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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 3-ethyl-3-methyl-pyrrolidine-2,5-dione
|authorTag={{RB}}
| image = Ethosuximide.png
|genericName=Ethosuximide
|aOrAn=a
|drugClass=anticonvulsant
|indicationType=treatment
|indication=[[absence (petit mal) epilepsy]]
|adverseReactions=[[anorexia]], [[vague gastric upset]], [[nausea and vomiting]], [[ataxia]], [[headache]], [[dizziness]], [[drowsiness]]
 
 
<!--Black Box Warning-->
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
 
* Content
 
<!--Adult Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Adult)-->
|fdaLIADAdult=====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.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=====Dosage====
* The optimal dose for most pediatric patients is 20 mg/kg/day.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Contraindications-->
|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.
 
: [[File:Entacapone Warning Table 1.png|none|500px]]
 
* 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.
|clinicalTrials======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=====
* 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=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
 
<!--Drug Interactions-->
|drugInteractions=* 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-->
|useInPregnancyFDA=* 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.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=* 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.
|useInPed=* Safety and effectiveness in pediatric patients below the age of 3 years have not been established.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
 
<!--Administration and Monitoring-->
|administration=* Oral
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
 
 
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
 
<!--Overdosage-->
|overdose=====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.
|drugBox={{Drugbox2
| verifiedrevid = 461096657
| IUPAC_name = (''RS'')-3-ethyl-3-methyl-pyrrolidine-2,5-dione
| image = Ethosuximide Wiki Str.png
| width = 120px
| width = 120px
| imagename = 1 : 1 mixture (racemate)
| image2 = Ethosuximide ball and so.png
| width2 = 150px
| drug_name = Ethosuximide
<!--Clinical data-->
| tradename = Zarontin
| Drugs.com = {{drugs.com|monograph|ethosuximide}}
| MedlinePlus = a682327
| pregnancy_category = D <small>(Australia, United States)</small>
| legal_status = [[Prescription drug|℞-only]] <small>(U.S.)</small>
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| bioavailability = 93%{{ref|bioavailability}}
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]], [[CYP2E1]])
| elimination_half-life = 53 hours
| excretion = [[Kidney|Renal]] (20%)
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 77-67-8
| CAS_number = 77-67-8
| ATC_prefix = N03
| ATC_prefix = N03
| ATC_suffix = AD01
| ATC_suffix = AD01
| PubChem = 3291
| PubChem = 3291
| DrugBank = APRD00318
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| C = 7 |H = 11 |N = 1 |O = 2
| DrugBank = DB00593
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3175
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5SEH9X1D1D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00539
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4887
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 696
 
<!--Chemical data-->
| C=7 | H=11 | N=1 | O=2  
| molecular_weight = 141.168 [[Gram|g]]/[[Mole (unit)|mol]]
| molecular_weight = 141.168 [[Gram|g]]/[[Mole (unit)|mol]]
| bioavailability = 93%{{ref|bioavailability}}
| smiles = O=C1NC(=O)CC1(C)CC
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]], [[CYP2E1]])
| InChI = 1/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
| elimination_half-life = 53 [[hour]]s
| InChIKey = HAPOVYFOVVWLRS-UHFFFAOYAB
| excretion = [[Kidney|Renal]] (20%)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category = D <small>([[Australia|Au]], [[United States|U.S.]])</small>
| StdInChI = 1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
| legal_status = [[Prescription drug|℞-only]] <small>(U.S.)</small>
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration = Oral
| StdInChIKey = HAPOVYFOVVWLRS-UHFFFAOYSA-N
}}
}}


'''Ethosuximide''' is a [[succinimide]] [[anticonvulsant]], used mainly in [[absence seizure]]s. It is sold by [[Pfizer]] under the name '''Zarontin®''' and was once also sold under the name '''Emeside'''®, both of which were discontinued from the United Kingdom market in capsule form in November of 2005.{{ref|no_more_capsules_UK}}
==Uses==
===Approved===
It is approved for absence seizures.{{ref|approved_use}}  Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug, [[valproic acid]].{{ref|approved_use}}


===Unapproved===
It was reported to have been used for [[intermittent explosive disorder]] in 1980 by Drs Andrulonis, Donnelly, Glueck, Stroebel, and Szabek.{{ref|Andrulonis_et_al_1980}}


===Dosage===
<!--Mechanism of Action-->
Therapeutic drug concentrations are individualized according to response and tolerance. Common Serum Therapeutic Range: 40-100 ug/mL. Potentially Toxic Serum Concentration: >100 ug/mL.
|mechAction=* 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-->
|structure=* Ethosuximide is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:
 
: [[File:Ethosuximide str.png|thumb|none|500px|This image is provided by the National Library of Medicine.]]


==Mechanism of Action==
<!--Pharmacodynamics-->
There is some controversy over the exact mechanism by which ethosuximide prevents absence seizures. While the view that ethosuximide is a T-type calcium channel blocker gained widespread support following its proposal, attempts to replicate the initial finding were inconsistent.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


In March of 1989, Coulter, Huguenard and Prince showed that ethosuximide and [[dimethadione]], both effective anti-absence agents, reduced low-threshold [[calcium|Ca<sup>2+</sup>]] [[current (electric)|current]]s in [[Voltage-dependent calcium channel|T-type Ca<sup>2+</sup> channel]]s in freshly removed [[thalamus|thalamic]] [[neuron]]s.{{ref|Coulter1989-1}} In June of that same year, they also found the mechanism of this reduction to be [[voltage]]-dependent, using acutely neurons of rats and guinea pigs; it was also noted that [[valproic acid]], which is also used in absence seizures, did not do that.{{ref|Coulter1989-2}} The next year, they showed that anticonvulsant succinimides did this and that the [[proconvulsant]] ones did not.{{ref|Coulter1990}} The first part was supported by Kostyuk et al in 1992, who reported a substantial reduction in current in [[dorsal root]] [[ganglion|ganglia]] at concentrations ranging from 7 [[mu (letter)|μ]][[concentration|M]] to 1 mM.{{ref|Kostyuk}}
<!--Pharmacokinetics-->
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


That same year, however, Herrington and Lingle found no such effect at concentrations of up to 2.5 mM.{{ref|Herrington-Lingle}} The year after, a study conducted on human [[neocortex|neocortical]] cells removed during surgery for intractable epilepsy, the first to use human tissue, found that ethosuximide had no effect on Ca<sup>2+</sup> currents at the concentrations typically needed for a therapeutic effect.{{ref|sayer1993}}
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.


In 1998, Slobodan M. Todorovic and Christopher J. Lingle of Washington University reported a 100% block of T-type current in dorsal root ganglia at 23.7 ± 0.5 mM, far higher than Kostyuk reported.{{ref|Todorovic_Lingle}} That same year, Leresche et al reported that ethosuximide had no effect on T-type currents, but did decrease noninactivating [[sodium|Na<sup>+</sup>]] current by 60% and the Ca<sup>2+</sup>-activated K<sup>+</sup> currents by 39.1 ± 6.4% in rat and cat thalamocortical cells. It was concluded that the decrease in Na<sup>+</sup> current is responsible for the anti-absence properties.{{ref|Leresche_et_al_1998}}
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


In the introduction of a paper published in 2001, Dr. Juan Carlos Gomora and colleagues at the [[University of Virginia]] in [[Charlottesville, Virginia|Charlottesville]] pointed out that past studies were often done in isolated neurons that had lost most of their T-type channels.{{ref|Gomora_et_al_2001}} Using cloned α1G, α1H, and α1I T-type calcium channels, Gomora's team found that ethosuximide blocked the channels with an IC<sub>50</sub> of 12 ± 2 mM and that of ''N''-desmethylmethsuximide (the active metabolite of [[mesuximide]]) is 1.95 ± 0.19 mM for α1G, 1.82 ± 0.16 mM for α1I, and 3.0 ± 0.3 mM for α1H. It was suggested that the blockade of open channels is facilitated by ethosuximide's physically plugging the channels when current flows inward.
<!--How Supplied-->
<!--==Metabolism==
|howSupplied=* Ethosuximide oral solution, USP 250 mg/5 mL is supplied as:
Ethosuximide is primarily metabolized by [[CYP3A4]] into, and by [[CYP2E1]] into.-->


==Adverse Effects==
* NDC 46672-641-16 - 16 fl. oz. bottles. Each 5 mL of oral solution contains 250 mg ethosuximide in a raspberry flavored base.
===Central Nervous System===
|storage=* Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from freezing and light.
====Common====
 
* drowsiness
* Dispense in a tight, light-resistant container with a child-resistant closure.
* mental confusion
|packLabel======PRINCIPAL DISPLAY PANEL=====
* [[insomnia]]
 
* nervousness
: [[File:Ethosuximide PDP.png|thumb|none|500px|This image is provided by the National Library of Medicine.]]
* [[headache]]
 
* [[Euphoria (emotion)|euphoria]]
====Ingredients and Appearance====
* [[ataxia]]
 
: [[File:Ethosuximide Ing and App.png|thumb|none|500px|This image is provided by the National Library of Medicine.]]
 
 
 
 
<!--Patient Counseling Information-->
|fdaPatientInfo=* Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking ethosuximide. Instruct patients to take ethosuximide only as prescribed.
 
* 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 (e.g., sore throat, fever).
 
* Patients, their caregivers, and families should be counseled that AEDs, including ethosuximide, 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.
 
* Prior to initiation of treatment with ethosuximide, the patient should be instructed that a rash may herald a serious medical event and that the patient should report any such occurrence to a physician immediately.
 
* 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
 
====MEDICATION GUIDE====
 
* ETHOSUXIMIDE ORAL SOLUTION USP, 250 mg/5 mL
 
: (eth oh sux’ imide)
 
* Read this Medication Guide before you start taking ethosuximide oral solution and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about ethosuximide oral solution, ask your healthcare provider or pharmacist.
 
=====What is the most important information I should know about ethosuximide oral solution?=====
 
=====Do not stop taking ethosuximide oral solution without first talking to your healthcare provider.=====
 
* Stopping ethosuximide oral solution suddenly can cause serious problems.
 
=====Ethosuximide oral solution can cause serious side effects, including:=====
 
* Rare but serious blood problems that may be life-threatening. Call your healthcare provider right away if you have:
 
:* fever, swollen glands, or sore throat that come and go or do not go away
:* frequent infections or an infection that does not go away
:* easy bruising
:* red or purple spots on your body
:* bleeding gums or nose bleeds
:* severe fatigue or weakness
* Systemic Lupus Erythematosus. Call your healthcare provider right away if you have any of these symptoms:
 
:* joint pain and swelling
:* muscle pain
:* fatigue
:* low-grade fever
:* pain in the chest that is worse with breathing
:* unexplained skin rash
* Like other antiepileptic drugs, ethosuximide oral solution may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
 
* Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
 
:* thoughts about suicide or dying
:* attempts to commit suicide
:* new or worse depression
:* new or worse anxiety
:* feeling agitated or restless
:* panic attacks
:* trouble sleeping (insomnia)
:* new or worse irritability
:* acting aggressive, being angry, or violent
:* acting on dangerous impulses
:* an extreme increase activity and talking (mania)
:* other unusual changes in behavior or mood
* How can I watch for early symptoms of suicidal thoughts and actions?
 
:* Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
:* Keep all follow-up visits with your healthcare provider as scheduled.
* Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
 
* Do not stop ethosuximide oral solution without first talking to a healthcare provider.
 
:* Stopping ethosuximide oral solution suddenly can cause serious problems.
:* Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
* Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
 
=====What is ethosuximide oral solution?=====
 
* Ethosuximide oral solution is a prescription medicine used to treat absence (petit mal) seizures.
 
=====Who should not take ethosuximide oral solution?=====
 
* Do not take ethosuximide oral solution if you are allergic to succinimides (methsuximide or ethosuximide), or any of the ingredients in ethosuximide oral solution. See the end of this Medication Guide for a complete list of ingredients in ethosuximide oral solution.
 
=====What should I tell my healthcare provider before taking ethosuximide oral solution?=====
 
* Before you take ethosuximide oral solution, tell your healthcare provider if you:
 
:* have or had liver problems
:* have or have had depression, mood problems or suicidal thoughts or behavior
:* have any other medical conditions
:* are pregnant or plan to become pregnant. It is not known if ethosuximide oral solution can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking ethosuximide oral solution. You and your healthcare provider should decide if you should take ethosuximide oral solution while you are pregnant.
:* If you become pregnant while taking ethosuximide oral solution, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can enroll in this registry by calling 1-888-233-2334.
:* are breast-feeding or plan to breast-feed. It is not known if ethosuximide can pass into breast milk. You and your healthcare provider should decide how you will feed your baby while you take ethosuximide oral solution.
* Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Taking ethosuximide oral solution with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.
 
* Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.
 
=====How should I take ethosuximide oral solution?=====
 
* Take ethosuximide oral solution exactly as prescribed. Your healthcare provider will tell you how much ethosuximide oral solution to take.
* Your healthcare provider may change your dose. Do not change your dose of ethosuximide oral solution without talking to your healthcare provider.
* If you take too much ethosuximide oral solution, call your healthcare provider or your local Poison Control Center right away.
=====What should I avoid while taking ethosuximide oral solution?=====
 
* Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking ethosuximide oral solution without first talking to your healthcare provider. Ethosuximide oral solution taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
* Do not drive, operate heavy machinery, or do other dangerous activities until you know how ethosuximide oral solution affects you. Ethosuximide oral solution can slow your thinking and motor skills.
=====What are the possible side effects of ethosuximide oral solution?=====
 
* See "What is the most important information I should know about ethosuximide oral solution?"
* Ethosuximide oral solution may cause other serious side effects, including:
 
* Serious allergic reactions. Call your healthcare provider right away if you have any of these symptoms:
:* skin rash
:* hives
:* sores in your mouth
:* blistering or peeling skin
* Changes in thinking, mood, or behavior. Some patients may get abnormally suspicious thoughts, hallucinations (seeing or hearing things that are not there), or delusions (false thoughts or beliefs).
* Grand mal seizures can happen more often or become worse
=====Call your healthcare provider right away, if you have any of the symptoms listed above.=====
 
* The most common side effects of ethosuximide oral solution include
 
* nausea or vomiting
* indigestion, stomach pain
* diarrhea
* weight loss
* loss of appetite
* hiccups
* hiccups
* impaired concentration
* fatigue
* irritability
* dizziness or lightheadedness
* [[hyperactivity]]
* unsteadiness when walking
* loss of taste
* headache
* [[night terror]]s
* loss of concentration
====Rare====
* Tell your healthcare provider about any side effect that bothers you or that does not go away.
* [[paranoia|paranoid]] [[psychosis]]
 
* increased libido
* These are not all the possible side effects with ethosuximide oral solution. For more information, ask your healthcare provider or pharmacist.
* exacerbation of [[clinical depression|depression]]
 
===Gastrointestinal===
* Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
* [[dyspepsia]]
 
* [[vomiting]]
=====How should I store ethosuximide oral solution?=====
* [[nausea]]
 
* cramps
* Store ethosuximide oral solution at 20° to 25°C (68° to 77°F). Preserve in tight containers. Protect from freezing and light.
* [[constipation]]
* Keep ethosuximide oral solution and all medicines out of the reach of children.
* [[diarrhea]]
 
* stomach pain
=====General information about ethosuximide oral solution=====
* loss of appetite
 
* weight loss
* Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ethosuximide oral solution for a condition for which it was not prescribed. Do not give ethosuximide oral solution to other people, even if they have the same condition. It may harm them.
* [[hyperplasia|gingival hyperplasia]]
 
* swelling of tongue
* This Medication Guide summarizes the most important information about ethosuximide oral solution. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ethosuximide oral solution that is written for healthcare professionals.
===Genitourinary===
 
* microscopic [[hematuria]]
For more information, call 404-351-4510.
* vaginal bleeding
 
===Hematopoietic===
=====What are the ingredients in ethosuximide oral solution?=====
''The following can occur with or without bone marrow loss:''
 
* [[pancytopenia]]
Active ingredient: ethosuximide
* [[agranulocytosis]]
 
* [[leukopenia]]
Inactive ingredients: 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.
* [[eosinophilia]]
 
===Integumentary===
This Medication Guide has been approved by the U.S. Food and Drug Administration.
* [[urticaria]]
 
* [[systemic lupus erythematosus]]
<!--Precautions with Alcohol-->
* [[Stevens-Johnson syndrome]]
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
* [[hirsutism]]
 
* [[itch|pruritic]] [[lupus erythematosus|erythematous rash]]es
<!--Brand Names-->
|brandNames=* Zarontin®<ref>{{Cite web | title = Ethosuximide | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e7d4b2a4-2dae-4026-a381-9d534d36c6b3}}</ref>
 
<!--Look-Alike Drug Names-->
|lookAlike=<!--Drug Shortage Status-->
|drugShortage=
}}
<!--Pill Image-->
 
 


===Ocular===
<!--Label Display Image-->
* [[myopia]]
==Complications==
* abnormal [[liver|liver function]]
==Drug Interactions==
[[valproic acid|Valproate]]s can either decrease or increase the levels of ethosuximide; However, combinations of [[valproic acid|valproate]]s and ethosuximide had a greater [[Protective Index]] than either drug alone.{{ref|combo}}


It may elevate serum [[phenytoin]] levels.


==References==
* [http://www.mentalhealth.com/drug/p30-z01.html#Head_1 Ethosuximide] Internet Mental Health.
* [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682327.html MedlinePlus Drug Information: Ethosuximide Oral]
* [http://www.pfizer.com/pfizer/download/uspi_zarontin_capsules.pdf Zarontin®] ''Pfizer.''
* [http://www.druglib.com/druginfo/zarontin/ Zarontin®] Drug information, published studies and current trials


==End Notes==
# {{note|bioavailability}} {{cite journal | first = P. N. | last = Patsalos | month = November | year = 2005 | title = Properties of Antiepileptic Drugs in the Treatment of Idiopathic Generalized Epilepsies | journal = Epilepsia | volume = 46 | issue = s9 | pages = 140-144 | id = PMID 16302888}}
# {{note|no_more_capsules_UK}} {{cite web | author = Epilepsy Research Foundation | year = 2005 | url = http://www.epilepsyresearch.org.uk/news/arch/0511ethosuximide.htm
| title = Withdrawal of Zarontin and Emeside tablets | accessdate = 2007-05-14}}
# {{note|approved_use}} {{cite web | author = Pharmaceutical Associates, Incorporated | year = 2000 | url = http://www.fda.gov/cder/foi/anda/2000/40253_Ethosuximide_Prntlbl.pdf | title = Ethosuximide Approval Label | format = PDF | work = Label and Approval History | publisher = [[Food and Drug Administration]] Center for Drug Evaluation and Research | accessdate = 2006-02-05}}
# {{note|approved_use}} "Drugs used in generalized seizures." Katzung, B. Basic and Clinical Pharmacology. 9th Ed. 2003. Lange Medical Books/McGraw-Hill.0071410929.
# {{note|Andrulonis_et_al_1980}} {{cite journal | first = P. A. | last = Andrulonis | coauthors = J. Donnelly, B. C. Glueck, C. F. Stroebel, and B. L. Szabek | month = November | year = 1980 | title = Preliminary data on ethosuximide and the episodic dyscontrol syndrome | journal = American Journal of Psychiatry | volume = 137 | issue = 11 | pages = 1455-6 | id = {{PMID|7435689}}}}
# {{note|Coulter1989-1}} Coulter DA, Huguenard JR, Prince DA. "Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons." ''Neurosci Lett.'' 1989 Mar 13;98(1):74-8. PMID 2710401
# {{note|Coulter1989-2}} "Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons." ''Annals of Neurology.'' 1989 Jun;25(6):582-93. PMID 2545161
# {{note|Coulter1990}} Coulter DA, Huguenard JR, Prince DA. "Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction." ''British Journal of Pharmacology.'' 1990 Aug;100(4):800-6. PMID 2169941
# {{note|Kostyuk}} Kostyuk PG, Molokanova EA, Pronchuk NF, Savchenko AN, Verkhratsky AN. "Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons." ''Neuroscience.'' 1992 Dec;51(4):755-8. PMID 1336826
# {{note|Herrington-Lingle}} {{cite journal
| author = Herrington J, Lingle CJ
| title = Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells
| journal = Journal of Neurophysiology
| date = 1992 Jul | volume = 68 | issue = 1 | pages = 213-32
| id = PMID 1325546
| url =  http://jn.physiology.org/cgi/reprint/68/1/213
}}
# {{note|sayer1993}} Sayer RJ, Brown AM, Schwindt PC, Crill WE. "Calcium currents in acutely isolated human neocortical neurons." ''Journal of Neurophysiology.'' 1993 May;69(5):1596-606. PMID 8389832 [http://jn.physiology.org/cgi/reprint/69/5/1596 Fulltext]
# {{note|Todorovic_Lingle}} {{cite journal | author=Todorovic SM, Lingle CJ | title=Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents | journal=Journal of Neurophysiology | volume=79 | issue=1 | year=1998 | pages=240-52 | id=PMID 9425195
| url = http://jn.physiology.org/cgi/content/full/79/1/240
}}
# {{note|Leresche_et_al_1998}} {{cite journal | author=Leresche N, Parri HR, Erdemli G, Guyon A, Turner JP, Williams SR, Asprodini E, Crunelli V | title=On the action of the anti-absence drug ethosuximide in the rat and cat thalamus | journal=Journal of Neuroscience | volume=18 | issue=13 | year=1998 | pages=4842-53 | id=PMID 9634550
| url = http://www.jneurosci.org/cgi/content/full/18/13/4842
}}
# {{note|Gomora_et_al_2001}} {{cite journal | author=Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E | title=Block of cloned human T-type calcium channels by succinimide antiepileptic drugs | journal=Molecular Pharmacology | volume=60 | issue=5 | year=2001 | pages=1121-32 | id=PMID 11641441
}}
# {{note|combo}} {{cite journal
| last = Bourgeois | first = BF
| title = Combination of valproate and ethosuximide: antiepileptic and neurotoxic interaction
| journal = The Journal of Pharmacology and Experimental Therapeutics
| date = 1988 Dec | volume = 247 | issue = 3 | pages = 1128-32
| id = PMID 3144596
}}


==External links==
* [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist FDA-Parke Davis-Zarontin Letters]
{{Anticonvulsants}}


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Latest revision as of 22:08, 21 September 2015

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

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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

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
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
Gastrointestinal System
Hemopoietic System
Nervous System
Psychiatric or psychological aberrations
  • 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
Special Senses
Genitourinary System

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

Template:Px
Template:Px
1 : 1 mixture (racemate)Ethosuximide
Systematic (IUPAC) name
(RS)-3-ethyl-3-methyl-pyrrolidine-2,5-dione
Identifiers
CAS number 77-67-8
ATC code N03AD01
PubChem 3291
DrugBank DB00593
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 141.168 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 93%[3]
Metabolism Hepatic (CYP3A4, CYP2E1)
Half life 53 hours
Excretion Renal (20%)
Therapeutic considerations
Pregnancy cat.

D (Australia, United States)

Legal status

℞-only (U.S.)

Routes Oral

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

PRINCIPAL DISPLAY PANEL
This image is provided by the National Library of Medicine.

Ingredients and Appearance

This image is provided by the National Library of Medicine.

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

Patient Counseling Information

  • Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking ethosuximide. Instruct patients to take ethosuximide only as prescribed.
  • 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 (e.g., sore throat, fever).
  • Patients, their caregivers, and families should be counseled that AEDs, including ethosuximide, 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.
  • Prior to initiation of treatment with ethosuximide, the patient should be instructed that a rash may herald a serious medical event and that the patient should report any such occurrence to a physician immediately.
  • 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

MEDICATION GUIDE

  • ETHOSUXIMIDE ORAL SOLUTION USP, 250 mg/5 mL
(eth oh sux’ imide)
  • Read this Medication Guide before you start taking ethosuximide oral solution and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about ethosuximide oral solution, ask your healthcare provider or pharmacist.
What is the most important information I should know about ethosuximide oral solution?
Do not stop taking ethosuximide oral solution without first talking to your healthcare provider.
  • Stopping ethosuximide oral solution suddenly can cause serious problems.
Ethosuximide oral solution can cause serious side effects, including:
  • Rare but serious blood problems that may be life-threatening. Call your healthcare provider right away if you have:
  • fever, swollen glands, or sore throat that come and go or do not go away
  • frequent infections or an infection that does not go away
  • easy bruising
  • red or purple spots on your body
  • bleeding gums or nose bleeds
  • severe fatigue or weakness
  • Systemic Lupus Erythematosus. Call your healthcare provider right away if you have any of these symptoms:
  • joint pain and swelling
  • muscle pain
  • fatigue
  • low-grade fever
  • pain in the chest that is worse with breathing
  • unexplained skin rash
  • Like other antiepileptic drugs, ethosuximide oral solution may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
  • Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry, or violent
  • acting on dangerous impulses
  • an extreme increase activity and talking (mania)
  • other unusual changes in behavior or mood
  • How can I watch for early symptoms of suicidal thoughts and actions?
  • Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
  • Keep all follow-up visits with your healthcare provider as scheduled.
  • Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
  • Do not stop ethosuximide oral solution without first talking to a healthcare provider.
  • Stopping ethosuximide oral solution suddenly can cause serious problems.
  • Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
  • Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
What is ethosuximide oral solution?
  • Ethosuximide oral solution is a prescription medicine used to treat absence (petit mal) seizures.
Who should not take ethosuximide oral solution?
  • Do not take ethosuximide oral solution if you are allergic to succinimides (methsuximide or ethosuximide), or any of the ingredients in ethosuximide oral solution. See the end of this Medication Guide for a complete list of ingredients in ethosuximide oral solution.
What should I tell my healthcare provider before taking ethosuximide oral solution?
  • Before you take ethosuximide oral solution, tell your healthcare provider if you:
  • have or had liver problems
  • have or have had depression, mood problems or suicidal thoughts or behavior
  • have any other medical conditions
  • are pregnant or plan to become pregnant. It is not known if ethosuximide oral solution can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking ethosuximide oral solution. You and your healthcare provider should decide if you should take ethosuximide oral solution while you are pregnant.
  • If you become pregnant while taking ethosuximide oral solution, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can enroll in this registry by calling 1-888-233-2334.
  • are breast-feeding or plan to breast-feed. It is not known if ethosuximide can pass into breast milk. You and your healthcare provider should decide how you will feed your baby while you take ethosuximide oral solution.
  • Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Taking ethosuximide oral solution with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.
  • Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.
How should I take ethosuximide oral solution?
  • Take ethosuximide oral solution exactly as prescribed. Your healthcare provider will tell you how much ethosuximide oral solution to take.
  • Your healthcare provider may change your dose. Do not change your dose of ethosuximide oral solution without talking to your healthcare provider.
  • If you take too much ethosuximide oral solution, call your healthcare provider or your local Poison Control Center right away.
What should I avoid while taking ethosuximide oral solution?
  • Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking ethosuximide oral solution without first talking to your healthcare provider. Ethosuximide oral solution taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how ethosuximide oral solution affects you. Ethosuximide oral solution can slow your thinking and motor skills.
What are the possible side effects of ethosuximide oral solution?
  • See "What is the most important information I should know about ethosuximide oral solution?"
  • Ethosuximide oral solution may cause other serious side effects, including:
  • Serious allergic reactions. Call your healthcare provider right away if you have any of these symptoms:
  • skin rash
  • hives
  • sores in your mouth
  • blistering or peeling skin
  • Changes in thinking, mood, or behavior. Some patients may get abnormally suspicious thoughts, hallucinations (seeing or hearing things that are not there), or delusions (false thoughts or beliefs).
  • Grand mal seizures can happen more often or become worse
Call your healthcare provider right away, if you have any of the symptoms listed above.
  • The most common side effects of ethosuximide oral solution include
  • nausea or vomiting
  • indigestion, stomach pain
  • diarrhea
  • weight loss
  • loss of appetite
  • hiccups
  • fatigue
  • dizziness or lightheadedness
  • unsteadiness when walking
  • headache
  • loss of concentration
  • Tell your healthcare provider about any side effect that bothers you or that does not go away.
  • These are not all the possible side effects with ethosuximide oral solution. For more information, ask your healthcare provider or pharmacist.
  • Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store ethosuximide oral solution?
  • Store ethosuximide oral solution at 20° to 25°C (68° to 77°F). Preserve in tight containers. Protect from freezing and light.
  • Keep ethosuximide oral solution and all medicines out of the reach of children.
General information about ethosuximide oral solution
  • Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ethosuximide oral solution for a condition for which it was not prescribed. Do not give ethosuximide oral solution to other people, even if they have the same condition. It may harm them.
  • This Medication Guide summarizes the most important information about ethosuximide oral solution. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ethosuximide oral solution that is written for healthcare professionals.

For more information, call 404-351-4510.

What are the ingredients in ethosuximide oral solution?

Active ingredient: ethosuximide

Inactive ingredients: 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.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

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

There is limited information regarding Ethosuximide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

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

  1. ↑ "Ethosuximide".
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