Disopyramide and Fosphenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fosphenytoin
Disopyramide
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 disopyramide exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Concurrent administration of fosphenytoin and disopyramide may result in reduced disopyramide exposure and may also cause additive QT interval prolongation. Consider disopyramide dose adjustments to achieve optimal clinical response when fosphenytoin is added to or withdrawn from a patient's regimen2.
Why it happens (mechanism)
Induction of hepatic drug-metabolizing enzymes by fosphenytoin; additive QT interval prolongation
Literature reports
2 reports — tap to read
a) Concomitant administration of disopyramide and phenytoin was reported to result in a decrease in the elimination half-life and mean AUC of disopyramide and an increase in the disopyramide elimination rate constant. Following a single oral dose of disopyramide, maximum disopyramide serum concentrations were not affected significantly during phenytoin therapy; however disopyramide serum levels in the subsequent 24-hour period were decreased significantly as compared to disopyramide alone. An increase in anticholinergic side effects was observed after phenytoin therapy. It is suggested that phenytoin can enhance the hepatic metabolism of disopyramide, resulting in increased anticholinergic effects and a decrease in therapeutic efficacy; the metabolite of disopyramide has a lower degree of antiarrhythmic efficacy and more anticholinergic activity than the parent compound. In an accompanying case report by the authors, a 59-year-old male required unusually high doses of disopyramide to control ventricular tachycardia during combined phenytoin administration. Unusually high serum concentrations of disopyramide were also reported in this patient 3.
b) Concurrent use of disopyramide and phenytoin has been reported to result in decreased plasma concentrations of disopyramide (25 to 75%) and subsequent increases in one of disopyramide's metabolites, MND, which has 20 times the anticholinergic activity of disopyramide 14.
Common questions
Can I take Disopyramide and Fosphenytoin together?
Reduced disopyramide exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Disopyramide and Fosphenytoin 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Disopyramide or Fosphenytoin 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)
- Aitio ML, Mansury L, Tala E, et al: The effect of enzyme induction on the metabolism of disopyramide in man. Br J Clin Pharmacol 1981; 11:279-285. PubMed
- Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
- Nightingale J & Nappi JM: Effect of phenytoin on serum disopyramide concentrations. Clin Pharm 1987; 6:46-50.
- Aitio ML & Vuorenmaa T: Enhanced metabolism and diminished efficacy of disopyramide by enzyme induction?. Br J Clin Pharmacol 1980; 9:149-152. PubMed
Keep reading about Fosphenytoin
Keep reading about Disopyramide
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist