Ethosuximide

Registered South African indications:

• Absence epilepsy

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to succinimides
• Porphyria

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Abrupt withdrawal

Forms avail. in SA and covered in this monograph: syr

Control of absence (petit mal) epilepsy

• Oral (syr): Initial: 500mg, dly; Titrate by 250mg at intervals of 4 to 7 days until control is achieved

Doses exceeding 1.5g, dly should be given in divided doses under strict supervision

Paed. forms avail. in SA and covered in this monograph: syr

Control of absence (petit mal) epilepsy

Younger than 3 years

• Not established for use

Between 3 - 6 years

• Oral (syr): Initial: 250mg, dly; Titrate by 250mg at intervals of 4 to 7 days until control is achieved; Maintenance: 20mg/kg/day

Older than 6 years

• Oral (syr): Initial: 500mg, dly; Titrate by 250mg at intervals of 4 to 7 days until control is achieved; Maintenance: 20mg/kg/day

Doses exceeding 1.5g, dly should be given in divided doses under strict supervision

May be administered in combination with other antiepileptics when other forms of epilepsy coexist with absence (petit mal) epilepsy

Pregnancy

• Caution
• The treatment with ethosuximide should not be interrupted during pregnancy without the consent of a physician as the sudden discontinuation of the treatment or uncontrolled reduction of the dose may result in recurrence of epileptic seizures which may harm the pregnant woman and/or the unborn child. Ethosuximide crosses the placenta. Studies in animals have shown reproductive toxicity. Specific congenital malformations have not been observed in children of mothers exposed to ethosuximide monotherapy during pregnancy. The risk of malformations during anti-epileptic therapy is increased by a factor of 2 to 3 compared to the expected incidence of about 3% in the general population. Most common malformations reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapies are associated with a higher risk of congenital malformation so that monotherapy should be practised during pregnancy whenever possible
• Patients should be informed of the increased risk of malformations and prenatal diagnostic measures should be offered
• The lowest effective dose ensuring seizure control must not be exceeded, particularly during the 20th and 40th day of pregnancy. The ethosuximide serum concentration of the pregnant woman must be regularly monitored
• Folic acid supplementation is recommended in patients planning to have a baby and during pregnancy. To prevent vitamin K1 deficiency and reduce the risk for haemorrhages in newborn infants, women should be given vitamin K1 during the last month of pregnancy

Breastfeeding

• Caution; not recommended
• Ethosuximide is excreted into breast milk reaching concentrations up to 94% of the maternal serum concentrations. Sedation, poor suckling and irritability have been observed in individual breastfed infants
• Breastfeeding should be discontinued during treatment with ethosuximide

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Aggression
• Ataxia
• Delusional paranoid disorder
• Depression
• Suicidal ideation
• Disturbed sleep
• Dizziness
• Drowsiness
• Euphoria
• Fatigue
• Headache
• Hyperactivity
• Irritability
• Lack of concentration
• Lethargy
• Night terrors
• Increased libido

Gastrointestinal Disorders

• Abdominal pain
• Anorexia
• Abdominal cramps
• Diarrhoea
• Epigastric pain
• Gastric distress
• Gingival hyperplasia
• Hiccups
• Nausea and vomiting
• Swollen tongue

Genitourinary Disorders

• Occult haematuria
• Proteinuria
• Vaginal haemorrhage

Endocrine and Metabolic Disorders

• Hirsutism
• Weight loss
• Anorexia

Musculoskeletal Disorders

•  Systemic lupus erythematosus

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Skin rash
• Stevens-Johnson syndrome
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Agranulocytosis
• Aplastic anaemia
• Eosinophilia
• Leukopenia
• Pancytopenia
• Hypersensitivity reaction
• Drug rash with eosinophilia and systemic symptoms (DRESS)

Sensory Disorders

• Myopia

• Central nervous system depressants
• Conivaptan
• CYP3A4 inducers
• CYP3A4 inhibitors
• Dabrafenib
• Enzalutamide
• Fusidic acid
• Idelalisib
• Mefloquine
• Mifepristone
• Mitotane
• St John's wort
• Stiripentol

• Full blood count
• Hepatic function
• Renal function
• Suicidality

Ethosuximide blocks T-type voltage-sensitive calcium channels which mediate the entry of calcium into excitable cells. This increases the seizure threshold.

Syrup (per 5ml) 250mg

• Zarontin (MC Pharma) originator