Drug Interaction Report

Codeine and Butorphanol Injection: Interaction Details

A pharmacist-reviewed analysis of the Codeine and Butorphanol Injection 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

Codeine

Tuzistra XR® (as a combination product containing Chlorpheniramine, Codeine)
+

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 55 documented Codeine interactions, 52 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 and/or precipitation of withdrawal symptoms, an increased risk of serotonin syndrome and an increased risk of hypotension, respiratory depression, profound sedation, coma, and death

Interaction Deep Dive

Avoid concomitant use of codeine with butorphanol (a serotonergic CNS depressant and a mixed opioid agonist/antagonist or a partial agonist opioid analgesic) as this may reduce the analgesic effect of codeine and may precipitate withdrawal symptoms, increase the risk for serotonin syndrome and may increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue codeine if serotonin syndrome is suspected and consider prescribing naloxone for the emergency treatment of opioid overdose1.

Why it happens (mechanism)

Competitive binding at opioid receptors; additive serotonergic effects; additive CNS depression

Common questions

Can I take Codeine and Butorphanol Injection together?

Reduced analgesic effect and/or precipitation of withdrawal symptoms, an increased risk of serotonin syndrome and an increased risk of hypotension, respiratory depression, profound sedation, coma, and death Always confirm with your pharmacist or prescriber before making any change.

How serious is the Codeine and Butorphanol Injection 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 Codeine or Butorphanol Injection 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 (1)

  1. Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
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Codeine

Keep reading about Codeine

All Codeine interactions (55) Codeine drug information
Also serious with: Linezolid Injection Ketoconazole Topical Dexamethasone Ophthalmic Furosemide Injection
Butorphanol Injection

Keep reading about Butorphanol Injection

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

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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.