Ethosuximide

Uses

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

Ethosuximide is also used to associated treatment for these conditions: Petit Mal Epilepsy

How Ethosuximide works

Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.

Dosage

Ethosuximide dosage

Ethosuximide is administered by the oral route. The initial dose for patients 3 to 6 years of age is 250 mg per day; for patients 6 years of age and older, 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. Theoptimaldose for mostpediatricpatients is 20 mg/kg/day. This dose has given averageplasmalevels within the acceptedtherapeutic 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). Theoptimaldose for most pediatric patients is 20 mg/kg/day.

Side Effects

Blood toxicities and disorders; headache, fatigue, lethargy, drowsiness, dizziness, ataxia, hiccup and mild euphoria; more rarely, psychotic states, rashes, hepatic and renal changes, and haematological disorders. SLE, erythema multiforme. Gum hypertrophy, swelling of tongue, irritability, hyperactivity, sleep disturbances, night terrors, inability to concentrate, aggressiveness, increased libido, myopia, vag bleeding.

Toxicity

Acute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression.

Precaution

Hepatic or renal impairment, porphyria. Complete blood cell count, liver function tests, and urinalysis should be performed periodically. May increase the risk of grand mal seizures when used alone in mixed types of epilepsy. Avoid sudden withdrawal. May impair ability to drive or operate machinery.

Interaction

Isoniazid may increase the serum concentration of ethosuximide, leading to toxicity. Antipsychotics, antidepressants, MAOIs, and mefloquine may antagonise anticonvulsant effects of ethosuximide. Plasma conc of ethosuximide may be reduced by carbamazepine, phenobarbital, phenytoin, and primidone; and affected by valproate. Chloroquine or hydroxychloroquine may increase risk of convulsions. Isoniazid.

Food Interaction

• Avoid alcohol.
• Take with food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Ethosuximide Drug Interaction

Moderate: brivaracetam, brivaracetam, duloxetine, duloxetine, divalproex sodium, divalproex sodium, perampanel, perampanel, clobazam, clobazamMinor: carbamazepine, carbamazepineUnknown: levetiracetam, levetiracetam, lamotrigine, lamotrigine, lacosamide, lacosamide, cholecalciferol, cholecalciferol

Ethosuximide Disease Interaction

Major: blood dyscrasias, renal/liver disease, SLEModerate: suicidal tendency, dialysis

Elimination Route

Bioavailability following oral administration is 93%.

Half Life

53 hours

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity. Pregnancy and lactation.

Innovators Monograph

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