WARNINGS AND PRECAUTIONS
There have been reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of GLYXAMBI. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is 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.
Empagliflozin, a component of GLYXAMBI, causes intravascular volume contraction and symptomatic hypotension may occur. Before initiating GLYXAMBI, assess and correct volume status in the elderly, in patients with renal impairment, low systolic blood pressure, or on diuretics. Monitor for hypotension.
Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, have been identified in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co transporter 2 (SGLT2) inhibitors, including empagliflozin. Fatal cases of ketoacidosis have been reported in patients taking empagliflozin. Patients who present 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, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. Patients on GLYXAMBI 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 receiving 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 including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). Consider temporary discontinuation in settings of reduced oral intake or fluid losses. Monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue GLYXAMBI promptly and institute treatment.
Empagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function should be evaluated prior to initiating of GLYXAMBI and periodically thereafter. More frequent monitoring is recommended in patients with eGFR <60 mL/min/1.73 m2. GLYXAMBI should be discontinued 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 with Concomitant Use with Insulin and Insulin Secretagogues
Insulin and insulin secretagogues are known to cause hypoglycemia. The use of empagliflozin or linagliptin in combination with these agents was associated with a higher rate of hypoglycemia compared with placebo. A lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycemia when used in combination with GLYXAMBI.
Genital Mycotic Infections
Empagliflozin, a component of GLYXAMBI, increases the risk for genital mycotic infections, especially in patients with prior infections. Monitor and treat as appropriate.
There have been reports of serious hypersensitivity reactions in patients treated with linagliptin, a component of GLYXAMBI. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with linagliptin, 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.
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 as a possible cause for severe joint pain and discontinue drug if appropriate.
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 GLYXAMBI.
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with GLYXAMBI.
The most common adverse reactions (≥5%) associated with GLYXAMBI were urinary tract infections, nasopharyngitis, and upper respiratory tract infections.
Coadministration of empagliflozin, a component of GLYXAMBI, with diuretics may enhance the potential for volume depletion.
The efficacy of linagliptin, a component of GLYXAMBI, may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Therefore, use of alternative treatments to GLYXAMBI is strongly recommended.
USE IN SPECIAL POPULATIONS
GLYXAMBI is not recommended during the second and third trimesters of pregnancy based on animal data showing adverse renal effects.
GLYXAMBI is not recommended while breastfeeding because of the potential for serious adverse reactions in breastfed infants.
Empagliflozin, a component of GLYXAMBI, 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.