Drug Interaction Report

Butorphanol Injection and Methadone: Interaction Details

A pharmacist-reviewed analysis of the Butorphanol Injection and Methadone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Methadone

Diskets Dolophine Methadose
+

Butorphanol Injection

Butorphic Dolorex Solution Stadol® Torbugesic Torphadine Vetorphic
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 258 documented Butorphanol Injection interactions, 245 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Reduced analgesic effect or precipitation of withdrawal symptoms and an increased risk of serotonin syndrome

Interaction Deep Dive

Avoid concomitant use of methadone with a mixed opioid agonist/antagonist or a partial agonist opioid analgesic as this may reduce the analgesic effect of methadone and may precipitate withdrawal symptoms. Additionally, observe the patient carefully when using methadone concomitantly with other drugs that affect the serotonergic system, especially during initiation and titration, as risk for serotonin syndrome is increased; discontinue methadone if serotonin syndrome is suspected1234.

Why it happens (mechanism)

Opioid receptor antagonism; additive serotonergic effects

Common questions

Can I take Butorphanol Injection and Methadone together?

Reduced analgesic effect or precipitation of withdrawal symptoms and an increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.

How serious is the Butorphanol Injection and Methadone interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Butorphanol Injection or Methadone need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (4)

  1. Product Information: DOLOPHINE(R) oral tablets, methadone HCl oral tablets. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2019. DailyMed
  2. Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
  3. Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
  4. Product Information: Methadone HCl injection, methadone HCl injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2023. DailyMed
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Methadone

Keep reading about Methadone

All Methadone interactions (129)
Also serious with: Ketoconazole Topical Palonosetron Injection Metronidazole Topical Diazepam Rectal
Butorphanol Injection

Keep reading about Butorphanol Injection

All Butorphanol Injection interactions (258) Butorphanol Injection drug information
Also serious with: Safinamide Samidorphan Tranylcypromine Isocarboxazid
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Methadone + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Grapefruit Kava L-tryptophan Lithium + 215 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.