Sodium Valproate (Paediatric — Epilepsy)

PAEDIATRIC DOSING IS RECORDED IN THE paedDose FIELD AND MUST BE VERIFIED AGAINST A CHILDREN'S FORMULARY. Verbatim SPC section 4.2 paediatric text: '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: Initial dosage should be 20 mg/kg of body weight per day; in severe cases this may be increased but only in patients in whom plasma valproic acid levels can be monitored. In children requiring doses higher than 40 mg/kg/day, clinical chemistry and haematological parameters should be monitored.' GENERAL: daily dosage requirements vary according to age and body weight. Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary; a method for measurement of plasma levels is available and may be helpful where there is poor control or side effects are suspected. In patients where adequate control has been achieved, Epilim Chrono formulations are interchangeable with other Epilim conventional or prolonged release formulations on an equivalent daily dosage basis. COMBINED THERAPY: when starting Epilim Crushable in patients already on other anticonvulsants, these should be tapered slowly; initiation should then be gradual with target dose reached after about 2 weeks. In certain cases it may be necessary to raise the dose by 5 to 10 mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbital and carbamazepine; once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced. ELDERLY: pharmacokinetics are modified but of limited clinical significance; dosage should be determined by seizure control. HEPATIC: salicylates should not be used concomitantly with valproate since they employ the same metabolic pathway; salicylates should not be used in children under 16 years of age, and in conjunction with valproate concomitant use in children under 3 years of age can increase the risk of liver toxicity. REGULATORY RESTRICTION (SPC section 4.2, applies directly to paediatric prescribing): 'No new female patients aged under 55 years should be initiated on valproate unless two specialists independently consider and document that there is no other effective or tolerated treatment.' 'Valproate should not be prescribed in female children and women of childbearing potential aged under 55 years unless two specialists independently consider and document that there is no other effective or tolerated treatment.' Valproate must be supervised by a specialist experienced in the management of epilepsy, and must be prescribed and dispensed according to the Valproate Pregnancy Prevention Programme. 'No new male children or men aged under 55 years should be initiated on valproate unless two specialists independently consider and document that there is no other effective or tolerated treatment or the risk of infertility or potential risk of testicular toxicity are not applicable'; the specialist should discuss and complete the risk acknowledgement form with the patient and/or carer at initiation. Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation. Discontinuation should normally only be done under the supervision of a specialist and in a gradual manner. NICE has advised that generic switching of valproate preparations is not normally recommended. US LABELLING (openFDA, valproic acid oral solution, NorthStar Rx, 2024-05-27) is NOT the basis of the fields above and differs from the UK SPC; quoted only for cross-check: complex partial seizures in adults and children 10 years or older - initiate at 10 to 15 mg/kg/day, increase by 5 to 10 mg/kg/week, optimal response ordinarily below 60 mg/kg/day; simple and complex absence seizures - initial 15 mg/kg/day increasing at one-week intervals by 5 to 10 mg/kg/day, maximum recommended dosage 60 mg/kg/day; if the total daily dose exceeds 250 mg it should be given in divided doses. SOURCE COMPLETENESS: eMC section 4.5 (interactions) was NOT captured in this bundle, and sections 4.4, 4.6 and 4.8 were truncated at the source-fetch limit - do not treat the lists below as complete.

dosePerKg 20 is the SPC's stated initial dosage for children UNDER 20 kg ('Initial dosage should be 20 mg/kg of body weight per day'), and is also the lower bound of the usual maintenance range for all children (20 to 30 mg/kg body weight per day). IMPORTANT WEIGHT-BAND DIFFERENCE: for children OVER 20 kg the SPC specifies a FLAT initial dose of 400 mg/day 'irrespective of weight', with spaced increases until control is achieved, and NOT a per-kg initial dose - do not apply 20 mg/kg as the starting dose in a child over 20 kg. For children under 20 kg, in severe cases the initial 20 mg/kg/day may be increased but only in patients in whom plasma valproic acid levels can be monitored. Monotherapy is recommended in children under the age of 3 years; the potential benefit should be weighed against the risk of liver damage or pancreatitis prior to initiation. Infants and in particular young children under the age of 3 years are those most at risk of severe liver damage, especially in cases of multiple anticonvulsant therapy; after the age of 3 years the incidence is significantly reduced. Concomitant salicylates should be avoided in children under 3 years of age due to the risk of liver toxicity, and salicylates should not be used in children under 16 years of age at all. When barbiturates are given concomitantly and sedation is observed, particularly in children, the barbiturate dosage should be reduced. Verify against a children's formulary before use.