Primidone and Fentanyl Transdermal Patch: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
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 CNS depression and reduced exposure of fentaNYL
Interaction Deep Dive
Concomitant use of fentaNYL with CNS depressant that are CYP3A4 inducers , may result in respiratory depression, hypotension, profound sedation, coma or death. It may also result in decreased efficacy of fentaNYL1,and may possibly lead to a withdrawal syndrome in a patient who had developed physical dependence to fentaNYL. Reserve concomitant prescribing of these drug for the use of patients whom alternative treatment options are inadequate. If concomitant use is required, monitor for signs of respiratory depression, sedation, or opioid withdrawal, and consider dose adjustments. Upon discontinuation of CYP3A4 inducer, plasma concentrations of fentaNYL will increase, which may increase or prolong the therapeutic and adverse effects of fentaNYL, including the risk of serious respiratory depression. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 4. As postoperative analgesia, start with a lower dose of fentaNYL injection and monitor patients for signs of respiratory depression, sedation, and hypotension. Keep fluids and other measures readily available to treat potential hypotension 3.
Why it happens (mechanism)
Additive CNS depression; induction of CYP3A4-mediated metabolism of fentaNYL
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 423.
Common questions
Can I take Primidone and Fentanyl Transdermal Patch together?
Increased risk of CNS depression and reduced exposure of fentaNYL Always confirm with your pharmacist or prescriber before making any change.
How serious is the Primidone 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Primidone 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 (4)
- Product Information: DURAGESIC(R) transdermal system, fentanyl transdermal system. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2018. DailyMed
- 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.
Keep reading about Primidone
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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