Valproic acid-associated pancreatitis: report of three cases and a brief review

Lott, John; Bond, Liz; Bobo, Robert C.; McClung, H J; Murray, Robert

doi:10.1093/clinchem/36.2.395

Cited by 24 publications

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“…[4][5][6] Following these letters, there have been several case reports of pancreatitis in children receiving valproic acid for epilepsy. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] An early case report and review of the literature helped clearly establish valproic acid as a cause of pancreatitis and warned about the need to consider pancreatitis in any patient presenting with abdominal pain and vomiting. 7 This report, however, was published in the gastroenterology literature, and there appeared to be little recognition by child neurologists of the risk of pancreatitis for children taking valproic acid for epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…2 Rarely, pancreatitis has been reported, usually as single case reports. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Recently, a case series of children with pancreatitis from valproic acid was reported, 23 suggesting that the problem might be more common than is appreciated. In the Pediatric Epilepsy Clinic of the Comprehensive Epilepsy Program at the University of Alberta, we recently encountered 11 patients on valproic acid who developed pancreatitis.…”

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confidence: 99%

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

2004

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

2004

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“…Pancreatitis associated with valproate (VPA) was first reported in 1979 (Batalden et al, 1979;Camfield et al, 1979). We identified 24 cases reported in the medical literature (Batalden et al, 1979;Camfield et al, 1979;Coulter and Allen, 1980;Lankisch et al, 1980;Sasaki et al, 1980;Murphy et al, 1981;Parker et al, 1981;Callaghan et al, 1982;Ng et al, 1982;Williams et al, 1983;Baskies, 1984; Wyllie et al, 1984;Tannhauser Barros et al, 1986;Braun et al, 1987;Rosenberg et al, 1987;Pippenger et al, 1989;Lott et al, 1990). Although VPA evidently can induce pancreatitis, little is known about the magnitude of the problem.…”

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confidence: 99%

Valproate‐Associated Pancreatitis

et al. 1993

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To assess the clinical characteristics of valproate (VPA)-associated pancreatitis, information from three sources was gathered: (a) a survey among 507 physicians with a special interest in treatment of epilepsy, (b) a review of the authors' patient population, and (c) a review of the literature. Of 366 physicians answering the survey, 53 (14.5%) reported a case of pancreatitis. Thirty-nine cases were available for review (24 from the medical literature, 12 from the survey, and 3 from the authors). Pancreatitis appeared to be more frequent in young persons (mean age 16.4 years) but may occur at any age. The highest risk appears to exist during the first months of treatment: 43.8% of the cases developed during the first 3 months, and 68.8% developed during the first year. Seventy-six percent of patients were receiving polytherapy, and 41% had some form of associated chronic encephalopathy. In most patients, the reaction was rapidly reversible when VPA was discontinued. It was severe in 6 patients, with 3 deaths reported. Rechallenge with VPA was attempted in 9 patients, with a high incidence of relapses. Asymptomatic elevation of serum amylase in patients receiving VPA was reported by 40 (10.9%) of the physicians surveyed. Awareness of the problem and early discontinuation of VPA may be effective in preventing serious reactions.

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“…The first case of acute pancreatitis due to VPA was reported in 1979 (4). Since then, 55 cases have been reported in the literature (2,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The patients have ranged from one to 65 years of age and have developed pancreatitis after using VPA from six days to 14 years.…”

Section: Discussionmentioning

confidence: 99%

“…There have been four deaths due to VPA-induced pancreatitis (8,11,14,16), all from the initial acute attack. Many other patients, however, have been 'rechallenged' with VPA after resolution of an episode of acute pancreatitis before it was recognized that VPA was the cause.…”

Section: Discussionmentioning

confidence: 99%

A Case of Chronic Pancreatic Insufficiency Due to Valproic Acid in a Child

Cooper

Groll

2001

Canadian Journal of Gastroenterology

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A 14-year-old child treated with valproic acid over several years for a seizure disorder developed abdominal pain with radiological evidence of acute pancreatitis. The association with valproic acid was not recognized, and the child continued to take the drug. The patient eventually developed steatorrhea and weight loss that improved with pancreatic enzyme replacement. Radiological evaluation showed an atrophic pancreas. Without evidence of other etiological factors, valproic acid by itself appeared to be the cause of chronic pancreatitis with exocrine pancreatic insufficiency in this patient.

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Valproic acid-associated pancreatitis: report of three cases and a brief review

Cited by 24 publications

References 0 publications

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

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

Valproate‐Associated Pancreatitis

A Case of Chronic Pancreatic Insufficiency Due to Valproic Acid in a Child

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