Ethosuximide Syrup

Generic Name: ethosuximide
Dosage Form: Syrup, usp 250 mg/5 ml

Rx Only

Rev. 03/03          Code 792A00

Ethosuximide Syrup Description

Ethosuximide Syrup, USP is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:

C7H11NO2                                                                                                                                                                                      MW 141.17

Each teaspoonful (5 mL), for oral administration, contains 250 mg ethosuximide, USP. Each teaspoonful also contains artificial raspberry flavor, citric acid, ethyl maltol, FD&C Red No. 40, FD&C Yellow No. 6, glycerin, purified water, saccharin sodium, sodium benzoate, sodium citrate, and sucrose.

Ethosuximide Syrup - 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.

Indications and Usage for Ethosuximide Syrup

Ethosuximide Syrup, USP 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, 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 (eg, sore throat, fever) develop, blood counts should be considered at that point. 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.

Cases of systemic lupus erythematosus have been reported with the use of ethosuximide. The physician should be alert to this possibility.

Usage in Pregnancy

Reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to phenytoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.

The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors, eg, genetic factors or the epileptic condition itself, may be more important than drug therapy in leading to birth defects. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong 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, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.

The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential.

Precautions

General

Ethosuximide, when used alone in mixed types of epilepsy, may increase the frequency of grand mal seizures in some patients.

As with other anticonvulsants, it is important to proceed slowly when increasing or decreasing dosage, as well as when adding or eliminating other medication. Abrupt withdrawal of anticonvulsant medication may precipitate absence (petit mal) status.

Information for Patients

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.

Patients taking ethosuximide should be advised of the importance of adhering strictly to the prescribed dosage regimen.

Patients should be instructed to promptly contact their physician when they develop signs and/or symptoms suggesting an infection (eg, sore throat, fever).

Drug Interactions

Since Ethosuximide Syrup, USP may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of both drugs are recommended (ethosuximide may elevate phenytoin serum levels, and valproic acid has been reported to both increase and decrease ethosuximide levels).

Pregnancy

See WARNINGS section.

Adverse Reactions

Gastrointestinal System

Gastrointestinal symptoms occur frequently and include anorexia, vague gastric upset, nausea and vomiting, cramps, epigastric and abdominal pain, weight loss, and diarrhea. There have been reports of gum hypertrophy and swelling of the tongue.

Hemopoietic System

Hemopoietic complications associated with the administration of ethosuximide have included leukopenia, agranulocytosis, pancytopenia, with or without bone marrow suppression, and eosinophilia.

Nervous System

Neurologic and sensory reactions reported during therapy with ethosuximide have included drowsiness, headache, dizziness, euphoria, hiccups, irritability, hyperactivity, lethargy, fatigue, and ataxia.

Psychiatric or psychological aberrations associated with ethosuximide administration have included disturbances of sleep, night terrors, inability to concentrate, and aggressiveness. These effects may be noted particularly in patients who have previously exhibited psychological abnormalities. There have been rare 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, pruritic erythematous rashes, and hirsutism.

Special Senses

Myopia

Genitourinary System

Vaginal bleeding, microscopic hematuria.

Overdosage

Acute overdoses produce CNS depression including coma with respiratory depression. A relationship between ethosuximide toxicity and its plasma levels has not been established. The therapeutic range of serum levels is 40 mcg/mL to 100 mcg/mL, although levels as high as 150 mcg/mL have been reported without signs of toxicity.

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. Hemodialysis may be useful to treat ethosuximide overdose. Forced diuresis and exchange transfusions are ineffective.

Ethosuximide Syrup Dosage and Administration

Ethosuximide Syrup, USP 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 Syrup, USP may be administered in combination with other anti-convulsants when other forms of epilepsy coexist with absence (petit mal). The optimal dose for most pediatric patients is 20 mg/kg/day.

How is Ethosuximide Syrup Supplied

Ethosuximide Syrup, USP 250 mg/5 mL is supplied as:

NDC 46672-641-16 – 16 fl oz bottles. Each 5 mL of Syrup contains 250 mg ethosuximide in a raspberry flavored base.

Storage

Store at controlled room temperature, 15ºC-30ºC (59ºF-86ºF) [see USP]. Protect from freezing and light.

Pharmacist

Dispense in a tight, light-resistant container with a child-resistant closure.

Distributed By:

VERSAPHARM, INC.

Marietta, GA 30062

Manufactured By:

MIKART, INC.

Atlanta, GA 30318

Code 792A00          Rev. 03/03

Ethosuximide (Ethosuximide)

PRODUCT INFO Product Code 46672-641 Dosage Form SYRUP Route Of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength ethosuximide (ethosuximide) Active 250 MILLIGRAM  In 5 MILLILITER artificial raspberry flavor Inactive   citric acid Inactive   ethyl maltol Inactive   FD&C red no. 40 Inactive   FD&C yellow no. 6 Inactive   glycerin Inactive   water Inactive   saccharin sodium Inactive   sodium benzoate Inactive   sodium citrate Inactive   sucrose Inactive

IMPRINT INFORMATION Characteristic Appearance Characteristic Appearance Color Score Shape Symbol Imprint Code Coating Size

PACKAGING # NDC Package Description Multilevel Packaging 1 46672-641-16 473 MILLILITER In 1 BOTTLE, PLASTIC None

Revised: 02/2006