INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ZARONTIN

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ZARONTIN

ZARONTIN (capsules)
ZARONTIN (syrup)

COMPOSITION:
Each Zarontin Capsule and each 5 mL of Zarontin Syrup contains 250 mg ethosuximide as the active ingredient.
Zarontin syrup contains 0,238% m/v sodium benzoate as preservative.

PHARMACOLOGICAL CLASSIFICATION:
A: 2.5 Anti-convulsants including anti-epileptics.

PHARMACOLOGICAL ACTION:
Mechanism of action
Ethosuximide is a succinimide anti-convulsant, chemically designated as alpha-ethyl-alpha-methyl-succinimide.
Ethosuximide suppresses the paroxysmal three-cycle-per-second spike and wave activity associated with lapses of consciousness which are 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.
Pharmacokinetics and metabolism
Ethosuximide is rapidly and completely absorbed from the gastrointestinal tract. It is freely distributed to all body tissues, except fat. There is no significant protein binding. Ethosuximide is extensively metabolized by the liver into inactive hydroxylated products and less than 20% of the parent compound is recovered from urine. The elimination half-life in children ranges from 30 to 36 hours, whereas in adults it ranges from 40 to 60 hours. Steady-state conditions are achieved after approximately 6 days in children and 12 days in adults.
Peak levels in children occur within 3 to 7 hours, whereas in adults within 2 to 4 hours.
Therapeutic serum concentrations are 283-708 micromol/L (40–100 micrograms/mL).

INDICATIONS:
Zarontin is indicated for the control of absence (petit mal) epilepsy.

CONTRA-INDICATIONS:
Hypersensitivity to succinimides or components of these products.

WARNINGS:
Blood dyscrasias, including some with fatal outcome, have been reported; therefore periodic blood counts should be performed.
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 diseases. Periodic urinalysis and liver function studies are advised for all patients receiving the drug.
Cases of systemic lupus erythematosus have been reported with the use of ethosuximide. The physician should be alert to this possibility.

DOSAGE AND DIRECTIONS FOR USE:
Zarontin Capsules:

Initial dose-	3 to 6 years:	1 capsule (250 mg)/day or 15 to 40 mg/kg of body weight a day.
	6 years and older:	2 capsules (500 mg)/day or 15 to 30 mg/kg of body weight a day.

Zarontin Syrup:

Initial dose-	3 to 6 years:	5 mL (250 mg)/day or 15 to 40 mg/kg of body weight a day
	6 years and older:	10 mL (500 mg)/day or 15 to 30 mg/kg of body weight a day.

The dosage must be individualised according to the patient's response. Dosage should be increased by small increments. One useful method is to increase the daily dosage by 250 mg every four to seven days until control is achieved with minimal side-effects. Dosages exceeding 1 g daily for a patient of up to 6 years or 1,5 g daily for an adult, in divided doses, should be administered only under the strictest supervision of the physician.
The optimal dose for most children is 20 mg/kg/day.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side Effects:
Gastrointestinal System: Gastrointestinal symptoms occur frequently and include anorexia, vague gastric upset, nausea and vomiting, cramps, epigastric and abdominal pain, weight loss and diarrhoea.
Haemopoietic System: Haemopoietic complications associated with the administration of ethosuximide have included leucopenia, agranulocytosis, pancytopenia, thrombocytopenia, aplastic anaemia and eosinophilia.
Nervous System: Neurologic and sensory reactions reported during therapy with ethosuximide have included drowsiness, headache, dizziness, euphoria, hiccups, dyskinesias, irritability, hyperactivity, lethargy, fatigue, and ataxia. Psychiatric or psychological aberrations associated with ethosuximide administration have included disturbances of sleep, night terrors, inability to concentrate, aggressiveness. These effects may be noted particularly in patients who have previously exhibited psychological abnormalities. There have been less frequent reports of paranoid psychosis, increased libido and increased state of depression with overt suicidal intentions.
Integumentary System: Dermatologic manifestations which have occurred with the administration of ethosuximide have included urticaria, Stevens-Johnson syndrome, systemic lupus erythematosus, and pruritic erythematous rashes.
Miscellaneous: Other reactions reported have included myopia, vaginal bleeding, swelling of the tongue, gum hypertrophy, and hirsutism.
Precautions:
Ethosuximide, when used alone in mixed types of epilepsy, may increase the frequency of grand mal seizures in some patients.
As with other anti-convulsants, it is important to proceed slowly when increasing or decreasing the dosage, as well as when adding or eliminating other medication. Abrupt withdrawal of anti-convulsant medication may precipitate absence (petit mal) states.
Hazardous Activities
Ethosuximide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a motor vehicle or other such activity requiring alertness; therefore, the patient should be cautioned accordingly.
Usage in Pregnancy
Safe usage of Zarontin in human pregnancy and lactation is not documented.
Recent reports suggest an association between the use of anti-convulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women.
Usage should not be discontinued if the medicine is administered to prevent major seizures because of the possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy.
Interactions:
Since ethosuximide may interact with concurrently administered anti-epileptic drugs, periodic serum level determinations of these drugs may be necessary (e.g. ethosuximide may elevate phenytoin serum levels whereas valproic acid has been reported to increase or decrease ethosuximide levels).

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects for signs and symptoms of overdosage.
Provide symptomatic and supportive treatment.
Treatment should include emesis (unless the patient is or could rapidly become obtunded, comatose, or convulsing) or gastric lavage, activated charcoal, cathartics and general supportive measures. Haemodialysis may be useful to treat ethosuximide overdose. Forced diuresis and exchange transfusions are ineffective.

IDENTIFICATION:

Zarontin Capsules:	Clear, pale yellow, soft gelatin capsules.
Zarontin Syrup:	A clear, slightly yellowish to slightly pinkish liquid with a characteristic odour.

PRESENTATION:

Zarontin Capsules:	Containers of 50 capsules.
Zarontin Syrup:	Bottles of 200 mL.

STORAGE INSTRUCTIONS:
Store in a cool (below 25°C), dry place.
KEEP OUT OF REACH OF CHILDREN.

REFERENCE NUMBERS:

Zarontin Capsules:	B558 (Act 101/1965)
Zarontin Syrup:	B559 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pfizer Laboratories (Pty) Ltd
102 Rivonia Road
SANDTON, 2196

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
5 October 1969.

        Revised: JUN00; OCT98; SEPT97;JULY95

Updated on this site: February 2005
Source: Pharmaceutical Industry
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