February 3, 2012 — Merck announced on February 2 that the US Food and Drug Administration (FDA) has approved sitagliptin and metformin hydrochloride (HCl) extended-release tablets (Janumet XR) for treatment of type 2 diabetes.
The new formulation, meant to be used as an adjunct to diet and exercise to improve glycemic control, combines sitagliptin (the active component of Januvia [Merck]), with extended-release metformin.
According to a company news release, "Janumet XR should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Janumet XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Janumet XR."
FDA approval was based on a clinical bioequivalence study showing that the new tablets were equivalent to coadministration of corresponding doses of the 2 individual medications, sitagliptin and metformin HCl extended release.
"Janumet XR is a new treatment that adds once-daily convenience to the powerful efficacy of Janumet for patients with type 2 diabetes," said Barry J. Goldstein, MD, PhD, vice president, diabetes and endocrinology, Merck, in the news release. "This is important because many patients with type 2 diabetes require treatment with multiple drugs to maintain blood sugar control, and Janumet XR is a new option to help more patients get to their glucose goals."
The labeling for the combination drug contains a boxed warning for lactic acidosis, a rare but serious complication caused by metformin accumulation. According to a Merck statement, the reported incidence of lactic acidosis in patients receiving metformin is approximately 0.03 cases/1000 patient-years, but when lactic acidosis occurs, it is fatal in approximately 50% of cases. Reported cases have occurred primarily in patients with diabetes who have significant renal impairment.
"There have been postmarketing reports of worsening renal function in patients taking sitagliptin with or without metformin, including acute renal failure, sometimes requiring dialysis. Before initiation of therapy with Janumet XR and at least annually thereafter, renal function should be assessed and verified as normal," the company advised in the release.
"In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Janumet XR treatment should not be initiated in any patient unless measurement of creatinine clearance demonstrates that renal function is not reduced. In addition, Janumet XR should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis."
Increased risk for lactic acidosis is also associated with excess alcohol intake, hepatic impairment, and acute congestive heart failure. "If acidosis is suspected, Janumet XR should be discontinued and the patient hospitalized immediately," the company added.
The manufacturer advises physicians to maintain the same total daily dose of sitagliptin and metformin when changing between Janumet and Janumet XR, and to titrate the dose up gradually to the maximum recommended dose to reduce gastrointestinal adverse effects.
The new extended-release tablets should be taken once daily with food (preferably in the evening) to reduce the gastrointestinal adverse effects associated with the metformin component. Patients should be warned that the tablets must not be split, broken, crushed, or chewed before swallowing, the company said.
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Cite this: FDA Approves Once-A-Day Drug for Type 2 Diabetes - Medscape - Feb 03, 2012.