Class
- Antiepileptic drug (AED)
Primidone
Commonly Prescribed for
(FDA approved in bold)
- Generalized tonic-clonic, psychomotor, and partial seizures (monotherapy and adjunctive, children and adults)
- Essential tremor
- Long QT syndrome
- Psychosis
Primidone
How the Drug Works
- Primidone and its 2 metabolites (phenobarbital and phenylethylmalonamide) raise seizure thresholds or alter seizure patterns
- The exact mechanism of action is unknown but likely enhances GABA-A receptor activity
- Depresses glutamate excitability, alters sodium, calcium and potassium channel conductance
Primidone
How Long Until It Works
- Seizures – should decrease by 2 weeks
- Essential tremor – should improve tremors in 1–2 weeks
Primidone
If It Works
- Seizures – goal is the remission of seizures. Continue as long as effective and well-tolerated. Consider tapering and slowly stopping after 2 years without seizures, depending on the type of epilepsy
- Essential tremors – tremors improve but usually do not remit. Use lowest effective dose
Primidone
If It Doesn’t Work
- Increase to highest tolerated dose
- Epilepsy: consider changing to another agent, adding a second agent or referral for epilepsy surgery evaluation. When adding a second agent, keep in mind drug interactions
Primidone
Best Augmenting Combos for Partial Response or Treatment-Resistance
- Epilepsy: drug interactions complicate multi-drug therapy. Primidone itself is a second-line agent in developed countries due to AE profile
Primidone
Tests
- CBC, hepatic and kidney function panels at baseline and every 6 months
Adverse Effects (AEs)
Primidone
How Drug Causes AEs
- CNS AEs are probably caused by effects of increased GABA activity and alteration of ion channel function
- Vitamin D deficiency is caused by induction of metabolism
Primidone
Notable AEs
- Ataxia, vertigo, sedation, nystagmus, diplopia
- Nausea, vomiting, anorexia
- Irritability, emotional disturbances, confusion, rash
- 20–25% of patients experience an idiosyncratic reaction with nausea and drowsiness and even obtundation – often on the first dose
Primidone
Life-Threatening or Dangerous AEs
- Megaloblastic anemia, rarely agranulocytosis
- Respiratory depression: use with caution in patients with asthma or pulmonary disease
Primidone
Weight Gain
- Common
Primidone
Sedation
- Problematic
Primidone
What to Do About AEs
- A small dose decrease may improve CNS AEs
- Do not take the first dose of medication alone, due to risk of idiosyncratic reaction
- Megaloblastic anemia: treat with folate
Primidone
Best Augmenting Agents for AEs
- No treatment for most AEs other than lowering dose or stopping drug
