Levetiracetam — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	20 mg/kg	q8h	Duration: Long-term (maintenance) Notes: Dose may be increased up to 60 mg/kg q8h if needed. For immediate seizure control, a loading dose of 60 mg/kg PO can be given.
Cat	PO	20 mg/kg	q8h	Duration: Long-term (maintenance) Notes: Dose may be increased to 30-40 mg/kg q8h if needed. Use with caution in renal impairment.
Horse	PO	20-30 mg/kg	q8h	Duration: Long-term (maintenance) Notes: For acute seizure control, IV administration may be used at 20-30 mg/kg slow IV.
Cattle	PO	20-30 mg/kg	q8h	Duration: As needed Notes: Off-label use; limited data. Monitor for adverse effects.
Small Ruminants	PO	20-30 mg/kg	q8h	Duration: As needed Notes: Off-label use; limited data.
Rabbit	PO	20-30 mg/kg	q8h	Duration: As needed Notes: Off-label use; limited data.
Birds/Poultry	PO	20-30 mg/kg	q8h	Duration: As needed Notes: Off-label use; limited data.

Clinical Indications & Species Uses

General Indications

Adjunctive therapy for refractory seizures in dogs and cats
Alternative for animals that do not tolerate other antiepileptics

Dog (Canine)

Adjunctive therapy for refractory epilepsy
Primary treatment for idiopathic epilepsy
Treatment of seizures secondary to brain tumors, trauma, or inflammatory disease

Cat (Feline)

Adjunctive therapy for refractory epilepsy
Treatment of seizures associated with brain disease

Horse (Equine)

Treatment of seizures (e.g., due to hepatic encephalopathy, trauma, or epilepsy)

Pharmacology & Mechanism of Action

Drug Class: Anticonvulsant | Pharmacological Group: Pyrrolidine derivative

Mechanism of Action: Levetiracetam is a second-generation antiepileptic drug with a unique mechanism of action. It binds to synaptic vesicle protein 2A (SV2A), which is involved in neurotransmitter release, thereby modulating synaptic transmission and reducing neuronal hyperexcitability. It also inhibits high-voltage-activated calcium currents and reduces the release of excitatory neurotransmitters, contributing to its anticonvulsant effects. Unlike many other antiepileptics, it does not affect GABAergic or glutamatergic receptors directly.

Pharmacodynamics: Levetiracetam exhibits broad-spectrum anticonvulsant activity in animal models of epilepsy, including both partial and generalized seizures. It has a rapid onset of action and is effective in reducing seizure frequency and severity. It does not produce significant sedation or cognitive impairment at therapeutic doses, making it a favorable choice for long-term management. Its antiepileptogenic properties may also help in preventing the development of epilepsy after brain injury.

⚡ Pharmacokinetics Summary

Absorption: Levetiracetam is rapidly and almost completely absorbed after oral administration in most species. In dogs, oral bioavailability is approximately 100%. Peak plasma concentrations are reached within 1-2 hours in dogs and cats. Food does not significantly affect absorption.

Distribution: Levetiracetam has a small volume of distribution (approximately 0.5-0.7 L/kg in dogs) and is minimally bound to plasma proteins (<10%). It crosses the blood-brain barrier readily, achieving cerebrospinal fluid concentrations similar to plasma. It also distributes into other tissues, including the placenta and milk.

Metabolism: In humans, levetiracetam is not extensively metabolized; the primary metabolic pathway is hydrolysis of the acetamide group to an inactive carboxylic acid metabolite (ucb L057). In dogs, metabolism is more extensive, with about 50% of the drug being metabolized, but the primary pathway is also hydrolysis. In cats, metabolism is similar to dogs. The enzyme responsible is not CYP450-dependent, so drug interactions are less likely.

Excretion: Levetiracetam and its metabolites are primarily excreted renally. In dogs, approximately 50% of the dose is excreted unchanged in urine, and the remainder as metabolites. In cats, renal excretion is also the main route. Clearance is proportional to renal function, and dose adjustments are necessary in animals with renal impairment.

Half-Life: Dog: 3-6 hours; Cat: 2-4 hours; Horse: 2-3 hours; Cattle: 2-4 hours (estimated); Rabbit: 2-3 hours (estimated); Birds: 2-4 hours (estimated).

Bioavailability: Oral bioavailability is nearly 100% in dogs and cats; in horses, it is approximately 100% as well.

Protein Binding: <10% in most species

Available Formulations & Strengths

Oral Tablet 250 mg, 500 mg, 750 mg, 1000 mg (PO)

Oral Solution 100 mg/mL (PO)

Injectable Solution 100 mg/mL (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to levetiracetam or any component of the formulation
Severe renal impairment (dose adjustment required, but not contraindicated if adjusted)
Use in animals with known hypersensitivity to pyrrolidone derivatives

Warnings & Clinical Precautions:

Use with caution in animals with renal impairment; dose adjustment is necessary.
Abrupt withdrawal may precipitate withdrawal seizures; taper dose gradually.
May cause sedation or behavioral changes, especially at higher doses.
Safety in pregnant or lactating animals has not been established; use only if clearly needed.
In food animals, observe withdrawal times; not approved for use in food animals in many countries.
Monitor for signs of behavioral changes (e.g., agitation, aggression) in some animals.

Adverse Effects & Reactions

Common:

Sedation
Ataxia
Vomiting
Diarrhea
Decreased appetite

Serious / Severe:

Behavioral changes (aggression, anxiety)
Pancreatitis (rare)
Renal toxicity (with overdose)
Bone marrow suppression (rare)

Rare:

Hypersensitivity reactions
Hepatotoxicity
Blood dyscrasias

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other anticonvulsants (e.g., phenobarbital, potassium bromide)	Additive sedation and possible synergistic anticonvulsant effects; monitor for excessive CNS depression.	Moderate
Probenecid	May decrease renal excretion of levetiracetam, increasing plasma levels.	Mild
NSAIDs (e.g., carprofen, meloxicam)	Potential for increased risk of gastrointestinal ulceration and bleeding, especially in animals with renal impairment.	Moderate
Cimetidine	May reduce renal clearance of levetiracetam, leading to increased plasma concentrations.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe sedation
Ataxia
Coma
Respiratory depression
Hypotension

Emergency Treatment Protocol: Treatment is primarily supportive. Induce vomiting if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids and symptomatic care. In severe cases, hemodialysis may be considered to enhance elimination. Monitor vital signs and neurological status.

Food Animal Withdrawal Times

🥩 Meat: 0 days🥛 Milk: 0 days🥚 Eggs: 0 days

Levetiracetam is not approved for use in food animals in many countries. If used off-label, withdrawal times should be determined based on regulatory guidelines and pharmacokinetic data. In the US, under AMDUCA, a withdrawal time must be established by a veterinarian; a conservative estimate of at least 5 days for meat and 7 days for milk is often recommended, but this is not officially established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C) in a dry place.

Handling & Special Conditions: Protect from moisture. Keep tablets in original container. Oral solution should be used within the expiration date and not refrigerated unless specified.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, levetiracetam is not FDA-approved for veterinary use, but it can be used legally under the Animal Medicinal Drug Use Clarification Act (AMDUCA) in a valid veterinarian-client-patient relationship. For food animals, a withdrawal time must be established. In the EU, similar extra-label use regulations apply.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Levetiracetam is a valuable anticonvulsant for dogs and cats, particularly for refractory epilepsy. Its favorable safety profile, minimal drug interactions, and lack of hepatic metabolism make it a good choice for animals with liver disease or those on multiple medications. It is often used as an add-on to phenobarbital or potassium bromide. Dosing is typically every 8 hours due to its short half-life. In dogs, therapeutic monitoring is not routinely required, but trough levels can be measured (target 5-45 µg/mL). In cats, similar dosing is used. For acute seizure control, IV formulation can be used. In horses, it is used for seizures associated with hepatic encephalopathy or other causes. Always taper the dose gradually to avoid withdrawal seizures. In food animals, extra-label use is limited and withdrawal times must be considered.

References & Literature

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