Phenobarbital

Phenobarbital is a long-acting barbiturate used primarily for seizure prevention in veterinary patients. It is an established maintenance treatment for epilepsy in dogs and cats and has an additional role in seizure emergencies. Other applications include selected neonatal seizures and phenobarbital-responsive sialadenosis in dogs, with smaller evidence bases for those conditions.

Group

Barbiturate anticonvulsant

Mechanism of Action

Phenobarbital enhances GABA-A-mediated chloride conductance, increasing inhibitory signaling and reducing repetitive neuronal firing. It mainly prolongs channel opening and also affects excitatory transmission at higher exposure. These actions reduce seizure propagation and recurrence. Its prolonged pharmacologic effect supports maintenance anticonvulsant therapy after an acute seizure has been controlled.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Epilepsy	2–8 mg/kg	PO	Every 12 h
Status epilepticus	10–20 mg/kg	IV	As needed	Give increments to effect; monitor cumulative exposure and respiration.
Epilepsy — Initial	2–2.5 mg/kg	PO	Every 12 h	Titrate to seizure control and serum concentration.
Epilepsy — Initial	2.5–3 mg/kg	PO	Every 12 h	Titrate to seizure control and serum concentration.
Epilepsy — Initial	3.5 mg/kg	PO	Every 12 h	Titrate to seizure control and serum concentration.
Rapid anticonvulsant loading — Loading	16–20 mg/kg	IV	Once
Epilepsy — Maintenance	2–5 mg/kg	PO	Every 12 h
Status epilepticus	5–8 mg/kg	IV	Every 4–6 h	After benzodiazepines; reassess respiration and cumulative exposure.
Sialadenosis case report	1 mg/kg	PO	Every 12 h	Single case after esophageal foreign-body removal; tapered after 3 months, not established universal therapy.
Sedation	2.2–6.6 mg/kg	PO	Every 12 h
Irritable bowel syndrome adjunct	2.2 mg/kg	PO	Every 12 h

Cats

Use / stage	Dose	Route	Schedule	Instructions
Epilepsy — Initial	1–2 mg/kg	PO	Every 12 h	Increase gradually to tolerated maintenance dose.
Epilepsy — Maintenance	2–4 mg/kg	PO	Every 12 h
Status epilepticus	10–20 mg/kg	IV	As needed	Give increments to effect; monitor cumulative exposure and respiration.
Epilepsy with transdermal formulation	9 mg/kg	TOPICAL	Every 12 h	PLO gel or Lipoderm; adjust using serum concentrations because exposure is variable.
Rapid anticonvulsant loading — Loading	16–20 mg/kg	IV	Once
Epilepsy — Maintenance	1–5 mg/kg	PO	Every 12 h
Situational vocalization or distress	2–3 mg/kg	PO	As needed

Horses

Use / stage	Dose	Route	Schedule	Instructions
Epilepsy	12 mg/kg	PO	Every 24 h
Epilepsy	12 mg/kg	PO	Every 12 h	Every-12-hour alternative may be needed after initial treatment.
Seizure control	5–20 mg/kg	IV		Infuse over 30 minutes; sodium chloride may be used for dilution.
Foal seizure control	2–5 mg/kg	IV		Foals only: give over 20 minutes, starting at the low end.
Seizure control — Loading	12 mg/kg	IV	Once	Over 20 minutes.
Seizure control — Maintenance	6.65 mg/kg	IV	Every 12 h	Over 20 minutes.
Epilepsy — Loading	16–20 mg/kg	IV	Once
Epilepsy — Maintenance	1–5 mg/kg	PO	Every 12 h	Adult horse regimen.
Foal seizure control — Loading	20 mg/kg	IV	Once	Dilute to 30-35 mL saline and infuse over 25-30 minutes.
Foal seizure control — Maintenance	9 mg/kg	IV	Every 8 h	Foals; dilute and infuse as for loading.
Foal oral seizure maintenance	100–500 mg/animal	PO	Every 12 h	Follows 16-20 mg/kg IV loading; individualize by serum level.

Ferrets

Use / stage	Dose	Route	Schedule
Rapid anticonvulsant loading — Loading	16–20 mg/kg	IV	Once
Epilepsy — Maintenance	1–2 mg/kg	PO	Every 8–12 h
Epilepsy	1–2 mg/kg	PO	Every 8–12 h

Indications

Maintenance treatment of epilepsy or recurrent seizure disorders in dogs and cats.
Loading or adjunctive treatment during status epilepticus and cluster-seizure management.
Treatment of selected neonatal foal seizures or seizures in other veterinary species.
Treatment of selected canine phenobarbital-responsive sialadenosis, supported by limited clinical reports.

Contraindications

Hepatic disease requires caution.

Interactions

Potent enzyme induction can lower many concurrent drug concentrations, including levetiracetam, theophylline, corticosteroids and cardiovascular drugs.
Avoid mixing alkaline injection with acidic medicines.

Adverse effects

Sedation, ataxia, polyphagia, hepatopathy; idiosyncratic cytopenias, pancreatitis with bromide and superficial necrolytic dermatitis.

Toxicity

Overdose causes profound sedation, ataxia, hypothermia and coma. Support ventilation/circulation; repeated activated charcoal can enhance elimination when airway protection permits. Dialysis or other enhanced-elimination treatment is reserved for severe cases.

Preparations

Preparation	Form	Strength	Route
Phenobarbital 15 mg	Tablet	15 mg / tablet	PO
Phenobarbital 30 mg	Tablet	30 mg / tablet	PO
Phenobarbital 60 mg	Tablet	60 mg / tablet	PO
Phenobarbital 100 mg	Tablet	100 mg / tablet	PO
Phenobarbital oral elixir 4 mg/mL	Oral Liquid	4 mg / mL	PO
Phenobarbital Lipoderm 250 mg/mL	Other	250 mg / mL	TOPICAL
Phenobarbital sodium injection 30 mg/mL	Injection	30 mg / mL	IV
Phenobarbital sodium injection 60 mg/mL	Injection	60 mg / mL	IV
Phenobarbital sodium injection 65 mg/mL	Injection	65 mg / mL	IV
Phenobarbital sodium injection 130 mg/mL	Injection	130 mg / mL	IV

Monitoring and Administration

Adjust to seizure control and serum concentrations. Reported therapeutic ranges: dogs 15-40 mcg/mL, or 10-36 with bromide; cats have reported ranges of 15-45 with narrower study targets; horses 15-20. Monitor CBC, liver function and lipids.

Sampling time is relatively unimportant; stored separator tubes may lower measured concentrations. Total thyroid hormone results can be altered.

An oral 10 mg/mL suspension made from tablets in equal Ora Plus/Ora Sweet was stable for 115 days in amber plastic at room temperature. Lipoderm 250 mg/mL retained potency for 8 weeks; feline absorption is variable.

Emergency dog/cat protocol uses 2-5 mg/kg boluses after diazepam, repeated every 20 minutes up to twice, with a separate 2-10 mg/hour phenobarbital infusion. Feline alternative uses 3 mg/kg IV every 20 minutes to cumulative 24 mg/kg in 24 hours, or a 10 mg/kg loading bolus. Cumulative weight-based limits are not per-dose caps.

Newer cited concentration targets emphasize lower exposure: dogs approximately 20-35 mcg/mL, cats 23-30 mcg/mL. Obtain CBC, chemistry and urine baseline; measure serum after 2-3 weeks and dose changes. Stable patients need periodic levels and hepatic/CBC monitoring; enzyme induction can increase clearance. A route-unspecified compulsive-behavior range and a cyclic bovine 5-g enzyme-induction report lack complete schedules and are not calculator protocols.