Safety profile

Further safety information across all indications

Empagliflozin is not recommended in severe hepatic impairment, breastfeeding, type 1 diabetes, and is contraindicated in patients with hypersensitivity to the active ingredient or any of its excipients. Empagliflozin should be avoided in pregnancy.

Ketoacidosis

• Cases of ketoacidosis, including life-threatening and fatal cases, have been reported in patients with diabetes mellitus 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 ketoacidosis is more likely to occur with higher doses of empagliflozin. Although ketoacidosis is less likely to occur in patients without diabetes mellitus, cases have also been reported in these patients.¹
• The risk of 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.¹
• In patients where ketoacidosis is suspected or diagnosed, treatment with empagliflozin should be discontinued immediately. Ketoacidosis may last longer after discontinuation of JARDIANCE® than expected from the plasma half-life.¹
• 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.¹
• Before initiating empagliflozin, factors in the patient history that may predispose to ketoacidosis should be considered.¹
• Patients who may be at higher risk of ketoacidosis 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.¹
• Restarting SGLT2 inhibitor treatment in patients with previous ketoacidosis while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved.¹
• JARDIANCE® should not be used in patients with type 1 diabetes. Data from a clinical trial program in patients with type 1 diabetes showed increased ketoacidosis occurrence with common frequency in patients treated with empagliflozin 10 mg and 25 mg as an adjunct to insulin compared to placebo.¹

Renal impairment

• Due to limited experience, it is not recommended to initiate treatment with empagliflozin in patients with an eGFR <20 ml/min/1.73 m².¹
• In patients with an eGFR <60 ml/min/1.73 m² the daily dose of empagliflozin is 10 mg (see section 4.2 of the SmPC for more details).¹
• The glucose lowering efficacy of empagliflozin is dependent on renal function, and is reduced in patients with an eGFR <45 ml/min/1.73 m² and is likely absent in patients with an eGFR <30 ml/min/1.73 m² (see section 4.2, 5.1 and 5.2 of the SmPC for more details).¹
• Monitoring of renal function.¹
• Assessment of renal function is recommended as follows:
• Prior to empagliflozin initiation and periodically during treatment, i.e. at least yearly (see sections 4.2, 4.8, 5.1 and 5.2 of the SmPC for more details).¹
• Prior to initiation of any concomitant medicinal product that may have a negative impact on renal function.¹

Risk for volume depletion

• Based on the mode of action of SGLT2 inhibitors, osmotic diuresis accompanying glucosuria may lead to a modest decrease in blood pressure (see section 5.1 of SmpC for further details). 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 with a history of hypotension or patients aged 75 years and older.¹
• 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 empagliflozin should be considered until the fluid loss is corrected.¹

Elderly

• The effect of empagliflozin on urinary glucose excretion is associated with osmotic diuresis, which could affect the hydration status. Patients aged 75 years and older may be at an increased risk of volume depletion. A higher number of these patients treated with empagliflozin had adverse reactions related to volume depletion as compared to placebo (see section 4.8 of SmpC for further details). 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).¹

Complicated urinary tract infections

• Cases of complicated urinary tract infections including pyelonephritis and urosepsis have been reported in patients treated with empagliflozin (see section 4.8 of SmpC for further details). Temporary interruption of empagliflozin should be considered in patients with complicated urinary tract infections.¹

Necrotising fasciitis of the perineum (Fournier's gangrene)

• Cases of necrotising fasciitis of the perineum, (also known as Fournier's gangrene), have been reported in female and male patients taking SGLT2 inhibitors including empagliflozin. This is a rare but serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment.¹
• Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier's gangrene is suspected, JARDIANCE® should be discontinued and prompt treatment (including antibiotics and surgical debridement) should be instituted.¹

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.¹

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.¹

Elevated haematocrit

• Haematocrit increase was observed with empagliflozin treatment (see section 4.8 of the SmPC for more details).¹ Patients with pronounced elevations in haematocrit should be monitored and investigated for underlying haematological disease.

Chronic kidney disease

• Patients with albuminuria may benefit more from treatment with empagliflozin.¹

Infiltrative disease or Takotsubo cardiomyopathy

• Patients with infiltrative disease or with Takotsubo cardiomyopathy have not been specifically studied. Therefore, efficacy in these patients has not been established.¹

Urine laboratory assessments

• Due to its mechanism of action, patients taking JARDIANCE® will test positive for glucose in their urine.¹

Interference with 1,5-anhydroglucitol (1,5-AG) assay

• Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Use of alternative methods to monitor glycaemic control is advised.¹

Latose

• The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.¹

Sodium

• Each tablet contains less than 1 mmol sodium (23 mg), that is to say essentially 'sodium free'.¹