ZARONTIN- ethosuximide solution
Parke-Davis Div of Pfizer Inc
DESCRIPTION
Zarontin (ethosuximide) is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide.
Each teaspoonful (5 mL), for oral administration, contains 250 mg ethosuximide, USP. Also contains citric acid, anhydrous, USP; FD&C red No. 40; FD&C yellow No. 6; flavor; glycerin, USP; purified water, USP; saccharin sodium, USP; sodium benzoate, NF; sodium citrate, USP; sucrose, NF.
Each ethosuximide capsule for oral administration contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol. The capsule contains FD&C yellow No. 6, gelatin, glycerin, and purified water.
CLINICAL PHARMACOLOGY
Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.
Zarontin Indications and Usage
Zarontin is indicated for the control of absence (petit mal) epilepsy.
CONTRAINDICATIONS
Ethosuximide should not be used in patients with a history of hypersensitivity to succinimides.
WARNINGS
Blood dyscrasias
Blood dyscrasias, including some with fatal outcome, have been reported to be associated with the use of ethosuximide; therefore, periodic blood counts should be performed. Should signs and/or symptoms of infection (e.g., sore throat, fever) develop, blood counts should be considered at that point.
Effects on Liver and Kidneys
Ethosuximide is capable of producing morphological and functional changes in the animal liver. In humans, abnormal liver and renal function studies have been reported. Ethosuximide should be administered with extreme caution to patients with known liver or renal disease. Periodic urinalysis and liver function studies are advised for all patients receiving the drug.
Systemic Lupus Erythematosus
Cases of systemic lupus erythematosus have been reported with the use of ethosuximide. The physician should be alert to this possibility.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Zarontin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
DOSAGE AND ADMINISTRATION
Zarontin is administered by the oral route. The initial dose for patients 3 to 6 years of age is one teaspoonful (250 mg) per day; for patients 6 years of age and older, 2 teaspoonfuls (500 mg) per day. The dose thereafter must be individualized according to the patient's response. Dosage should be increased by small increments. One useful method is to increase the daily dose by 250 mg every four to seven days until control is achieved with minimal side effects. Dosages exceeding 1.5 g daily, in divided doses, should be administered only under the strictest supervision of the physician. The optimal dose for most pediatric patients is 20 mg/kg/day. This dose has given average plasma levels within the accepted therapeutic range of 40 to 100 mcg/mL. Subsequent dose schedules can be based on effectiveness and plasma level determinations.
Ethosuximide is administered by the oral route. The initial dose for patients 3 to 6 years of age is one capsule (250 mg) per day; for patients 6 years of age and older, 2 capsules (500 mg) per day. The dose thereafter must be individualized according to the patient's response. Dosage should be increased by small increments. One useful method is to increase the daily dose by 250 mg every four to seven days until control is achieved with minimal side effects. Dosages exceeding 1.5 g daily, in divided doses, should be administered only under the strictest supervision of the physician. The optimal dose for most pediatric patients is 20 mg/kg/day. This dose has given average plasma levels within the accepted therapeutic range of 40 to 100 mcg/mL. Subsequent dose schedules can be based on effectiveness and plasma level determinations.
Ethosuximide may be administered in combination with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal). The optimal dose for most pediatric patients is 20 mg/kg/day
Zarontin may be administered in combination with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal). The optimal dose for most pediatric patients is 20 mg/kg/day.