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.
Tables
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:
- Increase in concentrations of one or both drugs, which may lead to excessive risk of toxicity; or
- 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:
- Pharmacokinetic studies have shown a moderate degree of interaction of unknown clinical significance; or
- 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.
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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