dual components, both sitagliptin and metformin are secreted in the milk of lactating rats. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when JANUMET is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of JANUMET in pediatric patients under 18 years have not been established.
8.5 Geriatric Use
JANUMET
Because sitagliptin and metformin are substantially excreted by the kidney, and because aging can be associated with reduced renal function, JANUMET should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. [See Warnings and Precautions (5.1, 5.4); Clinical Pharmacology (12.3).]
Sitagliptin
Of the total number of subjects (N=3884) in Phase II and III clinical studies of sitagliptin, 725 patients were 65 years and over, while 61 patients were 75 years and over. No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
Metformin hydrochloride
Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and young patients. Metformin should only be used in patients with normal renal function. The initial and maintenance dosing of metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dose adjustment should be based on a careful assessment of renal function. [See Contraindications (4); Warnings and Precautions (5.4); Clinical Pharmacology (12.3).]
10 OVERDOSAGE
Sitagliptin
During controlled clinical trials in healthy subjects, single doses of up to 800mg sitagliptin were administered. Maximal mean increases in QTc of 8.0msec were observed in one study at a dose of 800mg sitagliptin, a mean effect that is not considered clinically important [see Clinical Pharmacology (12.2)]. There is no experience with doses above 800mg 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 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 as indicated by the patient's clinical status.
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.
Metformin hydrochloride
Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metfor
