Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
- There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. In a cardiovascular outcomes trial enrolling participants with established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial), cases of definite acute pancreatitis were confirmed in 17 of 8240 (0.2%) patients receiving ONGLYZA compared to 9 of 8173 (0.1%) receiving placebo. Preexisting risk factors for pancreatitis were identified in 88% (15/17) of those patients receiving ONGLYZA and in 100% (9/9) of those patients receiving placebo. After initiation of ONGLYZA, observe patients for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA.
- In a cardiovascular outcomes trial enrolling participants with established ASCVD or multiple risk factors for ASCVD (SAVOR trial), more patients randomized to ONGLYZA (289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to placebo (228/8212, 2.8%). In a time-to-first-event analysis the risk of hospitalization for heart failure was higher in the ONGLYZA group (estimated Hazard Ratio: 1.27; 95% CI: 1.07, 1.51). Subjects with a prior history of heart failure and subjects with renal impairment had a higher risk for hospitalization for heart failure, irrespective of treatment assignment. Consider the risks and benefits of ONGLYZA prior to initiating treatment in patients at a higher risk for heart failure. Observe 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 ONGLYZA.
- ONGLYZA is contraindicated in patients with a history of a serious hypersensitivity reaction to ONGLYZA, such as anaphylaxis, angioedema, or exfoliative skin conditions. [See Warnings and Precautions (5.3) and Adverse Reactions (6.2).]
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Adverse Reactions with Monotherapy and with Add-On Combination Therapy
- The 10 mg dosage is not an approved dosage.
- In the add-on to metformin plus sulfonylurea trial, the overall incidence of reported hypoglycemia was 10.1% for ONGLYZA 5 mg and 6.3% for placebo. Confirmed hypoglycemia was reported in 1.6% of the ONGLYZA-treated patients and in none of the placebo-treated patients
8 USE IN SPECIFIC POPULATIONS
8.4 Pediatric Use
- Safety and effectiveness of ONGLYZA in pediatric patients under 18 years of age have not been established. Additionally, studies characterizing the pharmacokinetics of ONGLYZA in pediatric patients have not been performed.
17 PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
- Hypersensitivity Reactions
- Missed Dose
WARNINGS AND PRECAUTIONS
Use with Medications Known to Cause Hypoglycemia
- When Onglyza was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with Onglyza.
Use in Combination with Insulin
- In the add-on to insulin trial, the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between Onglyza and placebo, except for confirmed hypoglycemia.
- A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.
- In the add-on to glyburide study, the overall incidence of reported hypoglycemia was higher for Onglyza 2.5 mg and Onglyza 5 mg (13.3% and 14.6%) versus placebo (10.1%). The incidence of confirmed hypoglycemia in this study, defined as symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤50 mg/dL, was 2.4% and 0.8% for Onglyza 2.5 mg and Onglyza 5 mg and 0.7% for placebo…
- History of a serious hypersensitivity reaction to Onglyza , such as anaphylaxis, angioedema, or exfoliative skin conditions
WARNINGS AND PRECAUTIONS
- There have been postmarketing reports of acute pancreatitis in patients taking Onglyza. After initiation of Onglyza, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Onglyza 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 Onglyza.
- There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Onglyza. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with Onglyza , with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue Onglyza, assess for other potential causes for the event, and institute alternative treatment for diabetes.
- Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with Onglyza.
- Hypersensitivity-related events, such as urticaria and facial edema in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients who received Onglyza 2.5 mg, Onglyza 5 mg, and placebo, respectively. None of these events in patients who received ONGLYZA required hospitalization or were reported as life-threatening by the investigators. One saxagliptin-treated patient in this pooled analysis discontinued due to generalized urticaria and facial edema.
PATIENT COUNSELING INFORMATION
- Patients should be informed that acute pancreatitis has been reported during postmarketing use of saxagliptin. Before initiating Onglyza, patients should be questioned about other risk factors for pancreatitis, such as a history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. Patients should also be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue Onglyza and contact their physician if persistent severe abdominal pain occurs.
- Patients should be informed that serious allergic (hypersensitivity) reactions, such as angioedema, anaphylaxis, and exfoliative skin conditions, have been reported during postmarketing use of saxagliptin. If symptoms of these allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking Onglyza and seek medical advice promptly.