WARNINGS AND PRECAUTIONS
Pancreatitis: Acute pancreatitis, including fatal pancreatitis, has been reported in patients taking linagliptin. Take careful notice of potential signs and symptoms of pancreatitis and, if suspected, promptly discontinue GLYXAMBI 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 GLYXAMBI.
Heart Failure: Heart failure has been observed with two other members of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Consider risks and benefits of GLYXAMBI in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Monitor patients for signs and symptoms. Advise patients of the symptoms of heart failure and to immediately report such symptoms. If heart failure develops, consider discontinuation of GLYXAMBI.
Hypotension: Empagliflozin causes intravascular volume contraction and symptomatic hypotension may occur. Before initiating GLYXAMBI, assess and correct volume status in the elderly, and in patients with renal impairment, low systolic blood pressure, or on diuretics. Monitor for hypotension.
Ketoacidosis: Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been identified in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin. Fatal cases of ketoacidosis have been reported in patients taking empagliflozin. Patients who present with signs and symptoms of metabolic acidosis should be assessed for ketoacidosis, even if blood glucose levels are less than 250 mg/dL. If suspected, discontinue GLYXAMBI, evaluate, and treat promptly. Before initiating GLYXAMBI, consider risk factors for ketoacidosis. Patients may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis.
Acute Kidney Injury and Impairment in Renal Function: Empagliflozin causes intravascular volume contraction and can cause renal impairment. Acute kidney injury requiring hospitalization and dialysis have been identified in patients taking SGLT2 inhibitors, including empagliflozin; some reports involved patients younger than 65 years of age. Before initiating GLYXAMBI, consider factors that may predispose patients to acute kidney injury. Consider temporary discontinuation in settings of reduced oral intake or fluid losses. Monitor patients for signs and symptoms of acute kidney injury. If it occurs, discontinue GLYXAMBI and treat promptly.
Empagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Before initiating GLYXAMBI, evaluate renal function and monitor thereafter. More frequent monitoring is recommended in patients with eGFR <60 mL/min/1.73 m2. Discontinue GLYXAMBI in patients with a persistent eGFR <45 mL/min/1.73 m2.
Urosepsis and Pyelonephritis: Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been identified in patients receiving SGLT2 inhibitors, including empagliflozin. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate for signs and symptoms of urinary tract infections and treat promptly.
Hypoglycemia: The use of GLYXAMBI in combination with insulin or insulin secretagogues can increase the risk of hypoglycemia. A lower dose of insulin or the insulin secretagogue may be required.
Genital Mycotic Infections: Empagliflozin increases the risk for genital mycotic infections, especially in patients with prior infections. Monitor and treat as appropriate.
Hypersensitivity Reactions: Serious hypersensitivity reactions have been reported in patients treated with linagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue GLYXAMBI, assess for other potential causes for the event, and institute alternative treatment for diabetes.
Angioedema has also been reported with other DPP-4 inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with GLYXAMBI.
Increased Low-Density Lipoprotein Cholesterol (LDL-C): Monitor and treat as appropriate.
Severe and Disabling Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider linagliptin as a possible cause for severe joint pain and discontinue GLYXAMBI, if appropriate.
Bullous Pemphigoid: There have been reports of bullous pemphigoid requiring hospitalization. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue GLYXAMBI.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with GLYXAMBI.
MOST COMMON ADVERSE REACTIONS (≥5%): urinary tract infections, nasopharyngitis, upper respiratory tract infections
Empagliflozin: Coadministration with diuretics may enhance the potential for volume depletion.
Linagliptin: The efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Alternative treatments should be used.
USE IN SPECIAL POPULATIONS
Pregnancy: GLYXAMBI is not recommended, especially during the second and third trimesters.
Lactation: GLYXAMBI is not recommended while breastfeeding.
Geriatric Use: GLYXAMBI is expected to have diminished efficacy in elderly patients with renal impairment. Renal function should be assessed more frequently in elderly patients. The incidence of volume depletion-related adverse reactions and urinary tract infections increased in patients ≥75 years treated with empagliflozin.