Reprinted from www.antimicrobe.org

Table 11b. Drug Interactions Between NNRTIs and Other Drugs (Updated November 3, 2008) a

Concomitant Effect on NNRTI or Dosing Recommendations and Clinical Drug NNRTI Concomitant Drug Comment Class/Name Concentrations Antifungals

DLV, EFV No significant effect No dosage adjustment Fluconazole ETR ↑ ETR

NVP ↑ NVP Increased risk of hepatotoxicity Potential for bi- Consider monitoring NNRTI and itraconazole DLV, NVP directional interactions levels.

Monitor itraconazole level and adjust dose if Itraconazole EFV itraconazole ↓ clinical indicated. ↑ ETR Monitor itraconazole level and adjust dose if ETR ↓ itraconazole clinical indicated. DLV ↑ DLV No dosage adjustment necessary. EFV No data ↑ ETR Dose adjustment depending on other Ketoconazole ETR ↓ ketoconazole coadministered drugs. ketoconazole ↓ Coadministration not recommended. NVP NVP ↑ DLV, NVP No data Posaconazole ↓ 1. Alternative antifungal agents. EFV EFV ↑ Posaconazole 2. Monitoring posaconazole level.

ETR ↑ ETR No dosage adjustment necessary. DLV No data Monitor for toxicity. EFV ↑ EFV voriconazole ↓ Voriconazole 400mg BID and EFV 300mg QD Voriconazole ↑ ETR Monitor voriconazole level. ETR ↑ voriconazole Monitor for toxicity and antifungal outcome. NVP No data

Anticonvulsants

DLV DLV ↓ Contraindicated – do not coadminister. carbamazepine + EFV: both ↓ 1. Monitor anticonvulsant levels Carbamazepine EFV Phenobarbital 2. Alternative anticonvulsant. Phenytoin ↓ EFV with phenytoin Potential ↓ ETR and ↓ ETR Do not coadminister. anticonvulsants NVP No data

Concomitant Effect on NNRTI or Dosing Recommendations and Clinical Drug Class/Name NNRTI Concomitant Drug Comment Concentrations Anti- mycobacterials 1. CrCl 30– 60mL/min: reduce clarithromycin clarithromycin ↑ dose by 50% DLV DLV ↑ 2. CrCl <30mL/min: reduce clarithromycin dose by 75% 1. Monitor for efficacy Clarithromycin EFV clarithromycin ↓ 2. Alternative agent, such as azithromycin ETR ↑ ETR clarithromycin ↓ Alternative agent, such as azithromycin NVP ↑ 1. Monitor for efficacy NVP clarithromycin ↓ 2. Alternative agent DLV ↓ Coadministration not recommended. DLV rifabutin ↑ Without a PI: Rifabutin 450–600mg QD or 600mg EFV rifabutin ↓ 3x/week + EFV

1. Without a RTV-boosted PI: rifabutin 300mg Rifabutin QD + ETR ETR ↓ 2. With DRV/r or SQV/r: alternative ARV agent ETR Rifabutin ↓ to ETR 3. With LPV/r: rifabutin 150mg QOD or 3x/week + ETR

↓ NVP NVP ↑ Rifabutin No dosage adjustment necessary. DLV DLV ↓ Contraindicated—do not coadminister.

EFV ↓ EFV 1.EFV 600mg QD and monitor for viral response Rifampin 2. May use EFV 800mg if weight >60kg ↓ ETR ETR Do not coadminister.

NVP ↓ NVP Do not coadminister. Benzodiazepines No data DLV May ↑ alprazolam Do not coadminister. Alprazolam EFV, NVP, No data Monitor for therapeutic efficacy. ETR No data DLV May ↑ diazepam Consider alternative benzodiazepines. Diazepam EFV, NVP No data ETR ↑ diazepam Decreased dose of diazepam may be necessary. DLV, ETR, No data NVP Lorazepam EFV Lorazepam ↑ No dosage adjustment necessary.

No data 1. Do not coadminister with oral midazolam. DLV, EFV May ↑ midazolam 2. Parenteral midazolam can be used with Midazolam caution. ETR, NVP No data Concomitant Effect on NNRTI or Dosing Recommendations and Clinical Drug Class/Name NNRTI Concomitant Drug Comment Concentrations No data DLV, EFV Do not coadminister. Triazolam May ↑ triazolam ETR, NVP No data Herbal Products St. John’s wort All NNRTIs ↓ NNRTI Not recommended. Hormonal Contraceptives No data DLV Potential for ↑ ethinyl Clinical significance unknown. estradiol Use alternative or additional methods. Hormonal EFV ↑ ethinyl estradiol Contraceptives ↑ ethinyl estradiol ETR No effect on No dosage adjustment necessary. norethindrone levels. NVP ethinyl estradiol ↓ Use alternative or additional methods. HMG-CoA Reductase Inhibitors 1. Use lowest possible dose and monitor for No data, potential toxicity DLV ↑atorvastatin 2. Consider other HMG-CoA reductase inhibitors Atorvastatin EFV atorvastatin ↓ Adjust atorvastatin according to lipid responses ETR ↓ atorvastatin Adjust atorvastatin according to lipid response. No data, potential NVP ↓atorvastatin Adjust atorvastatin according to lipid response. DLV, EFV, No data Fluvastatin NVP ETR ↑ fluvastatin May adjust fluvastatin dose No data ; potential ↑ DLV statin Avoid concomitant use.

Lovastatin Adjust simvastatin dose according to lipid EFV simvastatin ↓ Simvastatin responses 1. Adjust lovastatin or simvastatin dose ↓ lovastatin ETR according to lipid responses. ↓ simvastatin 2. Avoid Simvastatin and lovastatin with RTV- boosted PI

DLV, NVP No data Pravastatin Adjust pravastatin dose according to lipid EFV pravastatin ↓ Rosuvastatin responses ETR No effect Dose: standard Methadone No effect on DLV Monitor for methadone toxicity and need for dose DLV Potential for ↑ methadone reduction 1. Potential for opiate withdrawal EFV Methadone ↓ 2. Increased methadone dose often necessary. Methadone ETR No effect Dose: standard

↓ methadone 1. Opiate withdrawal common NVP No effect on NVP 2. Increased methadone dose often necessary. Concomitant Effect on NNRTI or Dosing Recommendations and Clinical Drug NNRTI Concomitant Drug Comment Class/Name Concentrations Oral Anticoagulant DLV No data Monitor INR. Warfarin EFV, NVP No data Monitor INR. ETR ↑ warfarin Monitor INR.

Drug-Specific Interactions

NNRTI Effect on NNRTI or Concomitant Dosage Recommendations and Clinical Concomitant Drug Drug Class/Name Comment Concentrations Fluoxetine ↑ DLV No dosage adjustment necessary. Quinidine No data, potential Monitor quinidine level and toxicities. ↑quinidine DLV No data, potential ↑ Start with reduced dose: Sildenafil phosphodiesterase 1. Sildenafil 25mg Q48H Vardenafil inhibitor 2. Vardenafil 2.5mg Q24H Tadalafil 3. Tadalafil 5mg Q72H. Use with caution with antiarrhythmic level Antiarrhythmics ↓ antiarrhythmics monitoring Consider alternative corticosteroid for long- ETR Dexamethasone ↓ ETR term use. Increase sildenafil dose based on clinical Sildenafil ↓ sildenafil effect. a Adapted from http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (Accessed in December 2008) [Table 15b] Abbreviations: DLV = delavirdine, EFV = efavirenz, ETR = etravirine, NNRTI = non-nucleoside reverse transcriptase inhibitor, NVP = nevirapine, CBZ = carbamazepine.