EBM Consult

Primidone (Mysoline): Drug Monograph

    Brand Names
    • Mysoline
    Drug Class
    • Anticonvulsant
    Indications
    • Control of grand mal, psychomotor, and focal epileptic seizures, alone or with other anticonvulsants
    • May control grand mal seizures refractory to other anticonvulsant therapy
    Dosing (Adult)
    • No prior antiepileptic therapy:
      • Days 1-3: 100-125 mg at bedtime
      • Days 4-6: 100-125 mg twice daily
      • Days 7-9: 100-125 mg three times a day 
      • Days 10/maintenance: 250 mg three times a day 
      • Usual maintenance: 250 mg three or four times a day 
      • Maximum: 500 mg four times a day 
    • Already receiving other anticonvulsants:  
      • 100 to 125 mg at bedtime 
      • Increase gradually to maintenance dose as other drug is gradually decreased. Continue until satisfactory dosage level achieved or other medication is completely withdrawn. When therapy with primidone alone is the objective, transition from concomitant therapy should not be completed in <2 weeks
      • Maximum: 2 g/day
    Dosing (Pediatric)
    • Grand mal, psychomotor, and focal epileptic seizures (alone or with other anticonvulsants), <8 years:
      • Days 1-3: 50 mg at bedtime
      • Days 4-6: 50 mg twice daily
      • Days 7-9: 100 mg twice daily
      • Days 10/maintenance: 125-250 mg three times a day 
      • Usual maintenance: 125-25- mg three or 10-25 mg/kg/day in divided doses
    • ≥8 years, no prior antiepileptic therapy:
      • Days 1-3: 100-125 mg at bedtime
      • Days 4-6: 100-125 mg twice daily
      • Days 7-9: 100-125 mg three times a day
      • Days 10/maintenance: 250 mg three times a day
      • Usual maintenance: 250 mg three or four times a day
      • Maximum: 500 mg four times a day
    • Already receiving other anticonvulsants:
      • 100-125 mg at bedtime
      • Increase gradually to maintenance dose as other drug is gradually decreased. Continue until satisfactory dosage level achieved or other medication is completely withdrawn. When therapy with primidone alone is the objective, transition from concomitant therapy should not be completed in <2 weeks. 
      • Maximum: 2 g/day
    Renal Dosing
    • None (per manufacturer)
    • Other experts have suggested:
      • CrCL ≥ 50 mL/min = give every 12 h
      • CrCl 10 to 50 mL/min = give every 12 to 24 h
      • CrCl < 10 mL/min = give every 24 h
    Hepatic Dosing
    • None
    Dosage Forms
    • Tablets:  50 mg, 250 mg
    Black Box Warnings
    • None
    Contraindications
    • Porphyria
    • Hypersensitivity to phenobarbital
    Warnings
    • Abrupt withdrawal of antiepileptic medication may precipitate status epilepticus.
    • Suicidal behavior and ideation
    Adverse Reactions
    • Ataxia
    • Vertigo
    • Occasionally:  nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions. 
    • Rarely:  granulocytopenia, agranulocytosis, and redcell hypoplasia and aplasia
    Overdose
    • None
    Antidote
    • None
    Drug Interactions
    • None
    Special Populations
    • Pregnancy: Total daily dosage should not exceed 2 g. Complete blood count and a sequential multiple analysis-12 (SMA-12) test every 6 months. Effects of primidone in human pregnancy is unknown  
    • Labor and Delivery: None
    • Nursing Mothers: Primidone appears in breast milk in substantial quantities.  Nursing should be discontinued.  
    • Renal Impairment: None
    • Hepatic Impairment: None
    • Pediatric Patients: None
    • Geriatric Patients: None
    Pregnancy Rating
    • None
    Breasfeeding
    • Primidone appears in breast milk in substantial quantities.  Nursing should be discontinued.
    Chemical Structure

    • Scientific Name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H) pyrimidinedione
    • Empirical Formula: C12H14N2O2
    • Molecular Weight:  218.25

    Mechanism of Action
    • Primidone raises electro- or chemoshock seizure thresholds or alters seizure patterns in experimental animals. The mechanism(s) of primidone's antiepileptic action is not known. Primidone per se has anticonvulsant activity as do its two metabolites, phenobarbital and phenylethylmalonamide (PEMA). In addition to its anticonvulsant activity, PEMA potentiates the anticonvulsant activity of phenobarbital in experimental animals.
    Pharmacodynamics
    • None
    Pharmacokinetics
    • Absorption: > 90%
    • Distribution: Vd 0.6 to 0.75 L/kg;  Found in breast milk 
    • Metabolism: Phenobarbital, phenylethylmalonamide (metabolites)
    • Elimination: Urine by 15% to 65% as unchanged drug
    Counseling Points
    • Patients, their caregivers, and families should be counseled that primidone may increase the risk of suicidal thoughts and behavior. Symptoms of depressions may include any unusual changes in mood or behavior, the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to health care providers.  
    • Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant.
    References
    • Primidone (Mysoline).  Product Insert.  Valeant Pharmaceuticals N.A.  Aliso Viejo, CA.  2009.

MESH Terms & Keywords

  • Primidone, Mysoline, Anticonvulsant