Postmarketing reports of acute pancreatitis with sitagliptin products (Janumet, Januvia)
Published in NPS RADAR
Date published: About this date
Monitor and warn about signs and symptoms, particularly in people with risk factors | References
Cases of acute pancreatitis have been reported with sitagliptin (Januvia) and sitagliptin with metformin (Janumet).1 Health professionals should be vigilant for signs and symptoms of pancreatitis during treatment and should use sitagliptin products cautiously in people with a history of pancreatitis.
Report suspected adverse reactions to the Therapeutic Goods Administration (TGA) online or by using the 'Blue Card' distributed 3 times a year with Australian Prescriber. For information about reporting adverse reactions, see the TGA website.
Sitagliptin was first listed on the PBS in 2008, followed by sitagliptin with metformin in 2009. For more information about sitagliptin, see the NPS RADAR review Sitagliptin (Januvia) for type 2 diabetes and In brief item Sitagliptin with metformin (Janumet) fixed dose combination tablets PBS listed for type 2 diabetes mellitus.
Pancreatitis is a possible adverse effect, but a causal association has not been confirmed
Between October 2006 and February 2009 the US Food and Drug Administration (FDA) received 88 reports of acute pancreatitis in people taking sitagliptin or sitagliptin with metformin.1 Symptoms most commonly reported in these cases were nausea, vomiting and abdominal pain.1 Many cases were severe: 58 required hospitalisation (4 in intensive care) and 2 involved haemorrhagic or necrotising pancreatitis.1
In some reports the onset of pancreatitis was soon after starting sitagliptin or sitagliptin with metformin. Nineteen cases were within a month of starting treatment, and more than half of all cases resolved when treatment was stopped.1
A causative relationship between sitagliptin and pancreatitis has not been established. Diabetes itself is a risk factor for pancreatitis. Other risk factors such as hypercholesterolaemia, hypertriglyceridaemia and obesity were also present in 51% of the US cases.1 In clinical trials, the incidence of pancreatitis did not differ significantly between the sitagliptin (0.1%) and non-exposed groups (0%)2, although the data do not rule out a rare adverse effect.
In September 2009 the FDA issued a warning to health professionals about the reports of pancreatitis, and accordingly updated the US prescribing information in December 2009.3,4 The Australian product information for products containing sitagliptin was updated earlier that year to include pancreatitis as a postmarketing adverse event.5,6
Monitor and warn about signs and symptoms, particularly in people with risk factors
Be vigilant for the onset of persistent severe abdominal pain (sometimes radiating to the back), nausea, vomiting and/or anorexia in patients taking sitagliptin or sitagliptin with metformin.1 Advise them to promptly report any signs and symptoms, especially if they have any additional risk factors for pancreatitis.1
Use cautiously and closely monitor treatment in people with a history of pancreatitis.1 Sitagliptin has not been studied in these people.1 It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis with sitagliptin or sitagliptin with metformin.1
If pancreatitis is suspected, stop treatment and investigate (e.g. with a serum amylase test).1
- U.S. Food and Drug Administration. Information for Healthcare Professionals — Acute pancreatitis and sitagliptin (marketed as Januvia and Janumet), 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm183764.htm (accessed 14 January 2010).
- Williams-Herman D, Round E, Swern AS, et al. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocrine Disorders 2008;8:14. [PubMed]
- U.S. Food and Drug Administration. Januvia (sitagliptin) tablets. Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – December 2009. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm196611.htm (accessed 2 February 2010).
- U.S. Food and Drug Administration. Janumet (sitagliptin/metformin HCl) tablets. Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – December 2009. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm196610.htm (accessed 2 February 2010).
- Merck Sharp & Dohme (Aust.) Pty Ltd. Januvia product information. 10 March 2009.
- Merck Sharp & Dohme (Aust.) Pty Ltd. Janumet product information. 15 June 2009.