Valproic Acid—Induced Pancreatitis in Childhood Epilepsy: Case Series and Review

Abstract

In the past 6 years, 11 children on valproic acid have developed pancreatitis in our children's hospital. Valproic acid has been used as one of the primary anticonvulsants for generalized seizures in children for the past 25 years. A literature review reveals mostly singular reports of pancreatitis over the past decade. The charts of the 11 patients with valproic acid-induced pancreatitis were reviewed. Dosage, valproic acid serum levels, duration of therapy, and concomitant medications were examined. Families were contacted by telephone to determine the formulation (brand name vs generic) of valproic acid at the time of diagnosis. Six girls and five boys were studied. The ages ranged from 4 to 16 years. Eight of 11 children presented with an acute abdomen. Unexpectedly, three children presented with a flulike illness. Serum lipase values ranged from 341 to 5576 U/L (normal range < 190 U/L). The dose of valproic acid ranged from 20 to 50 mg/kg. Serum levels ranged from 334 to 884 micromol/L (therapeutic range 350-800 micromol/L). Six of the patients were on monotherapy. Seven children were on brand-name drugs. Four of the children had an abnormal neurologic syndromic diagnosis (West syndrome, Rett syndrome, Lowe syndrome, and Angelman's syndrome). Six of the children had a history of drug allergies with a skin rash. Valproic acid was reintroduced in one child and resulted in a second episode of pancreatitis. Resolution of symptoms usually took several weeks following discontinuation of the drug. No association was found with valproic acid dosage, type of preparation, serum levels, duration of therapy, or presence of concomitant medications. Pancreatitis is a severe adverse effect of valproic acid use in children. Dose, duration of treatment, serum valproic acid levels, generic preparation, and the presence of concomitant antiepileptic drugs do not appear to be risk factors. Children with known drug sensitivity might be at risk. Lipase levels at the time of an acute abdomen or a flulike illness in epileptic children taking valproic acid can reveal early stages of pancreatitis and are recommended.

Valproic acid-induced acute pancreatitis in pediatric age: case series and review of literature

“…In belong others articles have been published on this theme, followed by numerous reports (11)(12)(13)(14) and case control to establish, certainly, that VPA may cause the AP (15). Some authors have suggested that the problem of the risk AP VPAinduced may be more common than thought, pointing out that the risk increases after the first year of therapy and that its suspension causes a resolution of the symptoms(16).…”

Valproic acid induced acute necrotizing pancreatitis

“…Furthermore, dose, duration of treatment, serum valproic acid levels, generic preparation, and the presence of concomitant antiepileptic drugs have not shown any implication in causing pancreatitis. [15][16][17] Altered renal function test with raised serum creatinine of 6.4mg/ dl and urea of 126mg/dl in our patient with previously normal renal function could be due to contrast used for CECT -contrast induced nephropathy, although AP could also be attributable.…”

“…Sinclair notified 2 such cases in 5 and 8 years old child in her 11 case series of VPA associated pancreatitis in pediatric age group. 16 Younger age group and first year of initiation of treatment have been determined as risk factors for VPA associated pancreatitis. In most patients, early discontinuation of the drug resulted in successful resolution of the symptoms, as was in our case.…”

Valproic Acid Induced Acute Pancreatitis – A case report

“…But this mitochondrial b-oxidation enzyme deficient theory was challenged by other workers who did not find any change in amino acid levels responsible for VPA induced pancreatitis 9 . The diagnosis of pancreatitis is made on clinical findings 10 as well as increase in serum amylase and lipase values 11 . Abdominal ultrasound is useful in the preliminary evaluation of patients suspected of having acute pancreatitis and it should be done in the first 24-48 hours from the onset of the clinical symptoms 12 as was done in the present case.…”