Alogliptinside effects

The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis Heart Failure Hypersensitivity Reactions Hepatic Effects Severe and Disabling Arthralgia Bullous Pemphigoid Most common adverse reactions (incidence ≥4%) are nasopharyngitis, headache and upper respiratory tract infection. To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 14,778 patients with type 2 diabetes mellitus participated in 14 randomized, double-blind, controlled clinical trials of whom 9,052 subjects were treated with NESINA, 3,469 subjects were treated with placebo and 2,257 were treated with an active comparator. The racial distribution of patients exposed to trial medication was 71% White, 17% Asian, 6% Black or African American, 2% American Indian or Alaska Native, 0% Native Hawaiian/Other Pacific Islander and 5% Multiracial or other racial groups. The ethnic distribution was 30% Hispanic or Latino and 70% was not Hispanic or Latino. The mean duration of diabetes mellitus was seven years, the mean body mass index (BMI) was 31 kg/m 2 (49% of patients had a BMI ≥30 kg/m 2 ), and the mean age was 58 years (26% of patients ≥65 years of age). The mean exposure to NESINA was 49 weeks with 3,348 subjects treated for more than one year. In a pooled analysis of these 14 controlled clinical trials, the overall incidence of adverse reactions was 73% in patients treated with NESINA 25 mg compared to 75% with placebo and 70% with active comparator. Overall discontinuation of therapy due to adverse reactions was 6.8% with NESINA 25 mg compared to 8.4% with placebo or 6.2% with active comparator. Adverse reactions reported in ≥4% of adult patients treated with NESINA 25 mg and more frequently than in patients who received placebo are summarized in Table 1. Table 1. Adverse Reactions Reported in ≥4% of Adult Patients with Type 2 Diabetes Mellitus Treated with NESINA 25 mg and More Frequently Than in Patients Given Placebo in Pooled Trials Number of Patients (%) NESINA 25 mg Placebo Active Comparator N=6447 N=3469 N=2257 Nasopharyngitis 309 152 113 Upper Respiratory Tract Infection 287 121 113 Headache 278 101 121 Hypoglycemia Hypoglycemic events were documented based upon a blood glucose value and/or clinical signs and symptoms of hypoglycemia. In the monotherapy trial, the incidence of hypoglycemia was 1.5% in patients treated with NESINA compared to 1.6% with placebo. The use of NESINA as add-on therapy to glyburide or insulin did not increase the incidence of hypoglycemia compared to placebo. In a monotherapy trial comparing NESINA to a sulfonylurea in elderly patients, the incidence of hypoglycemia was 5.4% with NESINA compared to 26% with glipizide (Table 2). Table 2. Incidence and Rate of Hypoglycemia Adverse reactions of hypoglycemia were based on all reports of symptomatic and asymptomatic hypoglycemia; a concurrent glucose measurement was not required; intent-to-treat population in Placebo and Active-Controlled Trials in Adults with Type 2 Diabetes Mellitus when NESINA Was Used as Add-On Therapy to Glyburide, Insulin, Metformin, Pioglitazone or Compared to Glipizide or Metformin Add-On to Glyburide (26 Weeks) NESINA 25 mg Placebo N=198 N=99 Overall (%) 19 11 Severe (%) Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level or loss of consciousness or seizure 0 1 Add-On to Insulin (± Metformin) (26 Weeks) NESINA 25 mg Placebo N=129 N=129 Overall (%) 35 31 Severe (%) 1 2 Add-On to Metformin (26 Weeks) NESINA 25 mg Placebo N=207 N=104 Overall (%) 0 3 Severe (%) 0 0 Add-On to Pioglitazone (± Metformin or Sulfonylurea) (26 Weeks) NESINA 25 mg Placebo N=199 N=97 Overall (%) 14 5 Severe (%) 0 1 Compared to Glipizide (52 Weeks) NESINA 25 mg Glipizide N=222 N=219 Overall (%) 12 57 Severe (%) 0 3 Compared to Metformin (26 Weeks) NESINA 25 mg Metformin 500 mg twice daily N=112 N=109 Overall (%) 2 2 Severe (%) 0 0 Add-On to Metformin Compared to Glipizide (52 Weeks) NESINA 25 mg Glipizide N=877 N=869 Overall (%) 12 207 Severe (%) 0 4 In the EXAMINE trial, the incidence of investigator reported hypoglycemia was 6.7% in patients receiving NESINA and 6.5% in patients receiving placebo. Serious adverse reactions of hypoglycemia were reported in 0.8% of patients treated with NESINA and in 0.6% of patients treated with placebo. Renal Impairment In glycemic control trials in patients with type 2 diabetes mellitus, 3.4% of patients treated with NESINA and 1.3% of patients treated with placebo had renal function adverse reactions. The most commonly reported adverse reactions were renal impairment (0.5% for NESINA and 0.1% for active comparators or placebo), decreased creatinine clearance (1.6% for NESINA and 0.5% for active comparators or placebo) and increased blood creatinine (0.5% for NESINA and 0.3% for active comparators or placebo). In the EXAMINE trial of high CV risk type 2 diabetes mellitus patients, 23% of patients treated with NESINA and 21% of patients treated with placebo had an investigator reported renal impairment adverse reaction. The most commonly reported adverse reactions were renal impairment (7.7% for NESINA and 6.7% for placebo), decreased glomerular filtration rate (4.9% for NESINA and 4.3% for placebo) and decreased renal clearance (2.2% for NESINA and 1.8% for placebo). Laboratory measures of renal function were also assessed. Estimated glomerular filtration rate decreased by 25% or more in 21.1% of patients treated with NESINA and 18.7% of patients treated with placebo. Worsening of chronic kidney disease stage was seen in 16.8% of patients treated with NESINA and in 15.5% of patients treated with placebo.

6.2 Postmarketing

Experience The following adverse reactions have been identified during the postmarketing use of NESINA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders: acute pancreatitis, diarrhea, constipation, nausea, ileus Hepatobiliary Disorders: fulminant hepatic failure Immune System Disorders: hypersensitivity reactions including anaphylaxis Investigations: hepatic enzyme elevations Musculoskeletal and Connective Tissue Disorders: severe and disabling arthralgia, rhabdomyolysis Renal and Urinary Disorders: tubulointerstitial nephritis Skin and Subcutaneous Tissue Disorders: angioedema, rash, urticaria and severe cutaneous adverse reactions including Stevens-Johnson syndrome, bullous pemphigoid