Methadone and Sertraline Interaction
Drug interaction information between Methadone and Sertraline.
Methadone and Sertraline have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Methadone and Sertraline. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
Sertraline can change the amount of methadone in your blood, which might cause the methadone to stop working or lead to withdrawal.
FDA Label Information
Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, Some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of Methadone Hydrochloride Injection and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone (see CLINICAL PHARMACOLOGY ), resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent...
Methadone Also Interacts With
- Itraconazole major
- Safinamide major
- Phenobarbital moderate
- Tranylcypromine moderate
- Gabapentin minor
Sertraline Also Interacts With
- Clonazepam major
- Aspirin moderate
- Phenelzine moderate
- Fluoxetine minor
- Citalopram minor
Frequently Asked Questions
What SPL severity band is on file for Methadone + Sertraline?
Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Methadone has 41 labeled pairs on file vs Sertraline's 34. In the minor band specifically: Methadone has 37 (also Gabapentin, Trazodone, Tramadol, Cyclobenzaprine); Sertraline has 31 (also Fluoxetine, Citalopram, Paroxetine, Atenolol).
What mechanism field is on file for Methadone and Sertraline?
Sertraline can change the amount of methadone in your blood, which might cause the methadone to stop working or lead to withdrawal.
Methadone carries more major-labeled pairs than Sertraline
SPL source-record counts only. This page's band is minor · classes on file: Methadone (Opioid Agonist); Sertraline (Selective Serotonin Reuptake Inhibitor (SSRI)).
Methadone has 2 major-labeled pairs vs Sertraline's 1. This page itself is in the minor band, not the major band.
2 major · 2 moderate · 37 minor · 41 total
- Other minor peers for Methadone
- Gabapentin
- Trazodone
- Tramadol
- Cyclobenzaprine
1 major · 2 moderate · 31 minor · 34 total
- Other minor peers for Sertraline
- Fluoxetine
- Citalopram
- Paroxetine
- Atenolol
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.