THERAPEUTICS

Brands

• Mysoline

Generic?

• Yes

Class

• Antiepileptic drug (AED)

Commonly Prescribed for

(FDA approved in bold)

• Generalized tonic-clonic, psychomotor, and partial seizures (monotherapy and adjunctive, children and adults)

• Essential tremor

• Psychosis

How the Drug Works

• Primidone and its 2 metabolites (phenobarbital and phenylethylmalonamide [PEMA]) raise seizure thresholds or alter seizure patterns

• The exact mechanism of action is unknown but likely enhances GABAA receptor activity

• Depresses glutamate excitability, alters sodium, calcium, and potassium channel conductance

How Long Until It Works

• Seizures: should decrease by 2 weeks

• Essential tremor: should improve tremors in 1–2 weeks

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

If It Doesn’t Work

• Increase to highest tolerated dose

• Epilepsy: consider changing to another agent, adding a second agent, using a medical device, or a referral for epilepsy surgery evaluation. When adding a second agent, keep drug interactions in mind

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

Tests

• CBC, hepatic and kidney function panels at baseline and every 6 months

ADVERSE EFFECTS (AEs)

How the 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

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

Life-Threatening or Dangerous AEs

• Megaloblastic anemia, rarely agranulocytosis

• Respiratory depression: use with caution in patients with asthma or pulmonary disease