The FDA has requested that label information for the diabetes drug sitagliptin (Januvia) caution users about a heightened risk of acute pancreatitis.

“Eighty-eight postmarketing cases of acute pancreatitis, including two cases of hemorrhagic or necrotizing pancreatitis in patients using sitagliptin, were reported to the agency between Oct. 16, 2006 and Feb. 9, 2009,” the FDA said in an alert today.

The agency said it’s working with sitagliptin’s manufacturer, Merck & Co., on revisions to its prescribing information. The change also covers Janumet, which combines the sitagliptin with metformin. The revisions will include:

• Information regarding postmarketing reports of acute pancreatitis, including the severe forms, hemorrhagic or necrotizing pancreatitis
• Recommendations that healthcare professionals monitor patients carefully for the development of pancreatitis after initiation or dose increases of sitagliptin or sitagliptin/metformin, and to discontinue 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

The FDA noted that in the absence of such studies, it’s unclear whether these patients are at increased risk for developing recurrent pancreatitis while on the drug.

A statement indicating that sitagliptin or sitagliptin/metformin “should be used with caution and with appropriate monitoring in patients with a history of pancreatitis” will likely be included, the FDA said.

Acute pancreatitis is beginning to look like a class effect for the newer drugs against diabetes that act through the glucagon-like peptide-1 pathway.

Two years ago, the FDA demanded a similar label change for the incretin mimetic exenatide (Byetta), after 30 pancreatitis cases were reported. (See FDA Wants Pancreatitis Caution Added to Exenatide (Byetta) Label)

Both exenatide and sitagliptin act through receptors for GLP-1 — exenatide is a synthetic mimic of the peptide, while sitagliptin inhibits the dipeptidyl peptidase-4 enzyme that degrades GLP-1 in vivo.

Another DPP-4 inhibitor, saxagliptin (Onglyza), was approved in July. Its label does not mention pancreatitis risk.

Following the FDA announcement, Merck issued a statement saying its own analysis did not confirm an excess risk.

“Merck has thoroughly reviewed the safety data for sitagliptin, and sitagliptin was not associated with an increase in the incidence of pancreatitis in preclinical studies or in clinical trials of up to two years in duration with more than 6,000 patients,” the company said.

“Merck has also carefully reviewed postmarketing adverse experience reports, and Merck believes these data do not demonstrate that a causal relationship exists between sitagliptin and pancreatitis.”

The statement added that pancreatitis is a known complication of type 2 diabetes and pointed out that the FDA had previously acknowledged the difficulty in attributing the condition to antidiabetic drugs.

Related Article(s):

• FDA Wants Pancreatitis Caution Added to Exenatide (Byetta) Label

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