Januvia should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Use in Patients with Renal Insufficiency: A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis. (See Pharmacology and Pharmacokinetics under Actions and Dosage & Administration.)
Use with Medications Known to Cause Hypoglycemia: In clinical trials of Januvia as monotherapy and Januvia as part of combination therapy with metformin or pioglitazone, rates of hypoglycemia reported with Januvia were similar to rates in patients taking placebo. The use of Januvia in combination with medications known to cause hypoglycemia eg, sulfonylureas or insulin, has not been adequately studied.
Use in pregnancy: Pregnancy Category B: Reproduction studies have been performed in rats and rabbits. Doses of Januvia up to 125 mg/kg (approximately 12 times the human exposure at the maximum recommended human dose) did not impair fertility or harm the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Januvia should be used during pregnancy only if clearly needed.
Sitagliptin administered to pregnant female rats and rabbits from gestation days 6-20 (organogenesis) was not teratogenic at oral doses up to 250 mg/kg (rats) and 125 mg/kg (rabbits), or approximately 30- and 20-times human exposure at the maximum recommended human dose (MRHD) of 100 mg/day, based on AUC comparisons. Higher doses increased the incidence of rib malformations in offspring at 1000 mg/kg or approximately 100 times human exposure at the MRHD.
Sitagliptin administered to female rats from gestation day 6 to lactation day 21 decreased body weight in male and female offspring at 1000 mg/kg. No functional or behavioral toxicity was observed in offspring of rats.
Placental transfer of Sitagliptin administered to pregnant rats was approximately 45% at 2 hrs and 80% at 24 hrs post-dose. Placental transfer of Sitagliptin administered to pregnant rabbits was approximately 66% at 2 hrs and 30% at 24 hrs.
Use in lactation: Sitagliptin is secreted in the milk of lactating rats at a milk to plasma ratio of 4:1. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Januvia is administered to a nursing woman.
Use in children: Safety and effectiveness of Januvia in pediatric patients have not been established.
Use in the elderly: Of the total number of subjects (N=3884) in clinical safety and efficacy studies of Januvia, 725 patients were ≥65 years, while 61 patients were ≥75 years. No overall differences in safety or effectiveness were observed between subjects ≥65 years 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.
Sitagliptin is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter (see Pharmacology and Pharmacokinetics under Actions and Dosage & Administration).