Phenytoin
Diphenylhydantoin
Also known as: pro-Epanutin · Dilantin · Diphenylhydantoin · DPH
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Dosing by species
Dosing data for this drug is not yet available in the VetSheet formulary. Every other section below is complete. Consult the current product label before prescribing.
Overview
Phenytoin is a hydantoin-derivative anticonvulsant and Class IB antiarrhythmic agent.
Clinical Pearl: While historically used for epilepsy in veterinary medicine, its use in dogs has largely been abandoned due to a very short half-life (requiring frequent dosing) and a high risk of hepatotoxicity. It has been superseded by safer and more effective alternatives like phenobarbital, levetiracetam, and zonisamide.
Warning: Phenytoin is highly toxic to cats due to their deficient hepatic glucuronidation pathways, leading to severe accumulation and toxicity even at very low doses.
Mechanism of action
Diminishes the spread of focal neural discharges by promoting sodium efflux from neurons via the voltage-gated sodium channels → stabilizes the neuronal membrane → raises the threshold against hyperexcitability. It also acts on Purkinje fibers in the heart to shorten the action potential duration, functioning as a Class IB antiarrhythmic.
Safety & warnings
Contraindications
- Cats (due to severe toxicity)
- Hepatic dysfunction
- Bradycardia
- High-grade AV block
Adverse effects
- Hepatotoxicity (especially in dogs)
- Ataxia
- Sedation
- Gingival hyperplasia
- Peripheral neuropathy
- Hypotension and arrhythmias (with rapid IV administration)
Precautions
Warning: Highly toxic in cats. Warning: Rapid IV administration can cause severe hypotension, bradycardia, and cardiovascular collapse. Always administer IV slowly and monitor ECG.
Drug interactions
Unpredictable effects on serum concentrations of both drugs due to CYP450 induction
Inhibits hepatic metabolism of phenytoin, leading to increased levels and toxicity
Inhibits metabolism of phenytoin, increasing risk of toxicity
Phenytoin induces hepatic enzymes, increasing the clearance and reducing the efficacy of corticosteroids
Monitoring
- Serum drug concentrations (therapeutic range typically 10-20 mcg/mL, though rarely monitored now due to infrequent use)
- Liver enzymes (ALT, AST, ALP) and bilirubin
- ECG and blood pressure during IV administration
Pharmacokinetics
Half-life
Absorption
Variable and unpredictable oral absorption in dogs.
Distribution
Highly protein-bound (70-90%). Distributes rapidly into the CNS.
Metabolism
Undergoes extensive hepatic metabolism via CYP450 enzymes. Dogs metabolize phenytoin extremely rapidly, whereas cats metabolize it extremely slowly due to deficient glucuronidation.
Elimination
Excreted primarily in the urine as inactive metabolites.
Overdose
Clinical signs of overdose include severe ataxia, tremors, lethargy, vomiting, and paradoxical seizures. Rapid IV overdose leads to hypotension and cardiac arrest.
Treatment: Consists of supportive care, IV fluid therapy, and cardiovascular monitoring. There is no specific antidote.
Available products
Formulations
- Oral capsules: 25 mg, 50 mg, 100 mg, 300 mg
- Oral tablets: 100 mg
- Oral chewable tablets: 50 mg
- Oral suspension: 30 mg/5 ml
- Injectable solution: 50 mg/ml
- Injectable fosphenytoin: 75 mg/ml (equivalent to 50 mg/ml phenytoin)
Human-labeled
- Epanutin capsules (25 mg, 50 mg, 100 mg, 300 mg)
- Epanutin Infatabs (50 mg chewable)
- Epanutin suspension (30 mg/5 ml)
- pro-Epanutin injection (fosphenytoin 75 mg/ml)
Regulatory status
POM (Prescription Only Medicine). Primarily human-authorized products used off-label under the cascade.
POM (Prescription Only Medicine). Primarily human-authorized products used off-label under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature (15-30°C) in tight, light-resistant containers. Do not freeze the oral suspension or injectable solutions.
Client information
Administer exactly as directed by your veterinarian. Do not stop this medication abruptly, as it may trigger severe seizures.
Contact your veterinarian immediately if your pet develops jaundice (yellowing of the gums or eyes), severe lethargy, vomiting, or loss of coordination.
CRITICAL: Never give this medication to cats.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.