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Nov. 06, 2013

Tables

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

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

There is the potential for significant drug interactions and overlapping toxicities in patients receiving medications for treatment or prevention of opportunistic infections (OIs). These patients often are receiving other medications, including antiretrovirals that interfere with metabolism or elimination of OI medications. In particular, protease inhibitors and non-nucleoside reverse transcriptase inhibitors affect the CYP450 or other transporter systems and may be associated with clinically significant drug interactions. The integrase inhibitor raltegravir is metabolized by UGT1A1 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 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 (PK) data are available from studies involving HIV-infected adults, whereas data in children are extremely limited. New information continues to become available and it is important to carefully review a patient’s current medications, including prescription and over-the-counter medications. It is difficult to predict the interaction potential when three or more drugs with similar metabolic pathways are co-administered and there is substantial inter-patient variability in the magnitude of these interactions. When possible, alternative agents with less drug interaction potential or use of therapeutic drug monitoring should be considered. 

 

Table 5: Significant Drug Interactions for Drugs Used to Treat or Prevent Opportunistic Infections
Drug Name Overlapping Toxicities Recommendation
 * The drug interactions included in this table were selected on the basis of their potential clinical significance and are not inclusive of all potential drug interactions (see drug label and the drug interaction websites listed for complete information on drug interactions).
Acyclovir
(Zovirax)
 		 Overlapping Toxicities:
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Increased Concentrations (Both Drugs) and Overlapping Toxicities:
  • Antivirals: valacyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Albendazole Increases Albendazole Concentrations:
  • Anthelmintic drugs: praziquantel
 Caution advised.
Amikacin Overlapping Toxicities:
  • Anti-tuberculosis drugs (injectable): streptomycin, kanamycin
  • Nephrotoxic or ototoxic drugs
  • Antimycobacterial drugs: capreomycin
  • Antivirals: cidofovir
 Caution advised. Avoid combination of amikacin and cidofovir.
Amphotericin B 
Amphotericin B Lipid Complex 
(Abelcet)

Amphotericin B Liposome
(Ambisome)		 Overlapping Toxicities:
  • Bone marrow suppressant drugs: corticosteroids
  • Nephrotoxic drugs
  • Neuromuscular blocking drugs
 Caution advised.
Atovaquone Decreases Atovaquone Concentrations:
  • Antimycobacterial drugs: rifampin, rifabutin
  • ARVs: lopinavir/ritonavir, atazanavir/ritonavir
  • Antibiotics: doxycycline
 Co-administration of atovaquone and rifampin should be avoided.
Azithromycin Overlapping Toxicities:
  • Artemether/lumefantrine, chloroquine, quinine
 Caution advised. Increased risk of QT prolongation.
Boceprevir Please see Adult OI guidelines for information about drug interactions, including warnings about interactions between boceprevir and HIV protease inhibitors.
Capreomycin Overlapping Toxicities:
  • Nephrotoxic or ototoxic drugs
  • Neuromuscular blocking drugs
  • Antibacterial drugs: aminoglycosides (parenteral)
 Caution advised.
Caspofungin Decreases Caspofungin Concentrations:
  • Anticonvulsant drugs: phenytoin
  • Antimycobacterial drugs: rifampin
  • ARV drugs: efavirenz, nevirapine
 Increase in dose of caspofungin is recommended when co-administered with CYP450 inducers.
Cidofovir Overlapping Toxicities:
  • Antibacterial drugs: aminoglycosides
  • Antiviral drugs: foscarnet
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Ciprofloxacin Decreases Ciprofloxacin Absorption:
  • ARV drugs: 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: 
  • Artemether/lumefantrine, clarithromycin, quinine
 Caution advised.
Clarithromycin Increases Clarithromycin Concentrations:
  • ARV drugs: 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.
Increases Concentration of Other Medications:
  • ARV drugs: etravirine
 Consider alternative agent.
Decreases Clarithromycin Concentrations:
  • ARV drugs: efavirenz, etravirine, nevirapine
  • Antimycobacterial drugs: 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.
Clindamycin Decreases Clindamycin Antibacterial Efficacy:
  • Antibacterial drugs: chloramphenicol, erythromycins
 Avoid concomitant use.
Cycloserine Overlapping Toxicities:
  • Antimycobacterial drugs: ethionamide, isoniazid
 Caution advised.
Dapsone Decreases Dapsone Concentrations:
  • Antimycobacterial drugs: rifampin 
 Co-administration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.
Decreases Dapsone Absorption:
  • ARV drugs: didanosine suspension
  • Gastrointestinal drugs: antacids
 For co-administration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication.
Overlapping Toxicities:
  • Bone marrow suppressant drugs or drugs associated with hemolysis
 Caution advised.
Doxycycline Decreases Doxycycline Concentrations:
  • Anticonvulsant drugs: phenytoin, carbamazepine
  • Antimycobacterial drugs: rifampin
 Potential for decreased doxycycline efficacy. Monitor for therapeutic failure.
Erythromycin Increases Concentrations of Erythromycin and Co-Administered Medication:
  • Antifungals: itraconazole
 Monitor for toxicities of both drugs, potential for QT prolongation.
Ethambutol Overlapping Toxicities:
  • Neurotoxic drugs
 Caution advised.
Ethionamide Potential for Increased Toxicity Due to Overlapping Toxicity:
  • Neurotoxic drugs
  • Antimycobacterial drugs: cycloserine, isoniazid
 Caution advised.
Fluconazole Decreases Fluconazole Levels:
  • Anticonvulsant drugs: phenytoin
  • Antimycobacterial drugs: rifampin
  • ARV drugs: rilpivirine
 Monitor for efficacy. May need to increase fluconazole dose.
Increases Concomitant Drug Concentrations:
  • ARV drugs: saquinavir, tipranavir, nevirapine, and etravirine 
 May need to decrease dose of saquinavir. Avoid tipranivir with high doses of fluconazole (maximum fluconazole dose in adults: 200 mg). Caution advised with etravirine.
  • Antimycobacterial drugs: rifabutin
 May need to decrease dose of rifabutin.
  • Statins: simvastatin, lovastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
Flucytosine Increases Flucytosine Concentrations:
  • Nephrotoxic drugs
 Caution advised.
Foscarnet Overlapping Toxicities:
  • Antiviral drugs: cidofovir
  • Anti-pneumocystis drugs: pentamidine
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Ganciclovir Increases Ganciclovir Concentrations :
  • ARV drugs: tenofovir (concentrations also increased)
 Monitor for toxicities of these drugs.
Increases Concomitant Drug Concentrations:
  • ARV drugs: didanosine, tenofovir
 Caution advised.
Overlapping Toxicities:
  • Antibacterial drugs: imipenem-cilastatin
  • ARV drugs: zidovudine
  • Bone marrow suppressant drugs
  • Nephrotoxic drugs
 Caution advised. Increased risk of seizures with imipenem-cilastatin.
Interferon-Alfa Overlapping Toxicities:
  • ARV drugs: zidovudine, lamivudine
  • Bone marrow suppressant drugs
 Co-administration of zidovudine and lamivudine should be avoided if possible. Caution advised with other bone marrow suppressant drugs.
Isoniazid Decreases Isoniazid Concentrations:
  • Corticosteroids: glucocorticoids (e.g., prednisolone)
 Use with caution.
Decreases Isoniazid Absorption:
  • Gastrointestinal drugs: antacids
 Caution advised.
Increases Concomitant Drug Concentrations:
  • Diazepam
 Caution advised.
Decreases Concomitant Drug Concentrations:
  • Antifungal drugs: ketoconazole, itraconazole
 Co-administration should be avoided, if possible.
Overlapping Toxicities:
  • Antimycobacterial drugs: rifampin, cycloserine, ethionamide
  • Hepatotoxic drugs
  • Neurotoxic drugs
 Caution advised.
Itraconazole Increases Itraconazole Concentration:
  • Antibacterial: clarithromycin, erythromycin, ciprofloxacin
  • ARVs: protease inhibitors
 Monitor for toxicities. Monitor itraconazole concentration. Consider azithromycin instead of other macrolides. High doses of itraconazole are not recommended with PIs.
Increases Concomitant Drug Concentrations:
  • ARV drugs: etravirine, maraviroc, protease inhibitors
 Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily.
  • Statins: lovastatin, simvastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Antibacterial: clarithromycin, erythromycin
 Consider switching to azithromycin, which has less potential for drug interaction.
  • Sedatives/hypnotics: midazolam, alprazolam, diazepam
 Co-administration of midazolam and alprazolam should be avoided. Co-administration of diazepam should be avoided, if possible.
  • Cardiac: quinidine
 Co-administration of quinidine should be avoided. QT prolongation.
Decreases Itraconazole Concentrations:
  • ARV drugs: efavirenz, etravirine, nevirapine, rilpivirine
 Monitor itraconazole concentration. Co-administration of efavirenz should be avoided if possible.
  • Anticonvulsant drugs: carbamazepine, (fos)phenytoin
 Monitor itraconazole concentration.
  • Antimycobacterial drugs: rifampin, rifabutin, rifapentine, isoniazid
 Co-administration with rifampin should be avoided. Co-administration with rifabutin should be avoided, if possible. Monitor for toxicities. Monitor itraconazole concentration.
Decreases Itraconazole Absorption:
  • ARV drugs: didanosine
  • Gastrointestinal drugs: antacids, anticholinergics/antispasmodics, histamine H2-receptor antagonists, omeprazole, sucralfate
 Monitor itraconazole concentration.
Lumefantrine Increases Concomitant Drug Levels:
  • ARV drugs: nevirapine
 Monitor for nevirapine toxicity.
Overlapping Toxicities:
  • ARV drugs: protease inhibitors
  • Antibacterial drugs: macrolides, fluoroquinolones
  • Antifungal drugs: fluconazole, voriconazole
  • Antimalarial drugs: quinine, quinidine
  • Psychotropic drugs: quetiapine, tricyclic antidepressants
 Co-administration with fluconazole or voriconazole should be avoided. For all other drugs, co-administration should be avoided, if possible; monitor for toxicities (QT prolongation). 
Mefloquine Decreases Mefloquine Concentrations:
  • Antimalarial drugs: quinine
  • Antimycobacterial: rifampin
 Monitor for decreased mefloquine efficacy.
Co-administration of rifampin should be avoided, if possible; use rifabutin instead.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: ritonavir, possibly other protease inhibitors
 Monitor for virologic failure of protease inhibitor-containing ART regimen.
Overlapping Toxicities:
  • Anti-malarial drugs: quinine
  • Other drugs that can cause prolonged QT
 Avoid co-administration, if possible. Monitor for toxicities (EKG changes, cardiac arrest; also seizures with quinine). If co-administered with quinine, give mefloquine at least 12 hours after last dose of quinine.
Nitazoxanide Increases Concomitant Drug Concentrations:
  • Phenytoin 
 Potential for interaction with other medications that are highly protein bound. Use with caution as interaction will increase concentrations of concomitant medication.
Paromomycin Overlapping Toxicities:
  • Neuromuscular blocking drugs
 Use with caution.
Pentamidine Overlapping Toxicities:
  • Antiviral drugs: foscarnet
 Co-administration should be avoided, if possible. Monitor for toxicities (hypocalcaemia, QT prolongation).
  • ARV drugs: protease inhibitors, didanosine
 Co-administration should be avoided, if possible. Monitor for toxicities (QT prolongation with protease inhibitors; pancreatitis for didanosine).
  • Bone marrow suppressant drugs
 Monitor for toxicities.
  • Nephrotoxic drugs
 Monitor for toxicities.
  • Other drugs that can cause prolonged QT
 Monitor for toxicities. Avoid co-administration, if possible.
Posaconazole Decreases Posaconazole Drug Concentrations:
  • ARV drugs: efavirenz, fosamprenavir, rilpivirine
 Co-administration of fosamprenavir should be avoided. Co-administration of efavirenz should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
  • Anticonvulsant drugs: phenytoin
 Co-administration should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
  • Antimycobacterial drugs: rifabutin, rifampin
 Co-administration should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
Increases Concomitant Drug Concentrations:
  • ARV drugs: atazanavir, saquinavir, lopinavir, etravirine, and ritonavir
 Co-administration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary.
  • Antibacterial drugs: erythromycin, clarithromycin
 Co-administration should be avoided.
  • Anticonvulsant drugs: phenytoin
 Co-administration should be avoided.
  • Sedatives/hypnotics: midazolam, alprazolam, diazepam
 Co-administration should be avoided, if possible. Monitor for toxicities.
  • Antimycobacterial drugs: rifabutin
 Co-administration should be avoided.
  • Statins: simvastatin, lovastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Antimalarials: Quinidine, quinine, mefloquine, lumefantrine, halofantrine
 Co-administration should be avoided.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: fosamprenavir
 Co-administration should be avoided.
  • Other drugs that can cause prolonged QT
 Use with caution. Monitor for toxicities.
Proguanil Decreases Proguanil Concentrations:
  • Atazanavir/ritonavir, lopinavir/ritonavir, efavirenz
 Use with caution.
Pyrazinamide Overlapping Toxicities:
  • Antimycobacterial drugs: rifampin, ethionamide
  • Hepatotoxic drugs
 Use with caution. Monitor for hepatotoxicity.
Quinidine Increases Quinidine Concentrations:
  • Protease inhibitors
 Co-administration of PIs should be avoided. Increased risk of arrhythmia. Co-administration may be necessary in presence of life-threatening, severe malaria and in the absence of other therapy, while artesunate is obtained from the CDC.
  • Itraconazole, posaconazole, voriconazole
 Co-administration should be avoided. Increased risk of arrhythmia.
Decreases Quinidine Concentrations:
  • Etravirine
 Use with caution. Monitor quinidine levels.
Increases Concomitant Drug Concentrations:
  • Tricyclic antidepressants
 Co-administration should be avoided, if possible. Monitor for toxicities.
Overlapping Toxicities:
  • Other drugs that can prolong QT interval
 Co-administration should be avoided, if possible. Monitor for toxicities (QT prolongation).
Ribavirin Increases Concentrations Of Concomitant Drug:
  • ARV drugs: didanosine
 Co-administration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity.
Decreases Concentrations of Concomitant Drug:
  • Zidovudine, stavudine
 Co-administration should be avoided, if possible.
Overlapping Toxicities:
  • Zidovudine, all NRTIs
 Co-administration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine; lactic acidosis for all NRTIs).
Rifabutin Increases Rifabutin Concentrations:
  • HIV protease inhibitors 
 Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if co-administered with PIs.
  • Fluconazole
 Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction.
  • Voriconazole, itraconazole, posaconazole
 Co-administration should be avoided, if possible. If co-administered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Clarithromycin
 Co-administration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead.
Increases Concomitant Drug Concentrations:
  • Didanosine
 Use with caution. Monitor for didanosine toxicity.
Decreases Rifabutin Concentrations:
  • Efavirenz, etravirine
 Use with caution. Higher rifabutin dose required when efavirenz co-administered. Consider TDM.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: rilpivirine
 Co-administration should be avoided. 
  • ARV drugs: saquinavir, etravirine, maraviroc
 Co-administration should be avoided, if possible.
  • Antibacterial drugs: dapsone, atovaquone
 Use with caution. Monitor for dapsone treatment failure.
  • Antifungal drugs: azoles (except for fluconazole) 
 Co-administration should be avoided, if possible. If co-administered, 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 Decreases Concomitant Drug Concentrations:
  • Contraceptives: oral
 Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
  • ARV drugs: PIs ± ritonavir, nevirapine, raltegravir, rilpivirine
 Significantly decreases PI exposure; co-administration should be avoided. Nevirapine: use only if other options not available and close virologic and immunologic monitoring can be done; consider efavirenz instead. Raltegravir dose increase may be required. Rilpivirine co-administration should be avoided.
  • Antimicrobial: atovaquone, dapsone, clarithromycin, doxycycline
 Co-administration 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 .
  • Antifungal drugs: azoles, caspofungin
 Increase in dose of caspofungin is recommended when co-administered with CYP450 inducers. 

Azoles: Monitor for efficacy. May need to increase antifungal dose
  • Other: corticosteroids, methadone
 Caution advised with corticosteroids (decreased efficacy). 

Methadone: Monitor for efficacy and/or opiate withdrawal symptoms with methadone.
Overlapping Toxicities:
  • Bone marrow suppressant drugs
  • Hepatotoxic drugs
 Monitor for toxicities of these drugs.
Streptomycin Potential for Increased Toxicity Due to Overlapping Toxicity:
  • Nephrotoxic drugs
  • Neuromuscular blocking drugs
 Monitor for toxicities of these drugs.
Telaprevir Please see Adult OI guidelines for information about drug interactions, including warnings about interactions between telaprevir and HIV protease inhibitors. Caution advised.
Trimethoprim-Sulfamethoxazole Overlapping Toxicities:
  • Folate antagonists
  • Bone marrow suppressant drugs
 Monitor for toxicities of these drugs.
Valacyclovir Potential For Increased Concentrations (of Both Drugs) and Overlapping Toxicity:
  • Antivirals: acyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Valganciclovir Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicity:
  • Antivirals: valacyclovir, acyclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Voriconazole Decreases Voriconazole Concentrations:
  • Anticonvulsant drugs: carbamazepine, long-acting barbiturates
 Caution advised.
  • Antimycobacterial drugs: rifabutin, rifampin
 Rifabutin and Rifampin co-administration should be avoided.
  • ARV drugs: efavirenz, nevirapine, PIs boosted with ritonavir
 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.
Increases Voriconazole Concentrations:
  • ARV drugs: etravirine
 Monitor voriconazole concentrations to reduce toxicity. 
Increases Concomitant Drug Concentrations:
  • Antimycobacterial drugs: rifabutin
 Caution advised.
  • ARV drugs: protease inhibitors boosted with ritonavir, efavirenz, etravirine
 Caution advised.
  • Statins: simvastatin, lovastatin, atorvastatin
 Statins: Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Sedatives/hypnotics: midazolam, alprazolam, triazolam
 Co-administration should be avoided if possible. Monitor for toxicities.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; CDC = Centers for Disease Control and Prevention; EKG = electrocardiogram; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; OI = opportunistic infection; PI = protease inhibitors; PK = pharmacokinetic; TDM = therapeutic drug monitoring

 

Tables

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

Table 5: Significant Drug Interactions for Drugs Used to Treat or Prevent Opportunistic Infections
Drug Name Overlapping Toxicities Recommendation
 * The drug interactions included in this table were selected on the basis of their potential clinical significance and are not inclusive of all potential drug interactions (see drug label and the drug interaction websites listed for complete information on drug interactions).
Acyclovir
(Zovirax)
 		 Overlapping Toxicities:
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Increased Concentrations (Both Drugs) and Overlapping Toxicities:
  • Antivirals: valacyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Albendazole Increases Albendazole Concentrations:
  • Anthelmintic drugs: praziquantel
 Caution advised.
Amikacin Overlapping Toxicities:
  • Anti-tuberculosis drugs (injectable): streptomycin, kanamycin
  • Nephrotoxic or ototoxic drugs
  • Antimycobacterial drugs: capreomycin
  • Antivirals: cidofovir
 Caution advised. Avoid combination of amikacin and cidofovir.
Amphotericin B 
Amphotericin B Lipid Complex 
(Abelcet)

Amphotericin B Liposome
(Ambisome)		 Overlapping Toxicities:
  • Bone marrow suppressant drugs: corticosteroids
  • Nephrotoxic drugs
  • Neuromuscular blocking drugs
 Caution advised.
Atovaquone Decreases Atovaquone Concentrations:
  • Antimycobacterial drugs: rifampin, rifabutin
  • ARVs: lopinavir/ritonavir, atazanavir/ritonavir
  • Antibiotics: doxycycline
 Co-administration of atovaquone and rifampin should be avoided.
Azithromycin Overlapping Toxicities:
  • Artemether/lumefantrine, chloroquine, quinine
 Caution advised. Increased risk of QT prolongation.
Boceprevir Please see Adult OI guidelines for information about drug interactions, including warnings about interactions between boceprevir and HIV protease inhibitors.
Capreomycin Overlapping Toxicities:
  • Nephrotoxic or ototoxic drugs
  • Neuromuscular blocking drugs
  • Antibacterial drugs: aminoglycosides (parenteral)
 Caution advised.
Caspofungin Decreases Caspofungin Concentrations:
  • Anticonvulsant drugs: phenytoin
  • Antimycobacterial drugs: rifampin
  • ARV drugs: efavirenz, nevirapine
 Increase in dose of caspofungin is recommended when co-administered with CYP450 inducers.
Cidofovir Overlapping Toxicities:
  • Antibacterial drugs: aminoglycosides
  • Antiviral drugs: foscarnet
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Ciprofloxacin Decreases Ciprofloxacin Absorption:
  • ARV drugs: 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: 
  • Artemether/lumefantrine, clarithromycin, quinine
 Caution advised.
Clarithromycin Increases Clarithromycin Concentrations:
  • ARV drugs: 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.
Increases Concentration of Other Medications:
  • ARV drugs: etravirine
 Consider alternative agent.
Decreases Clarithromycin Concentrations:
  • ARV drugs: efavirenz, etravirine, nevirapine
  • Antimycobacterial drugs: 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.
Clindamycin Decreases Clindamycin Antibacterial Efficacy:
  • Antibacterial drugs: chloramphenicol, erythromycins
 Avoid concomitant use.
Cycloserine Overlapping Toxicities:
  • Antimycobacterial drugs: ethionamide, isoniazid
 Caution advised.
Dapsone Decreases Dapsone Concentrations:
  • Antimycobacterial drugs: rifampin 
 Co-administration should be avoided if possible. Consider alternatives for dapsone or use rifabutin.
Decreases Dapsone Absorption:
  • ARV drugs: didanosine suspension
  • Gastrointestinal drugs: antacids
 For co-administration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication.
Overlapping Toxicities:
  • Bone marrow suppressant drugs or drugs associated with hemolysis
 Caution advised.
Doxycycline Decreases Doxycycline Concentrations:
  • Anticonvulsant drugs: phenytoin, carbamazepine
  • Antimycobacterial drugs: rifampin
 Potential for decreased doxycycline efficacy. Monitor for therapeutic failure.
Erythromycin Increases Concentrations of Erythromycin and Co-Administered Medication:
  • Antifungals: itraconazole
 Monitor for toxicities of both drugs, potential for QT prolongation.
Ethambutol Overlapping Toxicities:
  • Neurotoxic drugs
 Caution advised.
Ethionamide Potential for Increased Toxicity Due to Overlapping Toxicity:
  • Neurotoxic drugs
  • Antimycobacterial drugs: cycloserine, isoniazid
 Caution advised.
Fluconazole Decreases Fluconazole Levels:
  • Anticonvulsant drugs: phenytoin
  • Antimycobacterial drugs: rifampin
  • ARV drugs: rilpivirine
 Monitor for efficacy. May need to increase fluconazole dose.
Increases Concomitant Drug Concentrations:
  • ARV drugs: saquinavir, tipranavir, nevirapine, and etravirine 
 May need to decrease dose of saquinavir. Avoid tipranivir with high doses of fluconazole (maximum fluconazole dose in adults: 200 mg). Caution advised with etravirine.
  • Antimycobacterial drugs: rifabutin
 May need to decrease dose of rifabutin.
  • Statins: simvastatin, lovastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
Flucytosine Increases Flucytosine Concentrations:
  • Nephrotoxic drugs
 Caution advised.
Foscarnet Overlapping Toxicities:
  • Antiviral drugs: cidofovir
  • Anti-pneumocystis drugs: pentamidine
  • Nephrotoxic drugs
 Monitor for toxicities of these drugs.
Ganciclovir Increases Ganciclovir Concentrations :
  • ARV drugs: tenofovir (concentrations also increased)
 Monitor for toxicities of these drugs.
Increases Concomitant Drug Concentrations:
  • ARV drugs: didanosine, tenofovir
 Caution advised.
Overlapping Toxicities:
  • Antibacterial drugs: imipenem-cilastatin
  • ARV drugs: zidovudine
  • Bone marrow suppressant drugs
  • Nephrotoxic drugs
 Caution advised. Increased risk of seizures with imipenem-cilastatin.
Interferon-Alfa Overlapping Toxicities:
  • ARV drugs: zidovudine, lamivudine
  • Bone marrow suppressant drugs
 Co-administration of zidovudine and lamivudine should be avoided if possible. Caution advised with other bone marrow suppressant drugs.
Isoniazid Decreases Isoniazid Concentrations:
  • Corticosteroids: glucocorticoids (e.g., prednisolone)
 Use with caution.
Decreases Isoniazid Absorption:
  • Gastrointestinal drugs: antacids
 Caution advised.
Increases Concomitant Drug Concentrations:
  • Diazepam
 Caution advised.
Decreases Concomitant Drug Concentrations:
  • Antifungal drugs: ketoconazole, itraconazole
 Co-administration should be avoided, if possible.
Overlapping Toxicities:
  • Antimycobacterial drugs: rifampin, cycloserine, ethionamide
  • Hepatotoxic drugs
  • Neurotoxic drugs
 Caution advised.
Itraconazole Increases Itraconazole Concentration:
  • Antibacterial: clarithromycin, erythromycin, ciprofloxacin
  • ARVs: protease inhibitors
 Monitor for toxicities. Monitor itraconazole concentration. Consider azithromycin instead of other macrolides. High doses of itraconazole are not recommended with PIs.
Increases Concomitant Drug Concentrations:
  • ARV drugs: etravirine, maraviroc, protease inhibitors
 Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily.
  • Statins: lovastatin, simvastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Antibacterial: clarithromycin, erythromycin
 Consider switching to azithromycin, which has less potential for drug interaction.
  • Sedatives/hypnotics: midazolam, alprazolam, diazepam
 Co-administration of midazolam and alprazolam should be avoided. Co-administration of diazepam should be avoided, if possible.
  • Cardiac: quinidine
 Co-administration of quinidine should be avoided. QT prolongation.
Decreases Itraconazole Concentrations:
  • ARV drugs: efavirenz, etravirine, nevirapine, rilpivirine
 Monitor itraconazole concentration. Co-administration of efavirenz should be avoided if possible.
  • Anticonvulsant drugs: carbamazepine, (fos)phenytoin
 Monitor itraconazole concentration.
  • Antimycobacterial drugs: rifampin, rifabutin, rifapentine, isoniazid
 Co-administration with rifampin should be avoided. Co-administration with rifabutin should be avoided, if possible. Monitor for toxicities. Monitor itraconazole concentration.
Decreases Itraconazole Absorption:
  • ARV drugs: didanosine
  • Gastrointestinal drugs: antacids, anticholinergics/antispasmodics, histamine H2-receptor antagonists, omeprazole, sucralfate
 Monitor itraconazole concentration.
Lumefantrine Increases Concomitant Drug Levels:
  • ARV drugs: nevirapine
 Monitor for nevirapine toxicity.
Overlapping Toxicities:
  • ARV drugs: protease inhibitors
  • Antibacterial drugs: macrolides, fluoroquinolones
  • Antifungal drugs: fluconazole, voriconazole
  • Antimalarial drugs: quinine, quinidine
  • Psychotropic drugs: quetiapine, tricyclic antidepressants
 Co-administration with fluconazole or voriconazole should be avoided. For all other drugs, co-administration should be avoided, if possible; monitor for toxicities (QT prolongation). 
Mefloquine Decreases Mefloquine Concentrations:
  • Antimalarial drugs: quinine
  • Antimycobacterial: rifampin
 Monitor for decreased mefloquine efficacy.
Co-administration of rifampin should be avoided, if possible; use rifabutin instead.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: ritonavir, possibly other protease inhibitors
 Monitor for virologic failure of protease inhibitor-containing ART regimen.
Overlapping Toxicities:
  • Anti-malarial drugs: quinine
  • Other drugs that can cause prolonged QT
 Avoid co-administration, if possible. Monitor for toxicities (EKG changes, cardiac arrest; also seizures with quinine). If co-administered with quinine, give mefloquine at least 12 hours after last dose of quinine.
Nitazoxanide Increases Concomitant Drug Concentrations:
  • Phenytoin 
 Potential for interaction with other medications that are highly protein bound. Use with caution as interaction will increase concentrations of concomitant medication.
Paromomycin Overlapping Toxicities:
  • Neuromuscular blocking drugs
 Use with caution.
Pentamidine Overlapping Toxicities:
  • Antiviral drugs: foscarnet
 Co-administration should be avoided, if possible. Monitor for toxicities (hypocalcaemia, QT prolongation).
  • ARV drugs: protease inhibitors, didanosine
 Co-administration should be avoided, if possible. Monitor for toxicities (QT prolongation with protease inhibitors; pancreatitis for didanosine).
  • Bone marrow suppressant drugs
 Monitor for toxicities.
  • Nephrotoxic drugs
 Monitor for toxicities.
  • Other drugs that can cause prolonged QT
 Monitor for toxicities. Avoid co-administration, if possible.
Posaconazole Decreases Posaconazole Drug Concentrations:
  • ARV drugs: efavirenz, fosamprenavir, rilpivirine
 Co-administration of fosamprenavir should be avoided. Co-administration of efavirenz should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
  • Anticonvulsant drugs: phenytoin
 Co-administration should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
  • Antimycobacterial drugs: rifabutin, rifampin
 Co-administration should be avoided, if possible. If co-administered, monitor posaconazole concentrations and adjust dose accordingly.
Increases Concomitant Drug Concentrations:
  • ARV drugs: atazanavir, saquinavir, lopinavir, etravirine, and ritonavir
 Co-administration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary.
  • Antibacterial drugs: erythromycin, clarithromycin
 Co-administration should be avoided.
  • Anticonvulsant drugs: phenytoin
 Co-administration should be avoided.
  • Sedatives/hypnotics: midazolam, alprazolam, diazepam
 Co-administration should be avoided, if possible. Monitor for toxicities.
  • Antimycobacterial drugs: rifabutin
 Co-administration should be avoided.
  • Statins: simvastatin, lovastatin, atorvastatin
 Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Antimalarials: Quinidine, quinine, mefloquine, lumefantrine, halofantrine
 Co-administration should be avoided.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: fosamprenavir
 Co-administration should be avoided.
  • Other drugs that can cause prolonged QT
 Use with caution. Monitor for toxicities.
Proguanil Decreases Proguanil Concentrations:
  • Atazanavir/ritonavir, lopinavir/ritonavir, efavirenz
 Use with caution.
Pyrazinamide Overlapping Toxicities:
  • Antimycobacterial drugs: rifampin, ethionamide
  • Hepatotoxic drugs
 Use with caution. Monitor for hepatotoxicity.
Quinidine Increases Quinidine Concentrations:
  • Protease inhibitors
 Co-administration of PIs should be avoided. Increased risk of arrhythmia. Co-administration may be necessary in presence of life-threatening, severe malaria and in the absence of other therapy, while artesunate is obtained from the CDC.
  • Itraconazole, posaconazole, voriconazole
 Co-administration should be avoided. Increased risk of arrhythmia.
Decreases Quinidine Concentrations:
  • Etravirine
 Use with caution. Monitor quinidine levels.
Increases Concomitant Drug Concentrations:
  • Tricyclic antidepressants
 Co-administration should be avoided, if possible. Monitor for toxicities.
Overlapping Toxicities:
  • Other drugs that can prolong QT interval
 Co-administration should be avoided, if possible. Monitor for toxicities (QT prolongation).
Ribavirin Increases Concentrations Of Concomitant Drug:
  • ARV drugs: didanosine
 Co-administration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity.
Decreases Concentrations of Concomitant Drug:
  • Zidovudine, stavudine
 Co-administration should be avoided, if possible.
Overlapping Toxicities:
  • Zidovudine, all NRTIs
 Co-administration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine; lactic acidosis for all NRTIs).
Rifabutin Increases Rifabutin Concentrations:
  • HIV protease inhibitors 
 Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if co-administered with PIs.
  • Fluconazole
 Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction.
  • Voriconazole, itraconazole, posaconazole
 Co-administration should be avoided, if possible. If co-administered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy).
  • Clarithromycin
 Co-administration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead.
Increases Concomitant Drug Concentrations:
  • Didanosine
 Use with caution. Monitor for didanosine toxicity.
Decreases Rifabutin Concentrations:
  • Efavirenz, etravirine
 Use with caution. Higher rifabutin dose required when efavirenz co-administered. Consider TDM.
Decreases Concomitant Drug Concentrations:
  • ARV drugs: rilpivirine
 Co-administration should be avoided. 
  • ARV drugs: saquinavir, etravirine, maraviroc
 Co-administration should be avoided, if possible.
  • Antibacterial drugs: dapsone, atovaquone
 Use with caution. Monitor for dapsone treatment failure.
  • Antifungal drugs: azoles (except for fluconazole) 
 Co-administration should be avoided, if possible. If co-administered, 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 Decreases Concomitant Drug Concentrations:
  • Contraceptives: oral
 Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended.
  • ARV drugs: PIs ± ritonavir, nevirapine, raltegravir, rilpivirine
 Significantly decreases PI exposure; co-administration should be avoided. Nevirapine: use only if other options not available and close virologic and immunologic monitoring can be done; consider efavirenz instead. Raltegravir dose increase may be required. Rilpivirine co-administration should be avoided.
  • Antimicrobial: atovaquone, dapsone, clarithromycin, doxycycline
 Co-administration 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 .
  • Antifungal drugs: azoles, caspofungin
 Increase in dose of caspofungin is recommended when co-administered with CYP450 inducers. 

Azoles: Monitor for efficacy. May need to increase antifungal dose
  • Other: corticosteroids, methadone
 Caution advised with corticosteroids (decreased efficacy). 

Methadone: Monitor for efficacy and/or opiate withdrawal symptoms with methadone.
Overlapping Toxicities:
  • Bone marrow suppressant drugs
  • Hepatotoxic drugs
 Monitor for toxicities of these drugs.
Streptomycin Potential for Increased Toxicity Due to Overlapping Toxicity:
  • Nephrotoxic drugs
  • Neuromuscular blocking drugs
 Monitor for toxicities of these drugs.
Telaprevir Please see Adult OI guidelines for information about drug interactions, including warnings about interactions between telaprevir and HIV protease inhibitors. Caution advised.
Trimethoprim-Sulfamethoxazole Overlapping Toxicities:
  • Folate antagonists
  • Bone marrow suppressant drugs
 Monitor for toxicities of these drugs.
Valacyclovir Potential For Increased Concentrations (of Both Drugs) and Overlapping Toxicity:
  • Antivirals: acyclovir, valganciclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Valganciclovir Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicity:
  • Antivirals: valacyclovir, acyclovir, ganciclovir, cidofovir
  • ARVs: tenofovir
 Monitor for toxicities of these drugs.
Voriconazole Decreases Voriconazole Concentrations:
  • Anticonvulsant drugs: carbamazepine, long-acting barbiturates
 Caution advised.
  • Antimycobacterial drugs: rifabutin, rifampin
 Rifabutin and Rifampin co-administration should be avoided.
  • ARV drugs: efavirenz, nevirapine, PIs boosted with ritonavir
 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.
Increases Voriconazole Concentrations:
  • ARV drugs: etravirine
 Monitor voriconazole concentrations to reduce toxicity. 
Increases Concomitant Drug Concentrations:
  • Antimycobacterial drugs: rifabutin
 Caution advised.
  • ARV drugs: protease inhibitors boosted with ritonavir, efavirenz, etravirine
 Caution advised.
  • Statins: simvastatin, lovastatin, atorvastatin
 Statins: Do not co-administer with simvastatin or lovastatin. Avoid use of atorvastatin if possible. Alternative statins such as fluvastatin, rosuvastatin, pravastatin are preferred or discontinue statin during antifungal therapy.
  • Sedatives/hypnotics: midazolam, alprazolam, triazolam
 Co-administration should be avoided if possible. Monitor for toxicities.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; CDC = Centers for Disease Control and Prevention; EKG = electrocardiogram; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; OI = opportunistic infection; PI = protease inhibitors; PK = pharmacokinetic; TDM = therapeutic drug monitoring

 

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