Methadone and Safinamide Interaction
Drug interaction information between Methadone and Safinamide.
Methadone and Safinamide have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Methadone and Safinamide. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Taking these together can cause a very serious and potentially fatal reaction in the brain and nervous system.
What To Do
Do not use these two drugs together.
FDA Label Information
7.2 Opioid Drugs Because serious, sometimes fatal reactions have been precipitated with concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, propoxyphene, or tramadol) and MAOIs, including selective MAO-B inhibitors, concomitant use of these drugs is contraindicated [see Warnings and Precautions (5.2) ] .
Methadone Also Interacts With
- Itraconazole major
- Phenobarbital moderate
- Tranylcypromine moderate
- Gabapentin minor
- Sertraline minor
Safinamide Also Interacts With
- Tramadol major
- Methylphenidate major
- Linezolid major
- Meperidine major
- Dextromethorphan major
Frequently Asked Questions
Can I take Methadone and Safinamide together?
This is a major interaction. Do not use these two drugs together.
How serious is the interaction between Methadone and Safinamide?
This interaction is classified as "major" severity by the FDA. Major interactions may be life-threatening or cause serious side effects.
Why do Methadone and Safinamide interact?
Taking these together can cause a very serious and potentially fatal reaction in the brain and nervous system.
Understanding the Methadone and Safinamide Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Methadone belongs to the Opioid Agonist class and Safinamide belongs to the MAO-B Inhibitor class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Taking these together can cause a very serious and potentially fatal reaction in the brain and nervous system. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Methadone has 41 total documented interactions on file in this dataset, and Safinamide has 10. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Do not use these two drugs together. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Methadone or Safinamide based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.