Documented interactions for Methadone (Methadone HCl (tablet)). Each entry cites the prescribing information or FDA safety communication it is based on.
| Severity | Interacts with | Class | Concern |
|---|---|---|---|
| Contraindicated | MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) | Monoamine oxidase inhibitor | Methadone with MAO inhibitors is contraindicated |
| Contraindicated | MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) | Monoamine oxidase inhibitor | Opioid with MAO inhibitors is contraindicated |
| Major | Alcohol (ethanol) | CNS depressant | Methadone with alcohol: additive respiratory depression |
| Major | Alcohol (ethanol) | CNS depressant | Opioid with alcohol: additive respiratory depression |
| Major | Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) | Benzodiazepine | Methadone with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death |
| Major | Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) | Benzodiazepine | Opioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death |
| Major | Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) | CNS depressant | Opioid with other CNS depressants: additive respiratory depression |
| Major | Other gabapentinoids (gabapentin, pregabalin) | Gabapentinoid | Opioid with gabapentinoid: serious breathing difficulties |
| Major | Other QT-prolonging drugs (class IA/III antiarrhythmics, some macrolides, haloperidol, methadone, ondansetron) | QT-prolonging agent | Methadone and QT prolongation: torsades de pointes risk |
With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor
MAO inhibitors impair methadone metabolism and potentiate its effects.
Severe unpredictable reactions including respiratory depression and death.
Do not combine.
Basis: Methadone hydrochloride tablets prescribing information, Contraindications. source
With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor
MAO inhibitors potentiate opioid effects and impair metabolism.
Severe unpredictable reactions including respiratory depression and death.
Do not combine.
Basis: Opioid-containing product labeling, Contraindications. source
With: Alcohol (ethanol) CNS depressant
Combined central nervous system and respiratory depression.
Respiratory depression, deep sedation, and death.
Avoid alcohol during methadone therapy.
Basis: Methadone hydrochloride tablets prescribing information, Drug Interactions. source
With: Alcohol (ethanol) CNS depressant
Both agents depress the central nervous system and breathing.
Respiratory depression, deep sedation, coma, and death.
Avoid alcohol during opioid therapy.
Basis: Opioid-containing product labeling, Warnings and Precautions. source
With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine
Additive CNS and respiratory depression. Methadone accumulates over days, so exposure rises after initiation.
FDA requires a boxed warning on methadone products describing this combination. Deaths have been reported in people on both drugs, particularly when benzodiazepines were added after methadone dosing had stabilized.
Avoid where possible; if used, use the lowest effective doses with careful monitoring.
Basis: Methadone hydrochloride tablets prescribing information, Boxed Warning. source
With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine
Additive depression of the central nervous system and respiratory drive.
FDA requires a boxed warning on opioid-containing products describing this combination.
Avoid where possible. If used, lowest effective doses for the shortest duration with monitoring.
Basis: FDA Drug Safety Communication (2016); opioid boxed warning. source
With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant
Additive central nervous system depression and slowed breathing.
Respiratory depression and overdose, particularly in older adults.
Disclose all sedating medications to the prescriber and pharmacist.
Basis: Opioid-containing product labeling, Warnings and Precautions. source
With: Other gabapentinoids (gabapentin, pregabalin) Gabapentinoid
Additive respiratory depression.
FDA warns of serious breathing difficulties and increased risk of death.
Use the lowest effective gabapentinoid dose and monitor for slowed breathing.
Basis: FDA Drug Safety Communication (2021). source
With: Other QT-prolonging drugs (class IA/III antiarrhythmics, some macrolides, haloperidol, methadone, ondansetron) QT-prolonging agent
Methadone prolongs the QT interval; other QT-prolonging drugs add to the effect.
Torsades de pointes, a potentially fatal arrhythmia, has been reported with methadone.
Prescribers review the full medication list for QT-prolonging drugs and may obtain an ECG or correct potassium and magnesium.
Basis: Methadone hydrochloride tablets prescribing information, Effects on the Electrocardiogram. source
We have documented 9 interaction classes for Methadone in our dataset. Usually avoided, or used only with explicit prescriber oversight and close monitoring. The most serious items on this page are marked contraindicated or major.
Alcohol interacts with most of the medications on this site because it adds to sedation and slows breathing. For the specific documented risk, see the relevant entry above. The general rule from labeling is to avoid alcohol.
No. An empty result only means our curated dataset has no matching rule. A pharmacist can run a full interaction screen against every medication and supplement you take.
This site provides educational information only and does not sell, prescribe or dispense medications. Always consult a licensed healthcare provider. This page is not medical advice.