FDA Issues Advisory for Januvia, Janumet

The FDA is revising the prescribing information for Januvia (sitagliptin) and Janumet (sitagliptin/metformin) to include information on reported cases of acute pancreatitis in patients using these products.
Sitagliptin, the first in a new class of diabetes drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors, is approved as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes.

Between October 16, 2006 and February 9, 2009, the FDA received reports of 88 postmarketing cases of acute pancreatitis, including two cases of hemorrhagic or necrotizing pancreatitis in patients using sitagliptin. Hospitalization was reported in 58 of the patients, four of whom were admitted to the intensive care unit. Two cases of hemorrhagic or necrotizing pancreatitis were identified in the review, and both required an extended stay in the hospital with medical management in the ICU. The most common adverse events reported in the 88 cases were abdominal pain, nausea and vomiting.

Additionally, the analysis found that 19 of the 88 reported cases of pancreatitis occurred within 30 days of starting sitagliptin or sitagliptin/metformin.  Furthermore, 47 of the 88 cases resolved once sitagliptin was discontinued. It is important to note that 45 cases were associated with at least one other risk factor for developing pancreatitis, such as diabetes, obesity, high cholesterol or high triglycerides.

Based on these reports, the FDA is working with the manufacturer of sitagliptin and sitagliptin/metformin to revise the prescribing information to include the following:

• Information regarding postmarketing reports of acute pancreatitis, including the severe forms, hemorrhagic or necrotizing pancreatitis
• Recommendation that healthcare professionals monitor patients carefully for pancreatitis after starting sitagliptin or sitagliptin/metformin or increasing the dose of either drug
• Recommendation that healthcare professionals discontinue a patient's use of sitagliptin or sitagliptin/metformin if pancreatitis is suspected while using these products
• Information noting that 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 while using sitagliptin or sitagliptin/metformin
• Information noting that sitagliptin or sitagliptin/metformin should be used with caution and with appropriate monitoring in patients with a history of pancreatitis

This information reflects the FDA's current analysis of data available to the agency concerning this drug. The FDA intends to issue an update when additional information or analyses become available.

The signs and symptoms of pancreatitis include nausea, vomiting, loss of appetite and persistent, severe abdominal pain, sometimes radiating to the back.

To report any unexpected adverse or serious events associated with the use of this drug, patients and health care providers should contact the FDA MedWatch program:

• By phone: 800-332-1088
• By fax: 800-FDA-0178
• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• By postal mail: Use postage-paid FDA Form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787