1 NAME OF THE MEDICINAL PRODUCT

Emeside Capsules

Ethosuximide Essential Generics 250 mg Capsules

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ethosuximide 250mg/capsule

3 PHARMACEUTICAL FORM

Capsule for oral use.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Ethosuximide 250 mg Capsules gives selective control of absence seizures (petit mal) even when complicated by grand mal.

It is also indicated for myoclonic seizures.

4.2 Posology and method of administration

Adults, the Elderly and Children over 6 Years: Start with a small dose - 500mg daily with increments of 250mg every five to seven days until control is achieved with 1000 - 1500 mg daily. Occasionally 2000 mg in divided doses may be necessary.

Children aged 0-6 years old and those who are unable to swallow capsules should be given ethosuximide oral liquid. Currently available clinical trial data regarding the use of ethosuximide in the paediatric population are described in section 5.1.

Effective plasma levels of ethosuximide normally lie between 40 and 100 mcg per ml, but the clinical response should be the criteria for the regulation of the dosage. The half-life of ethosuximide in the plasma is more than 24 hours but the daily dose if large is more comfortably divided between morning and evening.

Contraindications

Known hypersensitivity to succinimides. Porphyrias.

4.4 Special warnings and precautions for use

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of antiepileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for ethosuximide.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Use with caution in hepatic or renal impairment. Monitor liver/renal function and ethosuximide concentrations.

If Ethosuximide 250 mg Capsules is being substituted for another anti-epileptic drug the latter must not be withdrawn abruptly but the replacement made gradually with overlap of the preparations otherwise petit mal may break through.

Ethosuximide 250 mg Capsules should always be withdrawn slowly.

4.5 Interaction with other medicinal products and other forms of interaction

The plasma concentrations of ethosuximide may be reduced by carbamazepine, primidone, phenobarbitone and lamotrigine and increased by isoniazid. No consistent changes in levels of ethosuximide occur when used in combination with phenytoin or sodium valproate. Phenytoin levels however are increased by concomitant ethosuximide.

4.6 Pregnancy and lactation

Ethosuximide may be excreted into breast milk. Mothers receiving the drug should not breast feed. There is a recognised small increase in the incidence of congenital malformations in children born to mothers receiving anti-convulsants. For women planning pregnancy or who are already pregnant the risk should be weighed carefully against the benefit of treatment.

4.7 Effects on ability to drive and use machines

Patients should be cautioned that ethosuximide may cause drowsiness and if this occurs should avoid driving or operating machinery.

4.8 Undesirable effects

Blood dyscrasias (leucopenia, agranulocytosis, aplastic anaemia and pancytopenia) have been reported, some with fatal outcome. In most cases of leucopenia the blood picture has returned to normal on reduction of dose or discontinuation. In some instances, patients who become leucopenic on other anticonvulsant therapy have been satisfactorily treated with ethosuximide alone. Elevated neutrophil, monocyte and eosinophil counts have also been noted. Patients should be advised to seek immediate medical attention for full blood count tests if symptoms such as fever, sore throat, mouth ulcers, bruising or bleeding develop.

Ethosuximide when used alone in mixed types of epilepsy may increase the frequency of generalised tonic-clonic (grand mal) seizures in some patients.

Other adverse reactions reported include: weight loss, diarrhoea, abdominal pain, gum hypertrophy, swelling of the tongue, hiccoughs, irritability, hyperactivity, sleep disturbances, night terrors, inability to concentrate, aggressiveness, paranoid psychosis, increased libido, myopia, and vaginal bleeding.

Mild side effects, common at first but generally transient, include apathy, euphoria, fatigue, drowsiness, dizziness, headache, ataxia, dyskinesia, photophobia, depression, nausea, vomiting, anorexia and gastric upset.

Psychotic states thought to be induced or exacerbated by anticonvulsant therapy have been reported.

Rarely cases of skin rash and isolated cases of erythema nodosum have been reported. Lupuslike reactions have occasionally been reported in children given ethosuximide, varying from severe systemic immunological disorders, e.g. the nephrotic syndrome generally with complete recovery on drug withdrawal, to the detection of antinuclear antibodies without clinical features. Stevens-Johnson syndrome has also been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Where more than 2g has been thought to be ingested gastric lavage may be employed, if the time lapse is less than four hours.

Routine observation of respiration and circulation will indicate the need for supportive measures.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Ethosuximide gives selective control of absence seizures (petit mal) even when complicated by grand mal. It is also indicated for myoclonic seizures. Compared to other anti-convulsants, ethosuximide is more specific for pure petit mal.

The reduction of seizure frequency is thought to be achieved by depression of the motor cortex and elevation of the threshold to convulsive stimuli as seen by the suppression of the characteristic spike and wave EEG pattern.

In a double-blind randomized trial of 20 weeks duration in 453 children aged 2.5 to 13 years old with newly diagnosed childhood absence epilepsy, the efficacy, tolerability, and neuropsychlogical effects of ethosuximide, valproic acid and lamotrigine as monotherapy in childhood absence epilepsy were investigated. Those treated with either ethosuximide or valproic acid had higher freedom-from-failure rates (53% and 58%, respectively) than those given lamotrigine (29%; odds ratio with ethosuximide vs. lamotigine, 2.66; 95% confidence interval [CI], 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). In both prespecified and post hoc analyses, ethosuximide resulted in fewer attentional effects as compared with valproic acid (at week 16 and week 20, the percentage of subjects with a Confidence Index score of 0.60 or higher in the Conners’ Continuous Performance Test was greater in the valproic acid group than in the ethosuximide group (49% vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03) and the lamotigine group (49% vs. 24%; odds ratio, 3.04; 95% CI, 1.69 to 5.49; P<0.001).

5.2 Pharmacokinetic properties

Ethosuximide is readily absorbed from the gastro-intestinal tract and extensively metabolised in the liver. It is excreted in the urine mainly in the form of its metabolites. It is widely distributed throughout the body but is not significantly bound to plasma proteins so saliva concentrations may be useful for monitoring. Peak serum levels occur 1 to 7 hours after single oral dose. Therapeutic levels are between 40 and 100 mcg/ml. It has a long elimination half life: adults 40 - 60 hours; children 30 hours.

5.3 Preclinical safety data

None stated

6 PHARMACEUTICAL PARTICULARS

List of excipients

Polyethylene glycol 400

Gelatin

Glycerin

Sodium ethyl hydroxybenzoate Sodium propyl hydroxybenzoate Miglycol 812 (Fractionated coconut oil) Soya lecithin

6.2    Incompatibilities

None stated.

6.3    Shelf life

5 years

6.4    Special precautions for storage

Store below 30°C away from moisture, do not refrigerate.

6.5    Nature and content of container

Grey polypropylene container with a white low density polyethylene cap, containing 56, 112 or 500 capsules.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special instructions

7    MARKETING AUTHORISATION HOLDER

Chemidex Pharma Ltd.,

T/S Essential Generics, Chemidex Generics, Tarns Pharmaceuticals Chemidex House Egham Business Village,

Crabtree Road, Egham, Surrey TW20 8RB United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 17736/0085

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

29/01/2007

10    DATE OF REVISION OF THE TEXT

11/05/2015