Januvia Special Precautions

Pancreatitis: There have been reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. After initiation of JANUVIA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, JANUVIA should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using JANUVIA.
Use in Patients with Renal Impairment: A dosage adjustment is recommended in patients with eGFR<45 mL/min/1.73 m² and in patients with ESRD requiring hemodialysis or peritoneal dialysis. (See Patients with Renal Impairment under Dosage & Administration; Pharmacology: Pharmacokinetics under Actions.)
Use with Medications Known to Cause Hypoglycemia: As is typical with other antihyperglycemic agents, hypoglycemia has been observed when JANUVIA was used in combination with insulin or a sulfonylurea. (See Clinical Trials Experience under Adverse Reactions.) Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia. (See Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin under 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 Postmarketing Experience under Adverse Reactions.)
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.
Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or any other anti-diabetic drug.
Use in Children: Sitagliptin should not be used in children and adolescents 10 to 17 years of age because of insufficient efficacy.
A 54-week, double-blind study was conducted to evaluate the efficacy and safety of JANUVIA in pediatric patients (10 to 17 years of age) with type 2 diabetes who were not on anti-hyperglycaemic therapy for at least 12 weeks or were on a stable dose of insulin for at least 12 weeks. Patients were randomized and treated with JANUVIA 100 mg (N=95) or placebo (N=95) once daily for 20 weeks.
Treatment with JANUVIA 100 mg did not provide significant improvement in HbA_1c at 20 weeks.
In pediatric patients aged 10 to 17 years with type 2 diabetes, the profile of side effects was comparable to that observed in adults.
JANUVIA has not been studied in pediatric patients under 10 years of age.
Use in the Elderly: Of the total number of subjects (N=3884) in pre-approval clinical safety and efficacy studies of JANUVIA, 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.
This drug 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 Patients with Renal Impairment under Dosage & Administration; Pharmacology: Pharmacokinetics under Actions).