Zarontin (ethosuximide) is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:

Each Zarontin capsule contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol 400, NF. The capsule contains D&C yellow No. 10; FD&C red No. 3; gelatin, NF; glycerin, USP; and sorbitol.

Last updated on RxList: 5/14/2009

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

Zarontin 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.

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 20mg/kg/day.

Zarontin is supplied as:

N 0071-0237-24—Bottles of 100. Each capsule contains 250 mg ethosuximide.

Store at 25 ° C (77 ° F); excursions permitted to 15-30 ° C (59-86 ° F) [see USP Controlled Room Temperature].

Distributed by: Parke-Davis., Divinon of Pfizer lnc, NY, NY 10017. Revised April 2009

Last updated on RxList: 5/14/2009

Body As A Whole: Allergic reaction.

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.

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

Last updated on RxList: 5/14/2009

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 (eg, 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.

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.

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

Table 1: Risk by indication for antiepileptic drugs in the pooled analysis

Indication	Placebo Patients with Events Per 1000 Patients	Drug Patients with Events Per 1000 Patients	Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients	Risk Difference: Additional Drug Patients with Events Per 1000 Patients
Epilepsy	1.0	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1.0	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

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 Zarontin 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.

Usage in Pregnancy

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 methodological 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.

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.

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.

Pregnancy

To provide information regarding the effects of in utero exposure to Zarontin, physicians are advised to recommend that pregnant patients taking Zarontin enroll in the NAAED Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website: http://www.aedpregnancyregistry.org/

See WARNINGS.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 3 years have not been established. (See DOSAGE AND ADMINISTRATION section.)

Last updated on RxList: 5/14/2009

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.

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

Last updated on RxList: 5/14/2009

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.

Last updated on RxList: 5/14/2009

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 if they develop signs and/or symptoms (eg, sore throat, fever), suggesting an infection.

Patients, their caregivers, and families should be counseled that AEDs, including Zarontin, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of 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.

Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS: Pregnancy section).

Last updated on RxList: 5/14/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ETHOSUXIMIDE - ORAL

(eth-oh-SUX-uh-mide)

COMMON BRAND NAME(S): Zarontin

USES: This medication is used alone or with other medications to control certain types of seizure problems (e.g., absence or petit mal seizures). Controlling seizures helps to prevent injury from falling and allows you to lead a more normal life. Ethosuximide belongs to a class of drugs known as anticonvulsants. It works by controlling the abnormal electrical activity in the brain that occurs during a seizure.

HOW TO USE: Take this medication by mouth with or without food, usually 1-4 times daily or as directed by your doctor. Take with food or milk if stomach upset occurs. Your doctor will start you on a smaller dose once daily, increasing it every 4-7 days until you are taking the full dose.

If you are using the liquid form of this medication, measure your dose with a special measuring spoon or device. Do not use a household spoon because it may not provide the correct dose.

Dosage is based on your age, medical condition, blood levels of ethosuximide, and response to therapy. It may take several weeks to months until your doctor determines the correct dose for controlling your seizures.

This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, take it at the same time(s) each day.

It is very important to continue taking this medication (and other anticonvulsant medications) exactly as prescribed by your doctor. Do not take more or less of this drug than prescribed or stop taking it (or other anticonvulsant medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause seizure control to worsen or increase side effects.

Inform your doctor immediately if your seizure control worsens (e.g., the number of seizures increases).

SIDE EFFECTS: Dizziness, drowsiness, tiredness, headache, staggering walk/clumsiness, nausea, vomiting, loss of appetite, stomach pain/cramps, weight loss, or diarrhea may occur.

Many of these effects usually occur when you first start taking the medication but tend to disappear over time (usually in a few weeks). If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unusual swelling of the gums, swollen tongue, mental/mood changes, unusual/bad dreams, increased sexual interest, difficulty concentrating, unusual hair growth in females, vision changes.

This medication rarely may cause mood or behavior changes, such as anxiety, agitation, hostility, pressured/rapid speech, or thoughts of suicide. Tell your doctor immediately if you develop unusual (possibly sudden) mood changes.

Tell your doctor immediately if any of these rare but very serious side effects occur: fever, chills, persistent sore throat, easy bruising/bleeding, severe tiredness/weakness, pale skin, fast breathing even at rest.

This medication may infrequently cause a serious immune system problem (systemic lupus erythematosus). Tell your doctor immediately if you experience any of these unlikely but serious side effects: unusual tiredness, joint/muscle aches, unusual fever, butterfly-shaped facial rash, swollen glands, bloody/pink urine, swelling of the feet/ankles (edema).

Your doctor may need to order special tests if you experience these symptoms. Keep all laboratory and medical appointments.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking ethosuximide, tell your doctor or pharmacist if you are allergic to it; or to methsuximide; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain liver/blood problem (porphyria).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, kidney problems, severe lung disease, anemia, low white blood cell counts, mental/mood disorder (e.g., depression, psychosis).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages. Driving is usually not allowed by law if you have new or recent seizures.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially the drowsiness/dizziness effects.

Caution is advised when using this drug in children because they may be more sensitive to the effects of the drug, especially the drowsiness/dizziness effects.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: phenytoin, valproic acid.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: severe nausea/vomiting, loss of consciousness, difficulty waking up, very slow breathing.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., ethosuximide blood levels, blood counts, blood chemistries) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember unless it is less than 2 hours before the time for your next dose. In that case, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at about 77 degrees F (25 degrees C) away from light and moisture. Brief storage at 59-86 degrees F (15-30 degrees C) is permitted. Do not freeze liquid forms of this medication. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.