Januvia Pancreatitis Problems Refuted by Merck

Following an FDA alert issued Friday about reports of acute pancreatitis associated with use of Januvia and Janumet, Merck & Co., the maker of both diabetes drugs, issued a statement refuting that Januvia side effects increase the risk of acute pancreatitis.

The FDA announced that new information will be added to the prescribing information for Januvia (sitagliptin) and Janumet (sitagliptin/metformin) following at least 88 reports of pancreatitis between October 2006 and February 2009, including two cases of hemorrhagic or necrotizing pancreatitis, which can be fatal.

“Based on the temporal relationship of initiating sitagliptin (Januvia) or sitagliptin/metformin (Janumet) and development of acute pancreatitis in reviewed cases, FDA believes there may be an associated between these events,” wrote the drug regulatory agency in information provided to healthcare professionals on September 25. “Because acute pancreatitis is associated with considerable morbidity and mortality, and early recognition is important in reducing adverse health outcomes, FDA is recommending revisions to the prescribing information to alert healthcare professionals to this potentially serious adverse drug event.”

Merck issued a press release the same day as the FDA, disputing that there is any connection between Januvia and pancreatitis. They indicate that a thorough review of safety data for the diabetes drug sitagliptin, which is contained in both Januvia and Janumet, do not demonstrate any causal connection with acute pancreatitis. The drug maker also pointed out that reports of pancreatitis have been received with the use of other medications, including other type 2 diabetes drugs.

“Patients with type 2 diabetes are more likely to develop pancreatitis than other people, and as FDA noted in a publication earlier this year, ‘diagnosis [of drug-induced pancreatitis] poses a challenge since it can be difficult to rule out other causes,’” said John Amatruda, M.D., Senior Vice President and Franchise Head, Diabetes and Obesity, Merck Research Laboratories.

Januvia and Janumet are newer drugs approved for the treatment of adults with Type-2 diabetes. They are the first in a new class of medications known as dipeptidyl peptidase-4 (DPP-4) inhibitors. Januvia has rapidly become a strong selling medication for Merck, generating $462 million in sales worldwide in the second quarter of 2009.

Pancreatitis is an inflammation of the pancreas that can cause symptoms like severe upper abdominal pain which may radiate through the back, nausea, vomiting, high or low blood pressure, increased heart rates or elevated respiratory rates. Severe cases, involving necrotizing pancreatitis or hemorrhagic pancreatitis, can cause severe bleeding, multi-organ failure or death.

According to the FDA’s statement issued last week, they recommended that doctors monitor patients carefully for signs of pancreatitis from Januvia and Janumet after starting treatment or increasing dosage. The agency found that in 58 of the 88 cases of pancreatitis Januvia and Janumet users required hospitalization, and four required treatment in intensive care units (ICU).

Merck says that its own peer-reviewed analysis of 6,139 patients found only a 0.1% difference in the development of pancreatitis between people who used Januvia or Janumet and those who did not. The also company notes that it has added information on pancreatitis to the post-marketing adverse events section of the labeling for Januvia and Janumet earlier this year.