
(Genvoya, Stribild)
150 mg elvitegravir with 100 mg ritonavir200 mg BIDElvitegravir AUC: increased 48%; Cmin: increased 67%-Increased elvitegravir and ketoconazole effects-

Avoid if possible, avoid ketoconazole > 200 mg daily

Indinavir16, 254
(IDV)(Crixivan)
400 mg x 1 dose400 mg x 1 doseIndinavir AUC: increased 68%-Increased indinavir effectsInhibition of CYP450 3A4 by ketoconazole

May consider decreasing indinavir to 600 mg Q8H

Indinavir16, 254
(IDV)(Crixivan)
600 mg Q8H400 mg QDIndinavir AUC: decreased 18%-Decreased indinavir effects-

Dose adjustment not established

Antiretroviral (ARV)Dose of ARVDose of KetoconazoleEffect on ARV LevelsEffect on Ketoconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Lopinavir/ritonavir78
(LPV/r)(Kaletra)
400 mg/100 mg BID x 16 days200 mg x 1 doseLopinavir AUC: no significant change; Cmax: no significant change; Cmin: decreased 25%Ketoconazole AUC: increased 204%; Cmax: no significant changeIncreased ketoconazole effects; decreased lopinavir/ritonavir effects-

Manufacturer recommends against using high doses of ketoconazole(>200 mg daily)

Alternative Agents:
Fluconazole

Maraviroc2
(MVC)(Selzentry)
100 mg BID400 mg QDMaraviroc AUC: increased 400%; Cmax: increased 238%; Cmin: increased 275%-Increased maraviroc effectsInhibition of CYP450 3A4 by ketoconazole

Reduce maraviroc dose to 150 mg BID when used with ketoconazole

Nelfinavir24
(NFV)(Viracept)
500 mg Q8H x 5-6 days400 mg QD x 7 daysAUC: increased 35%; Cmax: increased 25%- Increased nelfinavir effectsInhibition of CYP450 3A4 by ketoconazole

No dose adjustment necessary

Nevirapine95
(NVP)(Viramune)
200 mg QD x 2 weeks then 200 mg BID x 2 weeks400 mg QD x 2 weeksLevels: increased 15-30%Ketoconazole AUC: decreased 63%; Cmax: decreased 40%Decreased ketoconazole effectsInduction of CYP450 3A4 by nevirapine

Do not coadminister

Rilpivirine567
(RPV)(Edurant)
150 mg QD400 mg QDRilvpivirine AUC: increased 49%; Cmin: increased 76%; Cmax: increased 30%Ketoconazole AUC: decreased 24%; Cmin: decreased 66%; Cmax: decreased 15%Decreased ketoconazole effects-

No dose adjustment necessary but monitor for failure of antifungal therapy

Ritonavir278
(RTV)(Norvir)
--Increased ritonavir levels-Increased ritonavir effectsInhibition of CYP450 3A4 by ketoconazole

Dose adjustment not established

Antiretroviral (ARV)Dose of ARVDose of KetoconazoleEffect on ARV LevelsEffect on Ketoconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Saquinavir282
(SQV)(Fortovase, Invirase)
1200 mg TID200 mg QDSaquinavir AUC: increased 69%; Cmax: increased 36% when studied in HIV-infected patientsNo significant changeIncreased saquinavir effectsInhibition of CYP450 3A4 by ketoconazole

Dose adjustment not established

Saquinavir282
(SQV)(Fortovase, Invirase)
1200 mg TID400 mg QD x 7 daysSaquinavir AUC: increased 190%; Cmax: increased 171%No significant changeIncreased saquinavir effectsInhibition of CYP450 3A4 by ketoconazole

Dose adjustment not established

Saquinavir281
(SQV)(Fortovase, Invirase)
2000 mg x 14 days400 mg QD x 14 daysSaquinavir AUC: decreased 78%; Cmax: decreased 76%; Cmin: decreased 87% (compared to saquinavir/ritonavir 2000 mg/100 mg QD)-Decreased saquinavir effectsInadequate boosting due to ketoconazole

Do not use ketoconazole as a pharmacokinetic "booster" with saquinavir

Saquinavir44
(SQV)(Fortovase, Invirase)
600 mg TID (hard gel caps) x 6 days200 mg QD x 6 daysAUC: increased 130%; Cmax: increased 147%-Increased saquinavir effectsInhibition of CYP450 3A4 by ketoconazole

-

"-" indicates that there are no data available
Interactions with Posaconazole
Antiretroviral (ARV)Dose of ARVDose of PosaconazoleEffect on ARV LevelsEffect on Posaconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Atazanavir501, 424
(ATV)(Reyataz)
300 mg QD400 mg BIDAtazanavir AUC: increased 268%; Cmax: increased 155%-Increased atazanavir effectsInhibition of CYP450 3A4 by posaconazole

Dose adjustment not established; Monitor closely for adverse effects during coadministration

Atazanavir519, 424
(ATV)(Reyataz)
300 mg QD with 100 mg ritonavir QD400 mg BIDAtazanavir AUC: increased 146%; Cmax: increased 53%-Increased atazanavir effectsInhibition of CYP450 3A4 by posaconazole

Dose adjustment not established; Monitor closely for adverse effects during coadministration

Efavirenz499, 424
(EFV)(Sustiva)
400 mg QD400 mg BIDNo significant changePosaconazole AUC: decreased 50%; Cmax: decreased 45%Decreased posaconazole effectsInduction of UGT by efavirenz

Dose adjustment not established

Elvitegravir/cobicistat623
(Genvoya, Stribild)
--Potentially increased effectsPotentially increased effects--

Monitor posaconazole concentrations with coadministration

Elvitegravir/ritonavir-boosted protease inhibitor519, 699
--Not studied; may increase elvitegravir levels-Potential increased elvitegravir adverse effects-

Monitor elvitegravir adverse effects

Etravirine405
(ETR)(Intelence)
--Possibly increased etravirine levels---

-

Fosamprenavir447
(FPV)(Lexiva)
1400 mg BID400 mg BIDAmprenavir AUC: decreased 65%; Cmax: decreased 36% (when compared to 700 mg/100 mg fosamprenavir/ritonavir)Posaconazole AUC: decreased 23%; Cmax: decreased 20%Decreased posaconazole and fosamprenavir efficacy-

Do not coadminister. If combination must be used monitor posaconazole concentrations.

Ritonavir503, 424
(RTV)(Norvir)
100 mg QD400 mg BIDRitonavir AUC: increased 80%; Cmax: increased 49%-Possibly increased ritonavir effectsInhibition of CYP450 3A4 by posaconazole; potential inhibition of UGT 1A1 by atazanavir

Dose adjustment not necessary

"-" indicates that there are no data available
Interactions with Voriconazole
Antiretroviral (ARV)Dose of ARVDose of VoriconazoleEffect on ARV LevelsEffect on Voriconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Atazanavir727, 515
(ATV)(Reyataz)
-200 mg PO Q12H-Voriconazole AUC: decreased 39% when given with ritonavir 100 mg BIDDecreased voriconazole effectsPossible induction of CYP450 by ritonavir

With unboosted atazanavir no dose adjustment necessary; monitor for toxicity. Do not coadminister with boosted protease inhibitors unless benefit outweighs risks. If coadministering, consider therapeutic drug monitoring.

Atazanavir/cobicistat727
(others)(Evotaz)
-- Not studied Not studied--

Avoid coadministration unless benefit outweighs risk. If coadministering, monitor voriconazole concentrations.

Bictegravir759
(Biktarvy)
75 mg x 1300 mg twice dailyCmax increased 9%; AUC increased 61%Not studiedPotentially increased bictegravir adverse effectsInhibition of CYP3A4

Consider using alternative agents; if co-administering, monitor for bictegravir adverse effects

Darunavir161
(DRV)(Prezista)
---Decreased voriconazole levelsDecreased voriconazole effectsPossible induction of CYP450 by ritonavir

Do not coadminister with boosted protease inhibitors unless benefit outweighs risks. If coadministering, consider therapeutic drug monitoring.

Efavirenz376
(EFV)(Sustiva)
300 mg QHS x 7 days400 mg Q12H on days 2-7Efavirenz AUC: increased 17%; Cmax: no significant changeVoriconazole Cmax: increased 23%--

No dose adjustment necessary

Antiretroviral (ARV)Dose of ARVDose of VoriconazoleEffect on ARV LevelsEffect on Voriconazole LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz376
(EFV)(Sustiva)
300 mg QHS x 7 days300 mg Q12H on days 2-7No significant changeVoriconazole AUC: decreased 55%; Cmax: decreased 36% (compared to voriconazole 200 mg BID)Decreased voriconazole effectsInduction of CYP450 3A4 by efavirenz

Do not coadminister at standard doses; increase voriconazole to 400 mg Q12H and decrease efavirenz to 300 mg QHS

Efavirenz376, 90, 379
(EFV)(Sustiva)
400 mg QD x 9 days400 mg PO Q12H on day 1, then 200 mg Q12H on days 2-8Efavrenz AUC: increased 44%; Cmax: increased 38%Voriconazole AUC: decreased 77%; Cmax: decreased 61%Increased efavirenz effects and decreased voriconazole effectsInhibition of CYP450 3A4 by voriconazole and induction of CYP450 3A4 by efavirenz

Do not coadminister at standard doses; increase voriconazole to 400 mg Q12H and decrease efavirenz to 300 mg QHS

Elvitegravir/cobicistat623
(Genvoya, Stribild)
--Potentially increased effectsNot studied; Potentially increased or decreased voriconazole levels--

Monitor voriconazole concentrations with coadministration

Elvitegravir/ritonavir-boosted protease inhibitor515, 699
--Not studied; may increase elvitegravir levelsNot studied; voriconazole levels reduced up to 39% when administered with ritonavir-boosted protease inhibitorsPossible decreased antifungal effectiveness-

Weigh risks and benefits of using combination; consider monitoring voriconazole levels if used.

Etravirine435, 405
(ETR)(Intelence)
200 mg BID200 mg BIDEtravirine AUC: increased 36%; Cmin: increased 52%; Cmax: increased 26%Voriconazole Cmin: increased 23%Possibly increased etravirine effectsInhibition of CYP450 3A4 by voriconazole

No dose adjustment necessary

Indinavir517, 382
(IDV)(Crixivan)
800 mg TID x 10 days200 mg Q12H x 7 daysNo significant effectNo significant effect--

No dose adjustment necessary

Lopinavir/ritonavir727, 78
(LPV/r)(Kaletra)
---Decreased voriconazole levelsDecreased voriconazole effectsPossible induction of CYP450 by ritonavir

Do not coadminister with boosted protease inhibitors unless benefit outweighs risks. If coadministering, consider therapeutic drug monitoring.

Ritonavir507, 505, 378
(RTV)(Norvir)
100 mg Q12H x 9 days400 mg Q12HNo significant changeVoriconazole AUC: decreased 39%; Cmax: decreased 24%Decreased voriconazole effectsInduction of CYP450 3A4 by ritonavir

Do not coadminister with boosted protease inhibitors unless benefit outweighs risks. If coadministering, consider therapeutic drug monitoring.

Alternative Agents:
Consider use of non-ritonavir containing antiretroviral regimens

Ritonavir727, 507, 505
(RTV)(Norvir)
400 mg Q12H x 9 days400 mg Q12HNo significant changeVoriconazole AUC: decreased 83%; Cmax: decreased 68%Decreased voriconazole effectsInduction of CYP450 3A4 by ritonavir

Do not coadminister with boosted protease inhibitors unless benefit outweighs risks. If coadministering, consider therapeutic drug monitoring.

Alternative Agents:
Consider use of non-ritonavir containing antiretroviral regimens

"-" indicates that there are no data available
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