Prescriber Update Articles

Drug-Induced Pancreatitis:  An Unlucky DIP

Website: December 2005
Prescriber Update 2005;26(2):32-33

Dr Michael Tatley, Director, CARM, New Zealand Pharmacovigilance Centre, Dunedin

Medicines are amongst the common causes of acute pancreatitis, although they may not initially be thought of as an obvious causative factor.  Those medicines more frequently implicated include anti-HIV agents, statins, tetracyclines and valproate.  Prescribers should have a high index of suspicion in patients presenting with acute pancreatitis without an apparent cause, particularly if it is recurrent.

Consider medicines as a potential cause of acute pancreatitis
Local and international reports implicate a range of commonly used medicines
Well-recognised but under-reported
References

Consider medicines as a potential cause of acute pancreatitis

The causes of acute pancreatitis are varied but gallstones have been identified as the causative factor in 30-60% of published cases.  Chronic alcohol consumption accounts for 15-30% of cases, with hypertriglyceridemia contributing to another 1.3-3.8%.  Drug-induced pancreatitis (DIP) is thought to account for 2-5% of cases of acute pancreatitis.¹

DIP can occur in both children and adults,^2,3 with as many as 13% of paediatric cases of acute pancreatitis being due to medicines.²  Time to onset can be six (or even nine²) months after commencement of the suspect causative medicine.³

Local and international reports implicate a range of commonly used medicines

As at October 2005, the Centre for Adverse Reactions Monitoring had received 55 reports of DIP.  In 23 of these cases, each patient was receiving only one suspect medicine.  In 11 of the reports where outcomes were known, there had been improvement following de-challenge.  The most frequently reported suspect agents were ACE inhibitors (n=6), valproate (n=4), tetracyclines (n=3), statins (n=3) and mesalazine (n=2).  The Australian Adverse Drug Reactions Advisory Committee has received 379 reports of DIP.  In approximately two-thirds of these cases patients were taking only one suspect medicine;⁴ the medicines implicated were similar to those in New Zealand.

In the literature,²,³,⁵ and the World Health Organisation's international database of adverse reactions, the most frequently reported medicines implicated in DIP are anti-HIV agents, atypical antipsychotics, azathioprine, mesalazine, oestrogens, statins, sulphonamides, tetracyclines, valproate and 6-mercaptopurine.

Well-recognised but under-reported

As is frequently the case in iatrogenic injury involving medicines, DIP is thought to be caused either by a hypersensitivity reaction or by the generation of a toxic metabolite.  It is not always clear which of these mechanisms is operative.¹

While medicines are regarded as a common cause of acute pancreatitis,¹ DIP is rarely reported.  Prescribers should have a high index of suspicion for DIP in patients with acute pancreatitis without an obvious cause, particularly if it is recurrent.  Where a medicine has been implicated in the aetiology of a patient's acute pancreatitis, the patient should not be re-exposed to that medicine.

Competing interests (author): none declared.

References

1. Greenberger NJ, Toskes PP. Acute and Chronic Pancreatitis. In Kasper DL, Braunwald E, Fauci AS, et al (Eds) Harrison's Principles of Internal Medicine 16th Edn. 2005: The McGraw-Hill Companies Inc, United States of America (on-line version accessed).
2. Pellock JM, Wilder BJ, Deaton R, Sommerville KW. Acute pancreatitis coincident with valproate use: A critical review. Epilepsia 2002;43(11):1421-1424.
3. Koller EA, Cross JT, Doraiswamy PM, Malozowski SN. Pancreatitis associated with atypical antipsychotics: From the Food and Drug Administration's MedWatch surveillance system and published reports. Pharmacotherapy 2003;23(9):1123-1130.
4. Personal communication, 14 November 2005. Medical Officer, Adverse Drug Reactions Unit, Therapeutic Goods Administration, Australia.
5. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: An update. J Clin Gastroenterol 2005;39(8):709-716.