Methadone with Desipramine Interaction Details
Brand Names Associated with Methadone
- Diskets®
- Dolophine®
- Methadone
- Methadose®
- Methadose® Oral Concentrate
- Westadone®
Brand Names Associated with Desipramine
- Desipramine
- Norpramin®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
Increased desipramine plasma levels; increased risk of serotonin syndrome; increased risk of paralytic ileus; increased risk of QT prolongation
Interaction Summary
Coadministration of desipramine and methadone resulted in increased plasma levels of desipramine in methadone-maintained patients. 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, the use of methadone with other drugs that affect cardiac conduction increases the risk of QT prolongation and when used with anticholinergic drugs may increase the risk of urinary retention and severe constipation, which may lead to paralytic ileus. If concomitant use is needed, carefully monitor the patient for serotonin syndrome, especially during treatment initiation and dosage adjustment, for the development of prolonged QT interval, and observe for signs and symptoms of urinary retention or reduced gastric motility. Discontinue methadone if serotonin syndrome is suspected . Additionally, monitoring desipramine levels may be helpful .
Severity
Major
Onset
Rapid
Evidence
Established
How To Manage Interaction
Coadministration of desipramine and methadone resulted in increased plasma levels of desipramine in methadone-maintained patients. 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, the use of methadone with other drugs that affect cardiac conduction increases the risk of QT prolongation and when used with anticholinergic drugs may increase the risk of urinary retention and severe constipation, which may lead to paralytic ileus. If concomitant use is needed, carefully monitor the patient for serotonin syndrome, especially during treatment initiation and dosage adjustment, for the development of prolonged QT interval, and observe for signs and symptoms of urinary retention or reduced gastric motility. Discontinue methadone if serotonin syndrome is suspected . Additionally, monitoring desipramine levels may be helpful .
Mechanism Of Interaction
Unknown; additive serotonergic effects; additive effects on gastric motility; additive effects on QT interval
Literature Reports
A) Coadministration of desipramine and methadone resulted in significantly increased desipramine serum levels in 5 men (mean age 36 years) in the methadone treatment program compared to treatment with desipramine alone. Three of the 5 patients received a single bedtime dose of desipramine 2.5 mg/kg for 10 days, followed by addition of methadone 0.5 mg/kg per day. The remaining 2 patients received both desipramine and methadone initially, followed by withdrawal of methadone while the desipramine was continued. Mean serum desipramine levels measured during desipramine monotherapy ranged from 37.3 to 85.3 ng/mL. In all 5 patients, desipramine serum levels were significantly higher when they received methadone concurrently, with increases ranging from 72.6% to 168.9% (mean, 108.3%) .
B) Coadministration of desipramine and methadone resulted in a lower ratio of desipramine dose to plasma concentrations in methadone-maintained patients compared to patients receiving desipramine alone. Study subjects belonged to 1 of 3 groups: 1) patients with major depressive disorder (group 1; n=39; mean age 38), 2) non-methadone treated cocaine abusers (group 2; n=22; mean age 30.2 years), and 3) methadone-maintained cocaine abusers (group 3; n=11; mean age 31.3 years). Methadone patients were receiving methadone for 4 months at a dose of 64 mg/day. Desipramine was initiated at 50 mg/day given as a single dose and gradually increased over the first week to a daily dose of 2.5 mg/kg for patients in groups 1 and 2, and a daily dose of 150 mg (approximately 2.5 mg/kg) for patients in group 3 for 3 weeks. Desipramine doses were adjusted for side effects and mean desipramine doses were 165 mg, 170 mg, and 127 mg for groups 1, 2, and 3 respectively (p=0.01, group 3 compared to others). Steady state plasma levels were assessed during the second through fourth weeks of treatment. The ratio +/- standard deviation (SD) of desipramine dose to blood level was significantly lower in the group 3 patients compared to groups 1 and 2 (0.9 +/- 0.4 versus 2.2 +/- 1.9 and 2 +/- 1.6, respectively; p=0.05). Additionally, the ratio of desipramine's 2-hydroxy metabolite to desipramine plasma levels was lower (0.19 +/-0.16) in group 3 patients compared to patients in groups 1 and 2 (0.5 +/- 0.31 and 0.39 +/- 0.26, respectively; p=0.01) .
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.
Desipramine Overview
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Desipramine is used to treat depression. Desipramine is in a class of medications called tricyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed for mental balance.
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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.
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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.
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