Phenobarbital — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	2.5-5 mg/kg	q12h	Duration: Long-term (lifelong for epilepsy) Notes: Titrate to maintain serum levels of 15-40 µg/mL (65-170 µmol/L). Start at lower end and adjust based on therapeutic drug monitoring.
Dog	IV	2-4 mg/kg (slow IV)	As needed for status epilepticus	Duration: Acute control Notes: Administer slowly over 10-15 minutes to avoid respiratory depression. May be repeated once if needed.
Cat	PO	2.5-5 mg/kg	q12h	Duration: Long-term Notes: Cats may require lower doses; monitor for adverse effects. Serum levels of 15-40 µg/mL are often targeted.
Cat	IV	2-4 mg/kg (slow IV)	As needed for status epilepticus	Duration: Acute control Notes: Use with caution; cats are more sensitive to barbiturate effects.
Horse	PO	2-5 mg/kg	q12h	Duration: Variable Notes: Not commonly used; may cause ataxia and sedation.
Cattle	PO	2-5 mg/kg	q12h	Duration: Variable Notes: Not commonly used; observe withdrawal times.
Small Ruminants	PO	2-5 mg/kg	q12h	Duration: Variable Notes: Not commonly used; observe withdrawal times.
Rabbit	PO	2-5 mg/kg	q12h	Duration: Variable Notes: Limited data; use with caution.
Birds/Poultry	PO	2-5 mg/kg	q12h	Duration: Variable Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Anticonvulsant for seizure disorders
Sedative-hypnotic (less common)

Dog (Canine)

Primary generalized epilepsy
Partial seizures
Status epilepticus (as adjunctive therapy)
Cluster seizures (as adjunctive therapy)
Sedation (rarely used)

Cat (Feline)

Primary generalized epilepsy
Partial seizures
Status epilepticus (as adjunctive therapy)
Sedation (rarely used)

Horse (Equine)

Seizures (rarely used)
Sedation (rarely used)

Cattle (Bovine)

Seizures (rarely used)
Sedation (rarely used)

Small Ruminants (Sheep / Goat)

Seizures (rarely used)
Sedation (rarely used)

Rabbit & Small Mammals

Seizures (rarely used)
Sedation (rarely used)

Avian & Poultry

Seizures (rarely used)
Sedation (rarely used)

Exotic & Other Species

Seizures (rarely used)
Sedation (rarely used)

Pharmacology & Mechanism of Action

Drug Class: Barbiturate | Pharmacological Group: Anticonvulsant, Sedative-Hypnotic

Mechanism of Action: Phenobarbital enhances the inhibitory action of gamma-aminobutyric acid (GABA) at GABA-A receptors in the central nervous system. It binds to the barbiturate site on the receptor-chloride channel complex, prolonging the duration of chloride channel opening (in contrast to benzodiazepines which increase frequency). This leads to hyperpolarization of neurons, reducing neuronal excitability and suppressing seizure activity. At higher doses, it also inhibits excitatory glutamate receptors, contributing to its sedative and anesthetic effects.

Pharmacodynamics: Phenobarbital produces dose-dependent central nervous system depression. At therapeutic anticonvulsant doses, it raises the seizure threshold and limits the spread of seizure activity without causing significant sedation in most animals. It also induces hepatic microsomal enzymes, leading to tolerance and drug interactions. Chronic use can cause polyphagia, polydipsia, and polyuria, especially in dogs. In cats, it may cause idiosyncratic reactions such as skin eruptions and blood dyscrasias.

⚡ Pharmacokinetics Summary

Absorption: Phenobarbital is well absorbed after oral administration, with peak plasma concentrations occurring within 1-4 hours in dogs and cats. Bioavailability is nearly complete (90-100%).

Distribution: It is widely distributed throughout the body, crosses the blood-brain barrier and placenta, and is distributed into milk. Volume of distribution is approximately 0.5-1.0 L/kg. Protein binding is low (20-45%).

Metabolism: Phenobarbital is extensively metabolized in the liver, primarily by hydroxylation via cytochrome P450 enzymes (CYP2C9, CYP2C19). It is a potent inducer of hepatic microsomal enzymes, which can increase its own metabolism and that of other drugs.

Excretion: Renal excretion of unchanged drug and metabolites occurs. In dogs, about 25-30% is excreted unchanged in urine; in cats, a larger proportion may be excreted unchanged. Biliary excretion also occurs.

Half-Life: Dog: 40-70 hours; Cat: 40-50 hours; Horse: 12-24 hours; Cattle: 12-24 hours (estimated); Rabbit: 4-8 hours (estimated).

Bioavailability: Oral bioavailability is approximately 90-100%.

Protein Binding: 20-45% in dogs and cats.

Available Formulations & Strengths

Oral Tablet 15 mg, 30 mg, 60 mg, 100 mg (PO)

Oral Elixir 20 mg/5 mL (PO)

Injectable Solution 65 mg/mL, 130 mg/mL (IV, IM, SC)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to barbiturates
Severe hepatic insufficiency
Severe respiratory disease with dyspnea or obstruction
Porphyria (barbiturates can precipitate acute attacks)

Warnings & Clinical Precautions:

Use with caution in patients with renal or cardiac disease.
Abrupt discontinuation can precipitate withdrawal seizures; taper dose gradually.
May cause paradoxical excitement in some animals, especially cats and horses.
Chronic use may lead to tolerance and dependence.
Monitor liver function and serum phenobarbital levels periodically.
In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
Phenobarbital is a controlled substance; handle and store securely.

Adverse Effects & Reactions

Common:

Sedation
Ataxia
Polyphagia
Polydipsia
Polyuria
Increased appetite and weight gain

Serious / Severe:

Hepatotoxicity
Blood dyscrasias (e.g., neutropenia, thrombocytopenia)
Stevens-Johnson syndrome (rare, especially in cats)
Respiratory depression (with overdose or rapid IV administration)
Paradoxical excitement

Rare:

Cutaneous eruptions
Facial edema
Megaeophagus (in dogs)
Cerebellar degeneration (with chronic high doses)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other CNS depressants (e.g., benzodiazepines, opioids, anesthetics)	Additive CNS depression and respiratory depression	High
Hepatic enzyme inducers (e.g., phenytoin, primidone)	Increased metabolism of phenobarbital, reduced efficacy	Moderate
Hepatic enzyme inhibitors (e.g., cimetidine, chloramphenicol)	Decreased metabolism of phenobarbital, increased toxicity	Moderate
Corticosteroids	Increased metabolism of corticosteroids, reduced efficacy	Moderate
Doxycycline	Decreased half-life of doxycycline, reduced efficacy	Moderate
Theophylline	Increased metabolism of theophylline, reduced efficacy	Moderate
Warfarin	Increased metabolism of warfarin, reduced anticoagulant effect	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

CNS depression
Coma
Respiratory depression
Hypotension
Hypothermia
Pulmonary edema
Cardiovascular collapse

Emergency Treatment Protocol: Treatment is primarily supportive. Induce emesis if recent oral ingestion and patient is conscious. Administer activated charcoal. Provide respiratory support (oxygen, mechanical ventilation if needed). Maintain blood pressure with IV fluids and vasopressors if necessary. Alkalinization of urine may enhance renal excretion of phenobarbital. In severe cases, hemodialysis or hemoperfusion may be considered. Monitor vital signs and neurological status closely.

Food Animal Withdrawal Times

🥩 Meat: 8 days🥛 Milk: 4 days

Withdrawal times are not established for phenobarbital in food animals; these are estimates based on pharmacokinetic data. Extra-label use requires veterinary oversight and extended withdrawal periods may be necessary. Consult FARAD for specific recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep in a tightly closed container. Store controlled substances securely.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not specifically approved for veterinary use, but widely used in veterinary medicine as an extra-label drug.

Extra-Label (Off-Label) Use: Phenobarbital is a controlled substance (Schedule IV). Extra-label use in food animals is permitted under AMDUCA with veterinary oversight, but withdrawal times must be extended and monitored. Not approved for use in food animals in the US.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Phenobarbital is the most commonly used first-line anticonvulsant in dogs and cats for chronic management of epilepsy. It is effective, inexpensive, and generally well-tolerated. Therapeutic drug monitoring is recommended to maintain serum concentrations within the therapeutic range (typically 15-40 µg/mL in dogs) and to minimize adverse effects. Liver enzyme induction occurs within weeks, so serum levels should be rechecked after 2-4 weeks of therapy and periodically thereafter. Adverse effects such as polyphagia and sedation often diminish with time. In cats, careful monitoring for idiosyncratic reactions is essential. For status epilepticus, phenobarbital is often used after benzodiazepines fail. It can be administered IV slowly, but respiratory depression is a risk. In food animals, use is rare and withdrawal times must be considered. Always taper the dose gradually to avoid withdrawal seizures.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)