Table 4. Significant Pharmacokinetic Interactions between Drugs Used to Treat or Prevent Opportunistic Infections

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Table 4. 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

 

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