Valproic acid-induced pancreatitis: 16 new cases and a review of the literature

Gerstner, Thorsten; Büsing, D; Bell, Nellie; Longin, Elke; Kasper, Johannes-Martin; Klostermann, W.E.M.; Hebing, B.; Hanefeld, F.; Eckel, U; Hoffmann, Reiner; Bettendorf, U; Weidner, Birgit; Wiemer‐Kruel, Adelheid; Brockmann, Knut; Neumann, Fritz-Wilhelm; Sandrieser, T; Wolff, Markus; König, Stephan

doi:10.1007/s00535-006-1961-4

Cited by 87 publications

(72 citation statements)

References 51 publications

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“…31 The incidence of sodium valproateinduced pancreatitis has been estimated to be 1:40,000. 32 The mechanism of valproate induced acute pancreatitis is "idiosyncratic," a direct toxic effect of free radicals on the pancreatic cell membrane by depletion of superoxide dismutase, catalase, and glutathione peroxidase has been assumed. 33,34 Long-term antiretroviral drug-based treatments cause serious toxic effects.…”

Section: Discussionmentioning

confidence: 99%

Profile of serious adverse drug events in a tertiary care hospital of South India - a five years experience

Jayanthi

Pasha

Sushma

2017

Int J Basic Clin Pharmacol

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Background: Adverse drug event (ADE) is said to be serious, when it is life-threatening, leads to hospitalization, disability, congenital anomaly, death or requires intervention to prevent permanent impairment or damage. The present study aimed to determine the pattern, causality, preventability of serious ADEs.Methods: This retrospective study was carried out to profile serious ADEs reported from Bangalore Medical College and Research Institute to Adverse Drug Reaction (ADR) Monitoring Centre, under Pharmacovigilance Programme of India from 2012 to 2016. Patient demographics, clinical and drug data, details of the ADE, onset time, causal drug details, outcome and severity were collected as per CDSCO form. Causality was assessed by WHO-ADR probability scale, preventability by modified Schumock and Thornton scale.Results: A total of 809 ADEs were reported, of which 50 (6.18%) were serious in nature. Male preponderance (74%) was observed, with 42% among patients aged 20-40 years. 56% of serious ADEs were reported from department of Dermatology. Steven Johnson Syndrome (SJS) (20%) contributed for most of the ADEs. Antiepileptics caused maximum number of serious ADEs (32%). 76% of the ADEs were found to be ‘probable’ and 4% were definitely preventable. 56% of them was life threatening and 86% required intensive interventions. 16% patients experienced serious ADEs during hospital stay.Conclusions: Serious ADEs constituted 6.18% of all ADEs reported. SJS was commonly seen with antimicrobials and hepatotoxicity with ATT. Antiepileptics and ATT contributed for majority of them. This study highlights the importance of monitoring and timely management of serious ADEs to commonly prescribed medications.

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Section: Discussionmentioning

confidence: 99%

Profile of serious adverse drug events in a tertiary care hospital of South India - a five years experience

Jayanthi

Pasha

Sushma

2017

Int J Basic Clin Pharmacol

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“…[14] Acute Pancreatitis Had Also Been Reported As A Very Rare Complication Of Valproic Acid Overdose With An Incidence Of 1:40,000. [15] The Exact Mechanism Of Valproate Induced Pancreatitis Is Unknown.…”

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confidence: 99%

Phenytoin and Sodium Valproate Intoxication and Management, a Case Report

PrakashYarramalle¹,

Munta²,

Rao³

et al. 2017

IJAR

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“…7,8 However, long-term administration of VPA (for 1 year) to mice and dogs had no effect on the pancreas, and in rats, there were only subtle microscopic findings of pancreatic lobular atrophy and vacuolization. 9 Short-term exposure to VPA by itself failed to induce any pancreatic changes in these animals.…”

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confidence: 99%

Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs

Eisses

Criscimanna

Dionise

et al. 2015

The American Journal of Pathology

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The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observationsdthat VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injurydwe hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained b-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury. We have recently gained a greater appreciation that the pancreas has a tremendous ability to recover and regenerate after injury.

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Valproic acid-induced pancreatitis: 16 new cases and a review of the literature

Abstract: The difference between 90 patients reported worldwide from 1979 to 2005 and the 16 new documented cases from only Germany over 10 years corroborates that the occurrence of this severe side effect is under reported.

Cited by 87 publications

References 51 publications

Profile of serious adverse drug events in a tertiary care hospital of South India - a five years experience

Profile of serious adverse drug events in a tertiary care hospital of South India - a five years experience

Phenytoin and Sodium Valproate Intoxication and Management, a Case Report

Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs

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