Fosphenytoin and Naldemedine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fosphenytoin
Naldemedine
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
Reduced naldemedine exposure and decreased efficacy
Interaction Deep Dive
Naldemedine is primarily metabolized by CYP3A4. Coadministration with rifampin 600 mg once daily (a strong CYP3A/P-glycoprotein inducer) significantly decreased the AUC and Cmax of naldemedine by 83% and 38%, respectively. Avoid concomitant use of naldemedine with a strong CYP3A inducer, as efficacy of naldemedine may be reduced1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of naldemedine
Common questions
Can I take Fosphenytoin and Naldemedine together?
Reduced naldemedine exposure and decreased efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fosphenytoin and Naldemedine interaction?
It is rated moderate. Can be significant — usually manageable with 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 Fosphenytoin or Naldemedine 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: SYMPROIC(R) oral tablets, naldemedine oral tablets. Shionogi Inc (per manufacturer), Florham Park, NJ, 2017. DailyMed
Keep reading about Fosphenytoin
Keep reading about Naldemedine
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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