Sitagliptin: uses, appearance and warnings

Sitagliptin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Sitagliptin tablets should not be used in patients with type 1 diabetes. Sitagliptin tablets have not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using sitagliptin tablets. [See Warnings and Precautions ( 5.1 ).] Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: • Sitagliptin tablets should not be used in patients with type 1 diabetes. ( 1 ) • Sitagliptin tablets have not been studied in patients with a history of pancreatitis. ( 1 , 5.1 )

• 100 mg tablets are brown, round, biconvex, film-coated tablets debossed with “SN” on one side and “100” on the other side. • 50 mg tablets are pink, round, biconvex, film-coated tablets debossed with “SN” on one side and “50” on the other side. • 25 mg tablets are dark pink, round, biconvex, film-coated tablets debossed with “SN” on one side and “25” on the other side. Tablets: 100 mg, 50 mg, and 25 mg ( 3 )

Sitagliptin tablets, USP are available as follows: 25 mg tablets are dark pink, round, biconvex, film-coated tablets debossed with “SN” on one side and “25” on the other side. NDC 0781-5766-31, 30 tablets in one bottle NDC 0781-5766-92, 90 tablets in one bottle 50 mg tablets are pink, round, biconvex, film-coated tablets debossed with “SN” on one side and “50” on the other side. NDC 0781-5768-31, 30 tablets in one bottle NDC 0781-5768-92, 90 tablets in one bottle 100 mg tablets are brown, round, biconvex, film-coated tablets debossed with “SN” on one side and “100” on the other side. NDC 0781-5770-31, 30 tablets in one bottle NDC 0781-5770-92, 90 tablets in one bottle NDC 0781-5770-10, 1000 tablets in one bottle Storage Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (69ºF to 86ºF) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container. KEEP OUT OF REACH OF CHILDREN.

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema. [See Warnings and Precautions ( 5.5 ); Adverse Reactions ( 6.2 ).] History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema ( 5.5 , 6.2 )

• Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue sitagliptin. ( 5.1 ) • Heart Failure: Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of sitagliptin in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. ( 5.2 ) • Acute Renal Failure: Has been reported postmarketing, sometimes requiring dialysis. Assessment of renal function is recommended prior to initiating sitagliptin and periodically thereafter. ( 5.3 ) • Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required. ( 5.4 , 7.1 ) • Hypersensitivity Reactions: There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Promptly stop sitagliptin, assess for other potential causes, institute appropriate monitoring and treatment. ( 5.5 , 6.2 ) • Severe and Disabling Arthralgia: Has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate. ( 5.6 ) • Bullous Pemphigoid: There have been postmarketing reports requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue sitagliptin. ( 5.7 ) 5.1 Pancreatitis There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin. After initiation of sitagliptin, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, sitagliptin 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 sitagliptin. 5.2 Heart Failure An association between dipeptidyl peptidase-4 (DPP-4) inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class. These trials evaluated patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Consider the risks and benefits of sitagliptin prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of sitagliptin. 5.3 Acute Renal Failure There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal impairment, some of whom were prescribed inappropriate doses of sitagliptin. A return to baseline levels of renal impairment has been observed with supportive treatment and discontinuation of potentially causative agents. Consideration can be given to cautiously reinitiating sitagliptin if another etiology is deemed likely to have precipitated the acute worsening of renal function. Assessment of renal function is recommended prior to initiating sitagliptin and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal impairment and in patients with ESRD requiring hemodialysis or peritoneal dialysis. [See Dosage and Administration ( 2.2 ); Use in Specific Populations ( 8.6 ).] 5.4 Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues When sitagliptin phosphate was used in combination with insulin or insulin secretagogues (e.g., sulfonylurea), medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. [See Adverse Reactions ( 6.1 ).] Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia. [See Drug Interactions ( 7.1 ).] 5.5 Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue sitagliptin, assess for other potential causes for the event, and institute alternative treatment for diabetes. [See Adverse Reactions ( 6.2 ).] Angioedema has also been reported with other DPP-4 inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with sitagliptin. 5.6 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. …

The following adverse reactions are also discussed elsewhere in the labeling: • Pancreatitis [see Warnings and Precautions ( 5.1 )] • Heart Failure [see Warnings and Precautions ( 5.2 )] • Acute Renal Failure [see Warnings and Precautions ( 5.3 )] • Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Severe and Disabling Arthralgia [see Warnings and Precautions ( 5.6 )] • Bullous Pemphigoid [see Warnings and Precautions ( 5.7 )] Adverse reactions reported in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, nasopharyngitis and headache. …

7.1 Insulin Secretagogues or Insulin Coadministration of sitagliptin with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. [See Warnings and Precautions ( 5.4 ).]