Updated Reviewed

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

The potential exists for significant drug interactions and overlapping toxicities in children receiving medications for treatment or prevention of opportunistic infections (OIs). These children often receive other medications, including antiretrovirals, that interfere with the metabolism or elimination of OI medications. In particular, protease inhibitors and non-nucleoside reverse transcriptase inhibitors affect the cytochrome P450 or other transporter systems and may be associated with clinically significant drug interactions. The integrase strand transfer inhibitors cabotegravir and raltegravir are primarily metabolized by uridine diphosphate glucuronosyltransferase 1A1 and may be a suitable option when trying to minimize interactions with other drug classes.

Table 5 provides clinicians with information regarding known or suspected drug interactions between drugs commonly used for the treatment or prevention of HIV-associated OIs and treatment of HIV infection. Drug interaction information is generally obtained from studies involving healthy adult volunteers. Some pharmacokinetic data are available from studies involving adults with HIV, whereas data in children are extremely limited. New information continues to become available, and carefully reviewing each child’s current medications, including prescription and over-the-counter medications, is important. predicting the interaction potential is difficult when three or more drugs with similar metabolic pathways are coadministered, and significant interpatient variability amplifies these challenges. When possible, alternative agents with less drug interaction potential or use of therapeutic drug monitoring should be considered.

 

Drug NameToxicitiesRecommendation
* The drug interactions included in this table were selected based on their potential clinical significance and are not inclusive of all potential drug interactions (see FDA Online Label Repository for complete information on drug interactions).
Acyclovir

 

Overlapping Toxicities

  • Nephrotoxic drugs
Avoid other nephrotoxic drugs.

Increased Concentrations (Both Drugs) and Overlapping Toxicities

  • Antivirals: valacyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
  • Immunosuppressive agents: mycophenolate
Monitor for toxicities of these drugs.
Albendazole

Increased Albendazole Concentrations

  • Anthelmintics: praziquantel

Decreased Albendazole Concentrations

  • Anticonvulsants: carbamazepine, phenobarbital, phenytoin
  • Antivirals: nirmatrelvir and ritonavir
Caution advised.
Amikacin

Overlapping Toxicities

  • Antituberculars (injectable): kanamycin, streptomycin
  • Nephrotoxic or ototoxic drugs
  • Antimycobacterials: capreomycin
  • ARVs: tenofovir
  • Antivirals: cidofovir
Caution advised. Avoid combining with cidofovir.

Amphotericin B 
Amphotericin B Lipid Complex 
 

Amphotericin B Liposome

Overlapping Toxicities

  • Bone marrow suppressants: corticosteroids
  • Nephrotoxic drugs
  • Neuromuscular blockers
Caution advised.
Artemether-Lumefantrine

Increased Drug Concentrations

  • ARVs: nevirapine
Monitor therapy when combined.

Overlapping Toxicities

  • ARVs: PIs
  • Antibacterials: fluoroquinolones, macrolides
  • Antifungals: fluconazole, voriconazole
  • Antimalarials: quinidine, quinine
  • Psychotropics: quetiapine, tricyclic antidepressants
Coadministration with fluconazole or voriconazole should be avoided. For all other drugs, coadministration should be avoided, if possible; monitor for toxicities (QT prolongation). 
Atovaquone

Decreased Atovaquone Concentrations

  • Antimycobacterials: rifampin, rifabutin
  • ARVs: lopinavir/ritonavir, atazanavir/ritonavir
  • Antibiotics: doxycycline
Coadministration of atovaquone and rifampin or atovaquone and rifabutin should be avoided.
Azithromycin

Overlapping Toxicities

  • Antimalarials: artemether/lumefantrine, chloroquine, quinine
Caution advised. Increased risk of QT prolongation.
Bedaquiline

Overlapping Toxicities

  • QT-prolonging agents
Bedaquiline may enhance the QTc-prolonging effects. Avoid concomitant use.
  • Fecal microbiota (live) (oral and rectal)
Avoid concomitant use.
Caspofungin

Decreased Caspofungin Concentrations

  • Anticonvulsants: phenytoin
  • Antimycobacterials: rifampin
  • ARVs: efavirenz, nevirapine
Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers.
Cidofovir

Overlapping Toxicities

  • Antibacterials: aminoglycosides
  • Antivirals: foscarnet
  • ARVs: tenofovir
  • Nephrotoxic drugs

Monitor for toxicities of these drugs.

Prehydrate with IV normal saline and probenecid to avoid nephrotoxicity.

Ciprofloxacin

Decreased Ciprofloxacin Absorption

  • ARVs: didanosine
  • Minerals: ferrous sulfate, zinc
  • Gastrointestinal drugs: antacids, sucralfate, magnesium-containing laxatives
Give oral ciprofloxacin 2 hours before or 6 hours after drugs that may interfere with absorption.

Overlapping Toxicities

  • Antimalarials: artemether/lumefantrine, quinine
  • Antibacterials: clarithromycin
Caution advised.
  • Fecal microbiota (live) (oral and rectal)
Avoid concomitant use.
Clarithromycin

Increased Clarithromycin Concentrations

  • ARVs: atazanavir/ritonavir, lopinavir/ritonavir
  • Antifungals: itraconazole (itraconazole concentrations also increased)

Caution advised. Concern for QTc prolongation.

Decrease clarithromycin dose or consider switching to azithromycin, which has less potential for drug interactions.

Increased Concomitant Drug Concentrations

  • ARVs: etravirine
Consider alternative ARV.

Decreased Clarithromycin Concentrations

  • ARVs: efavirenz, etravirine, nevirapine
  • Antimycobacterials: rifampin, rifabutin (rifabutin concentrations also increased)

Consider switching to azithromycin, which has less potential for drug interaction.

For concomitant use of rifabutin and clarithromycin, consider decreasing dose of rifabutin or switching to azithromycin.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Clarithromycin may reduce fecal microbiota (live) (rectal) effectiveness.
Clindamycin

Decreased Clindamycin Antibacterial Efficacy

  • Antibacterials: chloramphenicol, erythromycin

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Cycloserine

Overlapping Toxicities

  • Antimycobacterials: ethionamide, isoniazid
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Dapsone

Decreased Dapsone Concentrations

  • Antimycobacterials: rifampin
Coadministration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.

Decreased Dapsone Absorption

  • ARVs: atazanavir, didanosine suspension
  • Gastrointestinal drugs: antacids
For coadministration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication.

Overlapping Toxicities

  • Bone marrow suppressants or drugs associated with hemolysis
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Doxycycline

Decreased Doxycycline Concentrations

  • Anticonvulsants: carbamazepine, phenytoin
  • Antimycobacterials: rifampin
Potential for decreased doxycycline efficacy. Monitor for therapeutic failure.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Erythromycin

Increased Concentrations of Erythromycin

  • Antifungals: itraconazole (itraconazole concentrations also increased)

Increased Concomitant Drug Concentrations

  • ARVs: tenofovir
Monitor for toxicities of both drugs, potential for QT prolongation.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Ethambutol

Overlapping Toxicities

  • Neurotoxic drugs
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Ethionamide

Potential for Increased Toxicity Due to Overlapping Toxicity

  • Neurotoxic drugs
  • Antimycobacterials: cycloserine, isoniazid
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Fluconazole

Decreased Fluconazole Levels

  • Anticonvulsants: phenytoin
  • Antimycobacterials: rifampin
  • ARVs: rilpivirine
Monitor for efficacy. May need to increase fluconazole dose.

Increases Concomitant Drug Concentrations

  • ARVs: etravirine, nevirapine, saquinavir, tipranavir
May need to decrease dose of saquinavir. Avoid tipranavir with high doses of fluconazole (maximum fluconazole dose in adults: 200 mg). Caution advised with etravirine.
  • Antineoplastics: venetoclax
Decrease venetoclax dose by at least 50% in children requiring concomitant treatment.
  • Antimycobacterials: rifabutin
May need to decrease dose of rifabutin.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins, such as fluvastatin, rosuvastatin, and pravastatin, are preferred, or discontinue statin during antifungal therapy.
Flucytosine

Increased Flucytosine Concentrations

  • Nephrotoxic drugs

Overlapping Toxicities

  • QT-prolonging drugs

Caution advised.

Dose adjustments with therapeutic drug monitoring recommended with impaired renal function. 

Foscarnet

Overlapping Toxicities

  • Antivirals: cidofovir
  • Anti-pneumocystis drugs: pentamidine
  • Nephrotoxic drugs
Monitor for toxicities of these drugs.
Ganciclovir

Increased Ganciclovir Concentrations

  • ARVs: tenofovir (concentrations also increased)
Monitor for toxicities of these drugs.

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Caution advised.

Overlapping Toxicities

  • Antibacterials: imipenem-cilastatin
  • ARVs: zidovudine
  • Bone marrow suppressants
  • Nephrotoxic drugs
Caution advised. Increased risk of seizures with imipenem-cilastatin.
Isavuconazole

Increased Concomitant Drug Concentrations

  • Antineoplastics: venetoclax
Reduce venetoclax dose by at least 50% in children requiring concomitant treatment. Resume previous venetoclax dose two to three days after discontinuation of isavuconazole.
Isoniazid

Decreased Isoniazid Concentrations

  • Corticosteroids: glucocorticoids (e.g., prednisolone)
Use with caution.

Decreased Isoniazid Absorption

  • Gastrointestinal drugs: antacids

Caution advised.

Take ≥1 hour before aluminum-containing antacids.

Increased Concomitant Drug Concentrations

  • Sedatives/hypnotics: diazepam
Caution advised.

Decreased Concomitant Drug Concentrations

  • Antifungals: itraconazole, ketoconazole  
Coadministration should be avoided, if possible.

Overlapping Toxicities

  • Antimycobacterials: cycloserine, ethionamide, itraconazole
  • Hepatotoxic drugs
  • Neurotoxic drugs
Caution advised.
Itraconazole and Ketoconazole

Increased Azole Concentrations

  • Antibacterials: clarithromycin, ciprofloxacin, erythromycin
  • ARVs: PIs
Monitor for toxicities and monitor concentrations. Consider azithromycin instead of other macrolides. High doses of itraconazole are not recommended with PIs.

Increased Concomitant Drug Concentrations

  • ARVs: etravirine, maraviroc, PIs
Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Antibacterials: clarithromycin, erythromycin
Consider switching to azithromycin, which has less potential for drug interaction.
  • Sedatives/hypnotics: alprazolam, diazepam, midazolam
Coadministration of midazolam and alprazolam should be avoided. Coadministration of diazepam should be avoided, if possible.
  • Antimalarial: quinidine
Coadministration of quinidine should be avoided. QT prolongation may occur.

Decreased Azole Concentrations

  • ARVs: efavirenz, etravirine, nevirapine, rilpivirine
Monitor concentrations. Coadministration of efavirenz should be avoided if possible.
  • Anticonvulsants: carbamazepine, fosphenytoin
Monitor concentrations.
  • Antimycobacterials: isoniazid, rifabutin, rifampin, rifapentine
Coadministration with rifampin should be avoided. Coadministration with rifabutin should be avoided, if possible. Monitor for toxicities and monitor concentrations.

Decreased Azole Absorption

  • ARVs: didanosine
  • Gastrointestinal drugs: antacids, anticholinergics/antispasmodics, histamine H2-receptor antagonists, omeprazole, sucralfate
Monitor concentrations.
Mefloquine

Decreased Mefloquine Concentrations

  • Antimalarials: quinine
  • Antimycobacterials: rifampin

Monitor for decreased mefloquine efficacy.

Coadministration of rifampin should be avoided, if possible; use rifabutin instead.

Decreased Concomitant Drug Concentrations

  • ARVs: ritonavir, possibly other PIs
Monitor for virologic failure of PI-containing ART regimen.

Overlapping Toxicities

  • Antimalarials: quinine
  • QT-prolonging drugs
Avoid coadministration, if possible. Monitor for toxicities (EKG changes, cardiac arrest, and seizures with quinine). If coadministered with quinine, give mefloquine at least 12 hours after last dose of quinine.
Nitazoxanide

Increased Concomitant Drug Concentrations

  • Anticonvulsants: phenytoin
Potential for interaction with other medications that are highly protein-bound. Use with caution as interaction will increase concentrations of concomitant medication.
Pentamidine

Overlapping Toxicities

  • Antivirals: foscarnet
Coadministration should be avoided, if possible. Monitor for toxicities (hypocalcemia, QT prolongation).
  • ARVs: didanosine, PIs
Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation with PIs; pancreatitis for didanosine).
  • Bone marrow suppressants
Monitor for toxicities.
  • Nephrotoxic drugs
Monitor for toxicities.
  • QT-prolonging drugs
Monitor for toxicities. Avoid coadministration, if possible.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Posaconazole

Decreased Posaconazole Drug Concentrations

  • ARVs: efavirenz, fosamprenavir, rilpivirine
Coadministration of fosamprenavir should be avoided. Coadministration of efavirenz should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.
  • Anticonvulsants: phenytoin
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.
  • Antimycobacterials: rifabutin, rifampin
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.

Increased Concomitant Drug Concentrations

  • ARVs: atazanavir, etravirine, lopinavir, ritonavir, saquinavir
Coadministration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary.
  • Antibacterials: clarithromycin, erythromycin
Coadministration should be avoided.
  • Anticonvulsants: phenytoin
Coadministration should be avoided.
  • Sedatives/hypnotics: alprazolam, diazepam, midazolam
Coadministration should be avoided, if possible. Monitor for toxicities.
  • Antimycobacterials: rifabutin
Coadministration should be avoided.
  • Statins: atorvastatin, lovastatin, simvastatin
  • Antineoplastics: venetoclax
  • Immunosuppressives: sirolimus, tacrolimus
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Antimalarials: halofantrine, lumefantrine, mefloquine, quinidine, quinine
Coadministration should be avoided.

Decreased Concomitant Drug Concentrations

  • ARVs: fosamprenavir
Coadministration should be avoided.
  • QT-prolonging drugs
Use with caution. Monitor for toxicities.
Proguanil

Decreased Proguanil Concentrations

  • ARVs: Atazanavir/ritonavir, efavirenz, lopinavir/ritonavir
Use with caution.
Pyrazinamide

Overlapping Toxicities

  • Antimycobacterials: ethionamide, rifampin
  • Hepatotoxic drugs
Use with caution. Monitor for hepatotoxicity.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Quinidine

Increased Quinidine Concentrations

  • ARVs: PIs
Coadministration of PIs should be avoided. Increased risk of arrhythmia. Coadministration may be necessary in the presence of life-threatening, severe malaria and in the absence of other therapy, while artesunate is obtained from the CDC.
  • Antifungals: itraconazole, posaconazole, voriconazole
Coadministration should be avoided. Increased risk of arrhythmia.

Decreased Quinidine Concentrations

  • ARVs: etravirine
Use with caution. Monitor quinidine levels.

Increased Concomitant Drug Concentrations

  • Tricyclic antidepressants
Coadministration should be avoided, if possible. Monitor for toxicities.

Overlapping Toxicities

  • QT-prolonging drugs
Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation).
Ribavirin

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Coadministration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity.

Decreased Concomitant Drug Concentrations

  • ARVs: stavudine, zidovudine
Coadministration should be avoided, if possible.

Overlapping Toxicities

  • ARVs: zidovudine, all NRTIs
Coadministration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine, lactic acidosis for all NRTIs).
Rifabutin

Increased Rifabutin Concentrations

  • ARVs: cobicistat, PIs
Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if coadministered with PIs.
  • Fluconazole
Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction.
  • Voriconazole, itraconazole, posaconazole
Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Antibacterials: clarithromycin
Coadministration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead.

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Use with caution. Monitor for didanosine toxicity.

Decreased Rifabutin Concentrations

  • ARVs: efavirenz, etravirine
Use with caution. Higher rifabutin dose required with efavirenz. Consider TDM.

Decreased Concomitant Drug Concentrations

  • ARVs: rilpivirine, bictegravir, cabotegravir, dolutegravir, raltegravir, lenacapavir
Coadministration should be avoided.
  • ARVs: etravirine, maraviroc, saquinavir
Coadministration should be avoided, if possible.
  • Antibacterials: atovaquone, dapsone
Use with caution. Monitor for dapsone treatment failure.
  • Antifungals: azoles (except for fluconazole)
Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Contraceptives: oral
Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
Rifampin

Decreased Concomitant Drug Concentrations

  • Contraceptives: oral
Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
  • ARVs: PIs ± ritonavir, nevirapine, bictegravir, cabotegravir, dolutegravir, raltegravir, rilpivirine, maraviroc, cobicistat, zidovudine, lenacapavir

Significantly decreases exposure of ARVs; coadministration should be avoided if possible.

Nevirapine: use only if other options are not available and close virologic and immunologic monitoring can be done; consider efavirenz instead.

Raltegravir and dolutegravir dose increases may be required.

  • Antimicrobials: atovaquone, clarithromycin, dapsone, doxycycline
Coadministration of atovaquone and rifampin should be avoided. Consider switching clarithromycin to azithromycin, which has less potential for drug interaction. Dapsone and doxycycline efficacy may be reduced.
  • Antifungals: azoles, caspofungin

Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers.

Monitor azoles for efficacy. May need to increase azole dose.

  • Other: corticosteroids, methadone

Caution advised with corticosteroids (decreased efficacy).

Monitor for efficacy and/or opiate withdrawal symptoms with methadone.

Overlapping Toxicities

  • Bone marrow suppressants
  • Hepatotoxic drugs
Monitor for toxicities of these drugs.
Streptomycin

 Overlapping Toxicities

  • Nephrotoxic drugs
  • Neuromuscular blockers
Monitor for toxicities of these drugs.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Trimethoprim-Sulfamethoxazole (TMP-SMX)

Overlapping Toxicities

  • Folate antagonists
  • Bone marrow suppressants
Monitor for toxicities of these drugs.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use. 
Valacyclovir

Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities

  • Antivirals: acyclovir, cidofovir, ganciclovir, valganciclovir
  • ARVs: tenofovir, zidovudine

Monitor for toxicities of these drugs.

Avoid other nephrotoxic drugs.

Valganciclovir

Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities

  • Antivirals: acyclovir, cidofovir, ganciclovir, valacyclovir
  • ARVs: tenofovir, zidovudine

Monitor for toxicities of these drugs.

Avoid other nephrotoxic drugs.

Voriconazole

Decreased Voriconazole Concentrations

  • Anticonvulsants: carbamazepine, long-acting barbiturates
Caution advised.
  • Antimycobacterials: rifabutin, rifampin
Rifabutin and rifampin coadministration should be avoided.
  • ARVs: efavirenz, nevirapine, ritonavir-boosted PIs

Standard doses of efavirenz and voriconazole should not be used; voriconazole dose may need to be increased and efavirenz dose decreased, or use alternative antifungal agent.

Potential for increased PI concentrations and decreased voriconazole concentrations; consider monitoring voriconazole concentrations and adjust dose accordingly; monitor for PI-associated toxicities or consider using an alternative antifungal agent.

Increased Voriconazole Concentrations

  • ARVs: etravirine (etravirine concentrations also increased)
Monitor voriconazole concentrations to reduce toxicity.

Increased Concomitant Drug Concentrations

  • Antimycobacterials: rifabutin
Caution advised.
  • ARVs: ritonavir-boosted PIs, efavirenz
Caution advised.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Sedatives/hypnotics: alprazolam, midazolam, triazolam
Coadministration should be avoided if possible. Monitor for toxicities.

Key: ART = antiretroviral therapy; ARV = antiretroviral; CDC = Centers for Disease Control and Prevention; CYP450 = cytochrome P450; EKG = electrocardiogram; FDA = U.S. Food and Drug Administration; IV = intravenous; NRTI = nucleoside reverse transcriptase inhibitors; PI = protease inhibitors; QT = interval between Q and T waves; QTc = QT interval corrected for heart rate; TDM = therapeutic drug monitoring

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

Drug NameToxicitiesRecommendation
* The drug interactions included in this table were selected based on their potential clinical significance and are not inclusive of all potential drug interactions (see FDA Online Label Repository for complete information on drug interactions).
Acyclovir

 

Overlapping Toxicities

  • Nephrotoxic drugs
Avoid other nephrotoxic drugs.

Increased Concentrations (Both Drugs) and Overlapping Toxicities

  • Antivirals: valacyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
  • Immunosuppressive agents: mycophenolate
Monitor for toxicities of these drugs.
Albendazole

Increased Albendazole Concentrations

  • Anthelmintics: praziquantel

Decreased Albendazole Concentrations

  • Anticonvulsants: carbamazepine, phenobarbital, phenytoin
  • Antivirals: nirmatrelvir and ritonavir
Caution advised.
Amikacin

Overlapping Toxicities

  • Antituberculars (injectable): kanamycin, streptomycin
  • Nephrotoxic or ototoxic drugs
  • Antimycobacterials: capreomycin
  • ARVs: tenofovir
  • Antivirals: cidofovir
Caution advised. Avoid combining with cidofovir.

Amphotericin B

Amphotericin B Lipid Complex

Amphotericin B Liposome

Overlapping Toxicities

  • Bone marrow suppressants: corticosteroids
  • Nephrotoxic drugs
  • Neuromuscular blockers
Caution advised.
Artemether-Lumefantrine

Increased Drug Concentrations

  • ARVs: nevirapine
Monitor therapy when combined.

Overlapping Toxicities

  • ARVs: PIs
  • Antibacterials: fluoroquinolones, macrolides
  • Antifungals: fluconazole, voriconazole
  • Antimalarials: quinidine, quinine
  • Psychotropics: quetiapine, tricyclic antidepressants
Coadministration with fluconazole or voriconazole should be avoided. For all other drugs, coadministration should be avoided, if possible; monitor for toxicities (QT prolongation).
Atovaquone

Decreased Atovaquone Concentrations

  • Antimycobacterials: rifampin, rifabutin
  • ARVs: lopinavir/ritonavir, atazanavir/ritonavir
  • Antibiotics: doxycycline
Coadministration of atovaquone and rifampin or atovaquone and rifabutin should be avoided.
Azithromycin

Overlapping Toxicities

  • Antimalarials: artemether/lumefantrine, chloroquine, quinine
Caution advised. Increased risk of QT prolongation.
Bedaquiline

Overlapping Toxicities

  • QT-prolonging agents
Bedaquiline may enhance the QTc-prolonging effects. Avoid concomitant use.
  • Fecal microbiota (live) (oral and rectal)
Avoid concomitant use.
Caspofungin

Decreased Caspofungin Concentrations

  • Anticonvulsants: phenytoin
  • Antimycobacterials: rifampin
  • ARVs: efavirenz, nevirapine
Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers.
Cidofovir

Overlapping Toxicities

  • Antibacterials: aminoglycosides
  • Antivirals: foscarnet
  • ARVs: tenofovir
  • Nephrotoxic drugs

Monitor for toxicities of these drugs.

Prehydrate with IV normal saline and probenecid to avoid nephrotoxicity.

Ciprofloxacin

Decreased Ciprofloxacin Absorption

  • ARVs: didanosine
  • Minerals: ferrous sulfate, zinc
  • Gastrointestinal drugs: antacids, sucralfate, magnesium-containing laxatives
Give oral ciprofloxacin 2 hours before or 6 hours after drugs that may interfere with absorption.

Overlapping Toxicities

  • Antimalarials: artemether/lumefantrine, quinine
  • Antibacterials: clarithromycin
Caution advised.
  • Fecal microbiota (live) (oral and rectal)
Avoid concomitant use.
Clarithromycin

Increased Clarithromycin Concentrations

  • ARVs: atazanavir/ritonavir, lopinavir/ritonavir
  • Antifungals: itraconazole (itraconazole concentrations also increased)

Caution advised. Concern for QTc prolongation.

Decrease clarithromycin dose or consider switching to azithromycin, which has less potential for drug interactions.

Increased Concomitant Drug Concentrations

  • ARVs: etravirine
Consider alternative ARV.

Decreased Clarithromycin Concentrations

  • ARVs: efavirenz, etravirine, nevirapine
  • Antimycobacterials: rifampin, rifabutin (rifabutin concentrations also increased)

Consider switching to azithromycin, which has less potential for drug interaction.

For concomitant use of rifabutin and clarithromycin, consider decreasing dose of rifabutin or switching to azithromycin.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Clarithromycin may reduce fecal microbiota (live) (rectal) effectiveness.
Clindamycin

Decreased Clindamycin Antibacterial Efficacy

  • Antibacterials: chloramphenicol, erythromycin

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Cycloserine

Overlapping Toxicities

  • Antimycobacterials: ethionamide, isoniazid
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Dapsone

Decreased Dapsone Concentrations

  • Antimycobacterials: rifampin
Coadministration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.

Decreased Dapsone Absorption

  • ARVs: atazanavir, didanosine suspension
  • Gastrointestinal drugs: antacids
For coadministration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication.

Overlapping Toxicities

  • Bone marrow suppressants or drugs associated with hemolysis
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Doxycycline

Decreased Doxycycline Concentrations

  • Anticonvulsants: carbamazepine, phenytoin
  • Antimycobacterials: rifampin
Potential for decreased doxycycline efficacy. Monitor for therapeutic failure.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Erythromycin

Increased Concentrations of Erythromycin

  • Antifungals: itraconazole (itraconazole concentrations also increased)

Increased Concomitant Drug Concentrations

  • ARVs: tenofovir
Monitor for toxicities of both drugs, potential for QT prolongation.

Overlapping Toxicities

  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Ethambutol  

Overlapping Toxicities

  • Neurotoxic drugs
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Ethionamide

Potential for Increased Toxicity Due to Overlapping Toxicity

  • Neurotoxic drugs
  • Antimycobacterials: cycloserine, isoniazid
Caution advised.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Fluconazole

Decreased Fluconazole Levels

  • Anticonvulsants: phenytoin
  • Antimycobacterials: rifampin
  • ARVs: rilpivirine
Monitor for efficacy. May need to increase fluconazole dose.

Increases Concomitant Drug Concentrations

  • ARVs: etravirine, nevirapine, saquinavir, tipranavir
May need to decrease dose of saquinavir. Avoid tipranavir with high doses of fluconazole (maximum fluconazole dose in adults: 200 mg). Caution advised with etravirine.
  • Antineoplastics: venetoclax
Decrease venetoclax dose by at least 50% in children requiring concomitant treatment.
  • Antimycobacterials: rifabutin
May need to decrease dose of rifabutin.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins, such as fluvastatin, rosuvastatin, and pravastatin, are preferred, or discontinue statin during antifungal therapy.
Flucytosine

Increased Flucytosine Concentrations

  • Nephrotoxic drugs

Overlapping Toxicities

  • QT-prolonging drugs

Caution advised.

Dose adjustments with therapeutic drug monitoring recommended with impaired renal function.

Foscarnet

Overlapping Toxicities

  • Antivirals: cidofovir
  • Anti-pneumocystis drugs: pentamidine
  • Nephrotoxic drugs
Monitor for toxicities of these drugs.
Ganciclovir

Increased Ganciclovir Concentrations

  • ARVs: tenofovir (concentrations also increased)
Monitor for toxicities of these drugs.

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Caution advised.

Overlapping Toxicities

  • Antibacterials: imipenem-cilastatin
  • ARVs: zidovudine
  • Bone marrow suppressants
  • Nephrotoxic drugs
Caution advised. Increased risk of seizures with imipenem-cilastatin.
Isavuconazole

Increased Concomitant Drug Concentrations

  • Antineoplastics: venetoclax
Reduce venetoclax dose by at least 50% in children requiring concomitant treatment. Resume previous venetoclax dose two to three days after discontinuation of isavuconazole.
Isoniazid

Decreased Isoniazid Concentrations

  • Corticosteroids: glucocorticoids (e.g., prednisolone)
Use with caution.

Decreased Isoniazid Absorption

  • Gastrointestinal drugs: antacids

Caution advised.

Take ≥1 hour before aluminum-containing antacids.

Increased Concomitant Drug Concentrations

  • Sedatives/hypnotics: diazepam
Caution advised.

Decreased Concomitant Drug Concentrations

  • Antifungals: itraconazole, ketoconazole  
Coadministration should be avoided, if possible.

Overlapping Toxicities

  • Antimycobacterials: cycloserine, ethionamide, itraconazole
  • Hepatotoxic drugs
  • Neurotoxic drugs
Caution advised.
Itraconazole and Ketoconazole

Increased Azole Concentrations

  • Antibacterials: clarithromycin, ciprofloxacin, erythromycin
  • ARVs: PIs
Monitor for toxicities and monitor concentrations. Consider azithromycin instead of other macrolides. High doses of itraconazole are not recommended with PIs.

Increased Concomitant Drug Concentrations

  • ARVs: etravirine, maraviroc, PIs
Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Antibacterials: clarithromycin, erythromycin
Consider switching to azithromycin, which has less potential for drug interaction.
  • Sedatives/hypnotics: alprazolam, diazepam, midazolam
Coadministration of midazolam and alprazolam should be avoided. Coadministration of diazepam should be avoided, if possible.
  • Antimalarial: quinidine
Coadministration of quinidine should be avoided. QT prolongation may occur.

Decreased Azole Concentrations

  • ARVs: efavirenz, etravirine, nevirapine, rilpivirine
Monitor concentrations. Coadministration of efavirenz should be avoided if possible.
  • Anticonvulsants: carbamazepine, fosphenytoin
Monitor concentrations.
  • Antimycobacterials: isoniazid, rifabutin, rifampin, rifapentine
Coadministration with rifampin should be avoided. Coadministration with rifabutin should be avoided, if possible. Monitor for toxicities and monitor concentrations.

Decreased Azole Absorption

  • ARVs: didanosine
  • Gastrointestinal drugs: antacids, anticholinergics/antispasmodics, histamine H2-receptor antagonists, omeprazole, sucralfate
Monitor concentrations.
Mefloquine

Decreased Mefloquine Concentrations

  • Antimalarials: quinine
  • Antimycobacterials: rifampin

Monitor for decreased mefloquine efficacy.

Coadministration of rifampin should be avoided, if possible; use rifabutin instead.

Decreased Concomitant Drug Concentrations

  • ARVs: ritonavir, possibly other PIs
Monitor for virologic failure of PI-containing ART regimen.

Overlapping Toxicities

  • Antimalarials: quinine
  • QT-prolonging drugs
Avoid coadministration, if possible. Monitor for toxicities (EKG changes, cardiac arrest, and seizures with quinine). If coadministered with quinine, give mefloquine at least 12 hours after last dose of quinine.
Nitazoxanide

Increased Concomitant Drug Concentrations

  • Anticonvulsants: phenytoin
Potential for interaction with other medications that are highly protein-bound. Use with caution as interaction will increase concentrations of concomitant medication.
Pentamidine

Overlapping Toxicities

  • Antivirals: foscarnet
Coadministration should be avoided, if possible. Monitor for toxicities (hypocalcemia, QT prolongation).
  • ARVs: didanosine, PIs
Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation with PIs; pancreatitis for didanosine).
  • Bone marrow suppressants
Monitor for toxicities.
  • Nephrotoxic drugs
Monitor for toxicities.
  • QT-prolonging drugs
Monitor for toxicities. Avoid coadministration, if possible.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Posaconazole  

Decreased Posaconazole Drug Concentrations

  • ARVs: efavirenz, fosamprenavir, rilpivirine
Coadministration of fosamprenavir should be avoided. Coadministration of efavirenz should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.
  • Anticonvulsants: phenytoin
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.
  • Antimycobacterials: rifabutin, rifampin
Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly.

Increased Concomitant Drug Concentrations

  • ARVs: atazanavir, etravirine, lopinavir, ritonavir, saquinavir
Coadministration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary.
  • Antibacterials: clarithromycin, erythromycin
Coadministration should be avoided.
  • Anticonvulsants: phenytoin
Coadministration should be avoided.
  • Sedatives/hypnotics: alprazolam, diazepam, midazolam
Coadministration should be avoided, if possible. Monitor for toxicities.
  • Antimycobacterials: rifabutin
Coadministration should be avoided.
  • Statins: atorvastatin, lovastatin, simvastatin
  • Antineoplastics: venetoclax
  • Immunosuppressives: sirolimus, tacrolimus
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Antimalarials: halofantrine, lumefantrine, mefloquine, quinidine, quinine
Coadministration should be avoided.

Decreased Concomitant Drug Concentrations

  • ARVs: fosamprenavir
Coadministration should be avoided.
  • QT-prolonging drugs
Use with caution. Monitor for toxicities.
Proguanil

Decreased Proguanil Concentrations

  • ARVs: Atazanavir/ritonavir, efavirenz, lopinavir/ritonavir
Use with caution.
Pyrazinamide

Overlapping Toxicities

  • Antimycobacterials: ethionamide, rifampin
  • Hepatotoxic drugs
Use with caution. Monitor for hepatotoxicity.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Quinidine

Increased Quinidine Concentrations

  • ARVs: PIs
Coadministration of PIs should be avoided. Increased risk of arrhythmia. Coadministration may be necessary in the presence of life-threatening, severe malaria and in the absence of other therapy, while artesunate is obtained from the CDC.
  • Antifungals: itraconazole, posaconazole, voriconazole
Coadministration should be avoided. Increased risk of arrhythmia.

Decreased Quinidine Concentrations

  • ARVs: etravirine
Use with caution. Monitor quinidine levels.

Increased Concomitant Drug Concentrations

  • Tricyclic antidepressants
Coadministration should be avoided, if possible. Monitor for toxicities.

Overlapping Toxicities

  • QT-prolonging drugs
Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation).
Ribavirin

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Coadministration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity.

Decreased Concomitant Drug Concentrations

  • ARVs: stavudine, zidovudine
Coadministration should be avoided, if possible.

Overlapping Toxicities

  • ARVs: zidovudine, all NRTIs
Coadministration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine, lactic acidosis for all NRTIs).
Rifabutin

Increased Rifabutin Concentrations

  • ARVs: cobicistat, PIs
Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if coadministered with PIs.
  • Fluconazole
Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction.
  • Voriconazole, itraconazole, posaconazole
Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Antibacterials: clarithromycin
Coadministration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead.

Increased Concomitant Drug Concentrations

  • ARVs: didanosine
Use with caution. Monitor for didanosine toxicity.

Decreased Rifabutin Concentrations

  • ARVs: efavirenz, etravirine
Use with caution. Higher rifabutin dose required with efavirenz. Consider TDM.

Decreased Concomitant Drug Concentrations

  • ARVs: rilpivirine, bictegravir, cabotegravir, dolutegravir, raltegravir, lenacapavir
Coadministration should be avoided.
  • ARVs: etravirine, maraviroc, saquinavir
Coadministration should be avoided, if possible.
  • Antibacterials: atovaquone, dapsone
Use with caution. Monitor for dapsone treatment failure.
  • Antifungals: azoles (except for fluconazole)
Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Contraceptives: oral
Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
Rifampin

Decreased Concomitant Drug Concentrations

  • Contraceptives: oral
Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
  • ARVs: PIs ± ritonavir, nevirapine, bictegravir, cabotegravir, dolutegravir, raltegravir, rilpivirine, maraviroc, cobicistat, zidovudine, lenacapavir

Significantly decreases exposure of ARVs; coadministration should be avoided if possible.

Nevirapine: use only if other options are not available and close virologic and immunologic monitoring can be done; consider efavirenz instead.

Raltegravir and dolutegravir dose increases may be required.

  • Antimicrobials: atovaquone, clarithromycin, dapsone, doxycycline
Coadministration of atovaquone and rifampin should be avoided. Consider switching clarithromycin to azithromycin, which has less potential for drug interaction. Dapsone and doxycycline efficacy may be reduced.
  • Antifungals: azoles, caspofungin

Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers.

Monitor azoles for efficacy. May need to increase azole dose.

  • Other: corticosteroids, methadone

Caution advised with corticosteroids (decreased efficacy).

Monitor for efficacy and/or opiate withdrawal symptoms with methadone.

Overlapping Toxicities

  • Bone marrow suppressants
  • Hepatotoxic drugs
Monitor for toxicities of these drugs.
Streptomycin

Overlapping Toxicities

  • Nephrotoxic drugs
  • Neuromuscular blockers
Monitor for toxicities of these drugs.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Trimethoprim-Sulfamethoxazole (TMP-SMX)

Overlapping Toxicities

  • Folate antagonists
  • Bone marrow suppressants
Monitor for toxicities of these drugs.
  • Fecal microbiota (live) (oral/rectal)
Avoid concomitant use.
Valacyclovir

Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities

  • Antivirals: acyclovir, cidofovir, ganciclovir, valganciclovir
  • ARVs: tenofovir, zidovudine

Monitor for toxicities of these drugs.

Avoid other nephrotoxic drugs.

Valganciclovir

Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities

  • Antivirals: acyclovir, cidofovir, ganciclovir, valacyclovir
  • ARVs: tenofovir, zidovudine

Monitor for toxicities of these drugs.

Avoid other nephrotoxic drugs.

Voriconazole

Decreased Voriconazole Concentrations

  • Anticonvulsants: carbamazepine, long-acting barbiturates
Caution advised.
  • Antimycobacterials: rifabutin, rifampin
Rifabutin and rifampin coadministration should be avoided.
  • ARVs: efavirenz, nevirapine, ritonavir-boosted PIs

Standard doses of efavirenz and voriconazole should not be used; voriconazole dose may need to be increased and efavirenz dose decreased, or use alternative antifungal agent.

Potential for increased PI concentrations and decreased voriconazole concentrations; consider monitoring voriconazole concentrations and adjust dose accordingly; monitor for PI-associated toxicities or consider using an alternative antifungal agent.

Increased Voriconazole Concentrations

  • ARVs: etravirine (etravirine concentrations also increased)
Monitor voriconazole concentrations to reduce toxicity.

Increased Concomitant Drug Concentrations

  • Antimycobacterials: rifabutin
Caution advised.
  • ARVs: ritonavir-boosted PIs, efavirenz
Caution advised.
  • Statins: atorvastatin, lovastatin, simvastatin
Do not coadminister with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, and pravastatin are preferred; alternatively, discontinue statin during antifungal therapy.
  • Sedatives/hypnotics: alprazolam, midazolam, triazolam
Coadministration should be avoided if possible. Monitor for toxicities.

Key: ART = antiretroviral therapy; ARV = antiretroviral; CDC = Centers for Disease Control and Prevention; CYP450 = cytochrome P450; EKG = electrocardiogram; FDA = U.S. Food and Drug Administration; IV = intravenous; NRTI = nucleoside reverse transcriptase inhibitors; PI = protease inhibitors; QT = interval between Q and T waves; QTc = QT interval corrected for heart rate; TDM = therapeutic drug monitoring

 

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