Mysoline (primidone) is an established anticonvulsant medication indicated for the control of grand mal, psychomotor, and focal epileptic seizures. As a barbiturate derivative, it exerts its therapeutic effect by decreasing abnormal electrical activity in the brain, thereby stabilizing neuronal membranes and raising the seizure threshold. Its long-standing presence in neurological therapeutics provides clinicians with a well-understood profile for managing certain seizure disorders, particularly when other first-line treatments are unsuitable or ineffective. This product card provides a comprehensive overview for healthcare professionals considering its prescription.

Features

• Active Pharmaceutical Ingredient: Primidone
• Pharmacologic Class: Anticonvulsant, Barbiturate derivative
• Available Formulations: Scored, oral tablets (50 mg and 250 mg)
• Mechanism of Action: Raises the seizure threshold by decreasing neuron excitability; metabolized to phenobarbital and phenylethylmalonamide (PEMA), which contribute to its anticonvulsant activity
• Prescription Status: Available by prescription only

Benefits

• Provides effective prophylaxis and reduction in the frequency and severity of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.
• Offers a therapeutic option with a well-documented efficacy and safety profile developed over decades of clinical use.
• The active metabolites, phenobarbital and PEMA, contribute to a sustained anticonvulsant effect, potentially supporting stable 24-hour seizure control.
• Serves as a valuable alternative or adjunctive therapy for patients who have not achieved adequate control with other antiepileptic drugs.
• The scored tablet formulation allows for dosage flexibility to tailor treatment to individual patient response and tolerability.

Common use

Mysoline is primarily approved for the treatment of epilepsy. Its main indications include the control of grand mal (tonic-clonic), psychomotor (complex partial), and focal seizures. It may be used as monotherapy or as part of a combination antiepileptic drug regimen. Its use is determined by a neurologist or other physician specializing in seizure disorders, based on seizure type, patient history, and response to previous therapies. It is not indicated for absence (petit mal) seizures.

Dosage and direction

Dosage must be individualized for each patient based on clinical response and tolerability. Therapy is typically initiated at a low dose to minimize initial side effects and gradually titrated upward.

Adults and children over 8 years:

• Week 1: 100 to 125 mg at bedtime.
• Week 2: 100 to 125 mg twice daily.
• Week 3: 100 to 125 mg three times daily.
• Week 4: 250 mg three times daily.
• Usual Maintenance Dose: 250 mg three or four times daily. Doses may be increased to a maximum of 2 g daily in divided doses, if necessary and tolerated.

Children under 8 years:

• Week 1: 50 mg at bedtime.
• Week 2: 50 mg twice daily.
• Week 3: 100 mg twice daily.
• Week 4: 125 mg to 250 mg three times daily.
• Usual Maintenance Dose: 125 mg to 250 mg three times daily or 10 to 25 mg/kg/day in divided doses.

Administration: Tablets should be swallowed whole with a full glass of water. It can be taken with or without food, but consistency in administration relative to meals is advised to maintain stable plasma levels. Dosage adjustments should only be made under the direct supervision of the prescribing physician.

Precautions

• Hematologic Effects: Periodic evaluation of blood counts is recommended during prolonged therapy due to the risk of megaloblastic anemia, which may respond to folic acid therapy.
• Hepatic and Renal Impairment: Use with caution and possibly at reduced dosages in patients with significant hepatic or renal disease, as metabolism and excretion may be impaired.
• Suicidal Thoughts and Behavior: Antiepileptic drugs, including Mysoline, increase the risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be alerted to and monitor for the emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm.
• Pregnancy and Lactation: Mysoline is Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). It is excreted in breast milk and may cause drowsiness in the infant. The risk-benefit ratio must be carefully considered.
• Elderly Patients: Elderly patients may be more sensitive to the sedative effects and may exhibit excitement or confusion in place of sedation. Lower initial doses and slower titration are advised.
• Abrupt Withdrawal: Abrupt discontinuation of Mysoline may precipitate status epilepticus. Dosage should be withdrawn gradually unless safety concerns require immediate discontinuation.

Contraindications

Mysoline is contraindicated in patients with:

• Known hypersensitivity to primidone or any component of the formulation.
• Known hypersensitivity to phenobarbital (a major metabolite).
• Porphyria.
• Severe respiratory depression with hypoxia and/or CO2 retention.
• Severe hepatic impairment.

Possible side effect

Patients should be advised that many side effects, particularly drowsiness, vertigo, and ataxia, are most common during the initial phase of therapy and often diminish with continued treatment.

• Very Common (>10%): Ataxia, vertigo, drowsiness, fatigue, nausea, vomiting, anorexia.
• Common (1-10%): Emotional disturbances, diplopia, nystagmus, irritability, hyperkinesia in children.
• Uncommon (<1%): Skin rashes (e.g., maculopapular, morbilliform), sexual impotence, arthralgia, lymphadenopathy, hematologic disorders (leukopenia, thrombocytopenia, megaloblastic anemia).
• Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, systemic lupus erythematosus-like syndrome.

Drug interaction

Mysoline has significant drug interaction potential, primarily due to its metabolism and enzyme-inducing properties.

• CNS Depressants: Concomitant use with alcohol, other barbiturates, sedative-hypnotics, anxiolytics, opioids, or tranquilizers may result in additive CNS depressant effects (e.g., profound sedation, respiratory depression, coma).
• Enzyme Induction: Primidone and its metabolite phenobarbital are potent inducers of hepatic cytochrome P450 enzymes (e.g., CYP3A4). This can significantly increase the metabolism and decrease the efficacy of numerous drugs, including: oral anticoagulants (warfarin), corticosteroids, oral contraceptives and other hormonal contraceptives, tricyclic antidepressants, certain antivirals (e.g., protease inhibitors, non-nucleoside reverse transcriptase inhibitors), certain chemotherapeutic agents, calcium channel blockers, and many other anticonvulsants (e.g., carbamazepine, lamotrigine, valproate, tiagabine, zonisamide).
• Valproic Acid: Valproic acid may inhibit the metabolism of phenobarbital (a metabolite), leading to increased phenobarbital serum levels and potential toxicity.
• Isoniazid: May inhibit the metabolism of primidone, increasing its serum levels.
• Monoamine Oxidase Inhibitors (MAOIs): MAOIs may prolong the effects of primidone due to enzyme inhibition.

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed.
• The patient should not take a double dose to make up for a missed one.
• Maintaining a consistent schedule is critical for stable seizure control.

Overdose

Symptoms: Overdose is primarily characterized by profound CNS depression. Symptoms include coma, severe drowsiness, depressed reflexes, hypothermia, shallow breathing, hypotension, and pulmonary edema. Following large overdoses, pupillary constriction may occur. Management: There is no specific antidote for primidone overdose. Management consists of supportive care, with primary emphasis on maintaining an adequate airway, assisted ventilation, and support of blood pressure. Gastric lavage may be useful if performed soon after ingestion. Forced diuresis and alkalinization of urine may enhance the renal excretion of phenobarbital. Hemodialysis may be beneficial in severe cases, particularly due to the phenobarbital component. Serum levels of primidone and phenobarbital should be monitored.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep the bottle tightly closed.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the packaging.
• Properly dispose of any unused medication.

Disclaimer

This information is intended for educational purposes and as a summary for healthcare professionals. It is not exhaustive and does not contain all available information about this product. It does not constitute medical advice and must not be used for the diagnosis or treatment of any medical condition. A qualified healthcare professional must be consulted for the diagnosis and treatment of any and all medical conditions. The prescribing physician should be consulted for complete and current prescribing information, including boxed warnings, before initiating any therapy.

Reviews

• “Mysoline has been a cornerstone in my practice for managing refractory grand mal seizures. Its predictable pharmacokinetics, once titrated, offer reliable long-term control for a specific patient subset.” – Neurologist, 22 years of experience.
• “While newer agents are often first-line, Mysoline remains a crucial tool. Its cost-effectiveness and established efficacy profile make it a viable option, though its side effect and interaction profile requires vigilant management.” – Clinical Pharmacist Specialist in Neurology.
• “The initial titration period can be challenging for patients due to sedation, but for those who persist, it often provides excellent seizure freedom. Patient education on the transient nature of initial side effects is paramount.” – Epileptologist.
• “We use it cautiously in our elderly population due to the high risk of falls from ataxia and drowsiness. However, at low doses, it can be effective with close monitoring.” – Geriatrician.