Phenytoin and Nisoldipine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Nisoldipine
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 nisoldipine exposure
Interaction Deep Dive
Concomitant use of phenytoin or fosphenytoin (prodrug of phenytoin) and nisoldipine may reduce the exposure of nisoldipine. Consider nisoldipine dose adjustments to achieve optimal clinical response when phenytoin or fosphenytoin is added to or withdrawn from a patient's regimen123. In a controlled study, patients with epilepsy on chronic therapy with phenytoin had a remarkably dissimilar nisoldipine pharmacokinetic profile compared to healthy control subjects. Patients taking phenytoin had much lower dose-adjusted changes in the nisoldipine Cmax and AUC. There was wide interindividual variability in this interaction 4.
Why it happens (mechanism)
Induction of hepatic drug-metabolizing enzymes by phenytoin
Literature reports
1 report — tap to read
a) In a controlled study of 12 patients with epilepsy and 12 control subjects, the effects of concurrent administration of nisoldipine and phenytoin were assessed. Patients with epilepsy were receiving chronic phenytoin monotherapy and had stable plasma phenytoin concentrations. The control group was not taking any medications prior to the study. Based on the expectation that nisoldipine levels would be low and possibly undetectable in subjects taking phenytoin, these patients were given a single oral dose of nisoldipine 40 mg while control subjects were given nisoldipine 20 mg. Blood samples were taken over the next 48 hours, and the concentrations of nisoldipine were determined by gas chromatography. Patients taking phenytoin had extremely low nisoldipine plasma concentrations, with undetectable levels in a substantial proportion of cases. The mean dose-adjusted maximum concentration (Cmax) of nisoldipine in patients taking phenytoin was 0.19 mcg/L, compared to 1.06 mcg/L in control subjects. The dose-adjusted mean nisoldipine area under the concentration-time curve (AUC) was approximately 10-fold lower in patients taking phenytoin compared to control subjects. The interaction between phenytoin and nisoldipine was highly variable, and the authors suggested that nisoldipine should probably not be used in patients undergoing phenytoin therapy 4.
Common questions
Can I take Phenytoin and Nisoldipine together?
Reduced nisoldipine exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Nisoldipine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Phenytoin or Nisoldipine 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: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
- Michelucci R, Cipolla G, Passarelli D, et al: Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy. Epilepsia 1996; 37:1107-1110. PubMed
Keep reading about Phenytoin
Keep reading about Nisoldipine
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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