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

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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

Last Updated: September 22, 2017; Last Reviewed: September 22, 2017

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

This table lists the known or suspected/predicted pharmacokinetic interactions between drugs used for the treatment or prevention of HIV-associated opportunistic infections (OIs). Many of the drugs listed in this table may also interact with antiretroviral drugs. Clinicians should refer to the drug interaction tables in the most current Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents to assess interaction potentials between OI drugs and antiretroviral therapy (ART).

Throughout the table, three recommendations are commonly used when concomitant administration of two drugs may lead to untoward consequences. The rationale for these recommendations are summarized below:

"Do not co-administer"
Indicates there is either strong evidence or strong likelihood that the drug-drug interaction cannot be managed with a dose modification of one or both drugs, and will/may result in either:

  1. Increase in concentrations of one or both drugs, which may lead to excessive risk of toxicity; or
  2. Decrease in concentrations of one or both drugs, which may render one or both drugs ineffective.

"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 acceptable therapeutic options that provide a more favorable benefit-to-risk ratio. If other more favorable options exist, clinicians are advised to consider changing components of the regimen to accommodate a safer or more effective regimen.

"Use with caution"
Drug combinations are recommended to be used with caution when:

  1. Pharmacokinetic studies have shown a moderate degree of interaction of unknown clinical significance; or
  2. Based on the known metabolic pathway of the two drugs, there is a potential for pharmacokinetic interaction of unknown clinical significance.

Rifamycin-Related Interactions
Rifamycins are potent inducers of Phase I and Phase II drug metabolizing reactions. Daily doses of rifampin are well studied, and induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1200 mg) appear to produce the same maximum induction, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin is about 40% as potent a CYP3A4 inducer as rifampin, but this can vary by substrate and enzymatic reaction. In general, daily rifapentine (for active tuberculosis [TB] disease) is at least as potent an inducer as rifampin. However, the potential of drug interactions with once weekly rifapentine (prescribed with isoniazid for latent TB infection) is not well studied, but may result in reduction of exposure of drugs that are CYP3A4 substrates. When a rifamycin is used with a potential interacting drug, close monitoring for clinical efficacy of the other agent is advised.

Table 5. Significant Pharmacokinetic Interactions for Drugs Used to Treat or Prevent Opportunistic Infections
Drug Interacting Agent Effect on Primary and/or Concomitant Drug Concentrations
 Recommendations
Artemether/
Lumefantrine 		Clarithromycin ↑ Lumefantrine expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Artemether and lumefantrine possible Use with caution. Monitor for artemether- and lumefantrine-associated toxicities.
Erythromycin ↑ Lumefantrine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Lumefantrine possible Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Itraconazole ↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Posaconazole ↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Rifabutina ↓ Artemether, DHA, and lumefantrine expected Use with caution. Monitor for antimalarial efficacy.
Rifampina ↓ Artemether, DHA, and lumefantrine AUC by 89%, 85%, and 68% respectively Do not co-administer.
Rifapentinea ↓ Artemether, DHA, and lumefantrine expected Do not co-administer.
Voriconazole ↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Atovaquone
 Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↔ Atovaquone (based on data from atovaquone and atazanavir/ritonavir interaction) No dosage adjustment necessary.
Doxycycline Atovaquone conc. ↓ by approximately 40% with tetracycline.

No interaction study with doxycycline. 		Dose adjustment not established; if co-administered, take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifabutina Atovaquone Css↓ 34%; rifabutin Css↓ 19% Dose adjustment not established; if co-administered, take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifampina Atovaquone Css↓ 52%; rifampin Css↑ 37% Do not co-administer.
Rifapentinea ↓ Atovaquone expected Do not co-administer.
Bedaquiline
 Clarithromycin ↑ Bedaquiline expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Bedaquiline expected Co-administration should be avoided, if possible. Consider alternative HCV regimen.
Erythromycin ↑ Bedaquiline possible Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Bedaquiline possible Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Itraconazole ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Posaconazole ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Rifabutina ↓ Bedaquiline possible If co-administered, monitor for bedaquiline efficacy.
Rifampina Bedaquiline AUC ↓ 53% Do not co-administer.
Rifapentinea Bedaquiline AUC ↓ 55% (with daily rifapentine) Do not co-administer.
Voriconazole ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Caspofungin
 Rifabutina No data.

↓ Caspofungin possible. 		Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day.
Rifampina Caspofungin Cmin ↓ 30% Caspofungin dose should be increased to 70 mg/day.
Rifapentinea No data.

↓ Caspofungin possible. 		Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day.
Chloroquine
 Clarithromycin ↑ Chloroquine expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Erythromycin ↑ Chloroquine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Chloroquine possible Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Itraconazole ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Posaconazole ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Rifabutina ↓ Chloroquine expected Monitor for chloroquine efficacy.
Rifampina ↓ Chloroquine expected Monitor for chloroquine efficacy.
Rifapentinea ↓ Chloroquine expected Monitor for chloroquine efficacy.
Voriconazole ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Clarithromycin
 Artemether/ Lumefantrine ↑ Lumefantrine expected Co-administration should be avoided if possible. Consider azithromycin in place of clarithromycin.
Bedaquiline ↑ Bedaquiline expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Chloroquine ↑ Chloroquine expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir ↑ Daclatasvir expected ↓ Daclatasvir dose to 30 mg once daily.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Clarithromycin and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Elbasvir/
Grazoprevir 		↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity. Consider azithromycin in place of clarithromycin.
Fluconazole Clarithromycin AUC ↑ 18%, Cmin↑ 33% No dose adjustment necessary in patients with normal renal function. Monitor for clarithromycin toxicity.
Itraconazole ↑ Itraconazole and clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If co-administered, monitor for toxicities of both itraconazole and clarithromycin (e.g., QT prolongation), consider monitoring itraconazole conc. and adjust dose accordingly.
Mefloquine ↑ Mefloquine expected Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for mefloquine toxicity (e.g., QT prolongation).
Posaconazole ↑ Clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Quinine ↑ Quinine expected; ↑ clarithromycin possible Do not co-administer. Consider azithromycin in place of clarithromycin.
Rifabutina Clarithromycin AUC ↓ by 44%; 14-OH AUC ↑ 57%; rifabutin AUC ↑ 76% to 99%; des-Rbt AUC ↑ 375% Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin concentrations, and monitoring for rifabutin-associated toxicities (e.g., uveitis).
Rifampina Mean clarithromycin conc. ↓ 87%; rifampin AUC ↑ 60% Do not co-administer. Use azithromycin in place of clarithromycin.
Rifapentinea ↓ Clarithromycin expected; ↑ 14-OH and rifapentine expected Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for rifapentine-associated toxicities, consider monitoring clarithromycin and rifapentine concentrations and adjusting doses accordingly.
Simeprevir ↑ Simeprevir expected Do not co-administer. Consider azithromycin in place of clarithromycin.
Voriconazole ↑ Clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir Clarithromycin ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Erythromycin ↑ Daclatasvir possible No dosage adjustment. Monitor for daclatasvir-associated toxicities.
Fluconazole ↑ Daclatasvir possible No dosage adjustment. Monitor for daclatasvir-associated toxicities.
Itraconazole ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Posaconazole ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Rifabutina ↓ Daclatasvir expected Dose not established. Consider increasing daclatasvir dose to 90 mg once daily and monitor for therapeutic efficacy.
Rifampina Daclatasvir AUC ↓ 79% Do not co-administer.
Rifapentinea ↓ Daclatasvir expected Dose not established. Consider increasing daclatasvir dose to 90 mg once daily and monitor for therapeutic efficacy.
Simeprevir Simeprevir AUC ↑ 44%; daclatasvir AUC ↑ 96% No dosage adjustment. Monitor for simeprevir and daclatasvir-associated toxicities.
Voriconazole ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dapsone
 Rifabutina Dapsone AUC ↓ 27% to 40% Co-administration should be avoided if possible. Consider alternatives for dapsone.
Rifampina Dapsone conc. ↓ 7- to 10-fold and t1/2 ↓ from 24 to 11 hours Co-administration should be avoided, if possible. Consider alternatives for dapsone.
Rifapentinea ↓ Dapsone expected Co-administration should be avoided, if possible. Consider alternatives for dapsone.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir
 Artemether/ Lumefantrine ↑ Artemether and lumefantrine possible Use with caution. Monitor for artemether- and lumefantrine-associated toxicities.
Atovaquone ↔ Atovaquone (based on data from atovaquone and ritonavir/atazanavir interaction) No dosage adjustment necessary.
Bedaquiline ↑ Bedaquiline expected Co-administration should be avoided, if possible. Consider alternative HCV regimen.
Clarithromycin ↑ Clarithromycin and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Erythromycin ↑ Erythromycin expected and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Co-administration should be avoided, if possible. Consider azithromycin in place of erythromycin.
Itraconazole ↑ Itraconazole and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole levels. Monitor for itraconazole and HCV regimen-associated toxicities.
Posaconazole ↑ Posaconazole and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Monitor for posaconazole and HCV regimen-associated toxicities. Monitor posaconazole conc. and adjust dose if necessary.
Rifabutina ↑ Rifabutin expected; ↓ paritaprevir possible Co-administration should be avoided if possible. With co-administration, decrease rifabutin dose to 150 mg/day and monitor rifabutin conc. Monitor HCV regimen for efficacy.
Rifampina ↓ Paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not co-administer.
Rifapentinea ↓ Paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not co-administer.
Voriconazole Voriconazole AUC ↓ 39% (with ritonavir); ↑ paritaprevir expected Co-administer only if the benefits outweigh the risk. Monitor voriconazole conc. to guide dosage adjustments.
Doxycycline Atovaquone Atovaquone concentration ↓ by approximately 40% with tetracycline.

No interaction study with doxycycline. 		Dose adjustment not established; if co-administered, take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifabutina No data.

↓ Doxycycline possible. 		Monitor closely for doxycycline efficacy or consider alternative therapy.
Rifampina Doxycycline AUC ↓ by 59% Use with caution. Monitor closely for doxycycline efficacy or consider alternative therapy.
Rifapentinea No data.

↓ Doxycycline possible.		 Monitor closely for doxycycline efficacy or consider alternative therapy.
Elbasvir/
Grazoprevir		 Clarithromycin ↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity. Consider azithromycin in place of clarithromycin.
Itraconazole ↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.
Posaconazole ↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.
Rifabutina ↓ Elbasvir and grazoprevir possible Co-administration should be avoided if possible. Consider alternative HCV regimen.
Rifampina Grazoprevir AUC ↓ 7%, C24 ↓ 90%; ↓ elbasvir expected Do not co-administer.
Rifapentinea ↓ Elbasvir and grazoprevir possible Do not co-administer.
Voriconazole ↑ Elbasvir and grazoprevir expected Co-administration should be avoided if possible. If co-administered, monitor closely for hepatotoxicity.
Erythromycin Artemether/
Lumefantrine 		↑ Lumefantrine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Bedaquiline ↑ Bedaquiline possible Do not co-administer. Consider azithromycin in place of erythromycin.
Chloroquine ↑ Chloroquine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Daclatasvir ↑ Daclatasvir possible No dosage adjustment. Monitor for daclatasvir-associated toxicities.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Erythromycin and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Co-administration should be avoided, if possible. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Itraconazole Itraconazole AUC ↑ 36%; ↑ erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Mefloquine ↑ Mefloquine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Posaconazole ↑ Erythromycin expected Do not co-administer. Consider azithromycin in place of erythromycin.
Quinine ↑ Quinine expected; ↑ erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Rifabutina ↓ Erythromycin possible; ↑ rifabutin possible Use with caution. Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy or rifabutin toxicities (e.g., uveitis).
Rifampina ↓ Erythromycin expected Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy.
Rifapentinea ↓ Erythromycin expected Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy.
Simeprevir Simeprevir AUC ↑ 647%, Cmin ↑ 1,174%; erythromycin AUC ↑ 90%, Cmin ↑ 208% Do not co-administer. Consider azithromycin in place of erythromycin
Voriconazole ↑ Erythromycin expected Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole
 Artemether/
Lumefantrine 		↑ Lumefantrine possible Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Bedaquiline ↑ Bedaquiline possible Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Chloroquine ↑ Chloroquine possible Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Clarithromycin Clarithromycin AUC ↑ 18%, Cmin↑ 33% No dose adjustment necessary in patients with normal renal function. Monitor for clarithromycin toxicity.
Daclatasvir ↑ Daclatasvir possible No dosage adjustment. Monitor for daclatasvir-associated toxicities.
Erythromycin ↑ Erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Mefloquine ↑ Mefloquine possible Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Quinine ↑ Quinine expected; ↑ fluconazole possible Co-administration should be avoided, if possible. If co-administered, monitor for quinine and fluconazole toxicity (e.g., QT prolongation).
Rifabutina Rifabutin AUC ↑ 80%; ↔ fluconazole Use with caution. Monitor for rifabutin-associated toxicities (e.g., uveitis). Consider monitoring rifabutin conc.; may need to lower rifabutin dose to 150 mg/day.
Rifampina Fluconazole AUC ↓ 23% to 56% Monitor for antifungal efficacy; may need to raise fluconazole dose.
Rifapentinea ↓ Fluconazole expected Monitor for antifungal efficacy; may need to raise fluconazole dose.
Simeprevir ↑ Simeprevir possible Do not co-administer.
Itraconazole
 Artemether/
Lumefantrine 		↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Bedaquiline ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Chloroquine ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Clarithromycin ↑ Itraconazole and clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If co-administered, monitor for toxicities of both itraconazole and clarithromycin (e.g., QT prolongation), consider monitoring itraconazole conc. and adjusting dose accordingly.
Daclatasvir ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Itraconazole and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole levels. Monitor for itraconazole and HCV regimen-associated toxicities.
Elbasvir/
Grazoprevir 		↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.
Erythromycin Itraconazole AUC ↑ 36%; ↑ erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Mefloquine ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Quinine ↑ Quinine expected; ↑ itraconazole possible Co-administration should be avoided, if possible. If used concomitantly, monitor for quinine and itraconazole toxicity (e.g, QT prolongation), monitor itraconazole conc. and adjust dose accordingly.
Rifabutina Itraconazole AUC ↓ 70%; ↑ rifabutin expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifampina Itraconazole AUC ↓ 64% to 88% Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea ↓ Itraconazole expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Simeprevir ↑ Simeprevir expected Do not co-administer.
Ledipasvir/
Sofosbuvir		 Rifabutina ↓ Ledipasvir and sofosbuvir expected Do not co-administer.
Rifampina Ledipasvir AUC ↓ 59%; sofosbuvir AUC ↓ 72% Do not co-administer.
Rifapentinea ↓ Ledipasvir and sofosbuvir expected Do not co-administer.
Simeprevir Ledipasvir AUC ↑ 92%; simeprevir AUC ↑ 116% Do not co-administer.
TAF Ledipasvir AUC ↑ 79% No dosage adjustment.
TDF TDF AUC ↑ 98% (when given with EFV/FTC)

TDF AUC ↑ 40% (when given with RPV/FTC)

When used with EVG/c/TDF/FTC, ↑ TDF and ledipasvir expected 		Monitor for TDF-associated toxicities when coadministered with PI/r, PI/c, or EFV. Consider an alternative to PI/r plus TDF/FTC or alternative HCV therapy if possible.

Do not co-administer with EVG/c/TDF/FTC.

Consider TAF in place of TDF.
Linezolid Rifabutina No data.

↓ Linezolid possible. 		Monitor for linezolid efficacy.
Rifampina Linezolid AUC ↓ 32% Monitor for linezolid efficacy.
Rifapentinea No data.

↓ Linezolid possible. 		Monitor for linezolid efficacy.
Mefloquine Clarithromycin ↑ Mefloquine expected Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for mefloquine toxicity (e.g., QT prolongation).
Erythromycin ↑ Mefloquine possible Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Mefloquine possible Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Itraconazole ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Posaconazole ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Rifabutina ↓ Mefloquine possible Monitor for mefloquine efficacy.
Rifampina Mefloquine AUC ↓ 68% Do not co-administer. Use alternative antimalarial drug or rifabutin.
Rifapentinea ↓ Mefloquine expected Do not co-administer. Use alternative antimalarial drug or rifabutin.
Voriconazole ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Posaconazole
 Artemether/
Lumefantrine 		↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Bedaquiline ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Chloroquine ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Clarithromycin ↑ Clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Posaconazole and paritaprevir expected; ↑ ombitasvir and dasabuvir possible Monitor for posaconazole and HCV regimen-associated toxicities. Monitor posaconazole conc. and adjust dose if necessary.
Elbasvir/
grazoprevir		 ↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.
Erythromycin ↑ Erythromycin expected Do not co-administer. Consider azithromycin in place of erythromycin.
Mefloquine ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Quinine ↑ Quinine expected; ↑ posaconazole possible Co-administration should be avoided, if possible. If co-administered, monitor for quinine toxicities (e.g., QT prolongation).
Rifabutina Posaconazole AUC ↓ 49%; rifabutin AUC ↑ 72% Co-administration should be avoided, if possible. If co-administered, monitor posaconazole and rifabutin conc. and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities (e.g., uveitis).
Rifampina ↓ Posaconazole expected Co-administration should be avoided, if possible. If co-administered, monitor posaconazole conc. and adjust dose accordingly; monitor for clinical response.
Rifapentinea ↓ Posaconazole expected Co-administration should be avoided, if possible, or monitor posaconazole conc. and adjust dose accordingly; monitor clinical response.
Simeprevir ↑ Simeprevir expected Do not co-administer.
Quinine
 Clarithromycin ↑ Quinine expected; ↑ clarithromycin possible Do not co-administer. Consider azithromycin in place of clarithromycin.
Erythromycin ↑ Quinine expected; ↑ erythromycin possible Do not co-administer. Consider azithromycin in place of erythromycin.
Fluconazole ↑ Quinine expected; ↑ fluconazole possible Co-administration should be avoided, if possible. If co-administered, monitor for quinine and fluconazole toxicity (e.g., QT prolongation).
Itraconazole ↑ Quinine expected; ↑ itraconazole possible Co-administration should be avoided, if possible. If used concomitantly, monitor for quinine and itraconazole toxicity (e.g., QT prolongation), monitor itraconazole conc. and adjust dose accordingly.
Posaconazole ↑ Quinine expected; ↑ posaconazole possible Co-administration should be avoided, if possible. If co-administered, monitor for quinine toxicities (e.g., QT prolongation).
Rifabutina ↓ Quinine possible; ↑ rifabutin possible Monitor for quinine efficacy. Monitor rifabutin conc. and toxicity (e.g., uveitis).
Rifampina Quinine AUC ↓ 75% to 85% Do not co-administer.
Rifapentinea ↓ Quinine expected Do not co-administer.
Voriconazole ↑ Quinine expected Co-administration should be avoided, if possible. If co-administered, monitor for quinine toxicities (e.g., QT prolongation).
Rifabutina Artemether/
Lumefantrine 		↓ Artemether, DHA, and lumefantrine expected Use with caution. Monitor for antimalarial efficacy.
Atovaquone Atovaquone Css ↓ 34%; rifabutin Css ↓ 19% Dose adjustment not established; if co-administered, take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Bedaquiline ↓ Bedaquiline possible If co-administered, monitor for bedaquiline efficacy.
Caspofungin No data.
↓ Caspofungin possible. 		Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day.
Chloroquine ↓ Chloroquine expected Monitor for chloroquine efficacy.
Clarithromycin Clarithromycin AUC ↓ by 44%; 14-OH AUC ↑ 57%; rifabutin AUC ↑ 76% to 99%; des-Rbt AUC ↑ 375% Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin conc., and monitoring for rifabutin-associated toxicities (e.g., uveitis).
Daclatasvir ↓ Daclatasvir expected Dose not established. Consider increase daclatasvir dose to 90 mg once daily and monitoring for therapeutic efficacy.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↑ Rifabutin expected; ↓ paritaprevir possible Co-administration should be avoided if possible. With co-administration, decrease rifabutin dose to 150 mg/day and monitor rifabutin conc. Monitor HCV regimen for efficacy.
Dapsone Dapsone AUC ↓ 27% to 40% Co-administration should be avoided, if possible. Consider alternatives for dapsone.
Doxycycline No data.
↓ Doxycycline possible. 		Monitor closely for doxycycline efficacy or consider alternative therapy.
Elbasvir/
Grazoprevir		 ↓ Elbasvir and grazoprevir possible Co-administration should be avoided, if possible. Consider alternative HCV regimen.
Erythromycin ↓ Erythromycin possible; ↑ rifabutin possible Use with caution. Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy or rifabutin toxicities (e.g., uveitis).
Fluconazole Rifabutin AUC ↑ 80%; ↔ fluconazole Use with caution. Monitor for rifabutin-associated toxicities (e.g., uveitis). Consider monitoring rifabutin conc.; may need to lower rifabutin dose to 150 mg/day.
Itraconazole Itraconazole AUC ↓ 70%; ↑ rifabutin expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Ledipasvir/
Sofosbuvir 		↓ Ledipasvir and sofosbuvir expected Do not co-administer.
Linezolid No data.

↓ Linezolid possible. 		Monitor for linezolid efficacy.
Mefloquine ↓ Mefloquine possible Monitor for mefloquine efficacy.
Posaconazole Posaconazole AUC ↓ 49%; rifabutin AUC ↑ 72% Co-administration should be avoided, if possible. If co-administered, monitor posaconazole and rifabutin conc. and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities (e.g., uveitis).
Quinine ↓ Quinine possible; ↑ rifabutin possible Monitor for quinine efficacy. Monitor rifabutin conc. and toxicity (e.g., uveitis).
Simeprevir ↓ Simeprevir expected Do not co-administer.
Sofosbuvir ↓ Sofosbuvir expected Do not co-administer.
TAF ↓ TAF expected Do not co-administer
Velpatasvir/
Sofosbuvir 		↓ Velpatasvir and sofosbuvir expected Do not co-administer.
Voriconazole Voriconazole AUC ↓ 79%; rifabutin AUC ↑4-fold Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s). If coadministration is absolutely necessary, monitor voriconazole and rifabutin conc. to guide therapy.
Rifampina
 Artemether/
Lumefantrine 		↓ Artemether, DHA, and lumefantrine AUC by 89%, 85%, and 68%, respectively Do not co-administer.
Atovaquone Atovaquone Css ↓ 52% and t1/2 ↓ 40%; rifampin Css ↑ 37% Do not co-administer.
Bedaquiline Bedaquiline AUC ↓ 53% Do not co-administer.
Caspofungin Caspofungin Cmin ↓ 30% Caspofungin dose should be ↑ to 70 mg/day.
Chloroquine ↓ Chloroquine expected Monitor for chloroquine efficacy.
Clarithromycin Mean clarithromycin conc. ↓ 87%; rifampin AUC ↑ 60% Do not co-administer. Use azithromycin in place of clarithromycin.
Daclatasvir Daclatasvir AUC ↓ 79% Do not co-administer.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↓ Paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not co-administer.
Dapsone Dapsone conc. ↓ 7- to 10-fold and t1/2 ↓ from 24 to 11 hours Co-administration should be avoided, if possible. Consider alternatives for dapsone.
Doxycycline Doxycycline AUC ↓ by 59% Use with caution. Monitor closely for doxycycline efficacy or consider alternative therapy.
Elbasvir/
Grazoprevir		 Grazoprevir AUC ↓ 7%, C24 ↓ 90%; ↓ elbasvir expected Do not co-administer.
Erythromycin ↓ Erythromycin expected Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy.
Fluconazole Fluconazole AUC ↓ by 23% to 56% Monitor for antifungal efficacy. May need to increase fluconazole dose.
Itraconazole Itraconazole AUC ↓ 64% to 88% Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Ledipasvir/
Sofosbuvir 		Ledipasvir AUC ↓ 59%; sofosbuvir AUC ↓ 72% Do not co-administer.
Linezolid Linezolid AUC ↓ 32% Monitor for linezolid efficacy.
Mefloquine Mefloquine AUC ↓ 68% Do not co-administer. Use alternative antimalarial drug or rifabutin.
Posaconazole ↓ Posaconazole expected Co-administration should be avoided, if possible. If co-administered, monitor posaconazole conc. and adjust dose accordingly; monitor for clinical response.
Quinine Quinine AUC ↓ 75% to 85% Do not co-administer.
Simeprevir Simeprevir Cmin ↓92%, AUC ↓ 48%, Do not co-administer.
Sofosbuvir Sofosbuvir AUC ↓ 72% Do not co-administer.
TAF ↓ TAF expected Do not co-administer.
Velpatasvir/
Sofosbuvir 		Velpatasvir AUC ↓ 82%; sofosbuvir AUC ↓ 72% Do not co-administer.
Voriconazole Voriconazole AUC ↓ 96% Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea Artemether/
Lumefantrine 		↓ Artemether, DHA, lumefantrine expected Do not co-administer.
Atovaquone ↓ Atovaquone expected Do not co-administer.
Bedaquiline Bedaquiline AUC ↓ 55% (with daily rifapentine) Do not co-administer.
Caspofungin No data.

↓ Caspofungin possible. 		Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day.
Chloroquine ↓ Chloroquine expected Monitor for chloroquine efficacy.
Clarithromycin ↓ Clarithromycin expected; ↑ 14-OH and rifapentine expected Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for rifapentine-associated toxicities, consider monitoring clarithromycin and rifapentine conc. and adjusting doses accordingly.
Daclatasvir ↓ Daclatasvir expected Dose not established. Consider increasing daclatasvir dose to 90 mg once daily and monitoring for therapeutic efficacy
Dapsone ↓ Dapsone expected Co-administration should be avoided, if possible. Consider alternatives for dapsone.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		↓ Paritaprevir, ritonavir, ombitasvir, and dasabuvir expected. Do not co-administer.
Doxycycline No data.

↓ Doxycycline possible. 		Monitor closely for doxycycline efficacy or consider alternative therapy.
Elbasvir/
Grazoprevir		 ↓ Elbasvir and grazoprevir possible Do not co-administer.
Erythromycin ↓ Erythromycin expected Consider azithromycin in place of erythromycin. If co-administered, monitor for erythromycin efficacy.
Fluconazole ↓ Fluconazole expected Monitor for antifungal efficacy; may need to ↑ fluconazole dose.
Itraconazole ↓ Itraconazole expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Ledipasvir/
Sofosbuvir 		↓ Ledipasvir and sofosbuvir expected Do not co-administer.
Linezolid No data.

↓ Linezolid possible. 		Monitor for linezolid efficacy.
Mefloquine ↓ Mefloquine expected Do not co-administer. Use alternative antimalarial drug or rifabutin.
Posaconazole ↓ Posaconazole expected Co-administration should be avoided, if possible, or monitor posaconazole conc. and adjust dose accordingly; monitor for clinical response.
Quinine ↓ Quinine expected Do not co-administer.
Simprevir ↓ Simeprevir expected Do not co-administer.
Sofosbuvir ↓ Sofosbuvir expected Do not co-administer.
TAF ↓ TAF expected Do not co-administer.
Velpatasvir/
Sofosbuvir 		↓ Velpatasvir and sofosbuvir expected Do not co-administer.
Voriconazole ↓ Voriconazole expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Simeprevir
 Clarithromycin ↑ Simeprevir expected Do not co-administer. Consider azithromycin in place of clarithromycin.
Daclatasvir Simeprevir AUC ↑ 44%; daclatasvir AUC ↑ 96% No dosage adjustment. Monitor for simeprevir- and daclatasvir-associated toxicities.
Erythromycin Simeprevir AUC ↑ 647%, Cmin ↑ 1,174%; erythromycin AUC ↑ 90%, Cmin ↑ 208% Do not co-administer. Consider azithromycin in place of clarithromycin
Fluconazole ↑ Simeprevir possible Do not co-administer.
Itraconazole ↑ Simeprevir expected Do not co-administer.
Ledipasvir/
Sofosbuvir 		Ledipasvir AUC ↑ 92%; simeprevir AUC ↑ 116% Do not co-administer.
Posaconazole ↑ Simeprevir expected Do not co-administer.
Rifabutina ↓ Simeprevir expected Do not co-administer.
Rifampina Simeprevir Cmin ↓ 92%, AUC ↓ 48% Do not co-administer.
Rifapentinea ↓ Simeprevir expected Do not co-administer.
Voriconazole ↑ Simeprevir expected Do not co-administer.
Sofosbuvir Rifabutina ↓ Sofosbuvir expected Do not co-administer.
Rifampina Sofosbuvir AUC ↓ 72% Do not co-administer.
Rifapentinea ↓ Sofosbuvir expected Do not co-administer.
TAF
 Ledipasvir/
Sofosbuvir		 Ledipasvir AUC ↑79% No dosage adjustment.
Rifabutina ↓ TAF expected Do not co-administer
Rifampina ↓ TAF expected Do not co-administer
Refapentinea ↓ TAF expected Do not co-administer
Velpatasvir/
Sofosbuvir		 TAF AUC ↓ 13% No dosage adjustment.
TDF Ledipasvir/
Sofosbuvir		 TDF AUC ↑ 98% (when given with EFV/FTC)

TDF AUC ↑ 40% (when given with RPV/FTC)

When used with EVG/c/TDF/FTC, ↑ TDF and ledipasvir expected 		Monitor for TDF-associated toxicities when coadministered with PI/r, PI/c, or EFV. Consider an alternative to PI/r plus TDF/FTC or alternative HCV therapy if possible.

Do not co-administer with EVG/c/TDF/FTC.

Consider TAF in place of TDF.
Velpatasvir/
Sofosbuvir 		TDF AUC ↑35% to 40% when given with EVG/c/FTC or RPV/FTC

TDF AUC ↑ 81% when given with EFV/FTC 		Monitor for TDF-associated toxicities with PI/r or EFV co-administration.

Consider TAF in place of TDF.
Velpatasvir/Sofosbuvir
 Rifabutina ↓ Velpatasvir and sofosbuvir expected Do not co-administer.
Rifampina Velpatasvir AUC ↓ 82%; sofosbuvir AUC ↓ 72% Do not co-administer.
Rifapentinea ↓ Velpatasvir and sofosbuvir expected Do not co-administer.
TAF TAF AUC ↓ 13% No dosage adjustment.
TDF TDF AUC ↑35% to 40% when given with EVG/c/FTC or RPV/FTC

TDF AUC ↑ 81% when given with EFV/FTC 		Monitor for TDF-associated toxicities with PI/r or EFV co-administration.

Consider TAF in place of TDF.
Voriconazole
 Artemether/
Lumefantrine 		↑ Lumefantrine expected Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).
Bedaquiline ↑ Bedaquiline expected Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).
Chloroquine ↑ Chloroquine expected Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).
Clarithromycin ↑ Clarithromycin expected Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir ↑ Daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dasabuvir
Ombitasvir
Paritaprevir
Ritonavir 		Voriconazole AUC ↓ 39% (with ritonavir); ↑ paritaprevir expected Co-administer only if the benefits outweigh the risks. Monitor voriconazole conc. to guide dosage adjustments.
Elbasvir/
Grazoprevir		 ↑ Elbasvir and grazoprevir expected Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.
Erythromycin ↑ Erythromycin expected Do not co-administer. Consider azithromycin in place of erythromycin.
Mefloquine ↑ Mefloquine expected Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).
Quinine ↑ Quinine expected Co-administration should be avoided, if possible. If co-administered, monitor for quinine toxicities (e.g., QT prolongation).
Rifabutina Voriconazole AUC ↓ 79%; rifabutin AUC ↑ 4-fold Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s). If coadministration is absolutely necessary, monitor voriconazole and rifabutin conc. to guide therapy.
Rifampina Voriconazole AUC ↓ 96% Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea ↓ Voriconazole expected Do not co-administer. Consider alternative antifungal and/or antimycobacterial agent(s).
Simeprevir ↑ Simeprevir expected Do not co-administer.
Key to Acronyms: 14-OH = active metabolite of clarithromycin; AUC = area under the curve; C24 = concentration at 24h post dose; Cmin = minimum concentration; Css = concentration at steady state; CYP3A4 = Cytochrome P450 3A4; des-Rbt = desacetyl rifabutin; DHA = dihydroartemisinin; EFV = efavirenz; EVG = elvitegravir; FTC = emtricitabine; HCV = hepatitis C virus; PI/c = cobicistat-boosted protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; RPV = rilpivirine; T1/2 = half-life; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate

a Rifamycins are potent inducers of Phase I and Phase II drug-metabolizing reactions. Daily doses of rifampin are well studied, and induction increases over a week or more. Based on limited data, larger doses of rifampin (for example, 1200 mg) appear to produce the same maximum induction, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin is about 40% as potent a CYP3A4 inducer as rifampin, but this can vary by substrate and enzymatic reaction. In general, daily rifapentine (for active TB disease) is at least as potent an inducer as rifampin. However, the potential of drug interactions with once weekly rifapentine (for latent TB infection, along with isoniazid) is not well studied, but may result in reduction of exposure of drugs that are CYP3A4 substrates. When a rifamycin is used with a potential interacting drug, close monitoring for clinical efficacy of the other agent is advised.

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