Primidone (Mysoline, Wyeth-Ayerst)
Primidone (Mysoline) is an older antiepileptic medication with similarity to phenobarbital. Primidone is itself an active antiepileptic drug. It is metabolized to phenobarbital (long-lasting) and PEMA (phenyl-ethyl-malonic acid, short-acting), two additional antiepileptic drugs.
Mysoline is useful for partial seizures with or without secondary generalization. It may be better than is phenobarbital for myoclonic seizures, such as juvenile myoclonic epilepsy. In another arena, primidone is used to reduce hand and head tremor.
In the VA Cooperative Study of Antiepileptic Drugs, primidone exceeded the ability of phenytoin, carbamazepine and phenobarbital to control secondarily generalized tonic-clonic (grand mal) seizures, provided that the patient did not discontinue Mysoline because of sleepiness.
The limiting factor in primidone use is sedation. Primidone also has all of the side effects of phenobarbital, because it is metabolized to phenobarbital. Most patients should try a single test-dose of primidone 50 mg to see if they have an excessive degree of sedation. If they do not, then they can progress to the 250 mg pills.
Discontinuation of primidone can be very difficult. Primidone is a habit-forming drug, with withdrawal symptoms of seizures, anxiety, insomnia, and tremor. Unless side effects mandate rapid withdrawal, tapering should be very slow, over an interval of many months, using the 50 mg pills to decrease slowly.
Summary Data for Primidone
Pill sizes:
50 mg (square tab, grey, scored)
250 mg (square tab, yellow, scored)
Liquid for oral: None.
Injectable: None, but can substitute phenobarbital if unable to take primidone. The conversion is 10-to-1: 250 mg of primidone for 25 mg of phenobarbital.
Typical adult dose: 50 mg test dose to check for excessive sleepiness. If OK, then 125 mg at night for 3 - 7 days, then increase by 125 mg every 3 - 7 days to target dose of 750 - 2,000 mg/d in divided doses of 3 - 4 times per day.
Typical pediatric dose: 10 - 25 mg/kg/d in 3 divided doses.
Metabolism: half excreted unchanged in the kidney and half metabolized in the liver to PEMA and phenobarbital.
Half-life: primidone 8 - 24 hrs; PEMA 10 - 24 hrs; phenobarbital metabolite 2 - 5 days.
Serum levels: primidone 5 - 12 mcg/ml; phenobarbital 15-40 mcg/ml.
Pregnancy: Category D - can cause birth defects in humans.
Drugs that raise PRM levels: Valproate, Felbamate, INH.
Drugs that lower PRM levels: phenobarbital, Dilantin, Tegretol.
PRM increases effects of: acetaminophen, antidepressants, antipsychotics, antihistamines, benzodiazepines, opiates.
PRM decreases effects of other drugs: buproprion, buspirone, corticosteroids, Coumadin (interaction lowers INR, increases clotting), cyclosporine, doxyrubicin, lamotrigine, oral contraceptives, oxcarbazepine, phenytoin, protease inhibitors, quinidine, theophylline, thyroid hormone, topiramate, zonisamide; inactivates oral contraceptives.
Dangerous Side Effects (similar to phenobarbital, but more sedation)
Severe depression, suicide, Stevens-Johnson rash, blood count suppression, liver injury, worsening of porphyria, addiction, birth defects; rare worsening of seizures with toxic doses.
Commonest Side Effects
Sleepiness, fatigue, cognitive impairment, depression, hyperactivity in children and elderly.
Other Side Effects
Sedation, depression, cognitive impairment, attention deficit, hyperactivity, behavior and personality changes, dizziness, sexual dysfunction, rash or itching, sensitivity to the sun, anemia, nausea, vomiting, connective tissue growth (frozen shoulder, hand contractions), bone weakening, neuropathy-numbness, inactivates birth control pills.