Phenytoin Sodium
**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: 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)** โ promotes sodium efflux and limits sodium influx โ 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) โ slightly depresses phase 0 of the cardiac action potential and shortens phase 3 repolarization โ decreases overall action potential duration. It is particularly effective against digitalis-induced arrhythmias. - **Endocrine**: Inhibits the secretion of **insulin** and **vasopressin (ADH)**.
Dosing by species
- Treatment of ventricular arrhythmias ยท 2-3 mg/kg ยท PO ยท q24h ยท Diligent monitoring is required due to accumulation risk.
- Treatment of seizures ยท 2-3 mg/kg daily; 20 mg/kg per week ยท PO ยท daily or weekly ยท Use is very controversial in this species.
- Seizures ยท 2.83-16.43 mg/kg ยท PO ยท q8h ยท To obtain serum levels from 5-10 micrograms/mL. Suggest monitoring serum levels to adjust dosage.
- Digoxin induced arrhythmias ยท 10-22 mg/kg ยท PO ยท q12h ยท Adverse effects are muscle fasciculations and sedation.
- Treatment of ventricular dysrhythmias ยท 20 mg/kg initially for the first 3-4 doses, followed by a maintenance dose of 10-15 mg/kg ยท PO ยท q12h ยท For persistent ventricular extra systoles or ventricular tachycardia where conventional treatment has failed. Suggest monitoring plasma concentrations.
- Treatment of seizures ยท 15-40 mg/kg ยท PO ยท three times daily
- Treatment of seizures ยท 20-35 mg/kg ยท PO ยท three times daily
- Treatment of seizures ยท 8.8-17.6 mg/kg in divided doses ยท PO ยท divided doses ยท 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.
Routes of administration
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)
Drug interactions
- Chloramphenicol ยท Significantly increases the serum half-life of phenytoin (e.g., from 3 to 15 hours in dogs) by inhibiting its hepatic metabolism.
- Lithium ยท The toxicity of lithium may be enhanced.
- Meperidine ยท Phenytoin may decrease the analgesic properties of meperidine but enhance its toxic effects.
- Phenobarbital / Primidone ยท Altered pharmacologic effects; potential for additive hepatotoxicity. Weigh risks vs. benefits before combining.
- Allopurinol, Cimetidine, Diazepam, Isoniazid, Salicylates, Sulfonamides, Trimethoprim, Valproic Acid ยท May increase the pharmacologic effects and toxicity of phenytoin.
- Antacids, Barbiturates, Calcium, Folic Acid, Theophylline ยท May decrease the pharmacologic activity of phenytoin.
- Corticosteroids, Doxycycline, Estrogens, Furosemide, Quinidine ยท 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)
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).
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.