Glyxambi

Glyxambi Special Precautions

Manufacturer:

Boehringer Ingelheim

Distributor:

DKSH
The information highlighted (if any) are the most recent updates for this brand.
Full Prescribing Info
Special Precautions
GLYXAMBI should not be used in patients with type 1 diabetes.
Diabetic ketoacidosis: Rare cases of diabetic ketoacidosis (DKA), including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including empagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/L (250 mg/dL). It is not known if DKA is more likely to occur with higher doses of empagliflozin.
The risk of DKA 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.
In patients where DKA is suspected or diagnosed, treatment with empagliflozin should be discontinued immediately.
Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients.
Measurement of blood ketone levels is preferred to urine. Treatment with empagliflozin may be restarted when the ketone values are normal and the patient's condition has stabilised.
Before initiating empagliflozin, factors in the patient history that may predispose to ketoacidosis should be considered.
Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve [e.g. type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis], patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients.
Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved.
The safety and efficacy of empagliflozin in patients with type 1 diabetes have not been established and empagliflozin should not be used for treatment of patients with type 1 diabetes. Limited data from clinical trials suggest that DKA occurs with common frequency when patients with type 1 diabetes are treated with SGLT2 inhibitors.
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).
Use with medicinal products known to cause hypoglycaemia: Empagliflozin and linagliptin as single agents showed an incidence of hypoglycaemia comparable to placebo when used alone or in combination with other antidiabetics not known to cause hypoglycaemia (e.g. metformin, thiazolidinediones). When used in combination with antidiabetics known to cause hypoglycaemia (e.g. sulphonylureas and/or insulin), the incidence of hypoglycaemia of both agents was increased (see Adverse Reactions).
There are no data about the hypoglycaemic risk of GLYXAMBI when used with insulin and/or sulphonylurea. However, caution is advised when GLYXAMBI is used in combination with antidiabetics. A dose reduction of the sulphonylurea or insulin may be considered (see Dosage & Administration and Interactions).
Acute pancreatitis: Use of a 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 year, 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.
Monitoring of renal function: Due to the mechanism of action, the glycaemic efficacy of empagliflozin is dependent on renal function (see Dosage & Administration, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions). Therefore, assessment of renal function is recommended: prior to GLYXAMBI initiation and periodically during treatment, i.e. at least yearly, prior to initiation of any concomitant medicinal product that may have a negative impact on renal function.
Use in patients at risk for volume depletion: Based on the mode of action of SGLT2 inhibitors, osmotic diuresis accompanying therapeutic glucosuria may lead to a modest decrease in blood pressure (see Pharmacology: Pharmacodynamics under Actions). Therefore, caution should be exercised in patients for whom an empagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy (e.g. thiazide and loop diuretics, see also Interactions) 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 GLYXAMBI clinical trials, the incidence of urinary tract infections was overall similar between the patients treated with GLYXAMBI and the patients treated with empagliflozin or linagliptin. The frequencies were comparable to the incidence of urinary tract infections in empagliflozin clinical trials (see Adverse Reactions).
In a pool of 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 (see Adverse Reactions). Post-marketing cases of complicated urinary tract infections including pyelonephritis and urosepsis have been reported in patients treated with empagliflozin. Pyelonephritis and urosepsis were not reported from the clinical trials in patients treated with GLYXAMBI. However, temporary interruption of GLYXAMBI should be considered in patients with complicated urinary tract infections.
Lower limb amputations: An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with another SGLT2 inhibitor. It is unknown whether this constitutes a class effect. Like for all diabetic patients it is important to counsel patients on routine preventative foot-care.
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.
Cardiac failure: Experience with empagliflozin in New York Heart Association (NYHA) class I-II is limited, and there is no experience in clinical studies with empagliflozin in NYHA class III-IV. In the EMPA-REG OUTCOME study, 10.1 % of the patients were reported with cardiac failure at baseline. The reduction of cardiovascular death in these patients was consistent with the overall study population.
Urine laboratory assessments: Due to the mechanism of action of empagliflozin, patients taking GLYXAMBI will test positive for glucose in their urine.
Elevated haematocrit: Haematocrit increase was observed with empagliflozin treatment (see Adverse Reactions).
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.
Effect on ability to drive and use machines: GLYXAMBI has minor influence on the ability to drive and use machines. Patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines, in particular when GLYXAMBI is used in combination with other antidiabetic medicinal products known to cause hypoglycaemia (e.g. insulin and analogues, sulphonylureas).
Use in patients with renal impairment: In patients with an eGFR persistently below 45 mL/min/1.73 m2 or CrCl <45 mL/min, avoidance or discontinuation of GLYXAMBI may be necessary (for details see Dosage & Administration). GLYXAMBI should be discontinued when eGFR is persistently below 45 mL/min/1.73 m2 or CrCl is persistenly below 45 mL/min. In patients with end-stage renal disease or in patients on dialysis, GLYXAMBI should not be used, as empagliflozin is not expected to be effective in these patients (see Pharmacology: Pharmacokinetics under Actions).
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, special attention should be given to their volume intake in case of co-administered medicinal products which may lead to volume depletion (e.g. diuretics, ACE inhibitors). Therapeutic experience is limited with GLYXAMBI in patients > 75 years of age, and, no experience is available in patients aged 85 years and older. Initiation of therapy with GLYXAMBI in this population is not recommended (see Dosage & Administration).
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