BRYNOVIN

The pharmacokinetics of sitagliptin have been extensively characterized in healthy subjects and patients with type 2 diabetes mellitus. Following a single oral 100-mg dose to healthy volunteers, mean plasma AUC of sitagliptin was 8.52 µM

• hr, C max was 950 nM, and apparent terminal half-life (t 1/2 ) was 12.4 hours. Plasma AUC of sitagliptin increased in a dose-proportional manner and increased approximately 14% following 100 mg doses at steady-state compared to the first dose. The intra-subject ...

Overview of Clinical Trials The effectiveness of BRYNOVIN has been established for glycemic control in patients with type 2 diabetes mellitus based on adequate and well-controlled trials of sitagliptin tablets, referenced below as “sitagliptin”. There were approximately 5,200 patients with type 2 diabetes mellitus randomized in nine double-blind, placebo-controlled clinical safety and efficacy trials conducted to evaluate the effects of sitagliptin on glycemic control. In a pooled analysis of seven of these trials, the ethnic/racial distribution was approximately 59% white, 20% Hispanic or Lat...

The following adverse reactions are also discussed elsewhere in the labeling:

• Pancreatitis [see Warnings and Precautions ( 5.1 ) ]
• Heart Failure [see Warnings and Precautions ( 5.2 ) ]
• Acute Renal Failure [see Warnings and Precautions ( 5.3 ) ]
• Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions ( 5.4 ) ]
• Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 ) ]
• Severe and Disabling Arthralgia [ see Warnings and Precauti...

BRYNOVIN is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin or any of the excipients in BRYNOVIN. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported [see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6.2 )]. History of a serious hypersensitivity reaction to sitagliptin or any of the excipients in B...

• Pancreatitis : There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue BRYNOVIN. ( 5.1 )
• Heart failure : Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of BRYNOVIN in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. ( 5.2 )
• Acute Renal Failure : Has bee...

7 DRUG INTERACTIONS 7.1 Concomitant Use with Insulin or Insulin Secretagogues BRYNOVIN lowers blood glucose in patients with type 2 diabetes mellitus. Coadministration of BRYNOVIN with insulin or an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. [see Warnings and Precautions ( 5.4 )].