Phenytoin and Nizatidine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Nizatidine
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 phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased rick of phenytoin or fosphenytoin toxicity
Interaction Deep Dive
Concomitant use of phenytoin or fosphenytoin (prodrug of phenytoin) and H2 receptor antagonists, such as raNITIdine, may result in increased phenytoin or fosphenytoin exposure. Some patients may experience elevations in phenytoin or fosphenytoin serum levels when raNITIdine therapy is initiated4. Other reports have suggested a lack of an interaction 5. Monitor patients for signs of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) when receiving H2 antagonists concurrently. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when H2 antagonists is added to or withdrawn from a patient's regimen. Monitor phenytoin or fosphenytoin serum drug level during concurrent use of H2 antagonists and phenytoin or fosphenytoin 123.
Why it happens (mechanism)
Reduced phenytoin metabolism
Literature reports
2 reports — tap to read
a) Combined therapy with oral raNITIdine and phenytoin resulted in significant increases (40%) in steady-state phenytoin serum levels in one patient. Phenytoin was given orally as 400 mg/day and raNITIdine was added as 150 mg twice a day. Withdrawal of the raNITIdine resulted in reductions in phenytoin serum levels to the previous steady-state concentrations. This case report suggests that phenytoin serum levels should be monitored during the first month of combined raNITIdine therapy; however, additional studies are required to more fully evaluate this interaction 4.
b) Concomitant phenytoin and raNITIdine therapy produced no change in plasma phenytoin concentrations in 4 patients. This is contrary to cimetidine, which has been noted to produce significant increases in phenytoin concentrations and possible toxicity 5.
Common questions
Can I take Phenytoin and Nizatidine together?
Increased phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased rick of phenytoin or fosphenytoin toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Nizatidine 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 Nizatidine 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: 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
- Bramhall D & Levine M: Possible interaction of ranitidine with phenytoin. Drug Intell Clin Pharm 1988; 22:979-980. PubMed
- Watts RW, Hetzel DJ, Bochner F, et al: Lack of interaction between ranitidine and phenytoin. Br J Clin Pharmacol 1983; 15:499-500.
Keep reading about Phenytoin
Keep reading about Nizatidine
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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