Sodium valproate induced increased frequency of micturition and enuresis
A five year old boy, known case of seizure disorder since one year presented for routine follow up in the pediatrics OPD. He was on syrup Sodium valproate 5ml BD (25mg/kg/day) since two month duration. Syrup was of Sanofi-Synthelabo (India) Ltd with manufacturing date September 2010, expiry dated August 2012 and batch no 210114. Patient was taking the medicine regularly.\nParents of the patient noticed increased frequency of micturition and bed wetting in night one month after starting the present dose of medication and reported this on his follow up visit. The child had approximately 20 episodes per day. Increased frequency was not associated with pain or burning sensation during micturition. There was no history of fever. Child had normal frequency and control of urination prior to AED treatment. No family history suggestive of enuresis was obtained. Child was not on any other medication.\nAt the start of therapy, child was prescribed syp Sodium Valproate in the dose of 2.5ml BD, @ 15 mg/kg/day. He was asymptomatic for 6 months. As the boy once again presented with convulsions, dose of Valproate was increased to 3ml BD. Three months later, child again presented with h/o convulsions inspite of taking regular medication. TDM was done and drug concentration was found to be 37 μgm /dl, which is below the therapeutic concentration (50-100 μgm /dl). Hence the dose was further increased to 5ml BD. Now the child was seizure free since last three months. One month after starting this dose (5ml Bd), child's parents complained of increased frequency of micturition along with bed wetting in night (Enuresis). Child had achieved bladder control at the age of three years and nocturnal enuresis was never a problem with this child. But this time the bed wetting started at this increased dose. Enuresis or bed wetting occurred twice or thrice in the night almost daily for last two months. The child was a bit disstressed due to this devolupment as this has occurred almost after two years of attaining physiological control over micturition.\nOn investigation, complete blood count showed Hb 9.4mg/ dl, WBC 17.3 /cmm, platelets 3lakh. Liver function tests were done and found to be within normal limits (AST- 31IU/L, ALT- 9IU/L). Urine microscopy was within normal limits. Therapeutic drug monitoring of valproate was not done at this increased dose. After the other causes of increased frequency of micturition were ruled out child was diagnosed of Valproate induced increased frequency of micturition and enuresis. The Naranjo's criteria is frequently used for determination of causality for suspected ADRs.[] Causality assessment using the Naranjo's criteria revealed that the drug valproate was the probable cause of this ADR (overall score, 5).