From the Guidelines
Saxagliptin is contraindicated in patients with a history of serious hypersensitivity reactions to saxagliptin or other DPP-4 inhibitors, including anaphylaxis, angioedema, or exfoliative skin conditions, as well as in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
Key Considerations
- Caution is required in patients with moderate to severe renal impairment (CrCl <45 mL/min) or end-stage renal disease requiring hemodialysis, where dose adjustment to 2.5 mg once daily is necessary 1.
- Saxagliptin should be used cautiously in patients with heart failure, particularly NYHA class III-IV, due to potential increased risk of hospitalization for heart failure 1.
- The medication should be temporarily discontinued before procedures requiring restricted food and fluid intake.
- Patients with a history of pancreatitis should be monitored closely, as DPP-4 inhibitors have been associated with acute pancreatitis.
- Saxagliptin may cause hypoglycemia when used with insulin or insulin secretagogues, so dose adjustments of these medications may be needed.
Dosing Considerations
- Dose adjustment is required based on kidney function (sitagliptin, saxagliptin, alogliptin) 1.
- No dose adjustment is required for linagliptin.
Adverse Effects
- Pancreatitis has been reported, but causality has not been established 1.
- Postmarketing reports of bullous pemphigoid have been made, and the medication should be discontinued if suspected.
Clinical Context
These contraindications and precautions exist because saxagliptin works by inhibiting DPP-4 enzymes to increase incretin levels, which only helps regulate blood glucose in type 2 diabetes when some pancreatic function remains. According to the most recent and highest quality study available 1, saxagliptin has a neutral effect on major adverse cardiovascular events (MACE) and heart failure (HF), but its use requires careful consideration of the patient's renal function and history of pancreatitis.
From the FDA Drug Label
Saxagliptin tablets are contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin or any of the ingredients in saxagliptin tablets. Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported with saxagliptin tablets History of a serious hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to saxagliptin or any of the ingredients in saxagliptin tablets. (4) Saxagliptin tablets are contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin or any of the ingredients in saxagliptin tablets.
The contraindications for saxagliptin are:
- A history of a serious hypersensitivity reaction to saxagliptin or any of the ingredients in saxagliptin tablets.
- Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported with saxagliptin tablets 2, 2, 2.
From the Research
Contraindications for Saxagliptin
- There are no direct contraindications mentioned in the provided studies for saxagliptin, but certain precautions should be taken into consideration:
- Saxagliptin should be used with caution in patients with renal impairment, and the dose should be adjusted accordingly 3, 4, 5
- When saxagliptin is used in combination with a strong inhibitor of CYP3A4/A5, reduction in the daily dosage is recommended 3
- The use of saxagliptin in patients with hepatic impairment should be done with caution, but it can be used safely with proper monitoring 3
- Saxagliptin is generally well tolerated, but it may cause certain adverse effects, such as:
Special Considerations
- Patients with type 2 diabetes and cardiovascular disease or risk factors for cardiovascular disease can be treated with saxagliptin, as it has been shown to be generally well tolerated and effective in improving glycemic control in these patients 7
- Saxagliptin can be used in combination with other antihyperglycemic agents, such as metformin, sulfonylureas, and thiazolidinediones, to achieve better glycemic control 6