Methadone and Sertraline interaction
Methadone and Sertraline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Methadone (METHADOSE) label · effective 2026-04-27
Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.
Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of METHADOSE with serotonergic drugs.
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 and CYP3A4, CYP2B6,…
Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers.
Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions ( 5.9 )] .
From the Sertraline (sertraline hydrochloride) label · effective 2025-08-06
Avoid the concomitant use of drugs known to prolong the QTc interval.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.
Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of sertraline hydrochloride capsules with other drugs which prolong the QTc interval [see Warnings and Precautions ( 5.10 ), Clinical Pharmacology ( 12.2 )] .
Other Serotonergic Drugs Clinical Impact: Concomitant use of sertraline hydrochloride capsules with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.