Label Changes for:
Kombiglyze XR (saxagliptin + metformin XR FDC) tablets
Changes have been made to the CONTRAINDICATIONS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- 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
When saxagliptin 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 Kombizyme XR.
- History of a serious hypersensitivity reaction to Kombiglyze XR or saxagliptin, such as anaphylaxis, angioedema, or exfoliative skin conditions.
WARNINGS AND PRECAUTIONS
- There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin. After initiation of Kombiglyze XR , patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Kombiglyze XR 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 Kombiglyze XR.
- There have been postmarketing reports of serious hypersensitivity reactions in patients treated with saxagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue Kombiglyze XR , 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 Kombiglyze XR.
- 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 saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, respectively. None of these events in patients who received saxagliptin 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 Kombiglyze XR , 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 Kombiglyze XR 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 Kombiglyze XR and seek medical advice promptly.