NESINA tablets contain the active ingredient alogliptin, which is a selective, orally bioavailable inhibitor of the enzymatic activity of DPP-4. Chemically, alogliptin is prepared as a benzoate salt, which is identified as 2-({6-[(3 R )-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl}methyl)benzonitrile monobenzoate. It has a molecular formula of C 18 H 21 N 5 O 2 ∙C 7 H 6 O 2 and a molecular weight of 461.51 daltons. The structural formula is: Alogliptin benzoate is a white to off-white crystalline powder containing one asymmetric carbon in the aminopiperidine moiety. It is soluble in dimethylsulfoxide, sparingly soluble in water and methanol, slightly soluble in ethanol and very slightly soluble in octanol and isopropyl acetate. Each NESINA tablet contains 34 mg, 17 mg or 8.5 mg alogliptin benzoate, which is equivalent to 25 mg, 12.5 mg or 6.25 mg, respectively, of alogliptin and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, mannitol, and microcrystalline cellulose. In addition, the film coating contains the following inactive ingredients: ferric oxide (red or yellow), hypromellose, polyethylene glycol, and titanium dioxide and is marked with printing ink (Gray F1). Chemical Structure

NESINA ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. NESINA 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. Limitations of Use: Should not be used in patients with type 1 diabetes mellitus. Limitations of Use NESINA is not recommended for use in patients with type 1 diabetes mellitus.

25 mg tablets are light red, oval, biconvex, film-coated, with "TAK ALG-25" printed on one side

mg tablets are yellow, oval, biconvex, film-coated, with "TAK ALG-12.5" printed on one side

mg tablets are light pink, oval, biconvex, film-coated, with "TAK ALG-6.25" printed on one side. Tablets: 25 mg, 12.5 mg and 6.25 mg

The recommended dosage in patients with normal renal function or mild renal impairment is 25 mg orally once daily. Can be taken with or without food. Adjust dosage if moderate or severe renal impairment or end-stage renal disease (ESRD). Degree of Renal Impairment Creatinine Clearance (mL/min) Recommended Dosage Moderate ≥30 to <60 12.5 mg once daily Severe/ESRD <30 6.25 mg once daily 2.1 Recommended Dosage The recommended dosage of NESINA is 25 mg taken orally once daily. Do not split tablets. NESINA may be taken with or without food . Instruct patients if a dose is missed, not to double their next dose

Patients with Renal Impairment Assess renal function prior to initiation of NESINA and periodically thereafter . No dose adjustment of NESINA is necessary for patients with mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min). The dose of NESINA is 12.5 mg once daily for patients with moderate renal impairment (CrCl ≥30 to <60 mL/min). The dose of NESINA is 6.25 mg once daily for patients with severe renal impairment (CrCl ≥15 to <30 mL/min) or with end-stage renal disease (ESRD) (CrCl <15 mL/min or requiring hemodialysis). NESINA may be administered without regard to the timing of dialysis. NESINA has not been studied in patients undergoing peritoneal dialysis .

Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue NESINA. Heart failure: Consider the risks and benefits of NESINA prior to initiating treatment in patients at risk for heart failure. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of NESINA. Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with NESINA such as anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. If hypersensitivity reactions occur, discontinue NESINA, treat promptly, and monitor until signs and symptoms resolve. Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt NESINA and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart NESINA if liver injury is confirmed and no alternative etiology can be found. Hypoglycemia: Consider lowering the dosage of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating NESINA. Arthralgia: 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. Bullous pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue NESINA. 5.1 Pancreatitis Acute pancreatitis has been reported in the postmarketing setting and in randomized clinical trials. In glycemic control trials in patients with type 2 diabetes mellitus, acute pancreatitis was reported in 6 (0.2%) patients treated with NESINA 25 mg and 2 (<0.1%) patients treated with active comparators or placebo. In the EXAMINE trial (a cardiovascular outcomes trial of patients with type 2 diabetes mellitus and high cardiovascular (CV) risk), acute pancreatitis was reported in 10 (0.4%) of patients treated with NESINA and in 7 (0.3%) of patients treated with placebo. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using NESINA . After initiation of NESINA, patients should be observed for signs and symptoms of pancreatitis. If pancreatitis is suspected, NESINA should promptly be discontinued and appropriate management should be initiated

Heart Failure In the EXAMINE trial which enrolled patients with type 2 diabetes mellitus and recent acute coronary syndrome, 106 (3.9%) of patients treated with NESINA and 89 (3.3%) of patients treated with placebo were hospitalized for congestive heart failure. Consider the risks and benefits of NESINA 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. Patients should be advised of the characteristic symptoms of heart failure and should be instructed to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of NESINA

Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions in patients treated with NESINA . These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. If a serious hypersensitivity reaction is suspected, discontinue NESINA, assess for other potential causes for the event and institute alternative treatment for diabetes mellitus. Use caution in patients with a history of angioedema with another dipeptidyl peptidase-4 (DPP-4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with NESINA

Hepatic Effects There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking NESINA, although some of the reports contain insufficient information necessary to establish the probable cause . In glycemic control trials in patients with type 2 diabetes mellitus, serum alanine aminotransferase (ALT) elevations greater than three times the upper limit of normal (ULN) were reported in 1.3% of patients treated with NESINA 25 mg and 1.7% of patients treated with active comparators or placebo. In the EXAMINE trial (a cardiovascular outcomes trial of patients with type 2 diabetes mellitus and high cardiovascular (CV) risk), increases in serum alanine aminotransferase three times the upper limit of the reference range occurred in 2.4% of patients treated with NESINA and in 1.8% of patients treated with placebo. Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. In this clinical context, if the patient is found to have clinically significant liver enzyme elevations and if abnormal liver tests persist or worsen, NESINA should be interrupted and investigation done to establish the probable cause. NESINA should not be restarted in these patients without another explanation for the liver test abnormalities

Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Therefore, a lower dosage of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with NESINA

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

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 NESINA. If bullous pemphigoid is suspected, NESINA should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.

7.1 Insulin Secretagogues and Insulin Insulin and insulin secretagogues are known to cause hypoglycemia. Coadministration of NESINA with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue and insulin to reduce the risk of hypoglycemia .