Phenytoin Sodium
Diphenylhydantoin
Also known as: Dilantin · Phenytek · Diphenylhydantoin · DPH · Fenitoina · Phenantoinum · Phenytoinum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of seizures | 15-40 mg/kg | PO | three times daily | — | 🌎 NA |
| Treatment of seizures | 20-35 mg/kg | PO | three times daily | — | 🌎 NA |
| Treatment of seizures | 8.8-17.6 mg/kg in divided doses | PO | divided doses | — | 🌎 NA |
| Treatment of ventricular arrhythmias | Up to 10 mg/kg in increments of 2-4 mg/kg OR 20-35 mg/kg | IV or PO | three times daily (for PO) | — | 🌎 NA |
| Treatment of ventricular arrhythmias | 10 mg/kg slowly IV; 30-50 mg/kg PO | IV, PO | q8h (for PO) | — | 🌎 NA |
| Treatment (or prophylaxis) of digitalis intoxication | 50 mg/kg | PO | q8h | — | 🌎 NA |
| Treatment of hypoglycemia secondary to tumor | 6 mg/kg | PO | two to three times daily | — | 🌎 NA |
- Treatment of seizures: Gradually increase or decrease dose to maintain control. May take several days for seizure control. Note: Unlikely to attain necessary serum levels due to fast half-life.
- Treatment (or prophylaxis) of digitalis intoxication: Long-term use may cause increases in serum alkaline phosphatase and increased hepatic cell size.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of ventricular arrhythmias | 2-3 mg/kg | PO | q24h | — | 🌎 NA |
| Treatment of seizures | 2-3 mg/kg daily; 20 mg/kg per week | PO | daily or weekly | — | 🌎 NA |
- Treatment of ventricular arrhythmias: Diligent monitoring is required due to accumulation risk.
- Treatment of seizures: Use is very controversial in this species.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Seizures | 2.83-16.43 mg/kg | PO | q8h | — | 🌎 NA |
| Digoxin induced arrhythmias | 10-22 mg/kg | PO | q12h | — | 🌎 NA |
| Treatment of ventricular dysrhythmias | 20 mg/kg initially for the first 3-4 doses, followed by a maintenance dose of 10-15 mg/kg | PO | q12h | — | 🌎 NA |
- Seizures: To obtain serum levels from 5-10 micrograms/mL. Suggest monitoring serum levels to adjust dosage.
- Digoxin induced arrhythmias: Adverse effects are muscle fasciculations and sedation.
- Treatment of ventricular dysrhythmias: For persistent ventricular extra systoles or ventricular tachycardia where conventional treatment has failed. Suggest monitoring plasma concentrations.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Phenytoin sodium is a hydantoin-derivative anticonvulsant and Class IB antiarrhythmic agent. While historically significant in human medicine, its use in veterinary medicine is highly restricted due to unfavorable pharmacokinetic profiles in companion animals.
- Dogs: Rarely used for long-term epilepsy management because of a very short half-life and rapid hepatic autoinduction, which makes maintaining therapeutic serum levels nearly impossible without frequent, high-dose administration.
- Cats: Highly susceptible to toxic accumulation due to a severely prolonged half-life (up to 108 hours) and deficient glucuronidation pathways.
- Clinical Niche: Today, it is primarily reserved for treating digoxin-induced ventricular arrhythmias in dogs and horses, or specific rare neuromuscular conditions (e.g., myokemia and neuromyotonia in cats).
Clinical Pearl: Because of its ability to inhibit insulin secretion, it has been investigated as an adjunctive treatment for hypoglycemia secondary to insulinomas, though clinical benefits are often minimal.
Mechanism of action
Phenytoin exhibits both neurological and cardiac effects through the stabilization of excitable membranes:
- Neurological: Binds to and prolongs the inactive state of voltage-gated sodium channels (VGSCs) → promotes sodium efflux and limits sodium influx → stabilizes neuronal membranes and prevents the high-frequency repetitive firing necessary for seizure propagation from epileptogenic foci.
- Cardiac: Acts as a Class IB antiarrhythmic (similar to lidocaine) → slightly depresses phase 0 of the cardiac action potential and shortens phase 3 repolarization → decreases overall action potential duration. It is particularly effective against digitalis-induced arrhythmias.
- Endocrine: Inhibits the secretion of insulin and vasopressin (ADH).
Safety & warnings
Contraindications
- Hypersensitivity to phenytoin or other hydantoins
- Intravenous use is contraindicated in 2nd or 3rd degree heart block
- Sinoatrial block
- Adams-Stokes syndrome
- Sinus bradycardia
Adverse effects
- Dogs: Anorexia, vomiting, ataxia, sedation, gingival hyperplasia, hepatotoxicity (elevated ALT, decreased albumin, hepatic lipidosis)
- Cats: Ataxia, sedation, anorexia, dermal atrophy syndrome, thrombocytopenia
- Horses: Excitement, recumbency (at high plasma concentrations)
Precautions
Hepatotoxicity Warning: Chronic therapy in dogs requires regular monitoring of liver function due to the risk of hepatocellular hypertrophy, necrosis, and hepatic lipidosis.
- Pregnancy: Potentially teratogenic (FDA Category D / Papich Class C). It readily crosses the placenta and is excreted in maternal milk. Use only when benefits clearly outweigh risks.
- Feline Sensitivity: Cats metabolize phenytoin extremely slowly. Use is highly controversial and requires diligent monitoring to prevent severe toxicity.
- IV Administration: Must be given slowly. Rapid IV injection can cause severe hypotension and cardiac arrhythmias.
Drug interactions
Significantly increases the serum half-life of phenytoin (e.g., from 3 to 15 hours in dogs) by inhibiting its hepatic metabolism.
The toxicity of lithium may be enhanced.
Phenytoin may decrease the analgesic properties of meperidine but enhance its toxic effects.
Altered pharmacologic effects; potential for additive hepatotoxicity. Weigh risks vs. benefits before combining.
May increase the pharmacologic effects and toxicity of phenytoin.
May decrease the pharmacologic activity of phenytoin.
Phenytoin may decrease the pharmacologic activity of these agents via hepatic enzyme induction.
Monitoring
- Level of seizure control or arrhythmia resolution
- Signs of toxicity (sedation, ataxia)
- Body weight (monitor for anorexia)
- Liver enzymes (ALT, ALP) and serum albumin (especially with chronic therapy)
- Serum drug levels (if signs of toxicity appear or lack of efficacy is noted)
Pharmacokinetics
Half-life
Absorption
Nearly completely absorbed in humans, but in dogs, oral bioavailability may only be about 40%.
Distribution
Well distributed throughout the body. About 78% bound to plasma proteins in dogs (vs. 95% in humans). Protein binding may be reduced in uremic patients. Readily crosses the placenta and small amounts are excreted into milk.
Metabolism
Metabolized in the liver; much of the drug is conjugated to a glucuronide form. Phenytoin induces hepatic microsomal enzymes, enhancing the metabolism of itself (autoinduction) and other drugs.
Elimination
Excreted by the kidneys as metabolites.
Overdose
Clinical signs of overdosage are dose-dependent:
- Lower levels: Sedation, anorexia, and ataxia (wobbly gait).
- Higher levels: Coma, severe hypotension, and respiratory depression.
Treatment: Dogs rapidly clear the drug, so treatment depends on the severity of clinical signs. Severe intoxications require aggressive supportive care (IV fluids, cardiovascular and respiratory support).
Available products
Formulations
- Extended-release capsules: 30 mg, 100 mg, 200 mg, 300 mg
- Oral suspension: 25 mg/mL
- Chewable tablets: 50 mg
- Injection: 50 mg/mL
Veterinary
- None currently available
Human-labeled
- Phenytoin Sodium Extended-Release Capsules: 30 mg, 100 mg, 200 mg & 300 mg (Dilantin Kapseals, Phenytek)
- Phenytoin Oral Suspension: 25 mg/mL (Dilantin-125)
- Phenytoin Tablets: 50 mg chewable (Dilantin Infa-Tabs)
- Phenytoin Sodium Injection: 50 mg/mL (46 mg/mL phenytoin base)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store capsules at room temperature (below 86°F) and protect from light and moisture. Store injection at room temperature and protect from freezing. If injection is frozen/refrigerated, a precipitate may form which should resolubilize when warmed. Do not use precipitated solutions. Injectable solutions will precipitate at a pH less than 11.5.
Client information
- Strict Schedule: Give this medication exactly as prescribed. Missing doses can lead to breakthrough seizures or dangerous heart rhythms.
- Administration: Giving the medication with food may enhance absorption and decrease stomach upset.
- Watch for Side Effects: Notify your veterinarian immediately if your pet becomes extremely lethargic, loses their appetite, vomits, or appears wobbly/drunk (ataxic).
- Dental Health: In dogs, this drug can cause overgrowth of the gums (gingival hyperplasia). Regular dental check-ups and good oral hygiene are important.
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Safety Warning: Never share human medications with your pet. The way animals process this drug is vastly different from humans, and incorrect dosing can be fatal.
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.