Drug Interaction Report

Desvenlafaxine and Fentanyl Transdermal Patch: Interaction Details

A pharmacist-reviewed analysis of the Desvenlafaxine and Fentanyl Transdermal Patch 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

Desvenlafaxine

Pristiq
+

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 68 documented Desvenlafaxine interactions, 64 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 serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)

Interaction Deep Dive

Desvenlafaxine is a serotonergic drug; concomitant use with another agent that affects the serotonergic neurotransmitter system may result in an increased risk of serotonin syndrome and should be approached with extreme caution. Serotonin syndrome may be life-threatening. Symptoms may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If coadministration is required, monitor closely for signs and symptoms of serotonin syndrome, especially during treatment initiation and dose increases of either drug. If serotonin syndrome develops, discontinue both agents and initiate supportive symptomatic therapy1.

Why it happens (mechanism)

Additive serotonergic effects

Common questions

Can I take Desvenlafaxine and Fentanyl Transdermal Patch together?

Increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Desvenlafaxine and Fentanyl Transdermal Patch 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 Desvenlafaxine or Fentanyl Transdermal Patch 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: PRISTIQ(R) oral extended-release tablets, desvenlafaxine oral extended-release tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadelphia, PA, 2023. DailyMed
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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:

Desvenlafaxine + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Lithium Sida Cordifolia + 101 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.