SEIZORA

Posology Seizora is a prolonged release formulation which reduces peak concentration and ensures more even plasma concentrations throughout the day. Seizora may be given once or twice daily. Daily dosage requirements vary according to age and body weight.

Dosage Usual requirements are as follows:

Adults Dosage should start at 600 mg daily increasing by 200 mg at three-day intervals until control is achieved. e. 20 – 30 mg/kg/day body weight. Where adequate control is not achieved within this range the dose may be further increased to 2500 mg per day.

Special populations Paediatric population Children over 20 kg:

Initial dosage should be 400 mg/day (irrespective of weight) with spaced increases until control is achieved; this is usually within the range 20 – 30 mg/kg body weight per day. Where adequate control is not achieved within this range the dose may be increased to 35 mg/kg body weight per day.

In children requiring doses higher than 40 mg/kg/day, clinical chemistry and haematological parameters should be monitored.

Children under 20 kg:

An alternative formulation of sodium valproate should be used in this group of patients, due to the tablet size and need for dose titration. Liquid formulations of sodium valproate are available which would be more suitable for this patient group.

Elderly Although the pharmacokinetics of valproate are modified in the elderly, they have limited clinical significance and dosage should be determined by seizure control. The volume of distribution is increased in the elderly and because of decreased binding to serum albumin, the proportion of free drug is increased.

This will affect the clinical interpretation of plasma valproic acid levels. Renal impairment It may be necessary in patients with renal insufficiency to decrease the dosage, or to increase the dosage in patients on haemodialysis. 9).

4). 8). 4). Salicylates should not be used in children under 16 years of age (see aspirin/salicylate product information on Reye’s syndrome). 1). 6). Valproate must be supervised by a specialist experienced in the management of epilepsy.

The following CIOMS frequency rating is used, when applicable:

Very common (≥ 1/10); common (≥ 1/100 to ≤ 1/10); uncommon (≥ 1/1,000 to ≤ 1/100); rare (≥ 1/10,000 to ≤ 1/1,000); very rare (≤ 1/10,000); not known (cannot be estimated from the available data). 6). 1). 1).

Gastrointestinal disorders:

Very common: nausea Common: vomiting, gingival disorder (mainly gingival hyperplasia), stomatitis, gastralgia, diarrhoea The above adverse events frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment.

These problems can usually be overcome by taking Seizora with or after food. 4) Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder Sedation has been reported occasionally, usually when in combination with other anticonvulsants.

In monotherapy it occurred early in treatment on rare occasions and is usually transient. *Rare cases of lethargy occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed.

These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anti-convulsants, notably phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage.

An increase in alertness may occur; this is generally beneficial but occasionally aggression, hyperactivity and behavioural deterioration have been reported. 4). 2), obesity *Cases of isolated and moderate hyperammonaemia without change in liver function tests may occur, are usually transient and should not cause treatment discontinuation.

Although there is no specific evidence of sudden recurrence of underlying symptoms following withdrawal of valproate, discontinuation should normally only be done under the supervision of a specialist in a gradual manner. This is due to the possibility of sudden alterations in plasma concentrations giving rise to a recurrence of symptoms.

NICE has advised that generic switching of valproate preparations is not normally recommended due to the clinical implications of possible variations in plasma concentrations. 1 Special warnings Liver dysfunction: Conditions of occurrence: Severe liver damage, including hepatic failure sometimes resulting in fatalities, has been very rarely reported.

4) or degenerative disease associated with mental retardation. After the age of 3 years, the incidence of occurrence is significantly reduced and progressively decreases with age. 5). Additionally, salicylates should not be used in children under 16 years of age (see aspirin/salicylate product information on Reye’s syndrome).

5). In most cases, such liver damage occurred during the first 6 months of therapy, the period of maximum risk being 2 – 12 weeks.

Suggestive signs:

Clinical symptoms are essential for early diagnosis. In particular the following conditions, which may precede jaundice, should be taken into consideration, especially in patients at risk (see above: ‘Conditions of occurrence’): - non-specific symptoms, usually of sudden onset, such as asthenia, malaise, anorexia, lethargy, oedema and drowsiness, which are sometimes associated with repeated vomiting and abdominal pain.

- in patients with epilepsy, recurrence of seizures. These are an indication for immediate withdrawal of the drug. Patients (or their family for children) should be instructed to report immediately any such signs to a physician should they occur.

6). 6). 1. • Active liver disease, or personal or family history of severe hepatic dysfunction, especially drug related. 4). • Porphyria. g. 4). 4).