Fentanyl Transdermal Patch and Cyclobenzaprine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclobenzaprine
Fentanyl Transdermal Patch
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.
What happens
Increased risk of serotonin syndrome, an increased risk of CNS depression, an increased degree of respiratory depression and an increased risk of paralytic ileus.
Interaction Deep Dive
Coadministration of cyclobenzaprine and fentaNYL may cause additive CNS depression (including respiratory depression, hypotension, profound sedation, coma or death)5, and may potentially cause serotonin syndrome 4. Reserve the concomitant use of cyclobenzaprine and fentaNYL to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Concomitant use of both fentaNYL and cyclobenzaprine may also result in increased risk of urinary retention or severe constipation, which may lead to paralytic ileus. Monitor patients for signs and symptoms of serotonin syndrome, respiratory depression, hypotension, sedation, urinary retention or reduced gastric motility. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose. Discontinue fentaNYL if serotonin syndrome develops 3. Keep fluids and other measures readily available to treat potential hypotension 2.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression; enhanced neuromuscular blocking action of skeletal Muscle relaxants; reduced gastric motility
Literature reports
1 report — tap to read
a) Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics 312.
Common questions
Can I take Fentanyl Transdermal Patch and Cyclobenzaprine together?
Increased risk of serotonin syndrome, an increased risk of CNS depression, an increased degree of respiratory depression and an increased risk of paralytic ileus. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fentanyl Transdermal Patch and Cyclobenzaprine 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 Fentanyl Transdermal Patch or Cyclobenzaprine 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 (5)
- Product Information: ACTIQ(R) oral transmucosal lozenge, fentanyl citrate oral transmucosal lozenge. Teva Pharmaceuticals USA, Inc. (per FDA), Parsippany, NJ, 2023. DailyMed
- Product Information: Fentanyl citrate intravenous, intramuscular injection, fentanyl citrate intravenous, intramuscular injection. Hospira Inc (per FDA), Lake Forest, IL, 2023. DailyMed
- Product Information: FENTORA(R) buccal tablets, fentanyl citrate buccal tablets. Teva Pharmaceuticals USA Inc (per FDA), Parsippany, NJ, 2023.
- Rastogi R, Swarm RA, & Patel TA: Case scenario: opioid association with serotonin syndrome: implications to the practitioners. Anesthesiology 2011; 115(6):1291-1298. PubMed
- Product Information: FLEXERIL(R) oral tablets, cyclobenzaprine HCl oral tablets. McNeil Pediatrics (per FDA), Titusville, NJ, 2013. DailyMed
Keep reading about Cyclobenzaprine
Keep reading about Fentanyl Transdermal Patch
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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