Methadone with Nevirapine Interaction Details
Brand Names Associated with Methadone
- Diskets®
- Dolophine®
- Methadone
- Methadose®
- Methadose® Oral Concentrate
- Westadone®
Brand Names Associated with Nevirapine
- Nevirapine
- Viramune®
- Viramune® XR
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
An increased risk of opioid withdrawal symptoms (insomnia, pain, nausea, sweating, anxiety)
Interaction Summary
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-demethylation. 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. Therefore, use caution if these agents are coadministered. 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 .
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Clinicians should be alert to the possibility of opiate withdrawal in patients receiving methadone and nevirapine. Use caution if these agents are coadministered. Monitor methadone maintained patients in whom nevirapine therapy is initiated for symptoms of opiate withdrawal (insomnia, pain, nausea, sweating, anxiety), and adjust methadone doses accordingly.
Mechanism Of Interaction
Induction of CYP3A4-mediated methadone metabolism by nevirapine
Literature Reports
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 .
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 .
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 .
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 .
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 .
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 .
Methadone Overview
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Methadone is used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. It also is used to prevent withdrawal symptoms in patients who were addicted to opiate drugs and are enrolled in treatment programs in order to stop taking or continue not taking the drugs. Methadone is in a class of medications called opiate (narcotic) analgesics. Methadone works to treat pain by changing the way the brain and nervous system respond to pain. It works to treat people who were addicted to opiate drugs by producing similar effects and preventing withdrawal symptoms in people who have stopped using these drugs.
Nevirapine Overview
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Nevirapine is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children 15 days of age and older. Nevirapine should not be used to treat healthcare workers or other individuals exposed to HIV infection after contact with HIV-contaminated blood, tissues, or other body fluids. Nevirapine is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It works by decreasing the amount of HIV in the blood. Although nevirapine does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.