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Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Tables

Table 5. Significant Pharmacokinetic Interactions for Drugs Used to Treat or Prevent Opportunistic Infections

(Last updated:5/7/2013; last reviewed:5/7/2013)

 

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This table provides clinicians with information regarding known or suspected pharmacokinetic interactions between drugs commonly used for treatment or prevention of HIV-associated opportunistic infections or for treatment of HIV infection. Note that there may be substantial inter-patient variability in the magnitude of the interactions. Moreover, the table only provides suspected interactions between 2 drugs when used in combination, but cannot be used to predict the interaction potential when three or more drugs with similar metabolic pathways are co-administered. In these cases, alternative options with less drug interaction potential or therapeutic drug monitoring (if available), should be considered.

Throughout the table, two recommendations are commonly used when concomitant administration of two drugs may lead to untoward consequences. The definitions for these terms used in the Recommendations column are summarized below:

Co-administration should be avoided.

Indicates there is strong evidence or likelihood that the drug-drug interaction will result in either
  1. Markedly decreased concentrations of one or both drugs, which may render one or both drugs ineffective, or 
  2. Increased concentrations of one or both drugs, which may result in excessive risk of toxicity that cannot be managed with a dose modification of one or both drugs.
Co-administration should be avoided if possible. 

There is a potential for significant pharmacokinetic interactions. However, co-administration of the drugs may be necessary if there are no other reasonable options that provide a more favorable risk-benefit assessment. In some instances, a suggested strategy is provided with the recommendation based upon available knowledge and alternatives. If other more favorable options exist, the clinician is advised to consider changing components of the regimen to accommodate a more effective and/or safer regimen.

Table 5. Significant Pharmacokinetic Interactions for Drugs Used to Treat or Prevent Opportunistic Infections
Drug Interacting With  Effect on Primary and/or Concomitant Drug Concentrations
Recommendations
Artemether-Lumefantrine

Darunavir/ritonavir

Artemether AUC ↓ 16%; DHA AUC ↓ 18%; lumefantrine AUC ↑ 2.5-fold
Clinical significance unknown. Monitor for anti-malarial efficacy and lumefantrine toxicities.
Efavirenz
Artemether AUC ↓79%; DHA AUC ↓ 75%; lumefantrine AUC ↓ 56%
Clinical significance unknown. If used, monitor closely for anti-malarial efficacy.
Etravirine

Artemether AUC ↓ 38%; DHA AUC ↓ 15%; lumefantrine AUC ↓ 13%
Clinical significance unknown. If used, monitor closely for anti-malarial efficacy.
Lopinavir/ritonavir
Artemether AUC ↓ 40%; DHA AUC ↓ 17%; lumefantrine AUC ↑ 470%
Data based on single dose study. Clinical significance unknown. Monitor for anti-malarial efficacy and lumefantrine toxicities.
Nevirapine
Artemether AUC ↓ 72%; DHA AUC ↓ 37%; lumefantrine (no difference in one study, but AUC ↑ 55.6% in another study)
Clinical significance unknown. Monitor for anti-malarial efficacy.
Rifampin
Artemether AUC ↓ 89%; DHA AUC ↓ 85%; lumefantrine AUC ↓ 68%
Co-administration should be avoided.
Atovaquone
Atazanavir/ritonavir
Atovaquone AUC ↓ 46%; no data with unboosted atazanavir (based on a single-dose PK study using atovaquone 250 mg/proguanil 100 mg fixed-dose combination tablet; no interaction data between boosted or unboosted atazanavir and atovaquone suspension)
Dose adjustment not established; if co-administered, monitor for decreased atovaquone efficacy.
Doxycycline
Atovaquone concentrations ↓ 40% with tetracycline; interaction study with doxycycline not available
Dose adjustment not established; if co-administered, monitor for decreased atovaquone efficacy.
Efavirenz
Atovaquone AUC ↓ 75% (based on a single-dose PK study using atovaquone 250 mg/proguanil 100 mg fixed-dose combination tablet; no interaction data between efavirenz and atovaquone suspension)
Co-administration should be avoided if possible. If co-administered, monitor for decreased atovaquone efficacy.
Lopinavir/ritonavir
Atovaquone AUC ↓ 74% (based on a single-dose PK study using atovaquone 250 mg/proguanil 100 mg fixed-dose combination tablet; no interaction data between lopinavir/ritonavir and atovaquone suspension)
Co-administration should be avoided if possible. If co-administered, monitor for decreased atovaquone efficacy.
Rifabutin
Atovaquone AUC ↓ 34%; rifabutin AUC ↓ 19%
Dose adjustment not established; if co-administered, monitor for decreased atovaquone efficacy.
Rifampin
Atovaquone concentrations ↓ 52%; rifampin concentrations ↑ 37%
Co-administration should be avoided.
Zidovudine
Zidovudine AUC ↑ 31%
No dose adjustment necessary; monitor for zidovudine-associated toxicities.
Boceprevir
Atazanavir/ritonavir
Boceprevir AUC no change; atazanavir AUC ↓ 35%, Cmin ↓ 49%; ritonavir AUC ↓ 36%
Co-administration should be avoided.
Clarithromycin
May ↑ concentrations of clarithromycin
No dose adjustment necessary in patients with normal renal function. To avoid drug interaction, consider switching to azithromycin.
Darunavir/ritonavir
Boceprevir AUC ↓ 32%, Cmin ↓ 35%; darunavir AUC ↓ 44%, Cmin ↓ 59%; ritonavir AUC ↓ 27%
Co-administration should be avoided.
Efavirenz
Boceprevir AUC ↓ 19%, Cmin ↓ 44%; efavirenz AUC ↑ 20%
Significance unknown; co-administration should be avoided. 
Elvitegravir/cobicistat/
tenofovir/emtricitabine
No PK data, bi-directional interaction possible
Co-administration should be avoided.
Etravirine
Boceprevir AUC ↑ 10%, Cmin ↓12%; etravirine AUC ↓ 23%, Cmin ↓ 29%
Clinical significance of this interaction is unknown. 
Itraconazole, ketoconazole, posaconazole, voriconazole
Boceprevir AUC ↑ 230% when co-administered with ketoconazole 400 mg bid.

Concentrations of azoles may be ↑
Doses of ketoconazole and itraconazole should not exceed 200 mg/day. Consider monitoring azole drug concentrations and adjust dose accordingly. Monitor for boceprevir-associated toxicities.
Lopinavir/ritonavir
Boceprevir AUC ↓ 45%, Cmin ↓ 57%; lopinavir AUC ↓ 34%, Cmin ↓ 43%; ritonavir AUC ↓ 22%
Co-administration should be avoided.
Raltegravir
No significant interaction.
This combination can be co-administered without dosage adjustment
Rifabutin
↑ in rifabutin concentrations are anticipated, while exposure of boceprevir may be ↓
Co-administration should be avoided, if possible. If used in combination, consider monitoring rifabutin concentration and adjust dose accordingly.
Rifampin
No PK data. Significant ↓ in boceprevir exposure is anticipated.
Co-administration should be avoided.
Caspofungin
Efavirenz, nevirapine
Possible ↓ in caspofungin concentrations based on regression analyses of patient PK data. No formal PK study available.
Manufacturer recommends consider increasing maintenance dose of caspofungin to 70 mg/day when co-administered with CYP450 inducers.
Rifampin
Caspofungin Cmin ↓ 30%
Caspofungin dose should be increased to 70 mg/day.
Clarithromycin
Atazanavir
Atazanavir Cmin ↑ 91%, AUC ↑ 28%; clarithromycin AUC ↑ 94%, Cmin ↑ 160%

Co-administration with atazanavir/ ritonavir has not been studied.
Because of concerns for QTc prolongation when these drugs are used in combination, reduce clarithromycin dose by 50% or switch to azithromycin.
Boceprevir
Concentrations of clarithromycin may be ↑
No dose adjustment in patients with normal renal function. To avoid drug interaction, consider switching to azithromycin.
Darunavir/ritonavir
Clarithromycin AUC ↑ 57%, Cmin ↑ 174%
No dose adjustment in patients with normal renal function. To avoid drug interaction, consider switching to azithromycin.
Efavirenz
Clarithromycin AUC ↓ 39%
Significance unknown; consider switching to azithromycin.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Clarithromycin, cobicistat, and elvitegravir concentrations may be increased.
CrCl > 60 mL/min: no dosage adjustment.

CrCl 50–60 mL/min: reduce clarithromycin dose by 50%. To avoid drug interaction, consider switching to azithromycin.
Etravirine
Clarithromycin AUC ↓ 39%; etravirine Cmin ↑ 46%, AUC ↑ 42%
Significance unknown; consider switching to azithromycin.
Fluconazole
Clarithromycin AUC ↑ 18%, Cmin ↑ 33%
No dose adjustment necessary in patients with normal renal function.
Itraconazole
Possible bi-directional CYP3A4 inhibition and increased exposure of both drugs.
Monitor for toxicities of both itraconazole and clarithromycin, consider monitoring drug concentrations and adjust dose accordingly, or consider switching to azithromycin.
Lopinavir/ritonavir
Increased clarithromycin exposure expected.
No dose adjustment necessary in patients with normal renal function.

To avoid drug interaction, consider switching to azithromycin.
Maraviroc
Potential for inhibition of maraviroc metabolism and ↑ maraviroc concentration.
Decrease maraviroc dose to 150 mg BID or switch to azithromycin.
Nevirapine
Clarithromycin AUC ↓ 29%, Cmin ↓ 46%
Co-administration should be avoided if possible; consider switching to azithromycin.
Rifabutin
Clarithromycin AUC ↓ by 44%; rifabutin AUC ↑ 76%–99%.
Consider reducing rifabutin dose, monitor for rifabutin-associated toxicities, Consider monitoring serum concentration and adjust dose accordingly; or switch to azithromycin.
Rifampin
Mean clarithromycin concentration ↓ 87%
This combination should be avoided. Switch to azithromycin.
Saquinavir
Saquinavir Cmax ↑ 187%, AUC ↑ 177%; clarithromycin Cmax and AUC ↑ 40% (studied with saquinavir 1200 mg TID)

Clarithromycin has not been studied with ritonavir-boosted saquinavir.
No dose adjustment necessary in patients with normal renal function. Clarithromycin dose adjustment may be necessary in patients with renal dysfunction.

Monitor closely because of additive risk of QTc prolongation associated with increased concentrations of both drugs. Consider switching to azithromycin.
Telaprevir
Concentrations of both telaprevir and clarithromycin may be increased during co-administration.
Use with caution and monitor for adverse events, including QT prolongation. 

Reduce clarithromycin dose during concomitant use with telaprevir in patients with impaired renal function. Consider switching to azithromycin.
Tipranavir/ritonavir
Clarithromycin AUC ↑ 19%, Cmin ↑ 68%; tipranavir AUC ↑ 66%, Cmin ↑ 100%
Monitor for tipranavir-associated toxicities. 

No dose adjustment necessary in patients with normal renal function. Clarithromycin dose adjustment may be necessary in patients with renal dysfunction. Consider switching to azithromycin.
Dapsone
Rifampin
Dapsone concentrations ↓ 7 to 10-fold and half-life (t1/2) ↓ from 24 to 11 hours.
Co-administration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.
Doxycycline
Atovaquone
Atovaquone concentrations ↓ by approximately 40% with tetracycline; interaction study with doxycycline not available.
Until doxycycline-atovaquone interaction data become available, avoid this combination if possible. 
Rifampin
Doxycycline AUC ↓ by 59%
Potential for decreased doxycycline efficacy; monitor closely for therapeutic failure.
Erythromycin
Itraconazole
Itraconazole Cmax ↑ 44%, AUC ↑ 36%. Potential for ↑ in erythromycin concentration.
Monitor for toxicities of both drugs, potential for QT prolongation; monitor itraconazole concentrations and adjust dose accordingly, or consider alternative azole or macrolide.
Telaprevir
Concentrations of telaprevir and erythromycin may ↑ during co-administration.
Use with caution and monitor for adverse events, including QT prolongation.
Fluconazole
Clarithromycin
Clarithromycin AUC ↑ 18%, Cmin ↑ 33%  No dose adjustment necessary in patients with normal renal function.
Efavirenz
Efavirenz AUC ↑ 16%; no change in fluconazole AUC.
No dose adjustment necessary.
Etravirine
Etravirine AUC ↑ 86%, Cmin ↑ 109%
Co-administer with caution. Monitor for etravirine-associated toxicities.
Nevirapine
Nevirapine concentrations ↑ 100% (compared with historic control).
Co-administration should be avoided, if possible. If co-administered, monitor for nevirapine-associated toxicities.
Rifabutin
Rifabutin AUC ↑ 80%; no effect on fluconazole exposure.
Monitor for rifabutin-associated toxicities; consider monitoring rifabutin concentrations; may need to reduce rifabutin dose to 150 mg/day.
Rifampin
Fluconazole AUC ↓ 23%–56%; no change in rifampin exposure.
Monitor for antifungal efficacy; may need to increase fluconazole dose.
Saquinavir
Saquinavir Cmax ↑ 56%, AUC ↑ 50% (studied with saquinavir 1200 mg TID). 

Fluconazole has not been studied with ritonavir-boosted saquinavir.
Significance unknown. No dosage adjustment needed.
Tipranavir/ritonavir
Tipranavir AUC ↑ 50%, Cmin ↑ 69%
Monitor for tipranavir-associated toxicities; fluconazole doses >200 mg/day not recommended.
Zidovudine
Fluconazole ↓ glucuronidation of zidovudine; fluconazole 400 mg/day results in zidovudine AUC ↑ 74%
Monitor for zidovudine-associated toxicities.
Itraconazole
Boceprevir
Concentrations of itraconazole and/or boceprevir may be ↑
Itraconazole dose should not exceed 200 mg/day. Monitor itraconazole concentration and adjust dose accordingly.
Clarithromycin
Possible bi-directional CYP3A4 inhibition and ↑ exposure of both drugs.
Monitor for toxicities of both itraconazole and clarithromycin. Monitor itraconazole concentration and adjust dose accordingly.  Alternatively, consider switching to azithromycin.
Efavirenz
Itraconazole AUC ↓ 39%, Cmin ↓ 44% in PK studies; No change to efavirenz AUC.

Failure to achieve therapeutic itraconazole concentrations has been reported.
Co-administration should be avoided if possible. If used in combination, monitor itraconazole concentrations and adjust dose accordingly.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Cobicistat, elvitegravir, and itraconazole serum concentration may be ↑
Avoid itraconazole >200 mg/day. Monitor itraconazole serum concentrations with co-administration.
Erythromycin
Potential for bi-directional inhibition of metabolism and ↑ serum concentrations of both drugs.
Monitor for toxicities of both drugs, potential for QT prolongation; monitor itraconazole concentrations and adjust dose accordingly, or consider alternative azole or macrolide.
Etravirine
Etravirine concentration may be ↑; Itraconazole concentration may be ↓. Extent of the interaction unknown.
Dose adjustment with itraconazole may be necessary depending on the presence of other concomitant ARV drugs (e.g., PIs). Monitor itraconazole concentrations and adjust dose accordingly.
Maraviroc
Potential for inhibition of maraviroc metabolism and ↑ in maraviroc concentration.
Decrease maraviroc dose to 150 mg twice daily. 
Micafungin
Itraconazole AUC ↑ 22%
No dose adjustment necessary.
Nevirapine
Itraconazole Cmax ↓ 38%, AUC ↓ 61%; nevirapine: no change
Monitor itraconazole concentrations and adjust accordingly dose; monitor therapeutic efficacy.
PIs
Potential for bi-directional CYP3A4 inhibition with ↑ exposure of both drugs.
Monitor for PI-associated toxicities; monitor itraconazole concentrations and itraconazole-associated toxicities 
Rifabutin
Itraconazole AUC ↓ 70%; potential for inhibition of rifabutin metabolism and ↑ rifabutin exposure.
Co-administration should be avoided, if possible. If the combination is to be used, monitor itraconazole concentrations and adjust dose accordingly; monitor for rifabutin-associated toxicities and consider monitoring rifabutin concentrations.
Rifampin
Itraconazole AUC ↓ 64%–88%; no change in rifampin concentrations.
Co-administration should be avoided. Consider alternative antifungal and/or antimycobacterial agent(s).
Rilpivirine
Potential ↑ in rilpivirine exposure or ↓ in itraconazole.
No dose adjustment for rilpivirine; monitor for rilpivirine-associated toxicities. Consider monitoring itraconazole concentration and adjust dose as necessary.
Telaprevir
Concentrations of itraconazole and telaprevir may be ↑
If co-administration is necessary, high doses of itraconazole (>200 mg/day) are not recommended. Monitor for toxicities to both drugs. Consider monitoring itraconazole concentration and adjust dose accordingly.
Mefloquine
Rifampin
Mefloquine AUC ↓ 68%.
Co-administration should be avoided, if possible. Use alternative anti-malarial drug or rifabutin.
Ritonavir
When studied with ritonavir 200 mg twice daily—ritonavir AUC ↓ 31%, Cmin ↓ 43%; no substantial change in mefloquine PK.

Effect on exposure of ritonavir-boosted PIs unknown.
Use mefloquine with caution with PIs.
Micafungin
Itraconazole
Itraconazole AUC ↑ 22%
No dose adjustment necessary.
Posaconazole
Atazanavir 
(+/- ritonavir)
With unboosted-atazanavir—atazanavir AUC ↑ 268%; with ritonavir-boosted atazanavir—atazanavir AUC ↑ 146%
Co-administration should be avoided, if possible; or monitor atazanavir concentrations and adjust doses accordingly; monitor for atazanavir-associated toxicities.
Boceprevir
Posaconazole concentration may be ↑
Use with caution, considering monitoring posaconazole concentration and adjust dose accordingly.
Efavirenz
Posaconazole AUC ↓ 50%, Cmax ↓ 45%
Co-administration should be avoided, if possible; or monitor posaconazole concentrations and adjust doses accordingly.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Cobicistat, elvitegravir, and posaconazole concentrations may be ↑
Monitor posaconazole concentration and adjust dose accordingly. 
Etravirine
Etravirine exposure may be ↑; posaconazole exposure unlikely to be affected.
No dose adjustment necessary; monitor for etravirine-associated toxicities.
Fosamprenavir
Amprenavir AUC ↓ 65%; posaconazole AUC ↓ 23% (studied without ritonavir boosting). 

No data for fosamprenavir/ritonavir.
Co-administration should be avoided, or monitor drug concentrations and adjust doses accordingly.
Rifabutin
Posaconazole AUC ↓ 49%; rifabutin AUC ↑ 72%.
Co-administration should be avoided, if possible, or monitor posaconazole and rifabutin concentrations and adjust doses accordingly; monitor clinical response.
Rifampin
Posaconazole exposure may be ↓ significantly.
Co-administration should be avoided, if possible. If used, monitor posaconazole concentrations and adjust dose accordingly.
Rilpivirine
Potential ↑ in rilpivirine concentrations.
Monitor for rilpivirine-associated toxicities.
Ritonavir
Ritonavir AUC ↑ 80%, Cmax ↑ 49%   No ritonavir dose adjustment necessary.
Telaprevir
Concentrations of posaconazole and telaprevir may be ↑
Use with caution with increased monitoring for posaconazole- or telaprevir-associated toxicities, including QT prolongation. Consider monitoring posaconazole level and adjust dose accordingly.
Proguanil
Atazanavir/ritonavir
Proguanil AUC ↓ 41%; no data with unboosted atazanavir.
Use with caution.
Efavirenz
Proguanil AUC ↓ 43%
Use with caution.
Lopinavir/ritonavir
Proguanil AUC ↓ 38%
Use with caution.
Ribavirin
Didanosine
↑ intracellular concentrations of ddA-TP
↑ serious didanosine-associated mitochondrial toxicities. Co-administration should be avoided.
Rifabutin
Atovaquone
Atovaquone AUC ↓ 34%; rifabutin AUC ↓ 19%.
Co-administration should be avoided. If used, monitor for therapeutic response.
Boceprevir
↑ in rifabutin concentrations are anticipated, while exposure of boceprevir may be ↓
Co-administration should be avoided, if possible. If used in combination, consider monitoring rifabutin concentration and adjust dose accordingly.
Clarithromycin
Clarithromycin AUC ↓ 44%; rifabutin AUC ↑ 76%–99%.
Consider reducing rifabutin dose, monitor for rifabutin-associated toxicities, Consider monitoring serum concentration and adjust dose accordingly; or switch to azithromycin.
Efavirenz
Rifabutin AUC ↓ 38%; no change in efavirenz exposure.
Increase rifabutin dose to 450–600 mg/day; effect of efavirenz + PI(s) on rifabutin concentrations has not been studied.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Elvitegravir AUC ↓ 21%, Cmin ↓ 67%; rifabutin active metabolite (25-O-desacetyl rifabutin) AUC ↑ 625%
Co-administration should be avoided, if possible. Consider using alternative antimycobacterial agent or alternative ARV drug. If used, consider rifabutin 150 mg once daily or every other day, consider monitoring rifabutin concentrations and adjust dose accordingly.
Etravirine
Etravirine Cmin ↓ 35% and AUC ↓ 37%; rifabutin AUC ↓ 17%.
Use standard rifabutin dose of 300 mg daily if not used with a ritonavir-boosted PI. In patients receiving a ritonavir-boosted PI, consider alternative agents if possible, or use serum concentration to guide dosing of rifabutin.
Fluconazole
Rifabutin AUC ↑ 80%; no effect on fluconazole exposure.
Monitor for rifabutin toxicity and consider monitoring rifabutin concentrations and adjust dose accordingly; may need to reduce rifabutin dose to 150 mg/day.
Itraconazole
Itraconazole AUC ↓ 70%; potential for ↑ rifabutin exposure.
Co-administration should be avoided, if possible. If the combination is to be used, monitor itraconazole and rifabutin concentrations and adjust doses accordingly. Monitor for rifabutin-associated toxicities.
Maraviroc
Concentration of maraviroc may be ↓
If used without another strong CYP3A4 inducer or inhibitor, maraviroc 300 mg BID. If used with a strong CYP3A4 inhibitor, use maraviroc 150 mg BID.
Nevirapine
Rifabutin AUC ↑ 17%, 25-O-desacetyl rifabutin AUC ↑ 24%; nevirapine Cmin ↓ 16%.
No dose adjustment necessary.
PI boosted by ritonavir
Significant ↑ in rifabutin concentrations.
Use rifabutin 150 mg daily or 300 mg 3 times/week. Consider monitoring rifabutin concentrations and adjust dose accordingly.
Posaconazole
Posaconazole AUC ↓ 49%; rifabutin AUC ↑ 72%.
Co-administration should be avoided, if possible, or monitor posaconazole and rifabutin concentrations and adjust doses accordingly; monitor clinical response.
Rilpivirine
Rilpivirine AUC ↓ 46%
Co-administration should be avoided.
Telaprevir
Concentrations of telaprevir may be ↓, while rifabutin concentrations may be ↑
Co-administration should be avoided.
Voriconazole
Voriconazole AUC ↓ 79%; rifabutin AUC ↑ 3-fold.
Co-administration should be avoided, if possible. If used in combination, monitor voriconazole and rifabutin concentrations and adjust dose accordingly. Monitor for clinical responses and toxicities.
Rifampin
Artemether/
lumefantrine
Artemether AUC ↓ 89%; DHA AUC ↓ 85%; lumefantrine AUC ↓ 68%
Co-administration should be avoided.
Atovaquone
Atovaquone concentrations ↓ 52%; rifampin concentrations ↑ 37%
Co-administration should be avoided.
Boceprevir
No PK data. Significant ↓ in boceprevir exposure is anticipated.
Co-administration should be avoided.
Caspofungin
Caspofungin Cmin ↓ 30%
Caspofungin dose should be increased to 70 mg/day.
Clarithromycin
Mean clarithromycin concentrations ↓ 87%
This combination should be avoided; consider switching to azithromycin.
Dapsone
Dapsone concentrations ↓ 7- to 10-fold and half-life (t1/2) ↓ from 24 to 11 hours.
Co-administration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.
Doxycycline
Doxycycline AUC ↓ by 59%
Potential for decreased doxycycline efficacy; monitor closely for therapeutic failure.
Efavirenz
Efavirenz AUC ↓ 22%, Cmin ↓ 25%; no change in rifampin exposure.
Maintain efavirenz dose at 600 mg once daily and monitor for virologic response. Some clinicians suggest increasing efavirenz dose to 800 mg per day in patients >60 kg.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Cobicistat and elvitegravir concentrations may be significantly ↓
Co-administration should be avoided. Consider an alternative antimycobacterial agent or alternative antiretroviral drug regimen.
Etravirine
Potential significant ↓ in etravirine concentration.
Co-administration should be avoided.
Fluconazole
Fluconazole AUC ↓ by 23%–56%; no change in rifampin exposure.
Monitor for antifungal efficacy, may need to increase fluconazole dose.
Itraconazole
Itraconazole AUC ↓ 64%–88%; no change in rifampin concentrations.
Co-administration should be avoided. Consider alternative antifungal and/or antimycobacterial agent(s).
Maraviroc
Maraviroc AUC ↓ 63%, Cmin decreased 67%
Increase maraviroc dose to 600 mg twice daily or use alternative antimycobacterial agent.
Nevirapine
Nevirapine AUC ↓ by >50%, Cmin ↓ 21-37%; no change in rifampin concentrations.
This combination should be avoided if possible. If adding nevirapine to rifampin is necessary, initiate nevirapine at 200 mg twice daily (i.e., no lead-in period). Do not use nevirapine extended-release formulation.
Posaconazole
Posaconazole concentrations may be ↓ significantly.
Co-administration should be avoided if possible. If used, monitor posaconazole concentrations and adjust dose if necessary.
PI (+/- ritonavir-boosting)
Significantly ↓ PI exposure (>75%) despite ritonavir boosting
Co-administration should be avoided.
Raltegravir
Raltegravir AUC ↓ 40%, Cmin ↓ 60%
Increase raltegravir dose to 800 mg PO twice daily, monitor for antiretroviral efficacy, or switch to rifabutin.
Rilpivirine
Rilpivirine AUC ↓ 80%
Co-administration should be avoided.
Telaprevir
Telaprevir AUC ↓ 92%
Co-administration should be avoided.
Voriconazole
Voriconazole AUC ↓ 96%
Co-administration should be avoided.
Zidovudine
Zidovudine AUC ↓ 48%
Monitor for zidovudine efficacy.
Telaprevir
Atazanavir/ritonavir
Telaprevir AUC ↓ 20%, Cmin ↓ 15%; atazanavir Cmin ↑ 85%
No dosage adjustment necessary.
Clarithromycin
Concentrations of telaprevir and clarithromycin may be ↑ during co-administration.
Use with caution and monitor for adverse events, including QT prolongation.

Reduce clarithromycin dose during concomitant use with telaprevir in patients with impaired renal function. Consider switching to azithromycin.
Darunavir/ritonavir
Telaprevir AUC ↓ 35%, Cmin ↓ 32%; darunavir AUC and Cmin ↓ 40%.
Co-administration should be avoided.
Efavirenz Telaprevir AUC ↓ 26%; Cmin ↓ 47%
Increase telaprevir dose to 1125 mg every 8 hours.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
No data. Potential for bi-directional interactions. 
Co-administration should be avoided. 
Erythromycin
Concentrations of telaprevir and erythromycin may be ↑ during co-administration.
Use with caution and monitor for adverse events, including QT prolongation.
Fosamprenavir/ ritonavir
Telaprevir AUC ↓ 32%, Cmin ↓ 30%; amprenavir AUC ↓ 47%, Cmin ↓ 56%
Co-administration should be avoided.
Itraconazole
Concentrations of itraconazole and telaprevir may be ↑
If co-administration is necessary, high doses of itraconazole (>200 mg/day) are not recommended. Monitor for toxicities to both drugs. Consider monitoring itraconazole concentration and adjust dose accordingly.
Lopinavir/ritonavir
Telaprevir AUC ↓ 54%, Cmin ↓ 52%
Co-administration should be avoided.
Posaconazole
Concentrations of posaconazole and telaprevir may be ↑
Use with caution and monitor for posaconazole-associated toxicities, including QT prolongation. Consider monitoring posaconazole concentration and adjust dose accordingly.
Rifabutin
Concentrations of telaprevir may be ↑, while rifabutin concentrations may be ↑
Co-administration should be avoided
Rifampin
Telaprevir AUC ↓ 92%
Co-administration should be avoided
Tenofovir
Tenofovir Cmax, AUC, and Cmin ↑ 30%–41%
Monitor for tenofovir-associated toxicities.
Voriconazole
Potential interaction; magnitude and direction unknown.
Co-administration should be avoided unless benefit is considered to outweigh risks; monitor for voriconazole-associated toxicities, including QT prolongation. Consider monitoring voriconazole concentration and adjust dose accordingly.
Tenofovir















Acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir
Potential for competitive active tubular secretion with these antiviral drugs.
Monitor for efficacy and toxicities of the antiviral agents and tenofovir.
Atazanavir
Atazanavir AUC ↓ 25%, Cmin ↓ 40%; tenofovir AUC ↑ 24%.
Atazanavir dose should be 300 mg daily given with ritonavir 100 mg daily when co-administered with tenofovir; monitor for tenofovir-associated toxicities.
Darunavir/ritonavir
Tenofovir AUC ↑ 22%, Cmin ↑ 37%
Monitor for tenofovir-associated toxicities.
Didanosine
Didanosine AUC and Cmax ↑ 48%–60%
Co-administration should be avoided. If co-administered, didanosine dose should be decreased to 250 mg once daily.
Lopinavir/ritonavir
Tenofovir AUC ↑ 34%
Monitor for tenofovir-associated toxicities.
Telaprevir
Tenofovir Cmax, AUC and Cmin ↑ 30–41%
Monitor for tenofovir-associated toxicities.
Voriconazole
Boceprevir
Concentrations of voriconazole may be ↑
Use with caution. Consider monitoring voriconazole concentration and adjust dose accordingly.
Efavirenz
Voriconazole Cmax ↓ 36–61%, AUC ↓ 55–77%; efavirenz Cmax ↑ 38%, AUC ↑ 44%
Increase voriconazole maintenance dose to 400 mg q12h and decrease efavirenz to 300 mg daily. Consider monitoring voriconazole and/or efavirenz concentration and adjust doses accordingly.
Elvitegravir/cobicistat/
tenofovir/emtricitabine
Voriconazole, elvitegravir, and cobicistat concentrations may be ↑
Monitor for voriconazole-associated toxicities. Consider monitoring voriconazole concentration and adjust dose accordingly.
Etravirine
Voriconazole AUC ↑ 14%, Cmin ↑ 23%; etravirine AUC ↑ 36%, Cmin ↑ 52%
No dose adjustment necessary; monitor for etravirine-associated toxicities. Consider monitoring voriconazole concentration and adjust dose accordingly.
Nevirapine
Potential for ↓ voriconazole concentrations; however, no formal interaction data are available.
Monitor for therapeutic efficacy of voriconazole; consider monitoring voriconazole concentrations and adjust dose accordingly.
PI boosted with ritonavir
Voriconazole AUC ↓ 39% (studied with ritonavir 100 mg BID). No interaction data for individual boosted PIs; however, potential for ↑ PI concentrations and ↓ voriconazole concentrations.
Consider monitoring voriconazole concentrations and adjust dose accordingly; monitor for PI-associated toxicities.
Rifabutin
Voriconazole AUC ↓ 79%; rifabutin AUC ↑ 3-fold.
Co-administration should be avoided, if possible; if used in combination, monitor voriconazole and rifabutin concentrations, clinical responses, and toxicities from both drugs.
Rifampin
Voriconazole AUC ↓ 96%
Co-administration should be avoided.
Rilpivirine
No PK data. Possible ↑ rilpivirine concentration
Monitor efficacies and toxicities of both drugs. Consider monitoring voriconazole concentration and adjust dose accordingly.
Telaprevir
Potential interaction; magnitude and direction unknown.
Co-administration should be avoided unless benefit is considered to outweigh risks; monitor for voriconazole-associated toxicities, including QT prolongation. Consider monitoring voriconazole concentration and adjust dose accordingly.
Key to Acronyms: ARV = antiretroviral; AUC = area under the curve; BID = twice daily = Cmax = maximum concentration; Cmin = minimum concentration; CrCl = creatinine clearance; CYP3A4 = Cytochrome P450 3A4; ddA-TP = dideoxyadenosine triphosphate; DHA = dihydroartemisinin; PI = protease inhibitor; PK = pharmacokinetic; TID = three times a day