Primidone
5-ethyldihydro-5-phenyl-4,6(1H,5H)-pyrimidinedione
Also known as: Mysoline · Neurosyn · hexamidinum · primaclone · primidonum · Cyral · Epidona · Liskantin · Mylepsinum · Prysoline · Resimatil · Sertan
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 |
|---|---|---|---|---|---|
| Seizure control | 10-30 mg/kg per day divided into 2-3 doses | PO | divided into 2-3 doses | — | 🌎 NA |
| Seizure control | 10 mg/kg | PO | q8h | — | 🌎 NA |
- Seizure control: Initially
- Seizure control: Not recommended as first choice
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Seizure control | 20 mg/kg | PO | q12h | — | 🌎 NA |
- Seizure control: Extreme caution advised; many consider contraindicated in cats.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Primidone is a barbiturate-derivative anticonvulsant that acts primarily as a prodrug, being rapidly converted into phenobarbital and phenylethylmalonamide (PEMA) in dogs.
While historically used for seizure control (idiopathic epilepsy, epileptiform convulsions) in dogs, most veterinary neurologists no longer recommend its use as a first-line agent.
Clinical Pearl: The increased incidence of severe hepatotoxicity associated with primidone compared to phenobarbital is the major limiting factor for long-term therapy.
In dogs, the conversion rate of primidone to phenobarbital is approximately 4:1 (a 250 mg dose of primidone is roughly equivalent to 60 mg of phenobarbital). Some clinicians reserve primidone for refractory cases where phenobarbital alone is insufficient, theorizing that the PEMA metabolite may potentiate phenobarbital's anticonvulsant activity. It is considered highly toxic to cats and rabbits.
Mechanism of action
Primidone and its active metabolites, phenylethylmalonamide (PEMA) and phenobarbital, exert anticonvulsant effects by raising seizure thresholds and altering seizure patterns.
Mechanistic Pathway:
- Phenobarbital (Primary active metabolite): Binds to the allosteric barbiturate site on GABA_A receptors in the CNS → prolongs the duration of chloride channel opening → increases intracellular chloride influx → hyperpolarizes the postsynaptic neuron → globally depresses CNS excitability and raises the seizure threshold.
- PEMA: Has weak intrinsic anticonvulsant activity but is believed to synergistically potentiate the effects of phenobarbital.
- Primidone (Parent drug): May have some independent action on voltage-gated sodium channels, though its primary efficacy in veterinary species is attributed to its phenobarbital metabolite.
Safety & warnings
Contraindications
- Severe liver disease
- Demonstrated previous hypersensitivity to primidone or barbiturates
- Nephritis (large doses contraindicated)
- Severe respiratory dysfunction (large doses contraindicated)
- Cats (considered contraindicated by many clinicians due to high toxicity risk)
Adverse effects
- Anxiety and agitation (especially during initiation)
- Elevated liver enzymes (ALT, ALP, GLDH)
- Decreased serum albumin
- Hepatic lipidosis
- Hepatocellular hypertrophy and necrosis
- Extramedullary hematopoiesis
- Depression and sedation
- Ataxia
- Polydipsia (PD)
- Polyuria (PU)
- Polyphagia
- Anorexia
- Tachycardia
- Dermatitis
- Episodic hyperventilation
- Urolith formation (primidone uroliths reported)
- Megaloblastic anemia (rare)
Precautions
Species Warnings: Use with extreme caution, if at all, in cats. Primidone is considered highly toxic to felines.
Patient Conditions: Use cautiously in patients who are hypovolemic, anemic, have borderline hypoadrenal function, or have cardiac or respiratory disease.
Drug Transition: When converting dogs from primidone to phenobarbital, it is suggested to do this slowly (tapering 1/4 of the dose each month) to prevent withdrawal seizures.
Laboratory Interference: Barbiturates may cause falsely elevated bromosulfophthalein (BSP) retention. Primidone/phenobarbital can alter thyroid testing (decreased total and free T4, normal T3, normal/increased TSH); wait at least 4 weeks after discontinuation to perform thyroid testing. May cause a false-positive low-dose dexamethasone suppression test.
Drug interactions
Increased risk for hepatotoxicity, particularly with large or chronic doses of barbiturates.
Oral administration may decrease the GI absorption of primidone.
May prolong phenobarbital effects.
Barbiturates may affect phenytoin metabolism, and phenytoin may alter barbiturate levels; therapeutic monitoring indicated.
May induce enzymes that increase the metabolism of barbiturates.
May increase the CNS depressant effects of phenobarbital.
May increase the effects of phenobarbital; phenobarbital may also decrease chloramphenicol levels.
May increase the CNS depressant effects of phenobarbital.
May increase the effects of phenobarbital; phenobarbital may decrease phenothiazine serum concentrations.
May increase the effects of phenobarbital.
Phenobarbital may decrease anticoagulant effects by lowering serum concentrations.
Phenobarbital may decrease effects by lowering serum concentrations.
Phenobarbital may decrease effects by lowering serum concentrations.
Phenobarbital may decrease effects by lowering serum concentrations.
Phenobarbital may decrease effects by lowering serum concentrations (effect may persist for weeks after barbiturate is discontinued).
Phenobarbital may decrease effects by lowering serum concentrations.
Monitoring
- Anticonvulsant efficacy (seizure frequency and severity)
- Adverse effects (CNS depression, PU/PD, weight gain, signs of liver disease)
- Serum phenobarbital levels (therapeutic range in dogs thought to be 15-40 mcg/mL) if lack of efficacy or adverse reactions are noted
- Routine CBCs and liver enzyme panels at least every 6 months during chronic therapy
Pharmacokinetics
Half-life
Absorption
Slowly absorbed after oral administration in the dog, with peak levels occurring 2-4 hours after dosing. Bioavailability in humans is reported as 60-80%.
Distribution
Appears in maternal milk in substantial quantities.
Metabolism
Rapidly converted to phenylethylmalonamide (PEMA) and phenobarbital in the dog. Induces hepatic microsomal enzymes, increasing the rate of metabolism of itself and other drugs.
Elimination
Eliminated primarily via hepatic metabolism to active metabolites, which are subsequently cleared.
Overdose
Clinical Signs: Because primidone is rapidly metabolized to phenobarbital in dogs, signs of acute toxicity mirror barbiturate overdose: sedation progressing to coma, anorexia, vomiting, ataxia, and nystagmus.
Treatment:
- Decontamination: Removal of ingested product from the gut if appropriate (emesis or gastric lavage).
- Adsorbents: Activated charcoal is of considerable benefit in enhancing the clearance of phenobarbital (acts as a 'sink' for the drug to diffuse from the vasculature back into the gut), even if the drug was administered parenterally.
- Supportive Care: Provide respiratory and cardiovascular support.
- Enhanced Elimination: Forced alkaline diuresis can 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
- Oral suspension
Veterinary
- Primidone Tablets: 50 mg and 250 mg (Neurosyn®)
Human-labeled
- Primidone Tablets: 50 mg and 250 mg (Mysoline®, generic)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Tablets should be stored in well-closed containers, preferably at room temperature. Oral suspension should be stored in tight, light-resistant containers at room temperature; avoid freezing. Commercially available products generally have a 5-year expiration date.
Client information
Crucial for Success: Strict compliance with therapy is essential for successful epilepsy treatment. Give the medication at the exact same times each day.
- Behavioral Changes: Your dog may seem anxious, agitated, or unusually sleepy when starting this medication. These effects are often temporary and may resolve as their body adjusts.
- Increased Thirst/Appetite: You may notice your pet drinking, urinating, and eating more than usual. Monitor their weight and discuss diet management with your veterinarian.
- When to Call the Vet: Contact your veterinarian immediately if your pet develops severe lethargy, loss of appetite, vomiting, yellowing of the eyes/gums (jaundice), pale gums, or if seizures are not well controlled.
- Do Not Stop Abruptly: Never stop giving this medication suddenly without veterinary guidance, as this can trigger severe, life-threatening seizures.
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.