The Health Sciences Authority (HSA) would like to bring to the attention of healthcare professionals, post-marketing reports of acute pancreatitis in patients treated with Sitagliptin (Januvia®, Janumet®, Merck Sharp and Dohme).
Sitagliptin belongs to a new class of antidiabetic drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors. The inhibition of the enzyme DPP-4, slows down the inactivation of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulintropin polypeptide (GIP) thereby prolonging the action of these hormones in glucose homeostasis.Locally, sitagliptin has been licensed as a single agent, under the brand name Januvia® since April 2007, and as a combination product with metformin under the brand name Janumet® since April 2008.
Post-marketing reports of pancreatitis
Between October 2006 and February 2009, the US Food and Drug Administration (FDA) has been receiving post-market reports of acute pancreatitis in patients treated with sitagliptin and sitagliptin/metformin. As of 9 February 2009, a total of 88 cases of acute pancreatitis were received by the US FDA, including two cases of haemorrhagic or necrotising pancreatitis. The most common adverse events reported were abdominal pain, nausea and vomiting.
Of these 88 cases of acute pancreatitis, hospitalisation was reported in 58 (66%) patients, four of which were critical cases admitted to the intensive care unit (ICU). Both patients with haemorrhagic or necrotising pancreatitis required extended stay in the hospital with medical management in the ICU.
Further analysis of the reported cases found that 19 (22%) cases of pancreatitis occurred within 30 days of starting sitagliptin or sitagliptin/metformin. A positive de-challenge was also seen in 47 (53%) cases where pancreatitis resolved once sitagliptin was discontinued. Of note however, was that 45 (51%) of these cases were associated with at least one other risk factor for developing pancreatitis, such as obesity, high cholesterol and/or high triglycerides.
Actions taken by US FDA
The US FDA is working with the company to revise the prescribing information in the package inserts of sitagliptin and sitagliptin/metformin to alert healthcare professionals of this potentially serious adverse event. The prescribing information will be updated to include post-marketing reports of acute pancreatitis such as fatal and non-fatal haemorrhagic or necrotising pancreatitis. Healthcare professionals are also advised to monitor patients carefully for the development of pancreatitis after initiation and dosageincrements of sitagliptin, and to discontinue sitagliptin or sitagliptin/metformin if pancreatitis is suspected while using these products.
Sitagliptin has not been studied in patients with a history of pancreatitis. Therefore, it is not known whether these patients are at an increased risk for developing pancreatitis and the medication should be used with caution and with appropriate monitoring in patients with a history of pancreatitis.
Local situation and HSA's advisory
To date, HSA has not received any local reports of acute pancreatitis associated with Januvia® or Janumet®. The local package inserts for Januvia® and Janumet® are being updated with the post-marketing reports of pancreatitis.
Physicians are encouraged to monitor their patients carefully for the development of pancreatitis after the initiation or dosage increments of sitagliptin and to advise their patients taking Januvia® or Janumet® to look out for signs and symptoms of acute pancreatitis including persistent severe abdominal pain which may be accompanied by nausea, vomiting and anorexia. Early recognition is important in reducing adverse health outcomes. When pancreatitis is suspected, Januvia® or Janumet® should be discontinued.
Healthcare professionals are also encouraged to report adverse reactions suspected to be associated with the use of Januvia® and Janumet® to the Vigilance Branch of HSA.
References
- FDA Medwatch: Sitagliptin (marketed as Januvia and Janumet)
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm183800.htm
- FDA Information for Healthcare Professionals: Acute pancreatitis and sitagliptin
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsand Providers/DrugSafetyInformationforHeathcareProfessionals/ucm183764.htm