Last week, the U.S. Food and Drug Administration (FDA) approved the use of Nesina (alogliptin) tablets as treatment for for type 2 diabetes among adults. What are the side effects of this drug? According to the FDA media release, the most common side effects of Nesina are “stuffy or runny nose, headache, and upper respiratory tract infection.”
In the highlights of prescribing information for the drug, the FDA also mentions the following warnings and precautions:
WARNINGS AND PRECAUTIONS
There have been postmarketing reports of acute pancreatitis in patients taking NESINA. After initiation of NESINA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, NESINA should promptly be 42 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 NESINA.
5.2 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 [see Adverse Reactions (6.2)]. 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 NESINA.
5.3 Hepatic Effects
There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking NESINA, although some of the reports contain insufficient information necessary to establish the probable cause [see Adverse Reactions (6.2)]. In randomized controlled studies, serum alanine aminotransferase (ALT) elevations greater than three times the upper limit of normal (ULN) were observed: 1.3% in alogliptin-treated patients and 1.5% in all comparator-treated patients.
Patients with type 2 diabetes may have fatty liver disease which may cause liver test abnormalities, and they may also have other forms of liver disease, many of which can be treated or managed. Therefore, obtaining a liver test panel and assessing the patient before initiating NESINA therapy is recommended. In patients with abnormal liver tests, NESINA should be initiated with caution.
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.
5.4 Use with Medications Known to Cause Hypoglycemia
Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with NESINA.
5.5 Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with NESINA or any other antidiabetic drug.
These adverse reactions to Nesina during clinical trials might also interest you:
6.1 Clinical Studies 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 clinical practice.
Approximately 8500 patients with type 2 diabetes have been treated with NESINA in 14 randomized, double-blind, controlled clinical trials with approximately 2900 subjects randomized to placebo and approximately 2200 to an active comparator. The mean exposure to NESINA was 40 weeks with more than 2400 subjects treated for more than one year. Among these patients, 63% had a history of hypertension, 51% had a history of dyslipidemia, 25% had a history of myocardial infarction, 8% had a history of unstable angina, and 7% had a history of congestive heart failure. The mean duration of diabetes was 7 years, the mean body mass index (BMI) was 31 kg/m2 (51% of patients had a BMI ≥30 kg/m2), and the mean age was 57 years (24% of patients ≥65 years of age).
Two placebo-controlled monotherapy trials of 12 and 26 weeks of duration were conducted in patients treated with NESINA 12.5 mg daily, NESINA 25 mg daily and placebo. Four placebo-controlled add-on combination therapy trials of 26 weeks duration were also conducted: with metformin, with a sulfonylurea, with a thiazolidinedione, and with insulin.
Five placebo-controlled trials of 16 weeks up through two years in duration were conducted in combination with metformin, in combination with pioglitazone and with pioglitazone added to a background of metformin therapy.
Three active-controlled trials of 52 weeks in duration were conducted in patients treated with pioglitazone and metformin, in combination with metformin and as monotherapy compared to glipizide.
In a pooled analysis of these 14 controlled clinical trials, the overall incidence of adverse events was 66% in patients treated with NESINA 25 mg compared to 62% with placebo and 70% with active comparator. Overall discontinuation of therapy due to adverse events was 4.7% with NESINA 25 mg compared to 4.5% with placebo or 6.2% with active comparator.
In the clinical trial program, pancreatitis was reported in 11 of 5902 (0.2%) patients receiving NESINA 25 mg daily compared to 5 of 5183 (˂0.1%) patients receiving all comparators.
In a pooled analysis, the overall incidence of hypersensitivity reactions was 0.6% with NESINA 25 mg compared to 0.8% with all comparators. A single event of serum sickness was reported in a patient treated with NESINA 25 mg.
Hypoglycemic events were documented based upon a blood glucose value and/or clinical signs and symptoms of hypoglycemia.
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.
6.2 Postmarketing Experience
The following adverse reactions have been identified during the postmarketing use of 140 NESINA outside the United States. Because these reactions are reported voluntarily 141 from a population of uncertain size, it is not always possible to reliably estimate their 142 frequency or establish a causal relationship to drug exposure.
Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and 144 severe cutaneous adverse reactions including Stevens-Johnson syndrome; hepatic 145 enzyme elevations; fulminant hepatic failure; and acute pancreatitis.