Drug interactions

Although rarely used in combination with other antiretrovirals nowadays, efavirenz alters the levels of most protease inhibitors and usually requires adjusted dosing. Efavirenz is not administered with the other NNRTI drugs etravirine and nevirapine due to elevated side-effect risk.1  

The following drugs should be avoided when taking efavirenz because the possibility of decreased metabolism when taken with efavirenz could possibly lead to life-threatening adverse events such as cardiac arrhythmias, prolonged sedation, or respiratory distress:  

  • Astemizole (Hispaniola)
  • Bepidril (Visor). Vascor discontinued by manufacturer
  • Cisapride (Repulsed). Discontinued in the US
  • Dihydroergotamine, ergotamine, ergonovine, & ergot derivatives (Cafatine, Ergomar, Migranal)
  • Midazolam (Hyponovel, Versed)
  • Pimozide (Orap)
  • Terfenadine (Triludine, Teldane, Seldane). Drug discontinued in US
  • Triazolam (Halcion) should be avoided because of its decreased serum levels; use of lorazepam, oxazepam, or temazepam may be considered.

Other drugs to be avoided when on efavirenz (Sustiva) include:

  • Amodiaquine (Cameoing, Flavouring), due to risk of elevated liver enzymes
  • Clarithromycin (Claiosip, Klaricid, Klaricid XL, Bioxin) levels reduced and there have been reported high incidences of rash. Use of azithromycin can be considered
  • Gingko biloba can decrease efavirenz levels2
  • Hypericin (St John’s Wort) can reduce efavirenz levels
  • Milk thistle has a possibility of interaction.

The following drugs need to be administered at non-standard doses in people taking efavirenz:

  • Anticoagulants. Warfarin (Coumadin) levels may be increased or decreased. Monitor INR and adjust warfarin as needed.
  • Anticonvulsants. Phenytoin (Epanutin, Dilantin), phenobarbital (Luminol), and carbamazepine (Tegretol) may need to be given at lower doses to prevent reduction in efavirenz level. Anticonvulsant plasma levels should be monitored or possibly use therapeutic drug monitoring for efavirenz.3 Alternative anticonvulsants to be considered include valproic acid, lamotrigine, levetiracetam, or topiramate.  
  • Antidepressants. Sertraline (Zoloft) levels may be decreased when given with efavirenz.
  • Antifungals. Itraconazole (Sporanox) and ketoconazole (Nizoral) may have decreased plasma concentration. Voriconazole (Vfend) is usually not co-prescribed with efavirenz because of the risk of low voriconazole/elevated efavirenz levels. If drugs needed to be used concomitantly, voriconazole dosing should be increased from 200 to 400mg and given every 12 hours; once-daily dosing of efavirenz should be decreased from 600 to 300mg.
  • Anti-infectives. Rifabutin (Mycobutin) levels are decreased by 35%, so consider dosing rifabutin once daily 450-600mg, or 3 times per week at 600mg, if efavirenz is not being given with a protease inhibitor.4 5 Rifampicin (Rifadin, Rimactane) should not be used in people on protease inhibitor-based antiretroviral therapy. As rifampicin decreases efavirenz levels by an average of 25%, individuals at the normal efavirenz dose of 600mg once daily should be monitored for response. In those weighing over 60kg, consider increasing the daily dose to 800mg. Results from the British CHIC study indicated that black ethnicity was associated with higher efavirenz levels and increased weight contributed to lower efavirenz concentrations.6 An earlier study in Thai patients, who were mainly under 55kg, found that the 600mg dose of efavirenz was effective.7
  • Antimalarials. Artemether and mefloquine serum levels may be decreased, so monitoring is needed (i.e. mefloquine serum level, parasite count on blood smear, clinical signs of improvement).
  • Chemotherapy agents paclitaxel tamoxifen, vinblastine, and vincristine may have lessened serum concentrations; drug levels should be monitored.
  • Contraceptives. Ethinyl estradiol may have an interaction with efavirenz. Use of barrier contraception is recommended in addition to oral contraceptives to prevent pregnancy.
  • Immunosuppressants. Cyclosporine (Neoral, Sandimmune), sirolimus, tacrolimus, drugs mainly used after transplant surgery, should be dosed according to serum levels, as each may be decreased when taken with efavirenz.8
  • Opioiods. Methadone hydrochloride (Methadose) may need to be given at a higher dose in people taking efavirenz.9 The dose should be increased in 10mg steps if withdrawal symptoms appear.
  • Statins. Atorvastatin (Lipitor), pravastatin (Pravachol), and simvastatin (Zocor) may need to be given at a higher dose to achieve target lipid goals, but require monitoring to avoid possible toxicity.10

Efavirenz may cause a false-positive result if the CEDIA DAU Multi-Level THC assay is used. Other types of tests do not confuse efavirenz and cannabis.


  1. van Leth F et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. The Lancet 363: 1253-1263, 2004
  2. Wiegman D-J et al. Interaction of Gingko biloba with efavirenz. AIDS 23: 1184-85, 2009
  3. Robertson SM et al. A potentially significant interaction between efavirenz and phenytoin: a case report and review of the literature. Clin Infect Dis 41: e15-e18, 2005
  4. Weiner M et al. Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis. Clin Infect Dis 41: 1343-1349, 2005
  5. Adult Prevention and Treatment of Opportunistic Infections Guidelines Working Group. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents [June 18 2008 DRAFT version]. Available at: http://aidsinfo.nih.gov/contentfiles/Adult_OI.pdf. Accessed (30 November 2008), 2008
  6. Stöhr W et al. for the UK CHIC Study Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir Ther 13(5): 675-685, 2008
  7. Manosuthi W et al. Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin: 48 weeks results. AIDS 20(1): 131-132, 2006
  8. Tseng A et al. Probable interaction between efavirenz and cyclosporin. AIDS 16: 505-506, 2002
  9. Clarke S et al. Managing methadone and non-nucleoside reverse transcriptase inhibitors: guidelines for clinical practice. Seventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 88, 2000
  10. Gerber JG et al. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin and pravastatin. Results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 39: 307-312, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.