Tables

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

This table lists the known, predicted, or suspected PK interactions between drugs used for the treatment or prevention of HIV-associated OIs. Many of the drugs listed in this table may also interact with ARV drugs. Clinicians should see the Drug-Drug Interactions tables in the most current Adult and Adolescent Antiretroviral Guidelines to assess interaction potentials between OI drugs and ARV drugs.

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 coadminister.
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 or 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.

Coadministration should be avoided, if possible.
There is a potential for significant PK interactions. If other more favorable options exist, clinicians are advised to consider changing components of the regimen to accommodate a safer or more effective regimen. However, coadministration of the drugs may be necessary when there are no other acceptable therapeutic options that provide a more favorable benefit-to-risk ratio.

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

  • PK 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 PK interaction of unknown clinical significance.

Rifamycin Antibiotics-Related Interactions
Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug metabolizing reactions. Studies have demonstrated that with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1,200 mg) appear to produce the same maximum induction as lower doses, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin as a CYP3A4 inducer is about 40% of the potency of 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 (prescribed with isoniazid for latent TB infection) is not well studied, and may result in reduced exposure of drugs that are CYP3A4 substrates. When using a rifamycin antibiotic with a potential interacting drug is necessary, close monitoring for clinical efficacy of the coadministered agent is advised.

Note: To avoid redundancy, drug-drug interactions are listed only once by primary drug (listed alphabetically). Subsequently, when an interacting agent becomes the primary drug, guideline users are referred to the entry for the initial primary drug. See the Clarithromycin row for the first example of this format.

Table 5. Significant Pharmacokinetic Interactions between Drugs Used to Treat or Prevent Opportunistic Infections
Primary Drug Interacting Agent Effect on Primary and/or Concomitant Drug Concentrations Recommendations
Artemether/ Lumefantrine Clarithromycin ↑ lumefantrine expected Coadministration 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 toxicities.
Erythromycin ↑ lumefantrine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ lumefantrine possible Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Isavuconazole ↑ lumefantrine possible Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Itraconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Mefloquine ↓ lumefantrine possible If mefloquine is administered immediately before artemether/lumefantrine, monitor for decreased efficacy of artemether/lumefantrine and encourage food intake.
Posaconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Rifabutina ↓ artemether, DHA, and lumefantrine expected Use with caution. Monitor for antimalarial efficacy.
Rifampina Artemether AUC ↓ 89%

DHA AUC ↓ 85%

Lumefantrine AUC ↓ 68%
Do not coadminister.
Rifapentinea ↓ artemether, DHA, and lumefantrine expected Do not coadminister.
Voriconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Atovaquone Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↔ atovaquone (based on interaction data for atovaquone oral solution with ATV/r) No dosage adjustment necessary.
Doxycycline Atovaquone concentration ↓ approximately equal to 40% with tetracycline

No interaction study with doxycycline
Dose adjustment not established; if coadministered, instruct patient to take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifabutina Atovaquone Css ↓ 34%

Rifabutin Css ↓ 19%
Dose adjustment not established; if coadministered, instruct patient to take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifampina Atovaquone Css ↓ 52%

Rifampin Css ↑ 37%
Do not coadminister.
Rifapentinea ↓ atovaquone expected Do not coadminister.
Atovaquone/Proguanil Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↓ atovaquone and proguanil AUC (when coadministered with ATV/r or LPV/r) Consider alternative drug for malaria prophylaxis.
Bedaquiline Clarithromycin ↑ bedaquiline expected Do not coadminister.
Consider azithromycin in place of clarithromycin.
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↑ bedaquiline expected Coadministration should be avoided, if possible. Consider alternative HCV regimen.
Erythromycin ↑ bedaquiline possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ bedaquiline possible Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Isavuconazole ↑ bedaquiline possible Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Itraconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministration is required for >14 days, weigh the benefits of therapy against the risks of bedaquiline toxicities. If coadministered, monitor for bedaquiline toxicities.
Posaconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Rifabutina ↔ bedaquiline If coadministered, monitor for rifabutin toxicities.
Rifampina Bedaquiline AUC ↓ 53% Do not coadminister.
Rifapentinea Bedaquiline AUC ↓ 55% (with daily rifapentine) Do not coadminister.
Voriconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Caspofungin Rifabutina No data

↓ caspofungin possible
Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day or switch to another echinocandin (e.g., micafungin or anidulafungin).
Rifampina Caspofungin Cmin ↓ 30% If coadministered, caspofungin dose should be increased to 70 mg/day. Consider alternative echinocandin (e.g., micafungin or anidulafungin).
Rifapentinea No data

↓ caspofungin possible
Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day or switch to another echinocandin (e.g., micafungin or anidulafungin).
Chloroquine Clarithromycin ↑ chloroquine expected Do not coadminister.
Consider azithromycin in place of clarithromycin.
Erythromycin ↑ chloroquine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ chloroquine possible Coadministration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities.
Isavuconazole ↑ chloroquine possible Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Itraconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Posaconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Rifabutina ↓ chloroquine expected Monitor for chloroquine efficacy.
Rifampina ↓ chloroquine expected Monitor for chloroquine efficacy.
Rifapentinea ↓ chloroquine expected Monitor for chloroquine efficacy.
Voriconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Clarithromycin Artemether/Lumefantrine See Artemether/ Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Daclatasvir ↑ daclatasvir expected Decrease daclatasvir dose to 30 mg once daily.
Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir ↑ clarithromycin and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Elbasvir/Grazoprevir ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity. Consider azithromycin in place of clarithromycin.
Fluconazole Clarithromycin AUC ↑ 18% and Cmin↑ 33% No dose adjustment necessary in patients with normal renal function. Monitor for clarithromycin toxicity.
Isavuconazole ↑ isavuconazole and clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of both isavuconazole and clarithromycin. Role of isavuconazole TDM has not been established.
Itraconazole ↑ itraconazole and clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of both itraconazole and clarithromycin); consider monitoring itraconazole concentration and adjust dose accordingly.
Mefloquine ↑ mefloquine expected Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, monitor for mefloquine toxicity.
Posaconazole ↑ clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Quinine ↑ quinine expected

↑ clarithromycin possible
Do not coadminister.
Consider azithromycin in place of clarithromycin.
Rifabutina Clarithromycin AUC ↓ 44%

14-OH AUC ↑ 57%

Rifabutin AUC ↑ 76% to 99%

des-Rbt AUC ↑ 375%
Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin concentrations, and monitoring for rifabutin toxicities.
Rifampina Clarithromycin concentration ↓ 87%

Rifampin AUC ↑ 60%
Do not coadminister.
Use azithromycin in place of clarithromycin.
Rifapentinea ↓ clarithromycin expected

↑ 14-OH and rifapentine expected
Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, monitor for rifapentine toxicities; consider monitoring clarithromycin and rifapentine concentrations and adjusting doses accordingly.
Voriconazole ↑ clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin ↑ daclatasvir possible No dosage adjustment. Monitor for daclatasvir toxicities.
Fluconazole ↑ daclatasvir possible No dosage adjustment. Monitor for daclatasvir toxicities.
Isavuconazole ↑ daclatasvir possible Dose not established. Monitor for daclatasvir 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 coadminister.
Rifapentinea ↓ daclatasvir expected Dose not established. Consider increasing daclatasvir dose to 90 mg once daily and monitor for therapeutic efficacy.
TDF TFV AUC ↑ 10% No dosage adjustment.
Voriconazole ↑ daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dapsone Rifabutina Dapsone AUC ↓ 27% to 40% Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Rifampina Dapsone concentration ↓ 7-fold to 10-fold and T½ ↓ from 24 hours to 11 hours Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Rifapentinea ↓ dapsone expected Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Dasabuvir/ Ombitasvir/ Paritaprevir/ Ritonavir Artemether/Lumefantrine See Artemether/lumefantrine See Artemether/Lumefantrine
Atovaquone (oral solution) See Atovaquone (oral solution) See Atovaquone (oral solution)
Atovaquone/Proguanil See Atovaquone/Proguanil See Atovaquone/Proguanil
Bedaquiline See Bedaquiline See Bedaquiline
Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin ↑ erythromycin and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Coadministration should be avoided, if possible. Consider azithromycin in place of erythromycin.
Isavuconazole Isavuconazole ↑ 96% and RTV AUC ↓ 31% (when studied with LPV/r)

↑ or ↓ paritaprevir, ombitasvir, and dasabuvir possible
Coadministration should be avoided, if possible.

If coadministered, monitor for isavuconazole toxicity and HCV regimen-associated toxicities and efficacy.
Itraconazole ↑ itraconazole and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole concentration. Monitor for itraconazole- and HCV regimen-associated toxicities.
Mefloquine RTV AUC ↓ 31% (based on study with RTV 200 mg twice daily) Monitor for HCV antiviral activity.
Posaconazole ↑ posaconazole and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Monitor for posaconazole- and HCV regimen-associated toxicities. Monitor posaconazole concentration and adjust dose if necessary.
Rifabutina ↑ rifabutin expected

↓ paritaprevir possible
Coadministration should be avoided, if possible. With coadministration, decrease rifabutin dose to 150 mg/day and monitor rifabutin concentration. Monitor HCV regimen for efficacy.
Rifampina ↓ paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not coadminister.
Rifapentinea ↓ paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not coadminister.
Voriconazole Voriconazole AUC ↓ 39% (when given with RTV 100 mg twice daily)

↑ paritaprevir expected
Coadminister only if the benefits outweigh the risk. Monitor voriconazole concentration to guide dosage adjustments.
Doxycycline Atovaquone See Atovaquone See Atovaquone
Rifabutina No data

↓ doxycycline possible
Monitor closely for doxycycline efficacy or consider alternative therapy.
Rifampina Doxycycline AUC ↓ 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 See Clarithromycin See Clarithromycin
Erythromycin ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity. Consider azithromycin in place of erythromycin.
Isavuconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Itraconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Posaconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Rifabutina ↓ elbasvir and grazoprevir possible Coadministration should be avoided if possible. Consider alternative HCV regimen.
Rifampina Grazoprevir AUC ↓ 7% and C24h ↓ 90%

↓ elbasvir expected
Do not coadminister.
Rifapentinea ↓ elbasvir and grazoprevir expected Do not coadminister.
Voriconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided if possible. If coadministered, monitor closely for hepatotoxicity.
Erythromycin Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Fluconazole ↑ erythromycin possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Isavuconazole ↑ erythromycin and isavuconazole possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Itraconazole Itraconazole AUC ↑ 36%

↑ erythromycin possible
Do not coadminister.
Consider azithromycin in place of erythromycin.
Mefloquine ↑ mefloquine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Posaconazole ↑ erythromycin expected Do not coadminister.
Consider azithromycin in place of erythromycin.
Quinine ↑ quinine expected

↑ erythromycin possible
Do not coadminister.
Consider azithromycin in place of erythromycin.
Rifabutina ↓ erythromycin possible

↑ rifabutin possible
Use with caution. Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy or rifabutin toxicities.
Rifampina ↓ erythromycin expected Consider azithromycin in place of erythromycin. If co-coadministered, monitor for erythromycin efficacy.
Rifapentinea ↓ erythromycin expected Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy.
Voriconazole ↑ erythromycin expected Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ mefloquine possible Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ fluconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and fluconazole toxicity.
Rifabutina Rifabutin AUC ↑ 80%

↔ fluconazole
Use with caution. Monitor for rifabutin toxicities. Consider monitoring rifabutin concentration; may need to decrease rifabutin dose to 150 mg/day.
Rifampina Fluconazole AUC ↓ 23% to 56% Monitor for antifungal efficacy; may need to increase fluconazole dose.
Rifapentinea ↓ fluconazole expected Monitor for antifungal efficacy; may need to increase fluconazole dose.
Glecaprevir/ Pibrentasvir Rifabutina ↓ glecaprevir and pibrentasvir possible Coadminsitration should be avoided, if possible. Consider alternative agents.
Rifampina Glecaprevir AUC ↓ 88%

Pibrentasvir AUC ↓ 87%
Do not coadminister.
Rifapentinea ↓ glecaprevir and pibrentasvir possible Do not coadminister.
Consider alternative agents.
TDF TFV AUC ↑ 29% when coadministered as EFV/TDF/FTC Use usual dose. Monitor renal function or consider TAF.
TAF ↔ TFV concentration when coadministered as EVG/c/TAF/FTC No dose adjustment.
Isavuconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ isavuconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and isavuconazole toxicities.
Rifabutina ↓ isavuconazole expected

↑ rifabutin expected
Consider alternative agent(s). If alternative agents are not available, use with close monitoring for isavuconazole anti-fungal activity and rifabutin toxicity.
Rifampina Isavuconazole AUC ↓ 97% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea Significant ↓ isavuconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Itraconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ Mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ itraconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and itraconazole toxicities; monitor itraconazole concentration and adjust dose accordingly.
Rifabutina Itraconazole AUC ↓ 70%

↑ rifabutin expected
Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifampina Itraconazole AUC ↓ 64% to 88% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea ↓ itraconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Ledipasvir/Sofosbuvir Rifabutina ↓ ledipasvir and sofosbuvir expected Do not coadminister.
Rifampina Ledipasvir AUC ↓ 59%

Sofosbuvir AUC ↓ 72%
Do not coadminister.
Rifapentinea ↓ ledipasvir and sofosbuvir expected Do not coadminister.
TAF Ledipasvir AUC ↑ 79% (when given with EVG/c/TAF/FTC) No dosage adjustment.
TDF TFV AUC ↑ 98% (when given with EFV/FTC)

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

TFV AUC ↑ 50% (when given with DRV/r/FTC)
Monitor for TDF toxicities.

Consider TAF in place of TDF.
Linezolid Rifabutina ↓ linezolid possible Monitor for linezolid efficacy.
Rifampina Linezolid AUC ↓ 32% Monitor for linezolid efficacy.
Rifapentinea ↓ linezolid possible Monitor for linezolid efficacy.
Mefloquine Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Clarithromycin See Clarithromycin See Clarithromycin
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Posaconazole ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Rifabutina ↓ mefloquine possible Monitor for mefloquine efficacy.
Rifampina Mefloquine AUC ↓ 68% Do not coadminister.
Use alternative antimalarial drug or rifabutin.
Rifapentinea ↓ mefloquine expected Do not coadminister.
Use alternative antimalarial drug or rifabutin.
Voriconazole ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Posaconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine See Mefloquine See Mefloquine
Quinine ↑ quinine expected

↑ posaconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine toxicities.
Rifabutina Posaconazole AUC ↓ 49%

Rifabutin AUC ↑ 72%
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole and rifabutin concentrations and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities.
Rifampina Significant ↓ posaconazole expected Do not coadminister when treating invasive fungal infections.
If coadministered for treatment of non-invasive fungal infections, monitor posaconazole concentration and adjust dose accordingly; monitor for clinical response.
Rifapentinea ↓ posaconazole expected Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentration and adjust dose accordingly; monitor clinical response.
Quinine Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Itraconazole See Itraconazole See Itraconazole
Posaconazole See Posaconazole See Posaconazole
Rifabutina ↓ quinine possible

↑ rifabutin possible
Monitor for quinine efficacy.

Monitor rifabutin concentration and toxicity.
Rifampina Quinine AUC ↓ 75% to 85% Do not coadminister.
Rifapentinea ↓ quinine expected Do not coadminister.
Voriconazole ↑ quinine expected Coadministration should be avoided, if possible. If coadministered, monitor for quinine toxicities.
Rifabutina Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Dapsone See Dapsone See Dapsone
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir ↓ sofosbuvir expected Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir ↓ velpatasvir, voxilaprevir, and sofosbuvir expected Do not coadminister.
TAF ↓ TAF expected Do not coadminister.
Voriconazole Voriconazole AUC ↓ 79%

Rifabutin AUC ↑ 4-fold
Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s). If coadministration is absolutely necessary, monitor voriconazole and rifabutin concentrations to guide therapy.
Rifampina Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dapsone See Dapsone See Dapsone
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir Sofosbuvir AUC ↓ 72% Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir Sofosbuvir AUC ↓ 72%

Velpatasvir AUC ↓ 82%

Voxilaprevir AUC ↓ 73%
Do not coadminister.
TAF TAF plus Rifampin:
  • TAF AUC ↓ 56%,
  • TFV AUC ↓ 53%
  • TFV-DP AUC ↓ 36%
Intracellular TFV-DP concentration is 4.2-fold greater than with TDF alone.
If coadministered, monitor for HIV and HBV efficacy.

Note: FDA labeling recommends not to coadminister.
Voriconazole Voriconazole AUC ↓96% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dapsone See Dapsone See Dapsone
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir ↓ sofosbuvir expected Do not coadminister.
TAF ↓ TAF expected Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir ↓ sofosbuvir, velpatasvir, and voxilaprevir expected Do not coadminister.
Voriconazole ↓ voriconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Sofosbuvir Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
Sofosbuvir/Velpatasvir +/- Voxilaprevir Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
TAF TFV AUC ↑ 52% (when RPV/TAF/FTC given with SOF/VEL/VOX) No dosage adjustment.
TDF TFV AUC ↑ 35% to 40% (when given with EVG/c/FTC or RPV/FTC)

TFV AUC ↑ 81% (when given with EFV/FTC and SOF/VEL)

TFV AUC ↑ 39% (when given with DRV/r/FTC and SOF/VEL/VOX)
Monitor for TDF toxicities.

Consider TAF in place of TDF.
Tenofovir Alafenamide Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir
Tenofovir Disoproxil Fumarate Daclatasvir See Daclatasvir See Daclatasvir
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Sofosbuvir/Velpatasvir See Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir
Voriconazole
Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine See Mefloquine See Mefloquine
Quinine See Quinine See Quinine
Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
a Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug-metabolizing reactions. Studies have demonstrated that with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1,200 mg) appear to produce the same maximum induction as lower doses, 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, and may result in reduced exposure of drugs that are CYP3A4 substrates. When a rifamycin antibiotic is given with a potential interacting drug, close monitoring for clinical efficacy of the coadministered agent is advised.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key: 14-OH = active metabolite of clarithromycin; ARV = antiretroviral; ATV/r = atazanavir/ritonavir; AUC = area under the curve; C24h = concentration at 24 hours post dose; Cmin = minimum concentration; Css = concentration at steady state; CYP3A4 = Cytochrome P450 3A4; des-Rbt = desacetyl rifabutin; DHA = dihydroartemisinin; DRV/r = darunavir/ritonavir; EFV = efavirenz; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HCV = hepatitis C virus; LPV/r = lopinavir/ritonavir; OI = opportunistic infection; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SOF = sofosbuvir; T½ = half-life; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TFV= tenofovir; TFV-DP = tenofovir diphosphate; VEL = velpastavir; VOX = voxilaprevir

Tables

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

This table lists the known, predicted, or suspected PK interactions between drugs used for the treatment or prevention of HIV-associated OIs. Many of the drugs listed in this table may also interact with ARV drugs. Clinicians should see the Drug-Drug Interactions tables in the most current Adult and Adolescent Antiretroviral Guidelines to assess interaction potentials between OI drugs and ARV drugs.

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 coadminister.
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 or 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.

Coadministration should be avoided, if possible.
There is a potential for significant PK interactions. If other more favorable options exist, clinicians are advised to consider changing components of the regimen to accommodate a safer or more effective regimen. However, coadministration of the drugs may be necessary when there are no other acceptable therapeutic options that provide a more favorable benefit-to-risk ratio.

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

  • PK 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 PK interaction of unknown clinical significance.

Rifamycin Antibiotics-Related Interactions
Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug metabolizing reactions. Studies have demonstrated that with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1,200 mg) appear to produce the same maximum induction as lower doses, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin as a CYP3A4 inducer is about 40% of the potency of 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 (prescribed with isoniazid for latent TB infection) is not well studied, and may result in reduced exposure of drugs that are CYP3A4 substrates. When using a rifamycin antibiotic with a potential interacting drug is necessary, close monitoring for clinical efficacy of the coadministered agent is advised.

Note: To avoid redundancy, drug-drug interactions are listed only once by primary drug (listed alphabetically). Subsequently, when an interacting agent becomes the primary drug, guideline users are referred to the entry for the initial primary drug. See the Clarithromycin row for the first example of this format.

Table 5. Significant Pharmacokinetic Interactions between Drugs Used to Treat or Prevent Opportunistic Infections
Primary Drug Interacting Agent Effect on Primary and/or Concomitant Drug Concentrations Recommendations
Artemether/ Lumefantrine Clarithromycin ↑ lumefantrine expected Coadministration 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 toxicities.
Erythromycin ↑ lumefantrine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ lumefantrine possible Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Isavuconazole ↑ lumefantrine possible Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Itraconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Mefloquine ↓ lumefantrine possible If mefloquine is administered immediately before artemether/lumefantrine, monitor for decreased efficacy of artemether/lumefantrine and encourage food intake.
Posaconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Rifabutina ↓ artemether, DHA, and lumefantrine expected Use with caution. Monitor for antimalarial efficacy.
Rifampina Artemether AUC ↓ 89%

DHA AUC ↓ 85%

Lumefantrine AUC ↓ 68%
Do not coadminister.
Rifapentinea ↓ artemether, DHA, and lumefantrine expected Do not coadminister.
Voriconazole ↑ lumefantrine expected Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Atovaquone Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↔ atovaquone (based on interaction data for atovaquone oral solution with ATV/r) No dosage adjustment necessary.
Doxycycline Atovaquone concentration ↓ approximately equal to 40% with tetracycline

No interaction study with doxycycline
Dose adjustment not established; if coadministered, instruct patient to take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifabutina Atovaquone Css ↓ 34%

Rifabutin Css ↓ 19%
Dose adjustment not established; if coadministered, instruct patient to take atovaquone with fatty meal and monitor for decreased atovaquone efficacy.
Rifampina Atovaquone Css ↓ 52%

Rifampin Css ↑ 37%
Do not coadminister.
Rifapentinea ↓ atovaquone expected Do not coadminister.
Atovaquone/Proguanil Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↓ atovaquone and proguanil AUC (when coadministered with ATV/r or LPV/r) Consider alternative drug for malaria prophylaxis.
Bedaquiline Clarithromycin ↑ bedaquiline expected Do not coadminister.
Consider azithromycin in place of clarithromycin.
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir ↑ bedaquiline expected Coadministration should be avoided, if possible. Consider alternative HCV regimen.
Erythromycin ↑ bedaquiline possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ bedaquiline possible Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Isavuconazole ↑ bedaquiline possible Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Itraconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministration is required for >14 days, weigh the benefits of therapy against the risks of bedaquiline toxicities. If coadministered, monitor for bedaquiline toxicities.
Posaconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Rifabutina ↔ bedaquiline If coadministered, monitor for rifabutin toxicities.
Rifampina Bedaquiline AUC ↓ 53% Do not coadminister.
Rifapentinea Bedaquiline AUC ↓ 55% (with daily rifapentine) Do not coadminister.
Voriconazole ↑ bedaquiline expected Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Caspofungin Rifabutina No data

↓ caspofungin possible
Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day or switch to another echinocandin (e.g., micafungin or anidulafungin).
Rifampina Caspofungin Cmin ↓ 30% If coadministered, caspofungin dose should be increased to 70 mg/day. Consider alternative echinocandin (e.g., micafungin or anidulafungin).
Rifapentinea No data

↓ caspofungin possible
Monitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day or switch to another echinocandin (e.g., micafungin or anidulafungin).
Chloroquine Clarithromycin ↑ chloroquine expected Do not coadminister.
Consider azithromycin in place of clarithromycin.
Erythromycin ↑ chloroquine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole ↑ chloroquine possible Coadministration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities.
Isavuconazole ↑ chloroquine possible Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Itraconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Posaconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Rifabutina ↓ chloroquine expected Monitor for chloroquine efficacy.
Rifampina ↓ chloroquine expected Monitor for chloroquine efficacy.
Rifapentinea ↓ chloroquine expected Monitor for chloroquine efficacy.
Voriconazole ↑ chloroquine expected Coadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Clarithromycin Artemether/Lumefantrine See Artemether/ Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Daclatasvir ↑ daclatasvir expected Decrease daclatasvir dose to 30 mg once daily.
Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir ↑ clarithromycin and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Elbasvir/Grazoprevir ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity. Consider azithromycin in place of clarithromycin.
Fluconazole Clarithromycin AUC ↑ 18% and Cmin↑ 33% No dose adjustment necessary in patients with normal renal function. Monitor for clarithromycin toxicity.
Isavuconazole ↑ isavuconazole and clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of both isavuconazole and clarithromycin. Role of isavuconazole TDM has not been established.
Itraconazole ↑ itraconazole and clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of both itraconazole and clarithromycin); consider monitoring itraconazole concentration and adjust dose accordingly.
Mefloquine ↑ mefloquine expected Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, monitor for mefloquine toxicity.
Posaconazole ↑ clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Quinine ↑ quinine expected

↑ clarithromycin possible
Do not coadminister.
Consider azithromycin in place of clarithromycin.
Rifabutina Clarithromycin AUC ↓ 44%

14-OH AUC ↑ 57%

Rifabutin AUC ↑ 76% to 99%

des-Rbt AUC ↑ 375%
Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin concentrations, and monitoring for rifabutin toxicities.
Rifampina Clarithromycin concentration ↓ 87%

Rifampin AUC ↑ 60%
Do not coadminister.
Use azithromycin in place of clarithromycin.
Rifapentinea ↓ clarithromycin expected

↑ 14-OH and rifapentine expected
Use with caution. Consider azithromycin in place of clarithromycin. If coadministered, monitor for rifapentine toxicities; consider monitoring clarithromycin and rifapentine concentrations and adjusting doses accordingly.
Voriconazole ↑ clarithromycin expected Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Daclatasvir Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin ↑ daclatasvir possible No dosage adjustment. Monitor for daclatasvir toxicities.
Fluconazole ↑ daclatasvir possible No dosage adjustment. Monitor for daclatasvir toxicities.
Isavuconazole ↑ daclatasvir possible Dose not established. Monitor for daclatasvir 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 coadminister.
Rifapentinea ↓ daclatasvir expected Dose not established. Consider increasing daclatasvir dose to 90 mg once daily and monitor for therapeutic efficacy.
TDF TFV AUC ↑ 10% No dosage adjustment.
Voriconazole ↑ daclatasvir expected Reduce daclatasvir dose to 30 mg once daily.
Dapsone Rifabutina Dapsone AUC ↓ 27% to 40% Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Rifampina Dapsone concentration ↓ 7-fold to 10-fold and T½ ↓ from 24 hours to 11 hours Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Rifapentinea ↓ dapsone expected Coadministration should be avoided, if possible. Consider alternatives for dapsone.
Dasabuvir/ Ombitasvir/ Paritaprevir/ Ritonavir Artemether/Lumefantrine See Artemether/lumefantrine See Artemether/Lumefantrine
Atovaquone (oral solution) See Atovaquone (oral solution) See Atovaquone (oral solution)
Atovaquone/Proguanil See Atovaquone/Proguanil See Atovaquone/Proguanil
Bedaquiline See Bedaquiline See Bedaquiline
Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin ↑ erythromycin and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Coadministration should be avoided, if possible. Consider azithromycin in place of erythromycin.
Isavuconazole Isavuconazole ↑ 96% and RTV AUC ↓ 31% (when studied with LPV/r)

↑ or ↓ paritaprevir, ombitasvir, and dasabuvir possible
Coadministration should be avoided, if possible.

If coadministered, monitor for isavuconazole toxicity and HCV regimen-associated toxicities and efficacy.
Itraconazole ↑ itraconazole and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole concentration. Monitor for itraconazole- and HCV regimen-associated toxicities.
Mefloquine RTV AUC ↓ 31% (based on study with RTV 200 mg twice daily) Monitor for HCV antiviral activity.
Posaconazole ↑ posaconazole and paritaprevir expected

↑ ombitasvir and dasabuvir possible
Monitor for posaconazole- and HCV regimen-associated toxicities. Monitor posaconazole concentration and adjust dose if necessary.
Rifabutina ↑ rifabutin expected

↓ paritaprevir possible
Coadministration should be avoided, if possible. With coadministration, decrease rifabutin dose to 150 mg/day and monitor rifabutin concentration. Monitor HCV regimen for efficacy.
Rifampina ↓ paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not coadminister.
Rifapentinea ↓ paritaprevir, ritonavir, ombitasvir, and dasabuvir expected Do not coadminister.
Voriconazole Voriconazole AUC ↓ 39% (when given with RTV 100 mg twice daily)

↑ paritaprevir expected
Coadminister only if the benefits outweigh the risk. Monitor voriconazole concentration to guide dosage adjustments.
Doxycycline Atovaquone See Atovaquone See Atovaquone
Rifabutina No data

↓ doxycycline possible
Monitor closely for doxycycline efficacy or consider alternative therapy.
Rifampina Doxycycline AUC ↓ 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 See Clarithromycin See Clarithromycin
Erythromycin ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity. Consider azithromycin in place of erythromycin.
Isavuconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Itraconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Posaconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided, if possible. If coadministered, monitor closely for hepatotoxicity.
Rifabutina ↓ elbasvir and grazoprevir possible Coadministration should be avoided if possible. Consider alternative HCV regimen.
Rifampina Grazoprevir AUC ↓ 7% and C24h ↓ 90%

↓ elbasvir expected
Do not coadminister.
Rifapentinea ↓ elbasvir and grazoprevir expected Do not coadminister.
Voriconazole ↑ elbasvir and grazoprevir expected Coadministration should be avoided if possible. If coadministered, monitor closely for hepatotoxicity.
Erythromycin Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Fluconazole ↑ erythromycin possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Isavuconazole ↑ erythromycin and isavuconazole possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Itraconazole Itraconazole AUC ↑ 36%

↑ erythromycin possible
Do not coadminister.
Consider azithromycin in place of erythromycin.
Mefloquine ↑ mefloquine possible Do not coadminister.
Consider azithromycin in place of erythromycin.
Posaconazole ↑ erythromycin expected Do not coadminister.
Consider azithromycin in place of erythromycin.
Quinine ↑ quinine expected

↑ erythromycin possible
Do not coadminister.
Consider azithromycin in place of erythromycin.
Rifabutina ↓ erythromycin possible

↑ rifabutin possible
Use with caution. Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy or rifabutin toxicities.
Rifampina ↓ erythromycin expected Consider azithromycin in place of erythromycin. If co-coadministered, monitor for erythromycin efficacy.
Rifapentinea ↓ erythromycin expected Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy.
Voriconazole ↑ erythromycin expected Do not coadminister.
Consider azithromycin in place of erythromycin.
Fluconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ mefloquine possible Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ fluconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and fluconazole toxicity.
Rifabutina Rifabutin AUC ↑ 80%

↔ fluconazole
Use with caution. Monitor for rifabutin toxicities. Consider monitoring rifabutin concentration; may need to decrease rifabutin dose to 150 mg/day.
Rifampina Fluconazole AUC ↓ 23% to 56% Monitor for antifungal efficacy; may need to increase fluconazole dose.
Rifapentinea ↓ fluconazole expected Monitor for antifungal efficacy; may need to increase fluconazole dose.
Glecaprevir/ Pibrentasvir Rifabutina ↓ glecaprevir and pibrentasvir possible Coadminsitration should be avoided, if possible. Consider alternative agents.
Rifampina Glecaprevir AUC ↓ 88%

Pibrentasvir AUC ↓ 87%
Do not coadminister.
Rifapentinea ↓ glecaprevir and pibrentasvir possible Do not coadminister.
Consider alternative agents.
TDF TFV AUC ↑ 29% when coadministered as EFV/TDF/FTC Use usual dose. Monitor renal function or consider TAF.
TAF ↔ TFV concentration when coadministered as EVG/c/TAF/FTC No dose adjustment.
Isavuconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ isavuconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and isavuconazole toxicities.
Rifabutina ↓ isavuconazole expected

↑ rifabutin expected
Consider alternative agent(s). If alternative agents are not available, use with close monitoring for isavuconazole anti-fungal activity and rifabutin toxicity.
Rifampina Isavuconazole AUC ↓ 97% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea Significant ↓ isavuconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Itraconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine ↑ Mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Quinine ↑ quinine expected

↑ itraconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine and itraconazole toxicities; monitor itraconazole concentration and adjust dose accordingly.
Rifabutina Itraconazole AUC ↓ 70%

↑ rifabutin expected
Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifampina Itraconazole AUC ↓ 64% to 88% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea ↓ itraconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Ledipasvir/Sofosbuvir Rifabutina ↓ ledipasvir and sofosbuvir expected Do not coadminister.
Rifampina Ledipasvir AUC ↓ 59%

Sofosbuvir AUC ↓ 72%
Do not coadminister.
Rifapentinea ↓ ledipasvir and sofosbuvir expected Do not coadminister.
TAF Ledipasvir AUC ↑ 79% (when given with EVG/c/TAF/FTC) No dosage adjustment.
TDF TFV AUC ↑ 98% (when given with EFV/FTC)

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

TFV AUC ↑ 50% (when given with DRV/r/FTC)
Monitor for TDF toxicities.

Consider TAF in place of TDF.
Linezolid Rifabutina ↓ linezolid possible Monitor for linezolid efficacy.
Rifampina Linezolid AUC ↓ 32% Monitor for linezolid efficacy.
Rifapentinea ↓ linezolid possible Monitor for linezolid efficacy.
Mefloquine Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Clarithromycin See Clarithromycin See Clarithromycin
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Posaconazole ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Rifabutina ↓ mefloquine possible Monitor for mefloquine efficacy.
Rifampina Mefloquine AUC ↓ 68% Do not coadminister.
Use alternative antimalarial drug or rifabutin.
Rifapentinea ↓ mefloquine expected Do not coadminister.
Use alternative antimalarial drug or rifabutin.
Voriconazole ↑ mefloquine expected Coadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Posaconazole Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine See Mefloquine See Mefloquine
Quinine ↑ quinine expected

↑ posaconazole possible
Coadministration should be avoided, if possible. If coadministered, monitor for quinine toxicities.
Rifabutina Posaconazole AUC ↓ 49%

Rifabutin AUC ↑ 72%
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole and rifabutin concentrations and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities.
Rifampina Significant ↓ posaconazole expected Do not coadminister when treating invasive fungal infections.
If coadministered for treatment of non-invasive fungal infections, monitor posaconazole concentration and adjust dose accordingly; monitor for clinical response.
Rifapentinea ↓ posaconazole expected Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentration and adjust dose accordingly; monitor clinical response.
Quinine Clarithromycin See Clarithromycin See Clarithromycin
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Itraconazole See Itraconazole See Itraconazole
Posaconazole See Posaconazole See Posaconazole
Rifabutina ↓ quinine possible

↑ rifabutin possible
Monitor for quinine efficacy.

Monitor rifabutin concentration and toxicity.
Rifampina Quinine AUC ↓ 75% to 85% Do not coadminister.
Rifapentinea ↓ quinine expected Do not coadminister.
Voriconazole ↑ quinine expected Coadministration should be avoided, if possible. If coadministered, monitor for quinine toxicities.
Rifabutina Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Dapsone See Dapsone See Dapsone
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir ↓ sofosbuvir expected Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir ↓ velpatasvir, voxilaprevir, and sofosbuvir expected Do not coadminister.
TAF ↓ TAF expected Do not coadminister.
Voriconazole Voriconazole AUC ↓ 79%

Rifabutin AUC ↑ 4-fold
Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s). If coadministration is absolutely necessary, monitor voriconazole and rifabutin concentrations to guide therapy.
Rifampina Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dapsone See Dapsone See Dapsone
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir Sofosbuvir AUC ↓ 72% Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir Sofosbuvir AUC ↓ 72%

Velpatasvir AUC ↓ 82%

Voxilaprevir AUC ↓ 73%
Do not coadminister.
TAF TAF plus Rifampin:
  • TAF AUC ↓ 56%,
  • TFV AUC ↓ 53%
  • TFV-DP AUC ↓ 36%
Intracellular TFV-DP concentration is 4.2-fold greater than with TDF alone.
If coadministered, monitor for HIV and HBV efficacy.

Note: FDA labeling recommends not to coadminister.
Voriconazole Voriconazole AUC ↓96% Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Atovaquone See Atovaquone See Atovaquone
Bedaquiline See Bedaquiline See Bedaquiline
Caspofungin See Caspofungin See Caspofungin
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dapsone See Dapsone See Dapsone
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Doxycycline See Doxycycline See Doxycycline
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Fluconazole See Fluconazole See Fluconazole
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Isavuconazole See Isavuconazole See Isavuconazole
Itraconazole See Itraconazole See Itraconazole
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Linezolid See Linezolid See Linezolid
Mefloquine See Mefloquine See Mefloquine
Posaconazole See Posaconazole See Posaconazole
Quinine See Quinine See Quinine
Sofosbuvir ↓ sofosbuvir expected Do not coadminister.
TAF ↓ TAF expected Do not coadminister.
Sofosbuvir/Velpatasvir +/- Voxilaprevir ↓ sofosbuvir, velpatasvir, and voxilaprevir expected Do not coadminister.
Voriconazole ↓ voriconazole expected Do not coadminister.
Consider alternative antifungal and/or antimycobacterial agent(s).
Sofosbuvir Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
Sofosbuvir/Velpatasvir +/- Voxilaprevir Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
TAF TFV AUC ↑ 52% (when RPV/TAF/FTC given with SOF/VEL/VOX) No dosage adjustment.
TDF TFV AUC ↑ 35% to 40% (when given with EVG/c/FTC or RPV/FTC)

TFV AUC ↑ 81% (when given with EFV/FTC and SOF/VEL)

TFV AUC ↑ 39% (when given with DRV/r/FTC and SOF/VEL/VOX)
Monitor for TDF toxicities.

Consider TAF in place of TDF.
Tenofovir Alafenamide Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir
Tenofovir Disoproxil Fumarate Daclatasvir See Daclatasvir See Daclatasvir
Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir See Glecaprevir/Pibrentasvir
Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir See Ledipasvir/Sofosbuvir
Sofosbuvir/Velpatasvir See Sofosbuvir/Velpatasvir +/- Voxilaprevir See Sofosbuvir/Velpatasvir +/- Voxilaprevir
Voriconazole
Artemether/Lumefantrine See Artemether/Lumefantrine See Artemether/Lumefantrine
Bedaquiline See Bedaquiline See Bedaquiline
Chloroquine See Chloroquine See Chloroquine
Clarithromycin See Clarithromycin See Clarithromycin
Daclatasvir See Daclatasvir See Daclatasvir
Dasabuvir/Ombitasvir/ Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir See Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Elbasvir/Grazoprevir See Elbasvir/Grazoprevir See Elbasvir/Grazoprevir
Erythromycin See Erythromycin See Erythromycin
Mefloquine See Mefloquine See Mefloquine
Quinine See Quinine See Quinine
Rifabutina See Rifabutin See Rifabutin
Rifampina See Rifampin See Rifampin
Rifapentinea See Rifapentine See Rifapentine
a Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug-metabolizing reactions. Studies have demonstrated that with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1,200 mg) appear to produce the same maximum induction as lower doses, 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, and may result in reduced exposure of drugs that are CYP3A4 substrates. When a rifamycin antibiotic is given with a potential interacting drug, close monitoring for clinical efficacy of the coadministered agent is advised.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key: 14-OH = active metabolite of clarithromycin; ARV = antiretroviral; ATV/r = atazanavir/ritonavir; AUC = area under the curve; C24h = concentration at 24 hours post dose; Cmin = minimum concentration; Css = concentration at steady state; CYP3A4 = Cytochrome P450 3A4; des-Rbt = desacetyl rifabutin; DHA = dihydroartemisinin; DRV/r = darunavir/ritonavir; EFV = efavirenz; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HCV = hepatitis C virus; LPV/r = lopinavir/ritonavir; OI = opportunistic infection; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SOF = sofosbuvir; T½ = half-life; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TFV= tenofovir; TFV-DP = tenofovir diphosphate; VEL = velpastavir; VOX = voxilaprevir
Updated
Reviewed
Oct. 22, 2019

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