Nevirapine and Methadone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nevirapine
Methadone
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced methadone exposure and an increased risk of opioid withdrawal symptoms (insomnia, pain, nausea, sweating, anxiety)
Interaction Deep Dive
There have been several cases of methadone patients experiencing symptoms of opioid withdrawal following the initiation of nevirapine therapy. Nevirapine is an inducer of CYP3A4 enzymes, and methadone relies on CYP3A4 for N-demethylation6. In a study in HIV-1 positive subjects receiving chronic methadone, coadministration of nevirapine led to a 3-fold increase in methadone clearance resulting in withdrawal symptoms and requiring methadone dose adjustments. Increased methadone dosages may be necessary to prevent opiate withdrawal symptoms (insomnia, pain, nausea, sweating, anxiety). Monitor methadone maintained patients in whom nevirapine therapy is initiated for such symptoms and adjust methadone doses accordingly 12. Discontinuation of concomitant nevirapine (dual inducer of CYP3A4 and a CYP2B6) in methadone-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression. Therefore, when discontinuing a dual inducer of CYP2B6 and CYP3A4 in methadone-treated patients, consider dosage reduction of methadone and follow patients closely at frequent intervals for signs and symptoms of respiratory depression and sedation 5.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of methadone; induction of CYP2B6-mediated metabolism of methadone
Literature reports
6 reports — tap to read
a) A 32-year-old HIV-positive female was stabilized on methadone 80 mg daily for three years without a relapse or change in her dosage. Her HIV regimen included didanosine, stavudine, saquinavir, and nelfinavir. Because of intolerable adverse effects from didanosine, it was discontinued and nevirapine 200 mg twice daily was initiated. One week later, she presented with symptoms of methadone withdrawal, including body pain, vomiting, insomnia, sweating, and a sense of impending doom. Increasing her methadone dose to 130 mg daily resolved her opioid withdrawal symptoms 6.
b) Four intravenous drug abusers with HIV infection who were stabilized on a methadone maintenance program developed acute opioid withdrawal symptoms after nevirapine therapy was initiated. Symptoms of opioid withdrawal began six to 15 days after nevirapine was started and included abdominal cramping, agitation, piloerection, insomnia, lacrimation, palpitations, and rhinorrhea. Two patients refused further nevirapine treatment. The other two patients required a 33% and a 100% increase in their methadone dose for the opioid withdrawal symptoms to cease 7.
c) In a retrospective chart review, seven cases of opiate withdrawal were identified among patients receiving chronic methadone therapy following the initiation of nevirapine. In all of the cases, withdrawal symptoms occurred within four to eight days after the start of nevirapine. Three patients were found to have subtherapeutic methadone levels, and in each of the seven cases, a substantial increase in the methadone daily dose was required to alleviate opiate withdrawal symptoms. Four of the patients chose to discontinue nevirapine therapy, highlighting the need for close monitoring of opiate withdrawal symptoms and educating the patients on the possibility of this interaction 8.
d) A case report describes a 34-year-old white man with HIV and chronic hepatitis C, who had been receiving maintenance methadone therapy. He was being treated with nevirapine, stavudine, and didanosine while receiving a methadone dose of 40 mg/day. Two days after initiating treatment with nevirapine, the patient experienced cramps, tremor, rhinorrhea and abdominal pain. Over an eight day period these symptoms continued despite increasing the daily methadone dose to 90 mg/day. Nevirapine was discontinued and methadone dose was decreased to 40 mg/day. The patient's opioid withdrawal symptoms completely resolved. The patient was rechallenged with nevirapine two months later and there was a recurrence of opiate withdrawal symptoms. Nevirapine was discontinued and two months later the patient's regimen was changed to efavirenz, stavudine and didanosine, in addition to methadone 30 mg/day. Opiate withdrawal symptoms again occurred and efavirenz was discontinued after only 7 days of treatment 9.
e) A reduction in methadone exposure may occur after 7-10 days of therapy with nevirapine. An increase in methadone dose may be required. Eight HIV infected patients were receiving stable daily methadone maintenance therapy. On study day 1, patients received methadone. Patients then commenced antiretroviral therapy which included nevirapine 200 mg, increasing to 400 mg after 2 weeks of therapy. Pharmacokinetic data demonstrated a reduction in AUC for methadone of 57% and 51% reduction in maximum concentration of 48% and 36% when it is administered in combination with efavirenz and nevirapine, respectively. An increase in methadone dose may be required by some, but not all patients, after 7-10 days of antiretroviral therapy 10.
f) In HIV-1 positive subjects (n=9) receiving chronic methadone (individually dosed), coadministration of nevirapine 200 mg once daily for 14 days followed by 200 mg twice daily for 7 days or more, methadone clearance increased by 3-fold resulting in withdrawal symptoms. This prompted methadone dose adjustments in 10 mg increments in 7 of 9 patients. Nevirapine clearance was not significantly altered 12.
Common questions
Can I take Nevirapine and Methadone together?
Reduced methadone exposure and an increased risk of opioid withdrawal symptoms (insomnia, pain, nausea, sweating, anxiety) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nevirapine and Methadone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Nevirapine or Methadone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (10)
- Product Information: VIRAMUNE(R) oral suspension, nevirapine oral suspension. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
- Product Information: VIRAMUNE XR(R) oral extended-release tablets, nevirapine oral extended-release tablets. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
- Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
- Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
- Product Information: Methadone HCl injection, methadone HCl injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Heelon MW & Meade LB: Methadone withdrawal when starting an antiretroviral regimen including nevirapine. Pharmacotherapy 1999; 19:471-472. PubMed
- Otero MJ, Fuertes A, Sanchez R, et al: Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert. AIDS 1999; 13:1004-1005. DOI
- Altice FL, Friedland GH, & Cooney EL: Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. AIDS 1999; 13:957-962. PubMed
- Pinzani V, Faucherre V, Peyriere H, et al: Methadone withdrawal symptoms with nevirapine and efavirenz. Ann Pharmacother 2000; 34:405-407. DOI
- Clarke S, Mulcahy F, Tjia J, et al: Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Clin Infect Dis 2001; 33:1595-1597. PubMed
Keep reading about Nevirapine
Keep reading about Methadone
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