Valproic acid

Simple and complex absence seizures: the recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases; maximum recommended dosage 60 mg/kg/day. If satisfactory clinical response has not been achieved, measure plasma levels to determine whether they are in the usually accepted therapeutic range (50 to 100 mcg/mL); a good correlation has not been established between daily dose, serum concentrations and therapeutic effect. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. Conversion to monotherapy: concomitant antiepileptic drug dosage can ordinarily be reduced by approximately 25% every 2 weeks, started at initiation or delayed by 1 to 2 weeks if seizures are likely on reduction; monitor closely for increased seizure frequency. As the valproic acid dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine and/or phenytoin may be affected. Elderly: due to decreased unbound clearance and possibly greater sensitivity to somnolence, the starting dose should be reduced. Antiepilepsy drugs should not be abruptly discontinued in patients treated to prevent major seizures, because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. The label provides an initial daily dose table for 15 mg/kg/day by weight — 10 to 24.9 kg: 250 mg/day; 25 to 39.9 kg: 500 mg/day; 40 to 59.9 kg: 750 mg/day; 60 to 74.9 kg: 1,000 mg/day; 75 to 89.9 kg: 1,250 mg/day. Source note: no UK SPC posology was available in the fetched bundle — this draft is from the US oral solution label and must be verified against the UK SPC.

The label's per-kg regimen covers 'adults and pediatric patients down to the age of 10 years' for complex partial seizures: initiate at 10 to 15 mg/kg/day, increasing by 5 to 10 mg/kg/week; optimal clinical response is ordinarily achieved at daily doses below 60 mg/kg/day. For simple and complex absence seizures the recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day. A single per-kg figure is not stated for initiation — the label gives a range, so dosePerKg is left null. Pediatric patients under two years of age are at considerably increased risk of fatal hepatotoxicity and valproic acid should be used with extreme caution and as a sole agent in this group; it is contraindicated in children under two years suspected of having a POLG-related disorder. Pediatric patients between 3 months and 10 years have 50% higher weight-adjusted clearance than adults, and younger children — especially those receiving enzyme-inducing drugs — will require larger maintenance doses. Source: US oral solution labelling — verify against the UK SPC.