Ethosuximide

Ethosuximide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Ethosuximide is a anticonvulsant that is FDA approved for the treatment of absence (petit mal) epilepsy. Common adverse reactions include anorexia, vague gastric upset, nausea and vomiting,ataxia, headache, dizziness, drowsiness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• Ethosuximide is indicated for the control of absence (petit mal) epilepsy.

Dosage

• Ethosuximide 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 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ethosuximide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ethosuximide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Dosage

• The optimal dose for most pediatric patients is 20 mg/kg/day.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ethosuximide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ethosuximide in pediatric patients.

Contraindications

• Ethosuximide should not be used in patients with a history of hypersensitivity to succinimides.

<--Warnings-->

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 ethosuximide, 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.

• The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

• Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

• The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

• Anyone considering prescribing ethosuximide or any other AED must balance the risk of suicidal thoughts and behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

• Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Serious Dermatologic Reactions

• Serious dermatologic reactions, including Stevens-Johnson syndrome (SJS), have been reported with ethosuximide treatment. SJS can be fatal. The onset of symptoms is usually within 28 days, but can occur later. Ethosuximide should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS, use of this drug should not be resumed and alternative therapy should be considered.

Precautions

• 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.

Adverse Reactions

Clinical Trials Experience

Body As a Whole

Allergic reaction. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

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, pruritic erythematous rashes, and hirsutism.

Special Senses

Myopia

Genitourinary System

Vaginal bleeding, microscopic hematuria.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Ethosuximide in the drug label.

Drug Interactions

• Since ethosuximide may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of these drugs may be necessary (e.g., ethosuximide may elevate phenytoin serum levels and valproic acid has been reported to both increase and decrease ethosuximide levels).

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Ethosuximide crosses the placenta.

• 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.

• Cases of birth defects have been reported with ethosuximide. 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, e.g., 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.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ethosuximide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Ethosuximide during labor and delivery.

Nursing Mothers

• Ethosuximide is excreted in human breast milk. Because the effects of ethosuximide on the nursing infant are unknown, caution should be exercised when ethosuximide is administered to a nursing mother. Ethosuximide should be used in nursing mothers only if the benefits clearly outweigh the risks.

Pediatric Use

• Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

Geriatic Use

There is no FDA guidance on the use of Ethosuximide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Ethosuximide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Ethosuximide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Ethosuximide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Ethosuximide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Ethosuximide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Ethosuximide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Ethosuximide in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Ethosuximide in the drug label.

Overdosage

Acute overdoses

• Acute overdoses may produce nausea, vomiting, and 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.

Pharmacology

There is limited information regarding Ethosuximide Pharmacology in the drug label.

Mechanism of Action

• 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.

Structure

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

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Ethosuximide in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Ethosuximide in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Ethosuximide in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Ethosuximide in the drug label.

How Supplied

• Ethosuximide oral solution, USP 250 mg/5 mL is supplied as:

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

Storage

• Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from freezing and light.

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

Images

Drug Images

{{#ask: Page Name::Ethosuximide |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Ethosuximide |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Ethosuximide in the drug label.

Precautions with Alcohol

• Alcohol-Ethosuximide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

{{#subobject:

 |Page Name=Ethosuximide
 |Pill Name=No image.jpg
 |Drug Name=
 |Pill Ingred=|+sep=;
 |Pill Imprint=
 |Pill Dosage={{{dosageValue}}} {{{dosageUnit}}}
 |Pill Color=|+sep=;
 |Pill Shape=
 |Pill Size (mm)=
 |Pill Scoring=
 |Pill Image=
 |Drug Author=
 |NDC=

}}