GLYXAMBI: Severe renal impairment, end-stage renal disease, or dialysis; history of hypersensitivity reaction to empagliflozin, linagliptin, or any of the excipients in GLYXAMBI such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity.
JARDIANCE: History of serious hypersensitivity to empagliflozin or any of the excipients in JARDIANCE; severe renal impairment, end-stage renal disease, or dialysis.
TRADJENTA: History of hypersensitivity to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperactivity.
WARNINGS AND PRECAUTIONS
Pancreatitis: GLYXAMBI, TRADJENTA
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 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 or TRADJENTA.
Heart Failure: GLYXAMBI, TRADJENTA
Heart failure has been observed with 2 other members of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Consider risks and benefits of GLYXAMBI or TRADJENTA 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 or TRADJENTA.
Hypotension: GLYXAMBI, JARDIANCE
Empagliflozin causes intravascular volume contraction, and symptomatic hypotension may occur. Before initiating, assess and correct volume status in the elderly, in patients with renal impairment, low systolic blood pressure, or on diuretics. Monitor for hypotension.
Ketoacidosis: GLYXAMBI, JARDIANCE
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 <250 mg/dL. If suspected, discontinue, evaluate and treat promptly. Before initiating, consider risk factors for ketoacidosis. Patients may require monitoring and temporary discontinuation of therapy in situations known to predispose to ketoacidosis.
Acute Kidney Injury and Impairment in Renal Function: GLYXAMBI, JARDIANCE
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, 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 and treat promptly. Empagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Before initiating, evaluate renal function and monitor thereafter. More frequent monitoring is recommended in patients with eGFR <60 mL/min/1.73 m2. Discontinue in patients with a persistent eGFR <45 mL/min/1.73 m2.
Urosepsis and Pyelonephritis: GLYXAMBI, JARDIANCE
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: GLYXAMBI, JARDIANCE, TRADJENTA
The use in combination with insulin or insulin secretagogues can increase the risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required.
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): GLYXAMBI, JARDIANCE
Serious, life-threatening cases have occurred in both females and males. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue GLYXAMBI or JARDIANCE.
Genital Mycotic Infections: GLYXAMBI, JARDIANCE
Empagliflozin increases the risk for genital mycotic infections, especially in patients with prior infections. Monitor and treat as appropriate.
Hypersensitivity Reactions: GLYXAMBI, JARDIANCE, TRADJENTA
Discontinue GLYXAMBI, JARDIANCE or TRADJENTA, treat promptly, and monitor until signs and symptoms resolve. 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 linagliptin.
Increased Low‐Density Lipoprotein Cholesterol (LDL‐C): GLYXAMBI, JARDIANCE
Monitor and treat as appropriate.
Severe and Disabling Arthralgia: GLYXAMBI, TRADJENTA
Consider linagliptin as a possible cause for severe joint pain and discontinue if appropriate.
Bullous Pemphigoid: GLYXAMBI, TRADJENTA
There have been reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue.
Macrovascular Outcomes: GLYXAMBI, TRADJENTA
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction.
MOST COMMON ADVERSE REACTIONS (≥ 5%)
GLYXAMBI: Urinary tract infections, nasopharyngitis, and upper respiratory tract infections.
JARDIANCE: Urinary tract infections and female genital mycotic infections.
TRADJENTA: Nasopharyngitis, hypoglycemia (when used in combination with sulfonylurea).
DRUG INTERACTIONS: GLYXAMBI, JARDIANCE, TRADJENTA
Empagliflozin: Coadministration with diuretics may enhance the potential for volume depletion.
Linagliptin: The efficacy 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 and JARDIANCE are not recommended during the second and third trimesters of pregnancy. TRADJENTA should be used during pregnancy only if clearly needed.
Lactation: GLYXAMBI, JARDIANCE, and TRADJENTA are not recommended while breastfeeding.
Geriatric Use: Empagliflozin is expected to have diminished efficacy in elderly patients with renal impairment. Urinary tract infections and volume depletion‐related adverse reactions increased in patients ≥75 years treated with GLYXAMBI or JARDIANCE.