Januvia Special Precautions

General: JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Pancreatitis: There have been reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis (see Side Effects), in patients taking sitagliptin. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin. If pancreatitis is suspected, JANUVIA and other potentially suspect medicinal products should be discontinued.
Use in Patients with Renal Impairment: JANUVIA is renally excreted. To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with GFR <45 mL/min, as well as in ESRD patients requiring hemodialysis or peritoneal dialysis. (See Patients with Renal Impairment under Dosage & Administration.)
Hypoglycemia in Combination with a Sulfonylurea or with Insulin: In clinical trials of JANUVIA as monotherapy and JANUVIA as part of combination therapy with agents not known to cause hypoglycemia (i.e. metformin or a PPARγ agonist (thiazolidinedione)), rates of hypoglycemia reported with JANUVIA were similar to rates in patients taking placebo. As is typical with other antihyperglycemic agents, hypoglycemia has been observed when JANUVIA was used in combination with insulin or a sulfonylurea (see Side Effects). Therefore, to reduce the risk of sulfonylurea- or insulin-induced hypoglycemia, a lower dose of sulfonylurea or insulin may be considered (see Dosage & Administration).
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first 3 months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event, and institute alternative treatment for diabetes. (See Contraindications and Postmarketing Experience under Side Effects.)
Bullous Pemphigoid: Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving JANUVIA. If bullous pemphigoid is suspected, JANUVIA should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.
Use in Children: The safety and effectiveness of JANUVIA have not been established in pediatric patients.
Three 20-week double-blind, placebo-controlled studies each with 34-week extensions were conducted to evaluate the efficacy and safety of sitagliptin in 410 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes, with or without insulin therapy (HbA1c 6.5-10% for patients not on insulin, HbA1c 7-10% for patients on insulin). At study entry, patients in study 1 were not treated with oral antihyperglycemic agents; patients in studies 2 and 3 were on maximally tolerated metformin therapy. The primary efficacy endpoint was the change from baseline in HbA1c after 20 weeks of therapy. The pre-specified primary efficacy analyses included data from study 1 and pooled data from studies 2 and 3, regardless of glycemic rescue or treatment discontinuation.
In both efficacy analyses, the effect of treatment with sitagliptin was not significantly different from placebo. In study 1, the mean baseline HbA1c was 7.5%, and 12% of patients were on insulin therapy. At week 20, the change from baseline in HbA1c in patients treated with JANUVIA (N=95) was 0.06% compared to 0.23% in patients treated with placebo (N=95), a difference of -0.17% (95% CI: -0.62, 0.28). In studies 2 and 3, the mean baseline HbA1c was 8.0%, 15% of patients were on insulin and 72% were on metformin HCl doses of greater than 1,500 mg daily. At week 20, the change from baseline in HbA1c in patients treated with sitagliptin (N=107) was -0.23% compared to 0.09% in patients treated with placebo (N=113), a difference of -0.33% (95% CI: -0.70, 0.05).
Use in the Elderly: In clinical studies, the safety and effectiveness of JANUVIA in the elderly (≥65 years) were comparable to those seen in younger patients (<65 years). No dosage adjustment is required based on age. Elderly patients are more likely to have renal impairment; as with other patients, dosage adjustment may be required in the presence of significant renal impairment (see Patients with Renal Impairment under Dosage & Administration).