Drug Interaction Report

Fentanyl Transdermal Patch and Nitrous Oxide: Interaction Details

A pharmacist-reviewed analysis of the Fentanyl Transdermal Patch and Nitrous Oxide 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

Nitrous Oxide

No brand names on record
+

Fentanyl Transdermal Patch

Duragesic®
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 493 documented Fentanyl Transdermal Patch interactions, 469 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

Increased risk of profound sedation, respiratory depression, hypotension, coma and death and an increased risk of cardiovascular depression

Interaction Deep Dive

Concomitant use of fentaNYL (CNS depressant) with nitrous oxide (another CNS depressant) may cause additive CNS effects resulting in respiratory depression, hypotension, profound sedation, coma or death. Also, fentaNYL injection with nitrous oxide may result in cardiorespiratory depression2. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. If the decision is made to prescribe a CNS depressant concomitantly with fentaNYL, prescribe the lowest effective dosages and minimum durations of concomitant use and titrate the dosages based on clinical response. Inform and educate the patients and caregivers on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 31. As postoperative analgesia, start with a lower dose of fentaNYL injection and monitor patients for signs of respiratory depression, sedation, hypotension and cardiovascular depression. Keep fluids and other measures readily available to treat potential hypotension 2.

Why it happens (mechanism)

Additive CNS depression

Common questions

Can I take Fentanyl Transdermal Patch and Nitrous Oxide together?

Increased risk of profound sedation, respiratory depression, hypotension, coma and death and an increased risk of cardiovascular depression Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fentanyl Transdermal Patch and Nitrous Oxide 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.

Questions for your pharmacist

  • Does my dose of Fentanyl Transdermal Patch or Nitrous Oxide 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 (3)

  1. Product Information: ACTIQ(R) oral transmucosal lozenge, fentanyl citrate oral transmucosal lozenge. Teva Pharmaceuticals USA, Inc. (per FDA), Parsippany, NJ, 2023. DailyMed
  2. Product Information: Fentanyl citrate intravenous, intramuscular injection, fentanyl citrate intravenous, intramuscular injection. Hospira Inc (per FDA), Lake Forest, IL, 2023. DailyMed
  3. Product Information: FENTORA(R) buccal tablets, fentanyl citrate buccal tablets. Teva Pharmaceuticals USA Inc (per FDA), Parsippany, NJ, 2023.
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