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Tables

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

This table lists the known, predicted, or suspected pharmacokinetic (PK) interactions between drugs used for the treatment or prevention of HIV-associated opportunistic infections (OIs). Many of the drugs listed in this table may also interact with antiretroviral (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 rationales for these recommendations are summarized below:

Do not coadminister.

There is either strong evidence or strong likelihood that the PK 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. Therapeutic drug monitoring, if available, may facilitate any necessary dose adjustments.

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-Related Induction Interactions

Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug metabolizing reactions. They also affect various transporters. When a rifamycin antibiotic must be combined with an interacting drug, close monitoring for clinical efficacy of the coadministered agent is advised. Therapeutic drug monitoring, if available, may facilitate any necessary dose adjustments.

  • Rifampin (also known as rifampicin): Interactions may not be apparent in the first several days of rifampin therapy. However, with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger daily doses of rifampin (e.g., 1,200 mg or more) appear to produce the same maximum induction as lower doses, but the induction effect occurs more rapidly.
  • Rifabutin: In general, rifabutin as a cytochrome P450 3A4 (CYP3A4) inducer is about 40% of the potency of rifampin, but this can vary by substrate and enzymatic reaction. Rifabutin is also a substrate of CYP3A4 and may be subject to changes in drug exposure when given concomitantly with 3A4 inhibitors or inducers. Rifabutin dosage modification, therapeutic drug monitoring, and/or more frequent monitoring for rifabutin-related toxicities may be needed.
  • Rifapentine: In general, daily rifapentine is at least as potent an inducer as rifampin. However, the potential for drug interactions with once-weekly rifapentine is not well studied. Reduced exposure of concurrent drugs that are CYP3A4 substrates is likely to occur with once-weekly rifapentine, with the extent varying by drug.

Azole- and Macrolide-Related Inhibition Interactions

Azole antifungals, including fluconazole, isavuconazole, itraconazole, posaconazole, and voriconazole, are substrates and potent inhibitors of metabolic pathways, including cytochrome P450 enzymes and/or drug transporters (e.g., p-glycoprotein). Interactions involving azole antifungals are common. When an azole antifungal must be combined with an interacting drug, close monitoring for clinical toxicity and efficacy of the azole and/or the coadministered agent may be needed. Therapeutic drug monitoring, if available, may facilitate any necessary dose adjustments.

Macrolides have been shown to form complexes with drug-oxidizing enzymes, including cytochrome P450 enzymes, which render an inhibitory effect. In general, erythromycin and clarithromycin are moderate to strong inhibitors, while azithromycin’s propensity for causing clinically relevant drug interactions is lowest, as it does not form complexes with cytochrome P450 enzymes that lead to enzyme inactivation.

Pharmacodynamic Interactions

Pharmacodynamic interactions are not addressed in this table. For example, many of the drug classes listed below independently possess a risk for QTc prolongation, including azoles, macrolides, and certain anti-tuberculosis and antimalarial medications. Coadministration of drugs in these classes may require monitoring for QTc prolongation, particularly in patients with predisposing risk factors.

Therapeutic Drug Monitoring

Drug interactions can alter oral absorption or systemic clearance of drugs. More than one interaction can occur at the same time, with potentially opposing effects. Therapeutic drug monitoring (TDM), if available, may facilitate any necessary dose adjustments in these complicated patients. TDM allows the clinician to make informed, individualized decisions about dose adjustments that are more precise than standardized dose adjustments based upon anticipated, average effects.

Drugs that are marked with an asterisk (*) in the table below are known to have assays (for clinical and/or research purposes) available within the United States and typically in Europe as well. When TDM is appropriate, clinicians should contact their clinical laboratory to determine assay availability and turnaround time for their institution.

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 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.

Erythromycin

↑ lumefantrine expected

Coadministration should be avoided, if possible. 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

Daily and Weekly Rifapentine

↓ artemether, DHA, and lumefantrine expected

Do not coadminister.

Voriconazole

↑ lumefantrine expected

Coadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.

Atovaquone*

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

Daily and Weekly Rifapentine

↓ atovaquone expected

Do not coadminister.

Bedaquiline*

Clarithromycin

↑ bedaquiline expected

Do not coadminister. Consider azithromycin in place of clarithromycin.

Erythromycin

↑ bedaquiline expected

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 coadministered, monitor for bedaquiline toxicities.

If coadministration is required for >14 days, weigh the benefits of therapy against the risks of bedaquiline toxicities.

Posaconazole

↑ bedaquiline expected

Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.

Rifabutina

↔ bedaquiline

↓ rifabutin possible

If coadministered, separate time of administration; perform rifabutin TDM and adjust dose accordingly.

Rifampina

Bedaquiline AUC ↓ 53%

Do not coadminister.

Rifapentinea

Daily Rifapentine

Bedaquiline AUC ↓ 55%

Weekly Rifapentine

↓ bedaquiline expected

Do not coadminister.

Voriconazole

↑ bedaquiline expected

Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.

Brincidofovir

Clarithromycin

↑ brincidofovir expected

Coadministration should be avoided, if possible. If coadministered, postpone clarithromycin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.

Consider azithromycin in place of clarithromycin.

Erythromycin

↑ brincidofovir expected

Coadministration should be avoided, if possible. If coadministered, postpone erythromycin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.

Consider azithromycin in place of erythromycin.

Rifampin

↑ brincidofovir expected

Coadministration should be avoided, if possible. If coadministered, postpone rifampin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.

Caspofungin

Rifabutina

↓ 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

Daily Rifapentine

  • ↓ caspofungin expected

Weekly Rifapentine

  • ↓ 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 expected

Do not coadminister. Consider azithromycin in place of erythromycin.

Fluconazole

↑ chloroquine possible

Coadministration should be avoided, if possible. If coadministered, 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

Daily and Weekly Rifapentine

↓ 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.

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; perform itraconazole and clarithromycin TDM 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. If coadministered, monitor for toxicities of clarithromycin; perform clarithromycin TDM and adjust dose accordingly.

Quinine

↑ quinine expected

↑ clarithromycin possible

Do not coadminister. Consider azithromycin in place of clarithromycin.

Rifabutina

Clarithromycin AUC ↓ 44%

14-OH clarithromycin 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, perform clarithromycin and rifabutin TDM and adjust dose accordingly. Monitor for rifabutin toxicities.

Rifampina

Clarithromycin concentration ↓ 87%

Rifampin AUC ↑ 60%

Do not coadminister. Use azithromycin in place of clarithromycin.

Rifapentinea

Daily and Weekly Rifapentine

↓ clarithromycin expected

↑ 14-OH clarithromycin and rifapentine expected

Daily Rifapentine

  • Do not coadminister. Use azithromycin in place of clarithromycin.

Weekly Rifapentine

  • Use with caution. Consider azithromycin in place of clarithromycin.

If coadministered, monitor for rifapentine toxicities and clarithromycin efficacy; perform clarithromycin and rifapentine TDM and adjust doses accordingly.

Voriconazole

↑ clarithromycin expected

Coadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of clarithromycin; perform clarithromycin TDM and adjust dose accordingly.

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 t1/2 ↓ from 24 hours to 11 hours

Coadministration should be avoided, if possible. Consider alternatives for dapsone.

Rifapentinea

Daily and Weekly Rifapentine

↓ dapsone expected

Coadministration should be avoided, if possible. Consider alternatives for dapsone.

Doxycycline

Atovaquone

See Atovaquone.

See Atovaquone.

Rifabutina

↓ 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

Daily Rifapentine

  • ↓ doxycycline expected

Weekly Rifapentine

  • ↓ doxycycline possible

Use with caution. Monitor closely for doxycycline efficacy or consider alternative therapy.

Erythromycin

Artemether/Lumefantrine

See Artemether/Lumefantrine.

See Artemether/Lumefantrine.

Bedaquiline

See Bedaquiline.

See Bedaquiline.

Chloroquine

See Chloroquine.

See Chloroquine.

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 and rifabutin toxicities; perform rifabutin TDM and adjust dose accordingly.

Rifampina

↓ erythromycin expected

Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy.

Rifapentinea

Daily and Weekly Rifapentine

↓ 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.

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 expected

Use with caution. Monitor for rifabutin toxicities. Perform rifabutin TDM; 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

Daily and Weekly Rifapentine

↓ fluconazole expected

Monitor for antifungal efficacy; may need to increase fluconazole dose.

Glecaprevir/

Pibrentasvir

Rifabutina

↓ glecaprevir and pibrentasvir possible

Coadministration should be avoided, if possible. Consider alternative agents.

Rifampina

Glecaprevir AUC ↓ 88%

Pibrentasvir AUC ↓ 87%

Do not coadminister.

Rifapentinea

Daily and Weekly Rifapentine

↓ glecaprevir and pibrentasvir expected

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 necessary

Isavuconazole*

Artemether/Lumefantrine

See Artemether/Lumefantrine.

See Artemether/Lumefantrine.

Bedaquiline

See Bedaquiline.

See Bedaquiline.

Chloroquine

See Chloroquine.

See Chloroquine.

Clarithromycin

See Clarithromycin.

See Clarithromycin.

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 antifungal activity and rifabutin toxicity. Perform rifabutin TDM and adjust dose accordingly.

Rifampina

Isavuconazole AUC ↓ 97%

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).

Rifapentinea

Daily and Weekly Rifapentine

↓ 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.

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; perform itraconazole TDM 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

Daily and Weekly Rifapentine

↓ itraconazole expected

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).

Linezolid*

Rifabutina

↓ linezolid possible

Monitor for linezolid efficacy.

Rifampina

Linezolid AUC ↓ 32%

Monitor for linezolid efficacy. Perform linezolid TDM and adjust dose accordingly.

Rifapentinea

Daily Rifapentine

↓ linezolid expected

Weekly Rifapentine

↓ linezolid possible

Daily Rifapentine

Monitor for linezolid efficacy. Perform linezolid TDM and adjust dose accordingly.

Weekly Rifapentine

Monitor for linezolid efficacy.

Mefloquine*

Artemether/Lumefantrine

See Artemether/Lumefantrine.

See Artemether/Lumefantrine.

Clarithromycin

See Clarithromycin.

See Clarithromycin.

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

Daily and Weekly Rifapentine

↓ 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.

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, perform posaconazole and rifabutin TDM and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities.

Rifampina

↓ posaconazole expected

Do not coadminister when treating invasive fungal infections. If coadministered for treatment of noninvasive fungal infections, perform posaconazole TDM and adjust dose accordingly; monitor for clinical response.

Rifapentinea

Daily and Weekly Rifapentine

↓ posaconazole expected

Daily Rifapentine

Do not coadminister when treating invasive fungal infections. If coadministered for treatment of noninvasive fungal infections, perform posaconazole TDM and adjust dose accordingly; monitor for clinical response.

Weekly Rifapentine

Coadministration should be avoided, if possible. If coadministered, perform posaconazole TDM 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 for rifabutin toxicity.

Rifampina

Quinine AUC ↓ 75% to 85%

Do not coadminister.

Rifapentinea

Daily and Weekly Rifapentine

↓ 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.

Dapsone

See Dapsone.

See Dapsone.

Doxycycline

See Doxycycline.

See Doxycycline.

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.

Linezolid

See Linezolid.

See Linezolid.

Mefloquine

See Mefloquine.

See Mefloquine.

Posaconazole

See Posaconazole.

See Posaconazole.

Quinine

See Quinine.

See Quinine.

Sofosbuvir/Velpatasvir

↓ velpatasvir, sofosbuvir expected

Do not coadminister.

TAF

↓ TAF, TFV, TFV-DP expected

↑ TFV-DP expected versus TDF alone

If coadministered, monitor for HIV and HBV treatment efficacy.

Note: Interpretation extrapolated from TAF and rifampin (see Rifampin). FDA labeling recommends not to coadminister.

TDF

↔ TDF, TFV, TFV-DP expected

No dosage adjustment necessary.

Voriconazole

Voriconazole AUC ↓ 79%

Rifabutin AUC ↑ 4-fold

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).

Coadministration may be considered if both voriconazole and rifabutin TDM is available 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.

Dapsone

See Dapsone.

See Dapsone.

Doxycycline

See Doxycycline.

See Doxycycline.

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.

Linezolid

See Linezolid.

See Linezolid.

Mefloquine

See Mefloquine.

See Mefloquine.

Posaconazole

See Posaconazole.

See Posaconazole.

Quinine

See Quinine.

See Quinine.

Sofosbuvir/Velpatasvir

Sofosbuvir AUC ↓ 72%

Velpatasvir AUC ↓ 82%

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 treatment efficacy.

Note: FDA labeling recommends not to coadminister.

TDF

TDF Plus Rifampin 600 mg Daily

↔ TFV

No dosage adjustment necessary

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.

Dapsone

See Dapsone.

See Dapsone.

Doxycycline

See Doxycycline.

See Doxycycline.

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.

Linezolid

See Linezolid.

See Linezolid.

Mefloquine

See Mefloquine.

See Mefloquine.

Posaconazole

See Posaconazole.

See Posaconazole.

Quinine

See Quinine.

See Quinine.

TAF

Daily and Weekly Rifapentine

↓ TAF, TFV, TFV-DP possible

If coadministered, monitor for HIV and HBV treatment efficacy.

Note: FDA labeling recommends not to coadminister.

TDF

↔ TDF, TFV, TFV-DP expected

No dosage adjustment necessary

Sofosbuvir/Velpatasvir

↓ sofosbuvir, velpatasvir expected

Do not coadminister.

Voriconazole

↓ voriconazole expected

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).

Sofosbuvir*/ Velpatasvir

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 necessary

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

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

See Sofosbuvir/Velpatasvir.

See Sofosbuvir/Velpatasvir.

Tenofovir* Disoproxil Fumarate

Rifabutina

See Rifabutin.

See Rifabutin.

Rifampina

See Rifampin.

See Rifampin.

Rifapentinea

See Rifapentine.

See Rifapentine.

Glecaprevir/Pibrentasvir

See Glecaprevir/Pibrentasvir.

See Glecaprevir/Pibrentasvir.

Sofosbuvir/Velpatasvir

See Sofosbuvir/Velpatasvir.

See Sofosbuvir/Velpatasvir.

Voriconazole*

Artemether/Lumefantrine

See Artemether/Lumefantrine.

See Artemether/Lumefantrine.

Bedaquiline

See Bedaquiline.

See Bedaquiline.

Chloroquine

See Chloroquine.

See Chloroquine.

Clarithromycin

See Clarithromycin.

See Clarithromycin.

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 Refer to the subsection Rifamycin-Related Induction Interactions in the Table 4 introduction above.

* Drugs marked with asterisk (*) are those which are known to have assays available (for clinical and/or research purposes) within the United States and typically in Europe. When TDM is appropriate, clinicians should contact their clinical laboratory to determine assay availability and turnaround time for their institution.

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

Key: 14-OH = active metabolite of clarithromycin; AUC = area under the curve; Cmin = minimum concentration; Css = concentration at steady state; des-Rbt = desacetyl rifabutin; DHA = dihydroartemisinin; DRV/r = darunavir/ritonavir; EFV = efavirenz; EVG/c = elvitegravir/cobicistat; FDA = U.S. Food and Drug Administration; FTC = emtricitabine; HBV = hepatitis B virus; RPV = rilpivirine; SOF = sofosbuvir; t1/2 = half-life; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TFV= tenofovir; TFV-DP = tenofovir diphosphate; VEL = velpatasvir; VOX = voxilaprevir

Tables

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

Primary DrugInteracting AgentEffect on Primary and/or Concomitant Drug ConcentrationsRecommendations
Artemether/
Lumefantrine
Clarithromycin↑ lumefantrine expectedCoadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin.
Erythromycin↑ lumefantrine expectedCoadministration should be avoided, if possible. Consider azithromycin in place of erythromycin.
Fluconazole↑ lumefantrine possibleCoadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Isavuconazole↑ lumefantrine possibleCoadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Itraconazole↑ lumefantrine expectedCoadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Mefloquine↓ lumefantrine possibleIf mefloquine is administered immediately before artemether/lumefantrine, monitor for decreased efficacy of artemether/lumefantrine and encourage food intake.
Posaconazole↑ lumefantrine expectedCoadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Rifabutina↓ artemether, DHA, and lumefantrine expectedUse with caution. Monitor for antimalarial efficacy.
Rifampina

Artemether AUC ↓ 89%

DHA AUC ↓ 85%

Lumefantrine AUC ↓ 68%

Do not coadminister.
Rifapentinea

Daily and Weekly Rifapentine

↓ artemether, DHA, and lumefantrine expected

Do not coadminister.
Voriconazole↑ lumefantrine expectedCoadministration should be avoided, if possible. If coadministered, monitor for lumefantrine toxicities.
Atovaquone*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

Daily and Weekly Rifapentine

↓ atovaquone expected

Do not coadminister.
Bedaquiline*Clarithromycin↑ bedaquiline expectedDo not coadminister. Consider azithromycin in place of clarithromycin.
Erythromycin↑ bedaquiline expectedDo not coadminister. Consider azithromycin in place of erythromycin.
Fluconazole↑ bedaquiline possibleCoadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Isavuconazole↑ bedaquiline possibleCoadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Itraconazole↑ bedaquiline expected

Coadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.

If coadministration is required for >14 days, weigh the benefits of therapy against the risks of bedaquiline toxicities.

Posaconazole↑ bedaquiline expectedCoadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
Rifabutina

↔ bedaquiline

↓ rifabutin possible

If coadministered, separate time of administration; perform rifabutin TDM and adjust dose accordingly.
RifampinaBedaquiline AUC ↓ 53%Do not coadminister.
Rifapentinea

Daily Rifapentine

Bedaquiline AUC ↓ 55%

Weekly Rifapentine

↓ bedaquiline expected

Do not coadminister.
Voriconazole↑ bedaquiline expectedCoadministration should be avoided, if possible. If coadministered, monitor for bedaquiline toxicities.
BrincidofovirClarithromycin↑ brincidofovir expected

Coadministration should be avoided, if possible. If coadministered, postpone clarithromycin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.

Consider azithromycin in place of clarithromycin.

Erythromycin↑ brincidofovir expected

Coadministration should be avoided, if possible. If coadministered, postpone erythromycin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.

Consider azithromycin in place of erythromycin.

Rifampin↑ brincidofovir expectedCoadministration should be avoided, if possible. If coadministered, postpone rifampin for at least 3 hours after brincidofovir and monitor for brincidofovir toxicities.
CaspofunginRifabutina↓ caspofungin possibleMonitor for antifungal efficacy. Dose not established. Consider increasing caspofungin dose to 70 mg/day or switch to another echinocandin (e.g., micafungin or anidulafungin).
RifampinaCaspofungin Cmin ↓ 30%If coadministered, caspofungin dose should be increased to 70 mg/day. Consider alternative echinocandin (e.g., micafungin or anidulafungin).
Rifapentinea

Daily Rifapentine

  • ↓ caspofungin expected

Weekly Rifapentine

  • ↓ 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 expectedDo not coadminister. Consider azithromycin in place of clarithromycin.
Erythromycin↑ chloroquine expectedDo not coadminister. Consider azithromycin in place of erythromycin.
Fluconazole↑ chloroquine possibleCoadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Isavuconazole↑ chloroquine possibleCoadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Itraconazole↑ chloroquine expectedCoadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Posaconazole↑ chloroquine expectedCoadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Rifabutina↓ chloroquine expectedMonitor for chloroquine efficacy.
Rifampina↓ chloroquine expectedMonitor for chloroquine efficacy.
Rifapentinea

Daily and Weekly Rifapentine

↓ chloroquine expected

Monitor for chloroquine efficacy.
Voriconazole↑ chloroquine expectedCoadministration should be avoided, if possible. If coadministered, monitor for chloroquine toxicities.
Clarithromycin*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
FluconazoleClarithromycin AUC ↑ 18% and Cmin↑ 33%No dose adjustment necessary in patients with normal renal function. Monitor for clarithromycin toxicity.
Isavuconazole↑ isavuconazole and clarithromycin expectedCoadministration 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 expectedCoadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of both itraconazole and clarithromycin; perform itraconazole and clarithromycin TDM and adjust dose accordingly.
Mefloquine↑ mefloquine expectedUse with caution. Consider azithromycin in place of clarithromycin. If coadministered, monitor for mefloquine toxicity.
Posaconazole↑ clarithromycin expectedCoadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of clarithromycin; perform clarithromycin TDM and adjust dose accordingly.
Quinine

↑ quinine expected

↑ clarithromycin possible

Do not coadminister. Consider azithromycin in place of clarithromycin.
Rifabutina

Clarithromycin AUC ↓ 44%

14-OH clarithromycin 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, perform clarithromycin and rifabutin TDM and adjust dose accordingly. Monitor for rifabutin toxicities.
Rifampina

Clarithromycin concentration ↓ 87%

Rifampin AUC ↑ 60%

Do not coadminister. Use azithromycin in place of clarithromycin.
Rifapentinea

Daily and Weekly Rifapentine

↓ clarithromycin expected

↑ 14-OH clarithromycin and rifapentine expected

Daily Rifapentine

  • Do not coadminister. Use azithromycin in place of clarithromycin.

Weekly Rifapentine

  • Use with caution. Consider azithromycin in place of clarithromycin.

If coadministered, monitor for rifapentine toxicities and clarithromycin efficacy; perform clarithromycin and rifapentine TDM and adjust doses accordingly.

Voriconazole↑ clarithromycin expectedCoadministration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If coadministered, monitor for toxicities of clarithromycin; perform clarithromycin TDM and adjust dose accordingly.
Dapsone*RifabutinaDapsone AUC ↓ 27% to 40%Coadministration should be avoided, if possible. Consider alternatives for dapsone.
RifampinaDapsone concentration ↓ 7-fold to 10-fold and t1/2 ↓ from 24 hours to 11 hoursCoadministration should be avoided, if possible. Consider alternatives for dapsone.
Rifapentinea

Daily and Weekly Rifapentine

↓ dapsone expected

Coadministration should be avoided, if possible. Consider alternatives for dapsone.
DoxycyclineAtovaquoneSee Atovaquone.See Atovaquone.
Rifabutina↓ doxycycline possibleMonitor closely for doxycycline efficacy or consider alternative therapy.
RifampinaDoxycycline AUC ↓ 59%Use with caution. Monitor closely for doxycycline efficacy or consider alternative therapy.
Rifapentinea

Daily Rifapentine

  • ↓ doxycycline expected

Weekly Rifapentine

  • ↓ doxycycline possible
Use with caution. Monitor closely for doxycycline efficacy or consider alternative therapy.
ErythromycinArtemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
Fluconazole↑ erythromycin possibleDo not coadminister. Consider azithromycin in place of erythromycin.
Isavuconazole↑ erythromycin and isavuconazole possibleDo 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 possibleDo not coadminister. Consider azithromycin in place of erythromycin.
Posaconazole↑ erythromycin expectedDo 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 and rifabutin toxicities; perform rifabutin TDM and adjust dose accordingly.
Rifampina↓ erythromycin expectedConsider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy.
Rifapentinea

Daily and Weekly Rifapentine

↓ erythromycin expected

Consider azithromycin in place of erythromycin. If coadministered, monitor for erythromycin efficacy.
Voriconazole↑ erythromycin expectedDo not coadminister. Consider azithromycin in place of erythromycin.
Fluconazole*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
Mefloquine↑ mefloquine possibleCoadministration 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 expected

Use with caution. Monitor for rifabutin toxicities. Perform rifabutin TDM; may need to decrease rifabutin dose to 150 mg/day.
RifampinaFluconazole AUC ↓ 23% to 56%Monitor for antifungal efficacy; may need to increase fluconazole dose.
Rifapentinea

Daily and Weekly Rifapentine

↓ fluconazole expected

Monitor for antifungal efficacy; may need to increase fluconazole dose.

Glecaprevir/

Pibrentasvir

Rifabutina↓ glecaprevir and pibrentasvir possibleCoadministration should be avoided, if possible. Consider alternative agents.
Rifampina

Glecaprevir AUC ↓ 88%

Pibrentasvir AUC ↓ 87%

Do not coadminister.
Rifapentinea

Daily and Weekly Rifapentine

↓ glecaprevir and pibrentasvir expected

Do not coadminister. Consider alternative agents.
TDFTFV AUC ↑ 29% when coadministered as EFV/TDF/FTCUse usual dose. Monitor renal function or consider TAF.
TAF↔ TFV concentration when coadministered as EVG/c/TAF/FTCNo dose adjustment necessary
Isavuconazole*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
Mefloquine↑ mefloquine expectedCoadministration 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 antifungal activity and rifabutin toxicity. Perform rifabutin TDM and adjust dose accordingly.
RifampinaIsavuconazole AUC ↓ 97%Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea

Daily and Weekly Rifapentine

↓ isavuconazole expected

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Itraconazole*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
Mefloquine↑ mefloquine expectedCoadministration 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; perform itraconazole TDM and adjust dose accordingly.
Rifabutina

Itraconazole AUC ↓ 70%

↑ rifabutin expected

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
RifampinaItraconazole AUC ↓ 64% to 88%Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea

Daily and Weekly Rifapentine

↓ itraconazole expected

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Linezolid*Rifabutina↓ linezolid possibleMonitor for linezolid efficacy.
RifampinaLinezolid AUC ↓ 32%Monitor for linezolid efficacy. Perform linezolid TDM and adjust dose accordingly.
Rifapentinea

Daily Rifapentine

↓ linezolid expected

Weekly Rifapentine

↓ linezolid possible

Daily Rifapentine

Monitor for linezolid efficacy. Perform linezolid TDM and adjust dose accordingly.

Weekly Rifapentine

Monitor for linezolid efficacy.

Mefloquine*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
FluconazoleSee Fluconazole.See Fluconazole.
IsavuconazoleSee Isavuconazole.See Isavuconazole.
ItraconazoleSee Itraconazole.See Itraconazole.
Posaconazole↑ mefloquine expectedCoadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Rifabutina↓ mefloquine possibleMonitor for mefloquine efficacy.
RifampinaMefloquine AUC ↓ 68%Do not coadminister. Use alternative antimalarial drug or rifabutin.
Rifapentinea

Daily and Weekly Rifapentine

↓ mefloquine expected

Do not coadminister. Use alternative antimalarial drug or rifabutin.
Voriconazole↑ mefloquine expectedCoadministration should be avoided, if possible. If coadministered, monitor for mefloquine toxicities.
Posaconazole*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
MefloquineSee 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, perform posaconazole and rifabutin TDM and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities.
Rifampina↓ posaconazole expectedDo not coadminister when treating invasive fungal infections. If coadministered for treatment of noninvasive fungal infections, perform posaconazole TDM and adjust dose accordingly; monitor for clinical response.
Rifapentinea

Daily and Weekly Rifapentine

↓ posaconazole expected

Daily Rifapentine

Do not coadminister when treating invasive fungal infections. If coadministered for treatment of noninvasive fungal infections, perform posaconazole TDM and adjust dose accordingly; monitor for clinical response.

Weekly Rifapentine

Coadministration should be avoided, if possible. If coadministered, perform posaconazole TDM and adjust dose accordingly; monitor clinical response.

Quinine*ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
FluconazoleSee Fluconazole.See Fluconazole.
ItraconazoleSee Itraconazole.See Itraconazole.
PosaconazoleSee Posaconazole.See Posaconazole.
Rifabutina

↓ quinine possible

↑ rifabutin possible

Monitor for quinine efficacy.

Monitor for rifabutin toxicity.

RifampinaQuinine AUC ↓ 75% to 85%Do not coadminister.
Rifapentinea

Daily and Weekly Rifapentine

↓ quinine expected

Do not coadminister.
Voriconazole↑ quinine expectedCoadministration should be avoided, if possible. If coadministered, monitor for quinine toxicities.
Rifabutina*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
AtovaquoneSee Atovaquone.See Atovaquone.
BedaquilineSee Bedaquiline.See Bedaquiline.
CaspofunginSee Caspofungin.See Caspofungin.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
DapsoneSee Dapsone.See Dapsone.
DoxycyclineSee Doxycycline.See Doxycycline.
ErythromycinSee Erythromycin.See Erythromycin.
FluconazoleSee Fluconazole.See Fluconazole.
Glecaprevir/PibrentasvirSee Glecaprevir/Pibrentasvir.See Glecaprevir/Pibrentasvir.
IsavuconazoleSee Isavuconazole.See Isavuconazole.
ItraconazoleSee Itraconazole.See Itraconazole.
LinezolidSee Linezolid.See Linezolid.
MefloquineSee Mefloquine.See Mefloquine.
PosaconazoleSee Posaconazole.See Posaconazole.
QuinineSee Quinine.See Quinine.
Sofosbuvir/Velpatasvir↓ velpatasvir, sofosbuvir expectedDo not coadminister.
TAF

↓ TAF, TFV, TFV-DP expected

↑ TFV-DP expected versus TDF alone

If coadministered, monitor for HIV and HBV treatment efficacy.

Note: Interpretation extrapolated from TAF and rifampin (see Rifampin). FDA labeling recommends not to coadminister.

TDF↔ TDF, TFV, TFV-DP expectedNo dosage adjustment necessary.
Voriconazole

Voriconazole AUC ↓ 79%

Rifabutin AUC ↑ 4-fold

Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).

Coadministration may be considered if both voriconazole and rifabutin TDM is available to guide therapy.

Rifampina*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
AtovaquoneSee Atovaquone.See Atovaquone.
BedaquilineSee Bedaquiline.See Bedaquiline.
CaspofunginSee Caspofungin.See Caspofungin.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
DapsoneSee Dapsone.See Dapsone.
DoxycyclineSee Doxycycline.See Doxycycline.
ErythromycinSee Erythromycin.See Erythromycin.
FluconazoleSee Fluconazole.See Fluconazole.
Glecaprevir/PibrentasvirSee Glecaprevir/Pibrentasvir.See Glecaprevir/Pibrentasvir.
IsavuconazoleSee Isavuconazole.See Isavuconazole.
ItraconazoleSee Itraconazole.See Itraconazole.
LinezolidSee Linezolid.See Linezolid.
MefloquineSee Mefloquine.See Mefloquine.
PosaconazoleSee Posaconazole.See Posaconazole.
QuinineSee Quinine.See Quinine.
Sofosbuvir/Velpatasvir

Sofosbuvir AUC ↓ 72%

Velpatasvir AUC ↓ 82%

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 treatment efficacy.

Note: FDA labeling recommends not to coadminister.

TDF

TDF Plus Rifampin 600 mg Daily

↔ TFV

No dosage adjustment necessary
VoriconazoleVoriconazole AUC ↓96%Do not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Rifapentinea*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
AtovaquoneSee Atovaquone.See Atovaquone.
BedaquilineSee Bedaquiline.See Bedaquiline.
CaspofunginSee Caspofungin.See Caspofungin.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
DapsoneSee Dapsone.See Dapsone.
DoxycyclineSee Doxycycline.See Doxycycline.
ErythromycinSee Erythromycin.See Erythromycin.
FluconazoleSee Fluconazole.See Fluconazole.
Glecaprevir/PibrentasvirSee Glecaprevir/Pibrentasvir.See Glecaprevir/Pibrentasvir.
IsavuconazoleSee Isavuconazole.See Isavuconazole.
ItraconazoleSee Itraconazole.See Itraconazole.
LinezolidSee Linezolid.See Linezolid.
MefloquineSee Mefloquine.See Mefloquine.
PosaconazoleSee Posaconazole.See Posaconazole.
QuinineSee Quinine.See Quinine.
TAF

Daily and Weekly Rifapentine

↓ TAF, TFV, TFV-DP possible

If coadministered, monitor for HIV and HBV treatment efficacy.

Note: FDA labeling recommends not to coadminister.

TDF↔ TDF, TFV, TFV-DP expectedNo dosage adjustment necessary
Sofosbuvir/Velpatasvir↓ sofosbuvir, velpatasvir expectedDo not coadminister.
Voriconazole↓ voriconazole expectedDo not coadminister. Consider alternative antifungal and/or antimycobacterial agent(s).
Sofosbuvir*/ VelpatasvirRifabutinaSee Rifabutin.See Rifabutin.
RifampinaSee Rifampin.See Rifampin.
RifapentineaSee Rifapentine.See Rifapentine.
TAFTFV AUC ↑ 52% (when RPV/TAF/FTC given with SOF/VEL/VOX)No dosage adjustment necessary
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* AlafenamideGlecaprevir/PibrentasvirSee Glecaprevir/Pibrentasvir.See Glecaprevir/Pibrentasvir.
RifabutinaSee Rifabutin.See Rifabutin.
RifampinaSee Rifampin.See Rifampin.
RifapentineaSee Rifapentine.See Rifapentine.
Sofosbuvir/VelpatasvirSee Sofosbuvir/Velpatasvir.See Sofosbuvir/Velpatasvir.
Tenofovir* Disoproxil FumarateRifabutinaSee Rifabutin.See Rifabutin.
RifampinaSee Rifampin.See Rifampin.
RifapentineaSee Rifapentine.See Rifapentine.
Glecaprevir/PibrentasvirSee Glecaprevir/Pibrentasvir.See Glecaprevir/Pibrentasvir.
Sofosbuvir/VelpatasvirSee Sofosbuvir/Velpatasvir.See Sofosbuvir/Velpatasvir.
Voriconazole*Artemether/LumefantrineSee Artemether/Lumefantrine.See Artemether/Lumefantrine.
BedaquilineSee Bedaquiline.See Bedaquiline.
ChloroquineSee Chloroquine.See Chloroquine.
ClarithromycinSee Clarithromycin.See Clarithromycin.
ErythromycinSee Erythromycin.See Erythromycin.
MefloquineSee Mefloquine.See Mefloquine.
QuinineSee Quinine.See Quinine.
RifabutinaSee Rifabutin.See Rifabutin.
RifampinaSee Rifampin.See Rifampin.
RifapentineaSee Rifapentine.See Rifapentine.

a Refer to the subsection Rifamycin-Related Induction Interactions in the Table 4 introduction above.

* Drugs marked with asterisk (*) are those which are known to have assays available (for clinical and/or research purposes) within the United States and typically in Europe. When TDM is appropriate, clinicians should contact their clinical laboratory to determine assay availability and turnaround time for their institution.

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

Key: 14-OH = active metabolite of clarithromycin; AUC = area under the curve; Cmin = minimum concentration; Css = concentration at steady state; des-Rbt = desacetyl rifabutin; DHA = dihydroartemisinin; DRV/r = darunavir/ritonavir; EFV = efavirenz; EVG/c = elvitegravir/cobicistat; FDA = U.S. Food and Drug Administration; FTC = emtricitabine; HBV = hepatitis B virus; RPV = rilpivirine; SOF = sofosbuvir; t1/2 = half-life; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TFV= tenofovir; TFV-DP = tenofovir diphosphate; VEL = velpatasvir; VOX = voxilaprevir

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