Approved July 31, 2009

SAXAGLIPTIN HYDROCHLORIDE
(FDA Category 1S)

ONGLYZA(TM) (Bristol-Myers Squibb Company) is a dipeptidyl peptidase-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing blood stream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.

DOSING INFORMATION: 2.5 mg or 5 mg once daily taken regardless of meals.

PHARMACOKINETICS: Saxagliptin and its active metabolite reach peak plasma concentrations approximately 2 and 4 hours after oral administration. Protein binding for saxagliptin and its active metabolite are negligible. Metabolism is primarily mediated by CYP3A4 and CYP3A5. The major active metabolite, 5-hydroxy saxagliptin is also a dipeptidyl peptidase-4 inhibitor, and is one-half as potent as its parent compound. Saxagliptin is eliminated by both renal and hepatic pathways. Following a single oral dose of saxagliptin 5 mg, the mean elimination half-life was 2.5 and 3.1 hours for saxagliptin and its active metabolite, respectively.

CAUTIONS: Concomitant use with a sulfonylurea increased the risk of hypoglycemia and a lower dose of the sulfonylurea may be required. In patients with renal impairment and in patients taking strong cytochrome CYP3A4 or CYP3A5 inhibitors, the recommended dosage is 2.5 mg daily. The most common adverse effects included hypoglycemia, upper respiratory tract infection, urinary tract infection, and headache. In a pooled analysis, the incident rate of fractures was 1 per 100 patient-years for patients treated with saxagliptin 2.5 mg, 5 mg, and 10 mg compared with 0.6 per 100 patient-years for those treated with placebo. Causality was not established.

FDA APPROVED INDICATIONS: Saxagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.