Glyxambi Special Precautions

GLYXAMBI should not be used in patients with type 1 diabetes.
Diabetic ketoacidosis: Cases of diabetic ketoacidosis (DKA), a serious life-threatening condition requiring urgent hospitalization, have been reported in patients treated with empagliflozin, including fatal cases. In a number of reported cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/l (250 mg/dl).
The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness.
Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. If ketoacidosis is suspected, GLYXAMBI should be discontinued, patient should be evaluated, and prompt treatment should be instituted.
Patients who may be at higher risk of ketoacidosis while taking GLYXAMBI include patients on a very low carbohydrate diet (as the combination may further increase ketone body production), patients with an acute illness, pancreatic disorders suggesting insulin deficiency (e.g. type 1 diabetes, history of pancreatitis or pancreatic surgery), insulin dose reduction (including insulin pump failure), alcohol abuse, severe dehydration, and patients with a history of ketoacidosis. GLYXAMBI should be used with caution in these patients. When reducing the insulin dose (see Dosage & Administration) caution should be taken. In patients treated with GLYXAMBI consider monitoring for ketoacidosis and temporarily discontinuing GLYXAMBI in clinical situations known to predispose to ketoacidosis (e.g. prolonged fasting due to acute illness or surgery). In these situations, consider monitoring of ketones, even if GLYXAMBI treatment has been interrupted.
Necrotizing fasciitis of the perineum (Fournier's gangrene): Postmarketing cases of necrotizing fasciitis of the perineum (also known as Fournier's gangrene), a rare, but serious and life-threatening necrotizing infection, have been reported in female and male patients with diabetes mellitus treated with SGLT2 inhibitors, including empagliflozin. Serious outcomes have included hospitalization, multiple surgeries, and death.
Patients treated with GLYXAMBI who present with pain or tenderness, erythema, swelling in the genital or perineal area, fever, malaise should be evaluated for necrotizing fasciitis. If suspected, GLYXAMBI should be discontinued and prompt treatment should be instituted (including broad-spectrum antibiotics and surgical debridement if necessary).
Hypoglycaemia: In clinical trials of linagliptin or of empagliflozin as part of combination therapy with agents not known to cause hypoglycaemia (e.g. metformin, thiazolidinediones) rates of hypoglycaemia reported with linagliptin or empagliflozin were similar to rates in patients taking placebo (see Adverse Reactions).
Caution is advised when GLYXAMBI is used in combination with a sulphonylurea or insulin. A dose reduction of the sulphonylurea or insulin may be considered.
Acute pancreatitis: Use of dipeptidyl peptidase-4 (DPP 4) inhibitors has been associated with a risk of developing acute pancreatitis. Acute pancreatitis has been observed in patients taking linagliptin. In a cardiovascular and renal safety study (CARMELINA) with median observation period of 2.2 years, adjudicated acute pancreatitis was reported in 0.3% of patients treated with linagliptin and in 0.1% of patients treated with placebo. Patients should be informed of the characteristic symptoms of acute pancreatitis.
If pancreatitis is suspected, GLYXAMBI should be discontinued; if acute pancreatitis is confirmed, GLYXAMBI should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Use in patients with renal impairment: GLYXAMBI should not be initiated in patients with an eGFR less than 45 ml/min/1.73 m².
GLYXAMBI should be discontinued if eGFR is persistently less than 45 ml/min/1.73m².
Monitoring of renal function: Due to its mechanism of action, the efficacy of empagliflozin is dependent on renal function. Therefore, an assessment of renal function is recommended prior to the initiation of treatment with GLYXAMBI and also periodically during treatment, i.e., at least yearly.
Use in patients at risk for volume depletion: Based on the mode of action of SGLT-2 inhibitors, osmotic diuresis accompanying therapeutic glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients for whom an empagliflozin-induced decrease in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older.
In case of conditions that may lead to fluid loss (e.g., gastrointestinal illness), careful monitoring of volume status (e.g., physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended for patients receiving empagliflozin. Temporary interruption of treatment with GLYXAMBI should be considered until the fluid loss is corrected.
Urinary tract infections: In the pooled placebo-controlled double-blind trials of 18 to 24 weeks duration, the overall frequency of urinary tract infection reported as adverse event was similar in patients treated with empagliflozin 25 mg and placebo and higher in patients treated with empagliflozin 10 mg. Post-marketing cases of complicated urinary tract infections including pyelonephritis and urosepsis have been reported in patients treated with empagliflozin. Temporary interruption of GLYXAMBI should be considered in patients with complicated urinary tract infections.
Bullous pemphigoid: Bullous pemphigoid has been observed in patients taking linagliptin. In the CARMELINA study, bullous pemphigoid was reported in 0.2% of patients on treatment with linagliptin and in no patient on placebo. If bullous pemphigoid is suspected, GLYXAMBI should be discontinued.
Hepatic injury: Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established.
Effect on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
Use in the Elderly: A higher risk of volume depletion adverse reactions were reported in patients aged 75 years and older, treated with empagliflozin, especially at 25 mg/day (see Adverse Reactions). Therefore, GLYXAMBI should be prescribed with caution in these patients.