What are the uses of primidone?

Primidone Uses

Primidone is FDA-approved for controlling grand mal (generalized tonic-clonic), psychomotor (complex partial), and focal epileptic seizures, either as monotherapy or combined with other anticonvulsants, and is particularly valuable for grand mal seizures refractory to other treatments. 1

Primary Indications

Epilepsy/Seizure Disorders

• Grand mal (generalized tonic-clonic) seizures: Primidone is effective as first-line or rescue therapy, particularly when other anticonvulsants have failed 1
• Complex partial (psychomotor) seizures: FDA-approved indication for this seizure type 1
• Focal (partial) epileptic seizures: Approved for controlling localized seizure activity 1
• Refractory neonatal and infant seizures: Primidone at 25 mg/kg/day achieves seizure control within 5 days in 80% of cases (8 of 10 patients), with control by day 3 in 75% (6 of 8 patients) when primidone levels exceed 10 mcg/mL 2

Essential Tremor

• First-line treatment for essential tremor: Despite lacking formal FDA approval for this indication, primidone remains a primary treatment option for essential tremor 3
• Superior efficacy to propranolol: Primidone reduces tremor amplitude by 60% within 1-7 hours of a single 250 mg dose, demonstrating greater tremor suppression than beta-blockers 4
• Effective at low doses: Doses of 50-1,000 mg/day are effective, with low doses performing as well as high doses, though acute reactions to initial dosing cause intolerance in some patients 4
• Rapid onset: Tremor suppression occurs after just 2 doses, correlating with primidone plasma levels rather than its metabolite phenobarbital 5

Important Clinical Considerations

Mechanism and Metabolites

• Primidone is not a prodrug—it has intrinsic anticonvulsant activity independent of its metabolites (phenobarbital and phenylethylmalonamide), though these metabolites contribute to overall therapeutic effect 3
• The conversion rate of primidone to phenobarbital varies significantly between individuals 3
• For essential tremor, therapeutic effect correlates with primidone itself, not phenobarbital levels—substituting phenobarbital for primidone results in loss of tremor control 4

Contraindications

• Absolute contraindication: Patients with porphyria (genetic disorder) 1
• Allergy to phenobarbital: Do not use in patients with known phenobarbital hypersensitivity 1

NOT Recommended

• Febrile seizures in children: The American Academy of Pediatrics does not recommend continuous primidone therapy for febrile seizures, as potential toxicities (behavioral disturbances, irritability, sleep disturbances) outweigh the minor risks of simple febrile seizures, despite primidone's ability to reduce recurrence at 15-20 mg/kg/day 6

Therapeutic Drug Monitoring

• Target therapeutic range: 5-10 mg/L (23-46 mmol/L) for primidone 3
• Always monitor both primidone AND phenobarbital levels due to variable conversion rates 3
• In neonates/infants, seizure control correlates best with primidone and phenylethylmalonamide levels, not phenobarbital levels 2
• The evidence for routine therapeutic drug monitoring of primidone is considered "probably useless" for most patients, though phenobarbital monitoring is "recommended" 3

Critical Safety Warnings

• Suicidal ideation risk: Like all antiepileptic drugs, primidone carries a 1 in 500 risk of suicidal thoughts or actions—monitor for new or worsening depression, anxiety, agitation, or behavioral changes 1
• Never stop abruptly: Sudden discontinuation can precipitate status epilepticus (continuous seizures) in epilepsy patients 1
• Severe sedation: Especially during initial treatment phases 1
• Rare blood disorders: Monitor for hematologic abnormalities 1
• Pregnancy: May harm the fetus—discuss risks/benefits and consider enrollment in the NAAED Pregnancy Registry (1-888-233-2334) 1