Methadone has 41 known drug interactions based on U.S. FDA drug labeling data. Of these, 5 are contraindicated combinations that should be avoided entirely. 17 are classified as major interactions requiring close medical supervision. Notable interactions include combinations with Itraconazole, Ketoconazole, Levoketoconazole. Patients taking Methadone should inform their healthcare provider of all current medications — including over-the-counter drugs and supplements — to avoid potentially harmful combinations. Data sourced from OpenFDA and the NIH National Library of Medicine.
- Total
- 41
- Contraindicated
- 5
- Major
- 17
- Moderate
- 12
Contraindicated (5)
- Methadone + Itraconazole— Itraconazole increases methadone concentrations. Contraindicated during and 2 weeks after itraconazole treatment.
- Methadone + Ketoconazole— Coadministration of ketoconazole with methadone is contraindicated.
- Methadone + Levoketoconazole— Concomitant use is contraindicated due to increased risk of QT prolongation and torsades de pointes.
- Methadone + Safinamide Mesylate— Serious, sometimes fatal reactions reported with concomitant use of opioid drugs and MAOIs, including selective MAO-B in…
- Methadone + Selegiline Hydrochloride— Serious, sometimes fatal reactions reported with concomitant use of methadone and MAOIs including selective MAO-B inhibi…
Major (17)
- Methadone + Alprazolam— Concomitant use increases risk of respiratory depression due to actions at different CNS receptor sites.
- Methadone + Alprazolam C-Iv— Concomitant use increases risk of respiratory depression due to additive CNS effects at different receptor sites. Monito…
- Methadone + Anagrelide— Avoid use; may prolong QT interval and increase risk of arrhythmias with anagrelide.
- Methadone + Anagrelide Hydrochloride— Avoid concomitant use due to QT prolongation risk.
- Methadone + Carbamazepine— CYP inducer that decreases methadone plasma concentration, resulting in decreased efficacy or withdrawal symptoms.
- Methadone + Erythromycin— CYP3A4 inhibitor that increases methadone plasma concentration, resulting in increased opioid effects and potential fata…
- Methadone + Fingolimod— QT-prolonging drug with known torsades de pointes risk. Combined with fingolimod's QT prolongation and bradycardia effec…
- Methadone + Fingolimod Hydrochloride— QT-prolonging drug associated with torsades de pointes risk. Patients require overnight continuous ECG monitoring in med…
- Methadone + Fluconazole— CYP3A4 inhibitor that increases methadone plasma concentration, resulting in increased opioid effects and potential fata…
- Methadone + Fluvoxamine— SSRI and CYP inhibitor that increases methadone plasma concentration, resulting in increased opioid effects and potentia…
- Methadone + Lofexidine— Both drugs prolong QT interval. ECG monitoring is recommended when used concomitantly.
- Methadone + Lofexidine Hydrochloride— Both methadone and lofexidine prolong the QT interval. ECG monitoring is recommended when used concomitantly.
- Methadone + Metaxalone— Concomitant use may result in serotonin syndrome. Carefully observe patient during treatment initiation and dosage modif…
- Methadone + Phenytoin— CYP inducer that decreases methadone plasma concentration, resulting in decreased efficacy or withdrawal symptoms.
- Methadone + Rifampin— CYP3A4 inducer that decreases methadone plasma concentration, resulting in decreased efficacy or withdrawal symptoms.
- Methadone + Ritonavir— Protease inhibitor that increases methadone plasma concentration, resulting in increased opioid effects and potential fa…
- Methadone + Sertraline— SSRI that inhibits CYP2D6, increasing methadone plasma concentration and risk of overdose.
Moderate (12)
- Methadone + Abacavir— Abacavir increases oral methadone clearance. An increased methadone dose may be required in a small number of patients r…
- Methadone + Abacavir , Lamivudine And Zidovudine— Oral methadone clearance may increase with abacavir; increased methadone dose may be required in some patients.
- Methadone + Abacavir And Lamivudine— Increased methadone clearance; an increased methadone dose may be required in a small number of patients receiving abaca…
- Methadone + Abacavir Sulfate— Abacavir increases oral methadone clearance. An increased methadone dose may be required in a small number of patients.
- Methadone + Fingolimod Lauryl Sulfate— QT prolonging drug with torsades de pointes risk. Monitor overnight with continuous ECG in medical facility during initi…
- Methadone + Haloperidol Decanoate— Drug known to prolong QTc interval; caution advised when used with haloperidol decanoate due to risk of QT prolongation.
- Methadone + Haloperidol Lactate— Drug known to prolong QTc interval; caution advised when used with haloperidol due to risk of QT prolongation.
- Methadone + Lemborexant— CYP2B6 substrate whose AUC is decreased by lemborexant, potentially reducing efficacy. Monitor for adequate clinical res…
- Methadone + Levothyroxine Sodium— May increase serum thyroxine-binding globulin concentration, resulting in initial transient increase in FT4 followed by …
- Methadone + Liothyronine Sodium— May increase serum thyroxine-binding globulin concentration, altering T3 serum transport. Closely monitor thyroid hormon…
- Methadone + Lubiprostone— Methadone may dose-dependently reduce lubiprostone activation of ClC-2 in the gastrointestinal tract, potentially decrea…
- Methadone + Peginterferon Alfa-2a— PEGASYS increases methadone levels by 10-15%. Monitor for signs and symptoms of methadone toxicity.