Methadone with Nefazodone Interaction Details


Brand Names Associated with Methadone

  • Diskets®
  • Dolophine®
  • Methadone
  • Methadose®
  • Methadose® Oral Concentrate
  • Westadone®

Brand Names Associated with Nefazodone

  • Nefazodone
  • Serzone®

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Last updated Jan 02, 2024


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Interaction Effect

Increased risk of serotonin syndrome; increased risk of opioid adverse effects


Interaction Summary

Concomitant use of methadone and serotonergic drugs has resulted in serotonin syndrome and may occur with recommended dosages. The onset of symptoms may occur within several hours to a few days of concomitant use. Additionally, when methadone is used with a CYP3A4 inhibitor there is an increase in methadone plasma levels resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone is achieved. If concomitant use is needed, carefully monitor for serotonin syndrome, especially during treatment initiation and dosage adjustment. Discontinue methadone if serotonin syndrome is suspected. Consider a dosage reduction of methadone until stable clinical effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, observe signs of opioid withdrawal and consider increasing the methadone dosage until stable clinical effects are achieved.


Severity

Major


Onset

Rapid


Evidence

Probable


How To Manage Interaction

Concomitant use of methadone and serotonergic drugs has resulted in serotonin syndrome and may occur with recommended dosages. The onset of symptoms may occur within several hours to a few days of concomitant use. Additionally, when methadone is used with a CYP3A4 inhibitor there is an increase in methadone plasma levels resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone is achieved. If concomitant use is needed, carefully monitor for serotonin syndrome, especially during treatment initiation and dosage adjustment. Discontinue methadone if serotonin syndrome is suspected. Consider a dosage reduction of methadone until stable clinical effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, observe signs of opioid withdrawal and consider increasing the methadone dosage until stable clinical effects are achieved.


Mechanism Of Interaction

Additive serotonergic effects; inhibition of CYP3A4-mediated methadone metabolism


Literature Reports

A) A 28-year-old female who was admitted to a hospital for the management of an acute exacerbation of asthma had a stabilized medication regimen which included methadone 70 mg daily, diazepam 2 mg twice daily, albuterol, ipratropium, ranitidine, and spironolactone. Three weeks before admission, she had started fluvoxamine 100 mg daily. The patient's asthma was not considered to be in a significant exacerbation upon further testing, although hypoxemia and hypercapnia indicating hypoventilation was present. Methadone was decreased to 50 mg daily and diazepam was discontinued. Analysis of a blood sample taken at admission showed that the serum methadone concentration was 262 nanograms (ng)/mL. Twelve days later, oxygenation had improved and the methadone concentration was measured at 202 ng/mL. Diazepam may have compounded this interaction .

Methadone Overview

  • 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.

See More information Regarding Methadone

Nefazodone Overview

  • Nefazodone is used to treat depression. Nefazodone is in a class of medications called serotonin modulators. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

See More information Regarding Nefazodone

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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.