Sodium Valproate (Epilepsy in Elderly)

⚠️ THE ELDERLY QUESTION THIS PAGE EXISTS TO ANSWER — THE SPC'S OWN AND ONLY ANSWER, VERBATIM: '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.' There is NO reduced elderly starting dose, no elderly target range and no elderly maximum in this SPC. Any lower-and-slower start in an older patient is a clinical judgement, not a labelled figure, and none has been invented here. || Only the maximum survives sourcing: 2500 mg/day is confirmed verbatim. The 200 mg twice-daily start and the 500–1500 mg/day target range appear NOWHERE in this SPC, whose figures are a 600 mg daily start, 200 mg increments at three-day intervals and a 1000–2000 mg/day usual range. The live figures are unsourced and are replaced. (200 mg does appear in the SPC — as the increment size and the tablet strength, not as a starting dose.) || DOSE INCREASES IN COMBINATION THERAPY (§4.2, verbatim): 'When starting Epilim Chrono in patients already on other anti-convulsants, these should be tapered slowly; initiation of Epilim Chrono therapy should then be gradual, with target dose being reached after about 2 weeks. In certain cases, it may be necessary to raise the dose by 5 – 10 mg/kg/day when used in combination with anti-convulsants 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 Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of Epilim Chrono. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.' (The 5–10 mg/kg/day figure is a per-kg-per-DAY increment, not a per-dose amount.) || PLASMA LEVELS (§4.2): 'Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. However, a method for measurement of plasma levels is available and may be helpful where there is poor control or side effects are suspected.' Read with the elderly paragraph above: the raised free fraction in older patients affects how a total level is interpreted. || SWITCHING AND WITHDRAWAL (§4.4, verbatim): '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.' §4.2 adds that '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.' || ⚠️ VALPROATE PREGNANCY PREVENTION PROGRAMME AND THE UNDER-55 RESTRICTIONS — these are in §4.2 and apply irrespective of this page's elderly framing, because they turn on age, not indication. Female children and women of childbearing potential aged under 55 years: '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 must be supervised by a specialist experienced in the management of epilepsy... Where possible, existing female children and women of childbearing potential aged under 55 years should be switched to another treatment unless two specialists independently consider and document there is no other effective or tolerated treatment. For those continuing to receive valproate, the benefits and risks of valproate should be carefully reconsidered at regular treatment reviews, at least annually... Valproate must be prescribed and dispensed according to the Valproate Pregnancy Prevention Programme... Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation.' Male patients aged under 55 years: '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.' || PAEDIATRIC — DELIBERATELY OUT OF SCOPE FOR THIS PAGE, so paedDose is null. This page is the elderly epilepsy entry; the SPC's paediatric figures belong to the neurology entry and are recorded here only so they are not lost: '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 Epilim should be used in this group of patients, due to the tablet size and need for dose titration. Epilim Liquid (sugar-free), Epilim Syrup or Epilim Chronosphere are alternatives.' Every one of those per-kg figures is a mg/kg/DAY total, not a per-dose amount, and none has been entered into a weight calculator. Verify any under-18 use against a children's formulary.