Does Methadone Hydrochloride Interact with Mao Inhibitors?
Methadone Hydrochloride and Mao Inhibitors have a major drug interaction according to U.S. FDA drug labeling data. Inhibition of CYP3A4 increases methadone plasma concentration, resulting in increased opioid effects and risk of fatal overdose. The mechanism involves inhibition of cyp3a4-mediated hepatic n-demethylation. Patients taking both medications should consult their healthcare provider before starting, stopping, or changing the dosage of either drug. This information is based on official FDA drug labeling sourced from OpenFDA and the NIH National Library of Medicine.
- Severity
- Major
- Management
- Close medical supervision required
- Data Source
- U.S. FDA via OpenFDA
How This Interaction Works
The interaction between Methadone Hydrochloride and Mao Inhibitors occurs because inhibition of cyp3a4-mediated hepatic n-demethylation. Clinically, this means inhibition of cyp3a4 increases methadone plasma concentration, resulting in increased opioid effects and risk of fatal overdose. This is classified as a major interaction, meaning it could cause serious harm if not properly managed. Your healthcare provider may need to adjust dosages, substitute one medication, or increase monitoring frequency.
What To Tell Your Doctor or Pharmacist
If you are taking Methadone Hydrochloride and your doctor is considering prescribing Mao Inhibitors (or vice versa), make sure to:
- Inform your doctor and pharmacist of all current medications, including over-the-counter drugs and supplements
- Ask whether the benefits of combining these medications outweigh the risks for your specific situation
- Ask what symptoms to watch for that would indicate the interaction is causing problems
- Ask how frequently you should be monitored while these are co-prescribed
- Ask whether any dosage adjustments are needed
- Never stop or change either medication without first consulting your healthcare provider