Levetiracetam
**Levetiracetam** is a novel, structurally unique anticonvulsant used primarily as an adjunct therapy in veterinary medicine. * **Dogs:** Used as a third-line agent for refractory epilepsy or when phenobarbital or potassium bromide are contraindicated or poorly tolerated. Note that dogs may develop a 'honeymoon effect' where efficacy wanes over time. * **Cats:** Typically used as a second-line add-on when phenobarbital is insufficient, or as monotherapy if phenobarbital is not tolerated. **Clinical Pearl:** Levetiracetam is highly favored for patients with hepatic impairment because it undergoes minimal hepatic metabolism and does not rely on the cytochrome P450 enzyme system. However, its short half-life necessitates frequent (TID) dosing, which can be challenging for pet owners.
Mechanism: The exact mechanism of levetiracetam's antiseizure activity is not fully elucidated, but it is distinct from traditional anticonvulsants (which typically affect GABA or ion channels). * Binds specifically to **Synaptic Vesicle Protein 2A (SV2A)** in the central nervous system. * Binding to **SV2A** → modulates neurotransmitter release into the synaptic cleft → selectively prevents hypersynchronization of epileptiform burst-firing and propagation of seizure activity. * It does **not** affect normal neuronal excitability.
Dosing by species
- As an add-on to phenobarbital treatment for epilepsy · Initially, 20 mg/kg PO three times daily; slowly increase to effect · PO · TID
- As an adjunct to phenobarbital in suspected idiopathic epilepsy · Initially, 20 mg/kg PO three times daily. Monitor as below. If ineffective, increase dose in 20 mg/kg increments. · PO · TID
- As an add-on treatment for epilepsy in dogs refractory to phenobarbital and bromides · 20 mg/kg PO every 8 hours · PO · q8h
- As an add-on treatment for epilepsy in dogs refractory to phenobarbital and/or bromides · 7.1-23.8 mg/kg PO every 8 hours · PO · q8h
- Seizure management · 10-20 mg/kg PO q8h · PO · q8h
- Seizure management · Initially, 20 mg/kg PO q8h. May increase dose in 20 mg/kg increments until efficacy achieved, side effects become apparent, or the drug becomes cost prohibitive. · PO · q8h
- Seizure management · 20 mg/kg PO q8h; may also be given as an IV bolus (20 mg/kg). · PO/IV · q8h
- Single-dose pharmacokinetic study · 60 mg/kg IV bolus dose · IV · Once · Well tolerated and achieves plasma drug concentrations within or above the therapeutic range reported for humans for at least 8 hours.
- For status epilepticus · Initially, lorazepam at 0.2 mg/kg IV once, followed by a bolus IV loading dose of levetiracetam at 60 mg/kg. · IV · Once
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypersensitivity to levetiracetam or any of its components
- Severe renal disease
Adverse effects
- Sedation (most common in dogs)
- Lethargy (most common in cats)
- Decreased appetite (most common in cats)
- Behavior changes
- Gastrointestinal effects
- Sedation (dogs)
- Ataxia (dogs)
- Reduced appetite (cats)
- Hypersalivation (cats)
- Lethargy (cats)
Drug interactions
- NSAIDs (naproxen, ketorolac) · May increase the risk for seizures (reported in humans; veterinary significance unclear).
- Phenobarbital · Significantly increases levetiracetam clearance and reduces its half-life in dogs (from 3.43 hrs to 1.73 hrs); dosage adjustments may be required. · moderate
Monitoring
- Therapeutic drug monitoring (target range 5-45 mcg/mL) approximately one week after starting, then every 6-12 months (primarily to adjust dosage)
- Seizure activity log (frequency, duration, severity)
- Routine CBC and basic metabolic panel every 6 months
- Adverse effects (sedation, lethargy, appetite changes)
- Seizure frequency and severity
- Renal function (BUN, Creatinine, SDMA) especially in older patients
- Therapeutic drug monitoring is rarely required but can be performed
Overdose
Levetiracetam is a relatively safe agent. * **Dogs:** Doses of 1200 mg/kg/day (~20x therapeutic dose) caused only salivation and vomiting. * **Humans:** Doses of 6000 mg/kg caused drowsiness. Other reported effects include depressed consciousness, agitation, aggression, and respiratory depression. * **Treatment:** Basically supportive. The drug can be removed with hemodialysis. Contact an animal poison control center for significant overdoses.
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.