Methadone and Naltrexone interaction

Methadone and Naltrexone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Naltrexone label · effective 2026-01-30

Major

Naltrexone for extended-release injectable suspension is contraindicated in: Patients receiving opioid analgesics [see Warnings and Precautions ( 5.3 ) ] .

Contraindicationsby drug classView label on DailyMed
Major

Patients with current physiologic opioid dependence [see Warnings and Precautions ( 5.3 ) ] .

Contraindicationsby drug classView label on DailyMed
Major

Patients in acute opioid withdrawal [see Warnings and Precautions ( 5.3 ) ] .

Contraindicationsby drug classView label on DailyMed
Major

Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids [see Warnings and Precautions ( 5.3 ) ] .

Contraindicationsby drug classView label on DailyMed
Major

Naltrexone for extended-release injectable suspension is contraindicated in: Patients receiving opioid analgesics (4) .

Contraindicationsby drug classView label on DailyMed

From the Methadone (METHADOSE) label · effective 2026-04-27

Moderate

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Advise patients and caregivers that an opioid overdose reversal agent, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with METHADOSE itself [see Overdosage ( 10 )] .

Warnings and precautionsby drug classView label on DailyMed
Minor

Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: Patients maintained on methadone may experience withdrawal symptoms when given opioid antagonists, mixed agonist/antagonists, and partial agonists.

Drug interactionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

Not 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.