* In clinical trials of Januvia as monotherapy and sitagliptin as part of combination therapy with metformin and/or a PPARγ agent, rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.

†Based on incidence regardless of causal relationship.

‡Adverse reactions were identified through postmarketing surveillance.

§54-week time point

Across clinical studies, a small increase in white blood cell count (approximately 200 cells/microl difference in WBC vs. placebo; mean baseline WBC approximately 6,600 cells/microl) was observed due to an increase in neutrophils. This observation was seen in most but not all studies. This change in laboratory parameters is not considered to be clinically relevant.

No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with Januvia treatment.
4.9 Overdose

  During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were generally well tolerated. Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for periods of up to 28 days.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required.

Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5 % of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

  Pharmacotherapeutic group: Medicines used in diabetes, Dipeptidyl peptidase 4 (DPP-4) inhibitors, ATC code: A10BH01.

Januvia is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors. The improvement in glycaemic control observed with this agent may be mediated by enhancing the levels of active incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. The incretins are