Phenobarbital
Phenobarbital sodium, phenylethylbarbituric acid, phenylethylmalonylurea
Also known as: Luminal Sodium · Solfoton · Epiphen · Epityl · Phenoleptil · Fenobarbital · Phenemalum · Phenobarbitalum · Phenobarbitone · Phenylethylbarbituric acid · Phenylethylmalonylurea · Phenobarbital sodium
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 |
|---|---|---|---|---|---|
| Idiopathic epilepsy (initial dose) | 2-2.5 mg/kg | PO | q12h | — | 🌎 NA |
| Idiopathic epilepsy (initial maintenance) | 2.5-3 mg/kg | PO | q12h | — | 🌎 NA |
| Idiopathic epilepsy (rapid loading) | 16-20 mg/kg once IV loading dose, then 2-5 mg/kg PO q12h | IV/PO | Once then q12h | — | 🌎 NA |
| Status epilepticus | 2-5 mg/kg bolus (repeat at 20 min intervals up to 2x), or add to diazepam infusion at 2-10 mg/hour | IV | PRN | — | 🌎 NA |
| Status epilepticus (post-benzodiazepine) | 5-8 mg/kg | IV | q4-6h | — | 🌎 NA |
| Sialadenosis | 1 mg/kg | PO | q12h | 3 months | 🌎 NA |
| Sedation | 2.2-6.6 mg/kg | PO | q12h | — | 🌎 NA |
| Irritable bowel syndrome | 2.2 mg/kg | PO | q12h | — | 🌎 NA |
| Compulsive behaviors (adjunctive) | 2-20 mg/kg | PO | q12-24h | — | 🌎 NA |
- Idiopathic epilepsy (initial dose): Monitor serum concentrations 2-3 weeks after initiating. Target 20-35 mcg/mL.
- Idiopathic epilepsy (initial maintenance): Perform baseline CBC, chem, UA before starting.
- Status epilepticus: If seizures persist after diazepam therapy.
- Status epilepticus (post-benzodiazepine): Continue until seizures are under control.
- Sialadenosis: Slowly weaned off after 3 months.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Idiopathic epilepsy (initial dose) | 2-2.5 mg/kg | PO | q12h | — | 🌎 NA |
| Idiopathic epilepsy (maintenance) | 1-2 mg/kg | PO | q12h | — | 🌎 NA |
| Idiopathic epilepsy (rapid loading) | 16-20 mg/kg once IV loading dose, then 1-5 mg/kg PO q12h | IV/PO | Once then q12h | — | 🌎 NA |
| Status epilepticus | 2-5 mg/kg bolus (repeat at 20 min intervals up to 2x), or add to diazepam infusion at 2-10 mg/hour | IV | PRN | — | 🌎 NA |
| Emergency seizure control | 3 mg/kg (repeat q20m up to 24 mg/kg/24h) OR 10 mg/kg bolus | IV | PRN | — | 🌎 NA |
| Sedation (situational distress/travel) | 2-3 mg/kg | PO | PRN | — | 🌎 NA |
- Idiopathic epilepsy (initial dose): Optimum therapeutic levels 23-30 mcg/mL.
- Idiopathic epilepsy (maintenance): Adjust based on serum levels.
- Status epilepticus: If seizures persist after diazepam therapy.
- Emergency seizure control: Given along with IV diazepam.
- Sedation (situational distress/travel): For controlling excessive vocalization.
Ferrets
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Seizures | 1-2 mg/kg | PO | q8-12h (2-3 times daily) | — | 🌎 NA |
| Seizures (rapid loading) | Loading dose of 16-20 mg/kg once IV; maintenance dose of 1-2 mg/kg PO q8-12h | IV/PO | q8-12h | — | 🌎 NA |
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Seizures (Adults) | Loading dose of 12 mg/kg IV over 20 minutes, then 6.65 mg/kg IV over 20 minutes q12h | IV | q12h | — | 🌎 NA |
| Seizures (Adults) | Loading dose of 16-20 mg/kg once IV; maintenance dose of 1-5 mg/kg PO twice daily | IV/PO | q12h | — | 🌎 NA |
| Seizures (Foals) | Loading dose of 16-20 mg/kg once IV; maintenance dose of 100-500 mg (total dose) PO twice daily | IV/PO | q12h | — | 🌎 NA |
| Seizures (Foals) | 20 mg/kg diluted and infused over 25-30 minutes IV, then 9 mg/kg infused as above q8h | IV | q8h | — | 🌎 NA |
Cattle
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Enzyme induction in organochlorine toxicity | 5 grams | PO | Daily | 3-4 weeks on, 3-4 weeks off, repeat | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Phenobarbital is a long-acting barbiturate that serves as a cornerstone in veterinary medicine for the management of seizure disorders.
- Primary Use: It is widely considered the drug of first choice for treating idiopathic epilepsy in cats and remains one of the most common and effective first-line or adjunctive antiseizure medications in dogs and horses.
- Clinical Advantages: It offers a favorable pharmacokinetic profile, relative safety, proven efficacy, and low cost. It can effectively control seizures at sub-hypnotic doses.
- Hepatic Auto-induction: A unique pharmacological feature of phenobarbital is its ability to induce hepatic cytochrome P450 enzymes. Over time, the patient's liver becomes more efficient at metabolizing the drug, which often necessitates dose increases to maintain therapeutic serum levels.
- Other Uses: Beyond seizure control, it is occasionally used as an oral sedative (e.g., for feline travel anxiety or excessive vocalization) and has been used in the management of status epilepticus after initial control with benzodiazepines.
Mechanism of action
Phenobarbital exerts its antiseizure and sedative effects through multiple mechanisms within the central nervous system:
- GABA-A Receptor Modulation: Phenobarbital binds to the allosteric barbiturate site on the GABA-A receptor. Unlike benzodiazepines (which increase the frequency of chloride channel opening), phenobarbital increases the duration of chloride channel opening → enhanced influx of chloride ions → hyperpolarization of the postsynaptic neuronal membrane → increased seizure threshold and decreased spread of seizure activity.
- Glutamate Inhibition: It inhibits the release of excitatory neurotransmitters, specifically glutamate, thereby dampening CNS excitability.
- Calcium Channel Blockade: At high (anesthetic) doses, it inhibits the uptake of calcium at nerve endings, further reducing neurotransmitter release.
- Other Neurotransmitters: It has also been shown to inhibit the release of acetylcholine and norepinephrine.
Safety & warnings
Contraindications
- Known hypersensitivity to barbiturates
- Severe liver disease
- Nephritis (large doses)
- Severe respiratory depression
- Hepatic dysfunction
- Severe renal impairment
Adverse effects
- Dogs: Transient anxiety, agitation, or lethargy upon initiation
- Dogs: Polydipsia (PD), polyuria (PU), and polyphagia (PP)
- Dogs: Sedation and ataxia (especially at higher serum levels)
- Dogs: Elevated liver enzymes (ALT, ALP) - common and not always indicative of failure
- Dogs: Hepatotoxicity (uncommon, usually at levels >30-40 mcg/mL)
- Dogs: Rare blood dyscrasias (anemia, thrombocytopenia, neutropenia)
- Dogs: Rare superficial necrolytic dermatitis (SND)
- Cats: Ataxia, persistent sedation, lethargy
- Cats: Polyphagia, weight gain, PU/PD
- Cats: Rare immune-mediated reactions and bone marrow hypoplasia
- Cats: Coagulopathies (at very high doses)
- Blood dyscrasias (rare)
Precautions
Intravenous Administration: Must be given SLOWLY (not more than 60 mg/minute). Too rapid IV administration may cause profound respiratory depression.
Tissue Irritation: Do NOT administer subcutaneously (SC) or perivascularly. The injectable solution is highly alkaline and very irritating, potentially causing significant tissue necrosis.
- Patient Conditions: Use with extreme caution in patients that are hypovolemic, anemic, have borderline hypoadrenal function, or have pre-existing cardiac or respiratory disease.
- Feline Sensitivity: Cats are particularly sensitive to the respiratory depressant effects of barbiturates.
- Hepatic Function: Chronic administration induces hepatic microsomal enzymes. Monitor liver function closely, especially in dogs, as hepatotoxicity can occur at high serum concentrations.
- Endocrine Testing: Can alter thyroid testing (decreased T4, normal T3, normal/increased TSH) and may cause a false positive low-dose dexamethasone suppression test.
Drug interactions
Increased risk for hepatotoxicity, particularly with large or chronic doses of barbiturates.
Increased risk for hepatotoxicity secondary to carprofen metabolites.
May prolong phenobarbital effects.
Barbiturates may affect phenytoin metabolism, and phenytoin may alter barbiturate levels.
May induce enzymes that increase the metabolism of barbiturates.
Phenobarbital reduces levetiracetam elimination half-life by about 50% in dogs.
Phenobarbital may decrease anticoagulant effects by lowering serum concentrations.
Phenobarbital increases the metabolism and clearance of corticosteroids, potentially reducing their efficacy.
Phenobarbital decreases doxycycline serum concentrations; effect may persist for weeks after discontinuation.
Phenobarbital increases theophylline metabolism, lowering its serum concentrations.
May increase the effects of phenobarbital while phenobarbital may decrease chloramphenicol levels.
Increased hepatic metabolism and clearance of T4
Inhibits phenobarbital metabolism
Monitoring
- Anticonvulsant efficacy (seizure frequency and severity)
- Adverse effects (CNS depression, ataxia, PU/PD, weight gain)
- Serum phenobarbital levels (Dogs: 20-35 mcg/mL; Cats: 23-30 mcg/mL). Wait 5-6 half-lives (12-14 days in dogs, 9-10 days in cats) before measuring steady-state levels.
- Routine CBC, liver enzymes (especially ALT and AST), and bilirubin at least every 6 months during chronic therapy.
- Serum phenobarbital concentrations (trough levels)
- Liver enzymes (ALT, ALP, GGT)
- Serum bile acids
- Complete Blood Count (CBC)
- Renal function
Pharmacokinetics
Half-life
Absorption
Slowly absorbed from the GI tract. Bioavailability is approximately 90% in dogs and practically complete in adult horses. Peak levels occur 4-8 hours after oral dosing in dogs.
Distribution
Widely distributed throughout the body. Due to lower lipid solubility compared to other barbiturates, it does not distribute as rapidly into the CNS. Protein binding is 40-60%. Volume of distribution: Dogs ~0.75 L/kg, Horses ~0.8 L/kg.
Metabolism
Metabolized in the liver primarily by hydroxylated oxidation to p-hydroxyphenobarbital; sulfate and glucuronide conjugates are also formed. Induces hepatic microsomal enzymes, leading to auto-induction and increased clearance over time.
Elimination
Approximately 25% is excreted unchanged by the kidneys. Alkalinizing the urine or increasing urine flow increases excretion rates.
Overdose
Clinical Signs of Toxicity:
- Dogs: Ataxia, lethargy, sedation, recumbency, depression, hypothermia, and coma.
- Cats: Ataxia, sedation, and recumbency.
Treatment:
- Decontamination: Removal of ingested product from the gut if recent. Activated charcoal is highly effective and acts as a 'sink' to draw the drug from the vasculature back into the gut, enhancing clearance even if the drug was given parenterally.
- Supportive Care: Provide intensive respiratory and cardiovascular support.
- Enhanced Elimination: Forced alkaline diuresis can substantially augment elimination in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or anuric patients.
Available products
Formulations
- Tablets
- Capsules
- Oral elixir/suspension
- 12.5 mg oral tablet
- 15 mg oral tablet
- 25 mg oral tablet
- 30 mg oral tablet
- 50 mg oral tablet
- 60 mg oral tablet
- 100 mg oral tablet
- 4% (40 mg/ml) oral solution
- 15 mg/5 ml oral solution
- 15 mg/ml injectable solution
- 30 mg/ml injectable solution
- 60 mg/ml injectable solution
- 200 mg/ml injectable solution
Veterinary
- None currently labeled for veterinary use.
- Epiphen
- Epityl
- Phenoleptil
Human-labeled
- Phenobarbital Tablets: 15 mg, 16 mg, 30 mg, 60 mg, 90 mg, & 100 mg (Solfoton, generic)
- Phenobarbital Elixir: 15 mg/5mL, 20 mg/5mL (generic)
- Phenobarbital Sodium Injection: 30 mg/mL, 60 mg/mL, 65 mg/mL, & 130 mg/mL (Luminal Sodium, generic)
- Phenobarbital oral solution
Regulatory status
POM-V, POM CD SCHEDULE 3
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Tablets: Store in tight, light-resistant containers at room temperature (15-30°C); protect from moisture. Elixir: Store in tight containers at 20-25°C. Injection: Store at room temperature (15-30°C). Do not add to acidic solutions or use if precipitate forms.
Client information
Important Guidance for Pet Owners:
- Consistency is Key: For successful epilepsy treatment, you must give this medication at the same time every day. Missing even a single dose can trigger a seizure.
- Initial Side Effects: When starting the medication, your pet may act like a "drunken sailor" (wobbly, sleepy, or unusually hungry/thirsty). This is normal and usually improves significantly after the first 1 to 2 weeks as their body adjusts.
- Do Not Stop Abruptly: Never stop giving this medication suddenly without consulting your veterinarian, as this can cause severe, life-threatening seizures.
- Monitoring: Your veterinarian will need to draw blood periodically to check the drug levels in the blood and monitor liver function. This is crucial for your pet's safety and to ensure the dose is correct.
- Safety: Keep this medication strictly out of reach of children and other pets. Store it in child-resistant packaging.
- When to Call the Vet: Contact your veterinarian immediately if your pet's seizures are not controlled, if they become extremely lethargic, or if you notice signs like yellowing of the eyes/gums (jaundice) or severe weakness.
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.