Valproate pancreatitis with

In addition, an open-label study was conducted examining the efficacy of valproate in ten adolescents with chronic temper outbursts and mood lability ( 193). The authors report that valproate was associated with improvement in all subjects, that discontinuation led to relapse, and that there was subsequent improvement on rechallenge in five of six subjects. Although encouraging, these data are modest in terms of both the numbers and design and must be balanced against the risk of toxicity (e.g., hepatic and pancreatic) with valproate in children. 

Pancreatitis Cases of life-threatening pancreatitis have been reported in children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Warn... 

Indigestion, heartburn, and nausea are common side effects of valproate therapy. Use of the divalproex sodium preparation will help mitigate these effects. Patients may also be encouraged to take their doses with food. The symptomatic use of histamine H2 blockers, such as famotidine, is sometimes warranted. In most cases, however, dyspepsia is transient and not severe. Pancreatitis is a rare occurrence in patients receiving relatively high doses of valproate. If vomiting and severe abdominal pain develop during valproate therapy, serum amylase levels should be determined immediately. 

Sodium valproate is useful in the control of most seizure types and has the shortest half-life of the commonly used anticonvulsants (4—15 hours) a slowly absorbed form of the drug, divalproex sodium, is sometimes preferred. Valproate is relatively free from cognitive and behavioural side effects, but alopecia and weight gain frequently occur. The most severe side effect is idiosyncratic hepatotoxicity and pancreatitis, particularly in younger patients. However, these side effects are more frequent in patients taking valproate as a co-medication with other anticonvulsants. 

Adverse effects are most commonly manifest as acute pancreatitis. The strongest association is with alcohol abuse. High plasma calcium, including that caused by hypervitaminosis D, and parenteral nutrition also increase the risk. Corticosteroids, didanosine, azathoipurine, diuretics (including thiazides and frusemide), sodium valproate, mesalazine and paracetamol (in overdose) have also been causally related. 

Pancreatitis is a rare adverse effect of valproate and can occur in isolation or in association with liver toxicity. In a review of the patients of 366 physicians, 23% of patients taking valproic acid had asymptomatic increases in serum amylase activity but there were only 39 cases of valproate-associated pancreatitis (107). Pancreatitis usually presented with epigastric pain, nausea, and vomiting, and was more common in patients aged under 20 years and with mental retardation. In most cases the pancreatitis started within the first 3 months of treatment, but in 18% the onset was after 2 years. 

There have been over 50 published reports of acute pancreatitis associated with valproate (SEDA-18, 70) (84), including several confirmed by rechallenge. Deaths have occurred from hemorrhagic pancreatic necrosis complications can include pleural and pericardial effusions, coagulopathy, pseudocyst, ascites, wound infection, and pneumonia (SED-13, 151) (85). Hepatotoxicity can coexist. There is suggestive evidence that end-stage renal insufficiency (SEDA-22, 92) and mental retardation (84) can be predisposing factors. 

At least 132 patients have died of liver failure (and/or pancreatitis) (75). The risk is highest (1 600) in children under 2 years of age with complex neurological disorders taking valproate as part of a multidrug regimen (46,76). In older patients the incidence is no more than 1 37 000 for monotherapy and 1 12 000 for multidrug therapy. Deaths beyond 20 years of age are exceedingly rare. 

Valproate should be avoided in patients with a personal or family history of liver disorders or pancreatic dysfunction (75,119). 

Grosse P, Rusch L, Schmitz B. Pancreatitis complicating treatment with intravenous valproate three case reports. Epilepsia 1999 40(Suppl. 2) 267. 

Pellock JM, Wilder BJ, Deaton R, Sommerville KW. Acute pancreatitis coincident with valproate use a critical review. Epilepsia 2002 43(11) 1421. ... 

Hepatic disease hypersensitivity to valproate pregnancy (FDA category D) children < 2 years (especially those on multiple antiwnvulsant therapy, those with congenital metabolic disorders, those with severe seizure disorders, and those with organic brain disease) pancreatitis. 

A rare complication is fulminant hepatitis. Children <2 years of age with other medical conditions who were given multiple antiseizure agents were especially likely to suffer fatal hepatic injury there were no deaths reported for patients >10 years old who received only valproate. Acute pancreatitis and hyperammonemia have been associated with the use of valproic acid. Valproic acid can produce teratogenic effects such as neural tube defects. 

Jetha MM, Fiorillo L. Xanthomata and diabetes in an adolescent with familial dysbetalipoproteinemia 9 years after valproate-induced pancreatitis. Pediatr Diabetes August 2012 13(5) 444-7. 

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