Mitotane with Methadone Interaction Details
Brand Names Associated with Mitotane
- Lysodren®
- Mitotane
Brand Names Associated with Methadone
- Diskets®
- Dolophine®
- Methadone
- Methadose®
- Methadose® Oral Concentrate
- Westadone®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
Increased risk of methadone withdrawal symptoms
Interaction Summary
Concomitant use of methadone (a CYP3A4 substrate) with CYP3A4 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms. After stopping a CYP3A4 inducer, there may be an increase or prolongation of both the therapeutic effects and adverse reactions, which may cause serious respiratory depression, sedation, or death. In a pharmacokinetic study in patients receiving methadone maintenance, administration of phenytoin resulted in a reduction in methadone exposure and the development of withdrawal symptoms. If concomitant use is needed, consider increasing the methadone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider methadone dosage reduction and monitor for signs of respiratory depression and sedation.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of methadone (a CYP3A4 substrate) with CYP3A4 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms. After stopping a CYP3A4 inducer, there may be an increase or prolongation of both the therapeutic effects and adverse reactions, which may cause serious respiratory depression, sedation, or death. If concomitant use is needed, consider increasing the methadone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider methadone dosage reduction and monitor for signs of respiratory depression and sedation.
Mechanism Of Interaction
Induction of CYP3A4-mediated methadone metabolism
Literature Reports
A) In a pharmacokinetic study in patients receiving methadone maintenance, administration of phenytoin 250 mg twice daily for 1 day followed by 300 mg daily for 3 to 4 days resulted in an approximate 50% reduction in methadone exposure and the development of withdrawal symptoms. When phenytoin was discontinued, the incidence of withdrawal symptoms decreased and methadone exposure increased to a level similar to that prior to the phenytoin administration .
B) Twenty-one of 30 patients (70%) on methadone maintenance had withdrawal symptoms after rifampin (600 to 900 mg daily) was given. Onset of withdrawal symptoms was from 1 to 33 days after rifampin was started. Six of 7 patients with severe withdrawal symptoms had the onset within six days. Methadone plasma levels were measured in six of these patients both on and off rifampin. Results showed a 33% to 66% decrease in methadone plasma levels. Peak methadone plasma levels were also found to be consistently lower in patients on rifampin after a single dose of methadone. The major metabolite of methadone, pyrrolidine, increased 150% in a 24-hour urinary excretion study in four of the patients .
C) In one case withdrawal symptoms were noted 5 days after rifampin (450 mg per day) was started in a 24-year-old female maintained on methadone (40 mg per day) .
Mitotane Overview
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Mitotane is used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane is in a class of medications called antineoplastic agents. It works by slowing growth or reducing the size of the tumor.
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.
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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.