primidone
Mysoline

Available forms
Available by prescription only
Suspension: 250 mg/5 ml
Tablets: 50 mg, 250 mg

Indications and dosages
 Generalized tonic-clonic seizures, focal seizures, complex-partial (psychomotor) seizures. Adults and children age 8 and older: 100 to 125 mg P.O. h.s. on days 1 to 3; 100 to 125 mg P.O. b.i.d. on days 4 to 6; 100 to 125 mg P.O. t.i.d. on days 7 to 9; and maintenance dose of 250 mg P.O. t.i.d. on day 10. May need up to 2 g daily.
Children younger than age 8: 50 mg P.O. h.s. on days 1 to 3; 50 mg P.O. b.i.d. on days 4 to 6; 100 mg P.O. t.i.d. on days 7 to 9; and maintenance dose of 125 to 250 mg P.O. t.i.d. on day 10.
 Benign familial tremor (essential tremor). Adults: 750 mg P.O. daily.

Pharmacodynamics
Anticonvulsant action: Mechanism unknown. Acts as a nonspecific CNS depressant used alone or with other anticonvulsants to control refractory tonic-clonic seizures and to treat psychomotor or focal seizures. Some activity may be from phenobarbital, an active metabolite.

Pharmacokinetics
Absorption: Drug absorbed readily from GI tract. Phenobarbital appears in plasma after several days of continuous therapy; most laboratory assays detect both phenobarbital and primidone. Therapeutic levels 5 to 12 mcg/ml for primidone; 10 to 30 mcg/ml for phenobarbital.
Distribution: Primidone distributed widely throughout body.
Metabolism: Primidone metabolized slowly by liver to phenylethylmalonamide (PEMA) and phenobarbital; PEMA is major metabolite.
Excretion: Primidone excreted in urine; substantial amounts appear in breast milk.

Contraindications and precautions
Contraindicated in patients with phenobarbital hypersensitivity or porphyria.

Interactions
Drug-drug. Acetazolamide, succinimides: Decreases primidone levels. Monitor patient closely.
Carbamazepine, phenytoin: May decrease effects of primidone; increases conversion to phenobarbital. Monitor serum levels to prevent toxicity.
CNS depressants (such as narcotic analgesics): Causes excessive depression in patients taking primidone. Avoid using together.
Hormonal contraceptives: Barbiturates may render hormonal contraceptives ineffective. Advise patient to consider a different contraceptive method.
Drug-lifestyle. Alcohol use: Causes excessive depression in patients taking primidone. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, ataxia, emotional disturbances, vertigo, hyperirritability, fatigue, paranoia.
EENT: diplopia, nystagmus.
GI: anorexia, nausea, vomiting.
GU: impotence, polyuria.
Hematologic: megaloblastic anemia, thrombocytopenia.
Skin: morbilliform rash.

Effects on lab test results
• May decrease hemoglobin, hematocrit, and platelet count. May increase or decrease liver function test values.

Overdose and treatment
Signs and symptoms of toxicity resemble those of barbiturate intoxication, including CNS and respiratory depression, areflexia, oliguria, tachycardia, hypotension, hypothermia, and coma. Shock may occur.
 Treat overdose supportively: in conscious patient with intact gag reflex, induce emesis with ipecac; follow in 30 minutes with repeated doses of activated charcoal. Use lavage if emesis isn’t feasible. Alkalinization of urine and forced diuresis may hasten excretion. Hemodialysis may be needed. Monitor vital signs and fluid and electrolyte balance.

Special considerations
• Abrupt withdrawal of drug may cause status epilepticus; reduce dosage gradually.
• Barbiturates impair ability to perform tasks requiring mental alertness such as driving.
• Perform a CBC and liver function tests every 6 months.
Breast-feeding patients
• Considerable amounts of drug appear in breast milk. Women should use an alternative to breast-feeding during therapy.
Pediatric patients
• Drug may cause hyperexcitability in children younger than age 6.
Geriatric patients
• Reduce dosage in elderly patients; many have decreased renal function.

Patient education
• Explain rationale for therapy and potential risks and benefits.
• Teach patient signs and symptoms of adverse reactions.
• Tell patient to avoid alcohol and other sedatives to prevent added CNS depression.
• Instruct patient not to stop drug or to alter dosage without medical approval.
• Advise patient to avoid hazardous tasks that require mental alertness until degree of sedative effect is determined. Tell patient that dizziness and incoordination are common at first but will disappear.
• Recommend that patient wear a medical identification bracelet or necklace identifying him as having a seizure disorder and listing drug.
• Tell patient to shake oral suspension well before use.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use