"The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicines canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called keto"...
The following serious adverse reactions are described below or elsewhere in the prescribing information:
- Pancreatitis [see WARNINGS AND PRECAUTIONS]
- Heart Failure [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Hepatic Effects [see WARNINGS AND PRECAUTIONS]
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 participated in 14 randomized, double-blind, controlled clinical trials of whom 9052 subjects were treated with NESINA, 3469 subjects were treated with placebo and 2257 were treated with an active comparator. The mean duration of diabetes was seven years, the mean body mass index (BMI) was 31 kg/m² (49% of patients had a BMI ≥ 30 kg/m² ), and the mean age was 58 years (26% of patients ≥ 65 years of age). The mean exposure to NESINA was 49 weeks with 3348 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 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%
Patients Treated with NESINA 25 mg and More Frequently Than in Patients Given
Placebo in Pooled Studies
|Number of Patients (%)|
|NESINA 25 mg
|Nasopharyngitis||309 (4.8)||152 (4.4)||113 (5.0)|
|Upper Respiratory Tract Infection||287 (4.5)||121 (3.5)||113 (5.0)|
|Headache||278 (4.3)||101 (2.9)||121 (5.4)|
In the monotherapy study, 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 study 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* in
Placebo and Active-Controlled Studies when NESINA Was Used as Add-On Therapy to
Glyburide, Insulin, Metformin, Pioglitazone or Compared to Glipizide or
|Add-On to Glyburide (26 Weeks)||NESINA 25 mg||Placebo|
|Overall (%)||19 (9.6)||11 (11.1)|
|Severe (%)†||0||1 (1)|
|Add-On to Insulin (± Metformin) (26 Weeks)||NESINA 25 mg||Placebo|
|Overall (%)||35 (27)||31 (24)|
|Severe (%)†||1 (0.8)||2 (1.6)|
|Add-On to Metformin (26 Weeks)||NESINA 25 mg||Placebo|
|Overall (%)||0||3 (2.9)|
|Add-On to Pioglitazone (± Metformin or Sulfonylurea) (26 Weeks)||NESINA 25 mg||Placebo|
|Overall (%)||14 (7.0)||5 (5.2)|
|Severe (%)†||0||1 (1)|
|Compared to Glipizide (52 Weeks)||NESINA 25 mg||Glipizide|
|Overall (%)||12 (5.4)||57 (26)|
|Severe (%)†||0||3 (1.4)|
|Compared to Metformin (26 Weeks)||NESINA 25 mg||Metformin 500 mg twice daily|
|Overall (%)||2 (1.8)||2 (1.8)|
|Add-On to Metformin Compared to Glipizide (52 Weeks)||NESINA 25 mg||Glipizide|
|Overall (%)||12 (1.4)||207 (23.8)|
|Severe (%)†||0||4 (0.5)|
|*Adverse reactions of
hypoglycemia were based on all reports of symptomatic and asymptomatic
hypoglycemia; a concurrent glucose measurement was not required;
† Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level or loss of consciousness or seizure.
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.
In glycemic control trials in patients with type 2 diabetes, 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) [see Use in Specific Populations].
In the EXAMINE trial of high CV risk type 2 diabetes 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.
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.
Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria and severe cutaneous adverse reactions, including Stevens-Johnson syndrome, hepatic enzyme elevations, fulminant hepatic failure, severe and disabling arthralgia, acute pancreatitis, diarrhea, constipation, nausea, and ileus [see WARNINGS AND PRECAUTIONS].
Read the Nesina (alogliptin tablets) Side Effects Center for a complete guide to possible side effects
NESINA is primarily renally excreted. Cytochrome (CYP) P450-related metabolism is negligible. No significant drug-drug interactions were observed with the CYP-substrates or inhibitors tested or with renally excreted drugs [see CLINICAL PHARMACOLOGY].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/28/2016
Additional Nesina Information
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