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 Name | Toxicities | Recommendation |
---|---|---|
* 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
| Avoid other nephrotoxic drugs. |
Increased Concentrations (Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. | |
Albendazole | Increased Albendazole Concentrations
Decreased Albendazole Concentrations
| Caution advised. |
Amikacin | Overlapping Toxicities
| Caution advised. Avoid combining with cidofovir. |
Amphotericin B Amphotericin B Liposome | Overlapping Toxicities
| Caution advised. |
Artemether-Lumefantrine | Increased Drug Concentrations
| Monitor therapy when combined. |
Overlapping Toxicities
| 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
| Coadministration of atovaquone and rifampin or atovaquone and rifabutin should be avoided. |
Azithromycin | Overlapping Toxicities
| Caution advised. Increased risk of QT prolongation. |
Bedaquiline | Overlapping Toxicities
| Bedaquiline may enhance the QTc-prolonging effects. Avoid concomitant use. |
| Avoid concomitant use. | |
Caspofungin | Decreased Caspofungin Concentrations
| Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers. |
Cidofovir | Overlapping Toxicities
| Monitor for toxicities of these drugs. Prehydrate with IV normal saline and probenecid to avoid nephrotoxicity. |
Ciprofloxacin | Decreased Ciprofloxacin Absorption
| Give oral ciprofloxacin 2 hours before or 6 hours after drugs that may interfere with absorption. |
Overlapping Toxicities
| Caution advised. | |
| Avoid concomitant use. | |
Clarithromycin | Increased Clarithromycin Concentrations
| 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
| Consider alternative ARV. | |
Decreased Clarithromycin Concentrations
| 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
| Clarithromycin may reduce fecal microbiota (live) (rectal) effectiveness. | |
Clindamycin | Decreased Clindamycin Antibacterial Efficacy
Overlapping Toxicities
| Avoid concomitant use. |
Cycloserine | Overlapping Toxicities
| Caution advised. |
| Avoid concomitant use. | |
Dapsone | Decreased Dapsone Concentrations
| Coadministration should be avoided if possible. Consider alternatives for dapsone or use rifabutin. |
Decreased Dapsone Absorption
| For coadministration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication. | |
Overlapping Toxicities
| Caution advised. | |
| Avoid concomitant use. | |
Doxycycline | Decreased Doxycycline Concentrations
| Potential for decreased doxycycline efficacy. Monitor for therapeutic failure. |
Overlapping Toxicities
| Avoid concomitant use. | |
Erythromycin | Increased Concentrations of Erythromycin
Increased Concomitant Drug Concentrations
| Monitor for toxicities of both drugs, potential for QT prolongation. |
Overlapping Toxicities
| Avoid concomitant use. | |
Ethambutol | Overlapping Toxicities
| Caution advised. |
| Avoid concomitant use. | |
Ethionamide | Potential for Increased Toxicity Due to Overlapping Toxicity
| Caution advised. |
| Avoid concomitant use. | |
Fluconazole | Decreased Fluconazole Levels
| Monitor for efficacy. May need to increase fluconazole dose. |
Increases Concomitant Drug Concentrations
| 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. | |
| Decrease venetoclax dose by at least 50% in children requiring concomitant treatment. | |
| May need to decrease dose of rifabutin. | |
| 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
Overlapping Toxicities
| Caution advised. Dose adjustments with therapeutic drug monitoring recommended with impaired renal function. |
Foscarnet | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
Ganciclovir | Increased Ganciclovir Concentrations
| Monitor for toxicities of these drugs. |
Increased Concomitant Drug Concentrations
| Caution advised. | |
Overlapping Toxicities
| Caution advised. Increased risk of seizures with imipenem-cilastatin. | |
Isavuconazole | Increased Concomitant Drug Concentrations
| 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
| Use with caution. |
Decreased Isoniazid Absorption
| Caution advised. Take ≥1 hour before aluminum-containing antacids. | |
Increased Concomitant Drug Concentrations
| Caution advised. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. | |
Overlapping Toxicities
| Caution advised. | |
Itraconazole and Ketoconazole | Increased Azole Concentrations
| 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
| Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily. | |
| 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. | |
| Consider switching to azithromycin, which has less potential for drug interaction. | |
| Coadministration of midazolam and alprazolam should be avoided. Coadministration of diazepam should be avoided, if possible. | |
| Coadministration of quinidine should be avoided. QT prolongation may occur. | |
Decreased Azole Concentrations
| Monitor concentrations. Coadministration of efavirenz should be avoided if possible. | |
| Monitor concentrations. | |
| Coadministration with rifampin should be avoided. Coadministration with rifabutin should be avoided, if possible. Monitor for toxicities and monitor concentrations. | |
Decreased Azole Absorption
| Monitor concentrations. | |
Mefloquine | Decreased Mefloquine Concentrations
| Monitor for decreased mefloquine efficacy. Coadministration of rifampin should be avoided, if possible; use rifabutin instead. |
Decreased Concomitant Drug Concentrations
| Monitor for virologic failure of PI-containing ART regimen. | |
Overlapping Toxicities
| 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
| 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
| Coadministration should be avoided, if possible. Monitor for toxicities (hypocalcemia, QT prolongation). |
| Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation with PIs; pancreatitis for didanosine). | |
| Monitor for toxicities. | |
| Monitor for toxicities. | |
| Monitor for toxicities. Avoid coadministration, if possible. | |
| Avoid concomitant use. | |
Posaconazole | Decreased Posaconazole Drug Concentrations
| Coadministration of fosamprenavir should be avoided. Coadministration of efavirenz should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. |
| Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. | |
| Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. | |
Increased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary. | |
| Coadministration should be avoided. | |
| Coadministration should be avoided. | |
| Coadministration should be avoided, if possible. Monitor for toxicities. | |
| Coadministration should be avoided. | |
| 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. | |
| Coadministration should be avoided. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided. | |
| Use with caution. Monitor for toxicities. | |
Proguanil | Decreased Proguanil Concentrations
| Use with caution. |
Pyrazinamide | Overlapping Toxicities
| Use with caution. Monitor for hepatotoxicity. |
| Avoid concomitant use. | |
Quinidine | Increased Quinidine Concentrations
| 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. |
| Coadministration should be avoided. Increased risk of arrhythmia. | |
Decreased Quinidine Concentrations
| Use with caution. Monitor quinidine levels. | |
Increased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. Monitor for toxicities. | |
Overlapping Toxicities
| Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation). | |
Ribavirin | Increased Concomitant Drug Concentrations
| Coadministration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity. |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. | |
Overlapping Toxicities
| Coadministration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine, lactic acidosis for all NRTIs). | |
Rifabutin | Increased Rifabutin Concentrations
| Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if coadministered with PIs. |
| Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction. | |
| Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy). | |
| Coadministration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead. | |
Increased Concomitant Drug Concentrations
| Use with caution. Monitor for didanosine toxicity. | |
Decreased Rifabutin Concentrations
| Use with caution. Higher rifabutin dose required with efavirenz. Consider TDM. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided. | |
| Coadministration should be avoided, if possible. | |
| Use with caution. Monitor for dapsone treatment failure. | |
| Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy). | |
| Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended. | |
Rifampin | Decreased Concomitant Drug Concentrations
| Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended. |
| 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. | |
| 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. | |
| Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers. Monitor azoles for efficacy. May need to increase azole dose. | |
| Caution advised with corticosteroids (decreased efficacy). Monitor for efficacy and/or opiate withdrawal symptoms with methadone. | |
Overlapping Toxicities
| Monitor for toxicities of these drugs. | |
Streptomycin | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
| Avoid concomitant use. | |
Trimethoprim-Sulfamethoxazole (TMP-SMX) | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
| Avoid concomitant use. | |
Valacyclovir | Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. Avoid other nephrotoxic drugs. |
Valganciclovir | Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. Avoid other nephrotoxic drugs. |
Voriconazole | Decreased Voriconazole Concentrations
| Caution advised. |
| Rifabutin and rifampin coadministration should be avoided. | |
| 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
| Monitor voriconazole concentrations to reduce toxicity. | |
Increased Concomitant Drug Concentrations
| Caution advised. | |
| Caution advised. | |
| 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. | |
| 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 Name | Toxicities | Recommendation |
---|---|---|
* 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
| Avoid other nephrotoxic drugs. |
Increased Concentrations (Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. | |
Albendazole | Increased Albendazole Concentrations
Decreased Albendazole Concentrations
| Caution advised. |
Amikacin | Overlapping Toxicities
| Caution advised. Avoid combining with cidofovir. |
Amphotericin B Amphotericin B Lipid Complex Amphotericin B Liposome | Overlapping Toxicities
| Caution advised. |
Artemether-Lumefantrine | Increased Drug Concentrations
| Monitor therapy when combined. |
Overlapping Toxicities
| 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
| Coadministration of atovaquone and rifampin or atovaquone and rifabutin should be avoided. |
Azithromycin | Overlapping Toxicities
| Caution advised. Increased risk of QT prolongation. |
Bedaquiline | Overlapping Toxicities
| Bedaquiline may enhance the QTc-prolonging effects. Avoid concomitant use. |
| Avoid concomitant use. | |
Caspofungin | Decreased Caspofungin Concentrations
| Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers. |
Cidofovir | Overlapping Toxicities
| Monitor for toxicities of these drugs. Prehydrate with IV normal saline and probenecid to avoid nephrotoxicity. |
Ciprofloxacin | Decreased Ciprofloxacin Absorption
| Give oral ciprofloxacin 2 hours before or 6 hours after drugs that may interfere with absorption. |
Overlapping Toxicities
| Caution advised. | |
| Avoid concomitant use. | |
Clarithromycin | Increased Clarithromycin Concentrations
| 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
| Consider alternative ARV. | |
Decreased Clarithromycin Concentrations
| 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
| Clarithromycin may reduce fecal microbiota (live) (rectal) effectiveness. | |
Clindamycin | Decreased Clindamycin Antibacterial Efficacy
Overlapping Toxicities
| Avoid concomitant use. |
Cycloserine | Overlapping Toxicities
| Caution advised. |
| Avoid concomitant use. | |
Dapsone | Decreased Dapsone Concentrations
| Coadministration should be avoided if possible. Consider alternatives for dapsone or use rifabutin. |
Decreased Dapsone Absorption
| For coadministration with antacids or didanosine suspension, give dapsone 1 hour before or 4 hours after the other medication. | |
Overlapping Toxicities
| Caution advised. | |
| Avoid concomitant use. | |
Doxycycline | Decreased Doxycycline Concentrations
| Potential for decreased doxycycline efficacy. Monitor for therapeutic failure. |
Overlapping Toxicities
| Avoid concomitant use. | |
Erythromycin | Increased Concentrations of Erythromycin
Increased Concomitant Drug Concentrations
| Monitor for toxicities of both drugs, potential for QT prolongation. |
Overlapping Toxicities
| Avoid concomitant use. | |
Ethambutol | Overlapping Toxicities
| Caution advised. |
| Avoid concomitant use. | |
Ethionamide | Potential for Increased Toxicity Due to Overlapping Toxicity
| Caution advised. |
| Avoid concomitant use. | |
Fluconazole | Decreased Fluconazole Levels
| Monitor for efficacy. May need to increase fluconazole dose. |
Increases Concomitant Drug Concentrations
| 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. | |
| Decrease venetoclax dose by at least 50% in children requiring concomitant treatment. | |
| May need to decrease dose of rifabutin. | |
| 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
Overlapping Toxicities
| Caution advised. Dose adjustments with therapeutic drug monitoring recommended with impaired renal function. |
Foscarnet | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
Ganciclovir | Increased Ganciclovir Concentrations
| Monitor for toxicities of these drugs. |
Increased Concomitant Drug Concentrations
| Caution advised. | |
Overlapping Toxicities
| Caution advised. Increased risk of seizures with imipenem-cilastatin. | |
Isavuconazole | Increased Concomitant Drug Concentrations
| 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
| Use with caution. |
Decreased Isoniazid Absorption
| Caution advised. Take ≥1 hour before aluminum-containing antacids. | |
Increased Concomitant Drug Concentrations
| Caution advised. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. | |
Overlapping Toxicities
| Caution advised. | |
Itraconazole and Ketoconazole | Increased Azole Concentrations
| 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
| Caution advised. Monitor for toxicities. Decrease adult maraviroc dose to 150 mg twice daily. | |
| 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. | |
| Consider switching to azithromycin, which has less potential for drug interaction. | |
| Coadministration of midazolam and alprazolam should be avoided. Coadministration of diazepam should be avoided, if possible. | |
| Coadministration of quinidine should be avoided. QT prolongation may occur. | |
Decreased Azole Concentrations
| Monitor concentrations. Coadministration of efavirenz should be avoided if possible. | |
| Monitor concentrations. | |
| Coadministration with rifampin should be avoided. Coadministration with rifabutin should be avoided, if possible. Monitor for toxicities and monitor concentrations. | |
Decreased Azole Absorption
| Monitor concentrations. | |
Mefloquine | Decreased Mefloquine Concentrations
| Monitor for decreased mefloquine efficacy. Coadministration of rifampin should be avoided, if possible; use rifabutin instead. |
Decreased Concomitant Drug Concentrations
| Monitor for virologic failure of PI-containing ART regimen. | |
Overlapping Toxicities
| 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
| 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
| Coadministration should be avoided, if possible. Monitor for toxicities (hypocalcemia, QT prolongation). |
| Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation with PIs; pancreatitis for didanosine). | |
| Monitor for toxicities. | |
| Monitor for toxicities. | |
| Monitor for toxicities. Avoid coadministration, if possible. | |
| Avoid concomitant use. | |
Posaconazole | Decreased Posaconazole Drug Concentrations
| Coadministration of fosamprenavir should be avoided. Coadministration of efavirenz should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. |
| Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. | |
| Coadministration should be avoided, if possible. If coadministered, monitor posaconazole concentrations and adjust dose accordingly. | |
Increased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. Monitor for toxicities. Consider monitoring concentrations and adjust dose as necessary. | |
| Coadministration should be avoided. | |
| Coadministration should be avoided. | |
| Coadministration should be avoided, if possible. Monitor for toxicities. | |
| Coadministration should be avoided. | |
| 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. | |
| Coadministration should be avoided. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided. | |
| Use with caution. Monitor for toxicities. | |
Proguanil | Decreased Proguanil Concentrations
| Use with caution. |
Pyrazinamide | Overlapping Toxicities
| Use with caution. Monitor for hepatotoxicity. |
| Avoid concomitant use. | |
Quinidine | Increased Quinidine Concentrations
| 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. |
| Coadministration should be avoided. Increased risk of arrhythmia. | |
Decreased Quinidine Concentrations
| Use with caution. Monitor quinidine levels. | |
Increased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. Monitor for toxicities. | |
Overlapping Toxicities
| Coadministration should be avoided, if possible. Monitor for toxicities (QT prolongation). | |
Ribavirin | Increased Concomitant Drug Concentrations
| Coadministration should be avoided. Potential for increased risk of pancreatitis and mitochondrial toxicity. |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided, if possible. | |
Overlapping Toxicities
| Coadministration should be avoided, if possible. Monitor for toxicities (anemia for zidovudine, lactic acidosis for all NRTIs). | |
Rifabutin | Increased Rifabutin Concentrations
| Use with caution. Monitor for rifabutin toxicity. Reduce rifabutin dose if coadministered with PIs. |
| Use with caution. Monitor for rifabutin toxicity. Consider rifabutin dose reduction. | |
| Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy). | |
| Coadministration should be avoided, if possible. Monitor for rifabutin toxicity. Consider rifabutin dose reduction or using azithromycin instead. | |
Increased Concomitant Drug Concentrations
| Use with caution. Monitor for didanosine toxicity. | |
Decreased Rifabutin Concentrations
| Use with caution. Higher rifabutin dose required with efavirenz. Consider TDM. | |
Decreased Concomitant Drug Concentrations
| Coadministration should be avoided. | |
| Coadministration should be avoided, if possible. | |
| Use with caution. Monitor for dapsone treatment failure. | |
| Coadministration should be avoided, if possible. If coadministered, consider TDM and monitor for rifabutin toxicities (and azole clinical efficacy). | |
| Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended. | |
Rifampin | Decreased Concomitant Drug Concentrations
| Oral contraceptives less effective. Additional non-hormonal contraceptive or alternative recommended. |
| 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. | |
| 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. | |
| Increase in dose of caspofungin is recommended when coadministered with CYP450 inducers. Monitor azoles for efficacy. May need to increase azole dose. | |
| Caution advised with corticosteroids (decreased efficacy). Monitor for efficacy and/or opiate withdrawal symptoms with methadone. | |
Overlapping Toxicities
| Monitor for toxicities of these drugs. | |
Streptomycin | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
| Avoid concomitant use. | |
Trimethoprim-Sulfamethoxazole (TMP-SMX) | Overlapping Toxicities
| Monitor for toxicities of these drugs. |
| Avoid concomitant use. | |
Valacyclovir | Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. Avoid other nephrotoxic drugs. |
Valganciclovir | Potential for Increased Concentrations (of Both Drugs) and Overlapping Toxicities
| Monitor for toxicities of these drugs. Avoid other nephrotoxic drugs. |
Voriconazole | Decreased Voriconazole Concentrations
| Caution advised. |
| Rifabutin and rifampin coadministration should be avoided. | |
| 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
| Monitor voriconazole concentrations to reduce toxicity. | |
Increased Concomitant Drug Concentrations
| Caution advised. | |
| Caution advised. | |
| 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. | |
| 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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