January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page 31 

Table 15b. Drug Interactions between NNRTIs* and Other Drugs (Updated January 10, 2011)

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*DLV is not included in this table. Please refer to the FDA package insert for information regarding DLV drug interactions.

This table provides information relating to pharmacokinetic interactions between NNRTIs and non-ARV drugs. For interactions among 

ARV agents and for dosing recommendations, refer to Table 16b.

Concomitant 

Drug Class/Name NNRTI

Effect on NNRTI or 

Concomitant Drug 

Concentrations

Dosing Recommendations and Clinical Comments

Anticoagulants/Antiplatelets

Warfarin EFV, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.

ETR ↑ warfarin possible Monitor INR and adjust warfarin dose accordingly.

Clopidogrel ETR ↓ activation of clopidogrel 

possible

ETR may prevent metabolism of clopidogrel (inactive) to its active 

metabolite. Avoid coadministration, if possible.

Anticonvulsants

Carbamazepine

Phenobarbital

Phenytoin

EFV

carbamazepine + EFV: 

carbamazepine AUC ↓ 27% and 

EFV AUC ↓ 36%

phenytoin + EFV: ↓ EFV and ↓ 

phenytoin possible

Monitor anticonvulsant and EFV levels or, if possible, use alternative 

anticonvulsant. 

ETR ↓ anticonvulsant and ETR 

possible Do not coadminister. Consider alternative anticonvulsants. 

NVP ↓ anticonvulsant and NVP 

possible Monitor anticonvulsant and NVP levels and virologic responses.

Antidepressants

Bupropion EFV bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.

Paroxetine ETR No significant effect No dosage adjustment necessary.

Sertraline EFV sertraline AUC ↓ 39% Titrate sertraline dose based on clinical response.

Antifungals

Fluconazole

EFV No significant effect

ETR ETR AUC ↑ 86% No dosage adjustment. Use with caution.

NVP NVP AUC ↑ 110% Increased risk of hepatotoxicity possible with this combination 

Monitor NVP toxicity or use alternative antiretroviral agent.

Itraconazole

EFV itraconazole and OH-itraconazole 

AUC, Cmax, and Cmin ↓ 35%–44%

Dose adjustments for itraconazole may be necessary. Monitor 

itraconazole level and antifungal response.

ETR ↓ itraconazole possible

↑ ETR possible

Dose adjustments for itraconazole may be necessary. Monitor 

itraconazole level and antifungal response.

NVP ↓ itraconazole possible

↑ NVP possible

Consider monitoring NNRTI and itraconazole levels and antifungal 

response.

Posaconazole EFV posaconazole AUC ↓ 50%

↔ EFV

Consider alternative antifungal if possible or consider monitoring 

posaconazole level if available.

ETR ↑ ETR possible No dosage adjustment necessary

Voriconazole

EFV voriconazole AUC ↓ 77%

EFV AUC ↑ 44%

Contraindicated at standard doses.

Dose: voriconazole 400 mg BID, EFV 300 mg daily

ETR voriconazole AUC ↑ 14%

ETR AUC ↑ 36%

No dosage adjustment; use with caution. Consider monitoring 

voriconazole level.

NVP ↓ voriconazole possible

↑ NVP possible

Monitor for toxicity and antifungal response and/or voriconazole 

level. 

Antimycobacterials

Clarithromycin

EFV clarithromycin AUC ↓ 39% Monitor for efficacy or consider alternative agent, such as 

azithromycin, for MAC prophylaxis and treatment. 

ETR

clarithromycin AUC ↓ 39%

OH-clarithromycin AUC ↑ 21%

ETR AUC ↑ 42%

Consider alternative agent, such as azithromycin, for MAC 

prophylaxis and treatment. 

NVP clarithromycin AUC ↓ 31%

OH-clarithromycin AUC ↑ 42%

Monitor for efficacy or use alternative agent, such as azithromycin,

for MAC prophylaxis and treatment.
January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page 32 

Concomitant 

Drug Class/Name NNRTI

Effect on NNRTI or 

Concomitant Drug 

Concentrations

Dosing Recommendations and Clinical Comments

Antimycobacterials (continued)

Rifabutin

EFV rifabutin ↓ 38% Dose: rifabutin 450–600 mg once daily or 600 mg three times a week 

if EFV is not coadministered with a PI.

ETR

rifabutin and metabolite AUC ↓ 

17%

ETR AUC ↓ 37%

If ETR is used with an RTV-boosted PI, rifabutin should not be 

coadministered.

Dose: rifabutin 300 mg once daily if ETR is not coadministered with 

an RTV-boosted PI. 

NVP

rifabutin AUC ↑ 17% and 

metabolite AUC ↑ 24%

NVP Cmin ↓ 16%

No dosage adjustment necessary. Use with caution.

Rifampin

EFV EFV AUC ↓ 26%

Maintain EFV dose at 600 mg once daily and monitor for virologic 

response.

Some clinicians suggest EFV 800 mg dose in patients >60kg.

ETR Significant ↓ ETR possible Do not coadminister. 

NVP NVP ↓ 20%–58% Do not coadminister.

Benzodiazepines

Alprazolam EFV, ETR, NVP No data Monitor for therapeutic efficacy of alprazolam.

Diazepam ETR ↑ diazepam possible Decreased dose of diazepam may be necessary.

Lorazepam EFV lorazepam Cmax ↑ 16%, AUC no 

significant effect No dosage adjustment necessary

Midazolam EFV Significant↑ midazolam expected

Do not coadminister with oral midazolam.

Parenteral midazolam can be used with caution as a single dose and 

can be given in a monitored situation for procedural sedation.

Triazolam EFV Significant ↑ triazolam expected Do not coadminister.

Cardiac Medications

Dihydropyridine 

calcium channel 

blockers (CCBs)

EFV, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.

Diltiazem EFV diltiazem AUC ↓ 69% Titrate diltiazem dose based on clinical response. NVP ↓ diltiazem possible

Corticosteroids

Dexamethasone ETR* ↓ ETR possible Use systemic dexamethasone with caution or consider alternative 

corticosteroid for long-term use.

Herbal Products

St. John’s wort EFV, ETR, NVP ↓ NNRTI Do not coadminister.

Hormonal Contraceptives

Hormonal 

contraceptives

EFV

ethinyl estradiol ↔

levonorgestrel AUC ↓ 83%

norelgestromin AUC ↓ 64%

Use alternative or additional methods. Norelgestromin and 

levonorgestrel are active metabolites of norgestimate.

ETR

ethinyl estradiol AUC ↑ 22%

norethindrone: no significant 

effect

No dosage adjustment necessary.

NVP

ethinyl estradiol AUC ↓ 20%

norethindrone AUC ↓ 19% Use alternative or additional methods.

depomedroxyprogesterone 

acetate: no significant change No dosage adjustment necessary

Levonorgestrel EFV levonorgestrel AUC ↓ 58% Effectiveness of emergency postcoital contraception may be 

diminished.

HMG-CoA Reductase Inhibitors

Atorvastatin EFV, ETR, NVP atorvastatin AUC ↓ 32%–43% 

with EFV, ETR

Adjust atorvastatin according to lipid responses, not to exceed the 

maximum recommended dose. 

Fluvastatin ETR ↑ fluvastatin possible Dose adjustments for fluvastatin may be necessary.

* Error corrected January 18, 2011

Table 15b. Drug Interactions between NNRTIs* and Other Drugs

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January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page 33 

Concomitant 

Drug Class/Name NNRTI

Effect on NNRTI or 

Concomitant Drug 

Concentrations

Dosing Recommendations and Clinical Comments

HMG-CoA Reductase Inhibitors (continued)

Lovastatin

Simvastatin

EFV simvastatin AUC ↓ 68%

Adjust simvastatin dose according to lipid responses, not to exceed 

the maximum recommended dose. If used with RTV-boosted PI, 

simvastatin and lovastatin should be avoided.

ETR, NVP ↓ lovastatin possible

↓ simvastatin possible

Adjust lovastatin or simvastatin dose according to lipid responses, 

not to exceed the maximum recommended dose. If used with RTVboosted PI, simvastatin and lovastatin should be avoided. 

Pitavastatin EFV, ETR, NVP No data No dosage recommendation

Pravastatin

Rosuvastatin

EFV pravastatin AUC ↓ 44%

rosuvatatin: no data

Adjust statin dose according to lipid responses, not to exceed the 

maximum recommended dose.

ETR No significant effect expected 

with either pravastatin or 

rosuvastatin

No dosage adjustment necessary

Narcotics/Treatment for Opioid Dependence

Buprenorphine EFV buprenorphine AUC ↓ 50%

norbuprenorphine AUC ↓ 71%

No withdrawal symptoms reported. No dosage adjustment 

recommended, but monitor for withdrawal symptoms.

NVP No significant effect No dosage adjustment necessary

Methadone

EFV methadone AUC ↓ 52% Opioid withdrawal common; increased methadone dose often 

necessary.

ETR No significant effect No dosage adjustment necessary

NVP methadone AUC ↓ 41%

NVP: no significant effect

Opioid withdrawal common; increased methadone dose often 

necessary. 

Phosphodiesterase Type 5 (PDE5) Inhibitors

Sildenafil ETR sildenafil AUC ↓ 57% May need to increase sildenafil dose based on clinical effect. 

Tadalafil ETR ↓ tadalafil possible May need to increase tadalafil dose based on clinical effect.

Vardenafil ETR ↓ vardenafil possible May need to increase vardenafil dose based on clinical effect.

Miscellaneous Interactions

Atovaquone/proguanil EFV ↓ atovaquone AUC 75% 

↓ progaunil AUC 43%

No dosage recommendation. Consider alternative drug for malaria 

prophylaxis, if possible.

Acronyms: ARV = antiretroviral, AUC = area under the curve, CCB = calcium channel blocker, Cmax = maximum plasma concentration, 

Cmin = minimum plasma concentration, DLV = delavirdine, EFV = efavirenz, ETR = etravirine, FDA = Food and Drug Administration, 

INR = international normalized ratio, MAC = Mycobacterium avium complex, NNRTI = non-nucleoside reverse transcriptase inhibitor, NVP = nevirapine, 

OH-clarithromycin = active metabolite of clarithromycin, PDE5 = phosphodiesterase type 5, PI = protease inhibitor

Table 15b. Drug Interactions between NNRTIs* and Other Drugs

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