Glyxambi 5 Mg/10 mg/25 mg Tablets

GLYXAMBI tablets are indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate (see Sections 4.2 and 5.1 Clinical trials).

The recommended starting dose is GLYXAMBI 10/5 mg (empagliflozin 10 mg/linagliptin 5 mg) once daily. In patients tolerating GLYXAMBI 10/5 mg once daily and requiring additional glycaemic control, the dose can be increased to GLYXAMBI 25/5 mg (empagliflozin 25 mg/linagliptin 5 mg) once daily. In patients already on empagliflozin, the dose of GLYXAMBI should provide the dose of empagliflozin similar to the dose already being taken by the patient. GLYXAMBI can be taken with or without food and at any time of day.

Combination therapy
When GLYXAMBI is used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia (see Sections 4.5 and 4.8).

For patients taking metformin, the metformin dose should be continued.

Special Populations

Patients with renal impairment
Assess renal function prior to initiation of empagliflozin and periodically thereafter. Glycaemic control is reduced in patients with eGFR <30 mL/min/1,73 mu00b2. GLYXAMBI is contraindicated in patients with eGFR <30 mL/min/1,73 mu00b2. Therapeutic experience with GLYXAMBI is limited in patients with eGFR <60 mL/min. No dose adjustment is required for patients with eGFR u2265 30 mL/min/1,73 mu00b2 (see Sections 4.3 and 4.4).

Patients with hepatic impairment
No dose adjustment is recommended for patients with hepatic impairment.

Elderly patients
No dosage adjustment is recommended based on age. Therapeutic experience in patients aged 75 years and older is limited. Initiation of GLYXAMBI therapy in this population is not recommended (see Section 4.4). Patients aged 75 years and older should be prescribed with caution (see Section 4.4).

Paediatric population
GLYXAMBI should not be given to children under 18 years of age. The safety and effectiveness of GLYXAMBI in children below 18 years of age have not been established.

Missed dose
If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day.

Method of administration
For oral use.

Hypersensitivity to empagliflozin or linagliptin or any of the excipients listed in section 6.1. Patients with severe renal impairment (eGFR <30 mL/min/1,73mu00b2), end-stage renal disease and patients on dialysis. The efficacy of empagliflozin is dependent on renal function (see Section 4.4).

General
GLYXAMBI should not be used in patients with type 1 diabetes (see Section 4.1).

Diabetic ketoacidosis
GLYXAMBI should not be used for the treatment of diabetic ketoacidosis. Cases of diabetic ketoacidosis (DKA), a serious life-threatening condition requiring urgent hospitalisation, have been reported in post-marketing surveillance in patients treated with SGLT2 inhibitors, including empagliflozin. Fatal cases of ketoacidosis have been reported in patients taking empagliflozin. Patients treated with GLYXAMBI who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels as ketoacidosis associated with GLYXAMBI may be present even if blood glucose levels are less than 13,8 mmol/L. Signs and symptoms of ketoacidosis may include excessive thirst, nausea, vomiting, abdominal pain, generalised malaise, and shortness of breath. If ketoacidosis is suspected, GLYXAMBI should be discontinued, the patient should be evaluated and prompt treatment should be instituted. Treatment of ketoacidosis generally requires insulin, fluid, potassium and carbohydrate replacement. 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.

Before initiating GLYXAMBI, consider factors in the patient history that may predispose to ketoacidosis. Factors that predispose patients to ketoacidosis include a low carbohydrate diet, dehydration, acute illness, surgery, a previous ketoacidosis, insulin deficiency from any cause (including insulin pump failure, history of pancreatitis, or pancreatic surgery), malnourishment/reduced caloric intake or increased insulin requirements due to infections, and alcohol abuse. GLYXAMBI should be used with caution in these patients.

When reducing the insulin dose in patients requiring insulin, caution should be taken (see Section 4.2). Consider monitoring for ketoacidosis and temporarily discontinuing GLYXAMBI in clinical situations known to predispose to ketoacidosis. In these situations, consider monitoring of ketones, even if GLYXAMBI treatment has been interrupted. Treatment should be interrupted in patients who are hospitalised for acute serious medical illnesses.

Surgery
Treatment with GLYXAMBI should be ceased prior to major surgery. An increase in other glucose lowering medicines may be required during this time. Patients scheduled for non-urgent surgery who have not ceased empagliflozin should be assessed and consideration should be given to postponing the procedure. Treatment with GLYXAMBI may be restarted once the patient's condition has stabilised and oral intake is normal.

Hypoglycaemia
In clinical trials of linagliptin or of empagliflozin as part of combination therapy with medicines 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 Section 4.8). Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, caution is advised when GLYXAMBI is used in combination with a sulphonylurea and/or insulin. A dose reduction of the sulphonylurea or insulin may be considered.

Pancreatitis
Acute pancreatitis has been observed in patients taking linagliptin (see Section 4.8). If pancreatitis is suspected, GLYXAMBI should be discontinued.

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 BP. Therefore, caution should be exercised in patients for whom an empagliflozin-induced drop in BP 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, BP 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.

Urosepsis and pyelonephritis
There have been post-marketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalisation in patients receiving SGLT2 inhibitors, including empagliflozin. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated (see Section 4.8). Discontinuation of empagliflozin may be considered in cases of recurrent urinary tract infections.

Genital infections including life threatening necrotising fasciitis
SGLT2 inhibitors such as GLYXAMBI have been associated with an increased risk of genital infection in both males and females caused by bacteria and/or fungi. Genital fungal infections appear to be more common in females. Balanoposthitis in males may result in phimosis. Post-marketing cases of necrotising fasciitis of the perineum (also known as Fournieru2019s gangrene), a rare, but serious and life-threatening necrotising infection, have been reported in female and male patients with diabetes mellitus treated with SGLT2 inhibitors, including empagliflozin. Serious outcomes have included hospitalisation, 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 necrotising fasciitis. If suspected, GLYXAMBI should be discontinued and prompt treatment should be instituted (including broad-spectrum antibiotics and surgical debridement if necessary).

Lower limb amputations
An increase in cases of lower limb amputation (primarily of the toe) has been observed in a long-term clinical study with another SGLT2 inhibitor. The medicine in that study is not empagliflozin. However, it is unknown whether this constitutes a class effect. In a pooled safety analysis of 12 620 patients with T2DM the frequency of patients with lower limb amputations was similar between empagliflozin and placebo. In the largest placebo controlled trial in 7 020 patients (EMPA-REG OUTCOME trial), in which 88 % of all the cases of amputations were reported, lower limb amputations occurred in 1,8 % of patients treated with empagliflozin 10 mg, in 2,0 % of patients treated with empagliflozin 25 mg, and in 1,8 % of patients in the placebo arm. It is important to regularly examine the feet and counsel all diabetic patients on routine preventative foot care.

Bullous pemphigoid
Bullous pemphigoid has been observed in patients taking linagliptin. If bullous pemphigoid is suspected, GLYXAMBI should be discontinued.

Rhabdomyolysis
Rhabdomyolysis has been reported during use of DPP-4 inhibitor containing products such as GLYXAMBI. However, causality could not be assessed due to confounding factors such as concomitant use of medicines (statins, colchicine, etc.) or co-morbid conditions (renal failure, hypovolaemia, etc.), known to cause or predispose to development of rhabdomyolysis. Close monitoring of patients using DPP-4 inhibitor containing products in presence of predisposing risk factors is recommended.

Arthralgia
There have been post-marketing reports of joint pain, which may be severe, in patients taking DPP-4 inhibitors. Onset of symptoms following initiation of treatment may be rapid or may occur after longer periods. Discontinuation of therapy should be considered in patients who present with or experience an exacerbation of joint symptoms during treatment with linagliptin.

Combination with glucagon like peptide (GLP-1) analogues
Linagliptin has not been studied in combination with glucagon like peptide 1 (GLP-1) analogues.

Use in renal impairment
Empagliflozin increases serum creatinine and decreases eGFR (see Section 4.8). Renal function abnormalities can occur after initiating empagliflozin. Patients with hypovolaemia may be more susceptible to these changes. There have been post-marketing reports of acute kidney injury, some requiring hospitalisation and dialysis, in patients receiving SGLT2 inhibitors, including empagliflozin; some reports involved patients younger than 65 years of age. GLYXAMBI is contraindicated for use in patients with eGFR <30 mL/min/1,73 mu00b2 (see Sections 4.2 and 4.3). Therapeutic experience with GLYXAMBI is limited in patients with eGFR <60 mL/min. Monitoring of renal function is recommended: prior to empagliflozin initiation and periodically during treatment, i.e. at least yearly; prior to initiation of concomitant medicines that may reduce renal function and periodically thereafter. Patients treated with empagliflozin can experience an initial fall in eGFR. More intensive monitoring of renal function is recommended, particularly following treatment initiation, if empagliflozin is used in patients with an eGFR <60 mL/min/1,73 mu00b2, especially if the eGFR is <45 mL/min/1,73 mu00b2. GLYXAMBI should be discontinued when the eGFR is below 30 mL/min/1,73 mu00b2 or CrCl <30 mL/min (see Section 4.3).

Use in the elderly
Patients aged 75 years and older may be at increased risk of volume depletion, therefore, GLYXAMBI should be prescribed with caution in these patients (see Section 4.8). Therapeutic experience in patients aged 75 years and older is limited. Initiation of therapy with GLYXAMBI in this population is not recommended.

Paediatric use
The safety and effectiveness of GLYXAMBI in children below 18 years of age have not been established. GLYXAMBI is not recommended for use in patients under 18 years of age.

Effect on laboratory tests
Urine will test positive for glucose while patients are taking GLYXAMBI due to the nature of the mechanism of action of SGLT2 inhibitors (see Section 5.1).

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 alternative methods to monitor glycaemic control.

No interactions between the two components of this fixed-dose combination have been observed in clinical studies. No medicine interaction studies have been performed with GLYXAMBI and other medicinal products, however, such studies have been conducted with the individual active substances. No clinically meaningful pharmacokinetic interactions were observed when empagliflozin or linagliptin were co-administered with other commonly used medicinal products. Based on results of pharmacokinetic studies, no dose adjustment of GLYXAMBI is recommended when co-administered with commonly prescribed medicinal products (see Section 5.1), except those mentioned below.

Insulin and sulphonylureas
Insulin and sulphonylureas may increase the risk of hypoglycaemia. Therefore, a lower dose of insulin or sulphonylureas may be required to reduce the risk of hypoglycaemia when used in combination with GLYXAMBI (see Sections 4.2, 4.4, 4.8).

Diuretics
Empagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension (see Section 4.4).

Lithium
Empagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after empagliflozin initiation and dose changes. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium.

UGT inhibitors and inducers
Empagliflozin is primarily metabolised via UGT (see Section 5.2); however, a clinically relevant effect of UGT inhibitors on empagliflozin is not expected.

Rifampicin
A study was conducted to assess the effect of rifampicin, a potent inductor of P-glycoprotein and CYP3A4, on the pharmacokinetics of 5 mg linagliptin. Multiple co-administration of linagliptin with rifampicin, resulted in a 39,6 % and 43,8 % decreased linagliptin steady-state AUC and C max and about 30 % decreased DPP-4 inhibition at trough. Thus linagliptin in combination with strong P-glycoprotein inducers is expected to be clinically efficacious, although full efficacy might not be achieved.

Ritonavir
A study was conducted to assess the effect of ritonavir, a potent inhibitor of P-glycoprotein and CYP3A4, on the pharmacokinetics of linagliptin. Co-administration of a single 5 mg oral dose of linagliptin and multiple 200 mg oral doses of ritonavir increased the AUC and C max of linagliptin approximately two-fold and three-fold, respectively. Simulations of steady-state plasma concentrations of linagliptin with and without ritonavir indicated that the increase in exposure will not be associated with an increased accumulation. These changes in linagliptin pharmacokinetics were not considered to be clinically relevant. Therefore, clinically relevant interactions would not be expected with other P-glycoprotein or CYP3A4 inhibitors and dose adjustment is not required.

Pregnancy
There is a limited amount of data from the use of empagliflozin and linagliptin in pregnant women. It is recommended to avoid the use of GLYXAMBI during pregnancy unless clearly needed. In a study in pregnant rats, oral co-administration of 700 mg/kg empagliflozin and 140 mg/kg linagliptin during the period of organogenesis was associated with decreased foetal weight and an increased incidence of minor foetal skeletal abnormalities, occurring in conjunction with maternotoxicity. No adverse effects on embryofetal development were observed with administration of 300 mg/kg empagliflozin and 60 mg/kg linagliptin in combination, yielding approximately 100 and 230 times the exposure to empagliflozin and linagliptin in patients at the maximum recommended human dose.

Empagliflozin
Empagliflozin administered during the period of organogenesis was not teratogenic at doses up to 300 mg/kg in the rat or rabbit, which corresponds to approximately 48- and 122-times or 128- and 325-times the clinical dose of empagliflozin based on AUC exposure associated with the 25 mg and 10 mg doses, respectively. Doses of empagliflozin causing maternal toxicity in the rat also caused the malformation of bent limb bones at exposures approximately 155- and 393-times the clinical dose associated with the 25 mg and 10 mg doses, respectively. Maternally toxic doses in the rabbit also caused increased embryofetal loss at doses approximately 139- and 353-times the clinical dose associated with the 25 mg and 10 mg doses, respectively.

Empagliflozin administered to female rats from gestation day 6 to lactation day 20 resulted in reduced weight gain in offspring at >30 mg/kg/day maternal exposures approximately 4- and 11-times those seen with a clinical dose of 25 mg and 10 mg, respectively. No adverse effects on postnatal development were noted at 10 mg/kg/day (maternal exposures approximately equivalent to those seen with a clinical dose of 25 mg).

Specialised studies in rats with other members of the pharmacological class have shown toxicity to the developing kidney in the time period corresponding to the second and third trimesters of human pregnancy. Similar effects have been seen for empagliflozin at approximately 11 times the clinical AUC exposure associated with the 25 mg dose. These findings were absent after a 13 week drug-free recovery period.

Linagliptin
Linagliptin was shown to cross the placenta in rats and rabbits. In animal embryofetal development studies, linagliptin was shown to be not teratogenic in rats at oral doses up to 240 mg/kg/day (approximately 1 000 times the exposure in patients at the MRHD, based on plasma AUC) and up to 150 mg/kg/day in the rabbit (approximately 2 000 times human exposure). However, post-implantation loss was increased in both species at these upper dose levels (together with maternotoxicity), and there was an increase in runts and a slight increase in the incidence of foetal visceral variations in the rabbit. No adverse effects on embryofetal development were observed at up to 30 mg/kg/day in the rat (50 times human exposure) and up to 25 mg/kg/day in the rabbit (78 times human exposure).

Breastfeeding
Mothers should not breastfeed their infants when taking GLYXAMBI. No data in humans are available on excretion of empagliflozin and linagliptin into milk. Available nonclinical data in animals have shown excretion of empagliflozin and linagliptin and its metabolites in milk.

Fertility
No studies on the effect on human fertility have been conducted for GLYXAMBI or with the individual components. Animal studies conducted with empagliflozin alone and linagliptin alone do not indicate adverse effects on fertility in patients.

Empagliflozin
Studies in rats at doses of empagliflozin up to 700 mg/kg/day, do not indicate direct or indirect harmful effects with respect to fertility. In female rats this dose was 90- and 155-fold the systemic AUC exposure anticipated with a human dose of 10 and 25 mg.

Linagliptin
No adverse effects on fertility were observed in male and female rats given linagliptin orally up to the highest dose of 240 mg/kg/day (yielding approximately 1 000 times the plasma AUC obtained in patients at the maximum recommended human dose [MRHD] of 5 mg/day) prior to and throughout mating.

No studies on the effects on the ability to drive and use machines have been performed. If patients experience dizziness, they should avoid potentially hazardous tasks such as driving or operating machinery.

Adverse events in clinical trials
A total of 2 173 patients with type 2 diabetes were treated in clinical studies to evaluate the safety of GLYXAMBI, of which 1 005 patients were treated with GLYXAMBI. In clinical trials, patients were treated for up to 24 or 52 weeks. The most frequent adverse reaction was urinary tract infection (see u2018Description of selected adverse reactionsu2019). Overall, the safety profile of GLYXAMBI was comparable to the safety profiles of the individual components (empagliflozin and linagliptin). The adverse reactions shown in Table 1 listed by system organ class, are based on the safety profiles of empagliflozin and linagliptin monotherapy, and were also reported in clinical trials and post-marketing surveillance with GLYXAMBI. No additional adverse reactions were identified with GLYXAMBI as compared to the individual components.

Tabulated list of adverse reactions
The adverse reactions are listed by absolute frequency. Frequencies are defined as very common (u2265 1/10), common (u2265 1/100 to <1/10), uncommon (u2265 1/1 000 to <1/100), rare (u2265 1/10 000 to <1/1 000), or very rare (<1/10 000), and not known (cannot be estimated from the available data).

Table 1 Adverse reactions and assigned frequencies, derived from clinical trials or post-marketing experience

GLYXAMBI Adverse reactions

System Organ Class MedDRA term (Preferred Terms) GLYXAMBI 10/5 mg (empagliflozin/linagliptin) GLYXAMBI 25/5 mg (empagliflozin/linagliptin)

Infections and infestations

Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection 1, 4 Common Common

Urinary tract infection 1, 4 Common Common

Urosepsis 6 Not known Not known

Pyelonephritis 6 Not known Not known

Necrotising fasciitis of the perineum (Fournieru2019s gangrene) 6 Not known Not known

Nasopharyngitis 2 Common Common

Immune system disorders

Hypersensitivity 2 Uncommon Uncommon

Angio-oedema 3,6 Not known Uncommon

Urticaria 3,6 Uncommon Not known

Metabolism and nutrition disorders

Hypoglycaemia (when used with sulphonylurea or insulin) 4 Common Common

Ketoacidosis 6 Uncommon Not known

Renal and urinary disorders

Increased urination 1, 4 Common Common

Dysuria 1 Uncommon Uncommon

Reproductive system and breast disorders

Phimosis 6 Not known Not known

Respiratory, thoracic and mediastinal disorders

Cough 2 Common Common

Skin and subcutaneous tissue disorders

Rash 3, 6 Common Uncommon

Pruritus 1 Uncommon Common

Bullous pemphigoid 3,a Not known Not known

Severe cutaneous adverse reactions (SCARs) 3,b Not known Not known

Gastrointestinal disorders

Pancreatitis 2 Uncommon Not known

Mouth ulceration 3 Rare Not known

Constipation Common Common

Musculoskeletal and connective tissue disorders

Arthralgia 3 Common Common

Rhabdomyolysis 3 Not known Not known

General disorders and administration site conditions

Thirst 1 Not known Uncommon

Investigations

Blood creatinine increased 1,4 Not known Uncommon

Glomerular filtration rate decreased 1,4 Uncommon Uncommon

Lipase increased 2,5 Common Common

Haematocrit increased 1,4 Not known Not known

Serum lipids increased 1,4 Common Common

Amylase increased 2,c Common Uncommon

Vascular disorders

Volume depletion 1,4 Uncommon Uncommon

1 derived from empagliflozin experiences 2 derived from linagliptin experiences 3 derived from linagliptin post-marketing experience 4 refer to subsections below for additional information 5 based on lipase elevations >3 x ULN observed in clinical trials 6 derived from empagliflozin post-marketing experiences a In the CARMELINA study (see section 5.1 Clinical Trials), bullous pemphigoid was reported in 0,2 % patients treated with linagliptin and in no patients treated with placebo b such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), erythema multiforme and erythroderma (generalised exfoliative dermatitis) c In the CAROLINA study (see section 5.1, Clinical Trials), amylase increase to >3xULN was reported in 0,99 % of patients treated with linagliptin and in 0,54 % of patients treated with glimepiride.

Description of selected adverse reactions
The frequencies below are calculated for adverse reactions regardless of causality. Hypoglycaemia in pooled clinical trials of GLYXAMBI in patients with type 2 diabetes and inadequate glycaemic control on background metformin, the incidence of confirmed hypoglycaemic events was low (<1,5 %; for confirmed clinical events per trial see Table 2). One patient administered GLYXAMBI experienced a confirmed (investigator-defined), major hypoglycaemic event in the active- or placebo controlled trials and none required assistance.

Table 2 Confirmed hypoglycaemic events u2013 GLYXAMBI 10/5 mg and GLYXAMBI 25/5 mg

Trial 1275.1 (Add-on to Metformin) GLYXAMBI 10/5 mg GLYXAMBI 25/5 mg Empagliflozin 10 mg Empagliflozin 25 mg Linagliptin 5 mg Number of patients analysed, N (%) 136 (100,0) 137 (100,0) 141 (100,0) 141 (100,0) 132 (100,0) Patients with endpoint, N (%) 3 (2,2) 5 (3,6) 2 (1,4) 5 (3,5) 3 (2,3) Trial 1275.1 (Treatment nau00efve) GLYXAMBI 10/5 mg GLYXAMBI 25/5 mg Empagliflozin 10 mg Empagliflozin 25 mg Linagliptin 5 mg Number of patients analysed, N (%) 136 (100,0) 136 (100,0) 135 (100,0) 135 (100,0) 135 (100,0) Patients with endpoint, N (%) 0 (0,0) 0 (0,0) 4 (3,0) 1 (0,7) 1 (0,7) Trial 1275.9 (Add-on to metformin + Linagliptin 5 mg) Empagliflozin 10 mg Empagliflozin 25 mg Placebo Number of patients analysed, N (%) 112 (100,0) 110 (100,0) 110 (100,0) Patients with endpoint, N (%) 0 (0,0) 3 (2,7) 1 (0,9) Trial 1275.10 (Add-on to Metformin + Empagliflozin) Metformin + Empagliflozin 10 mg Metformin + Empagliflozin 25 mg Linagliptin 5 mg Placebo Linagliptin 5 mg Placebo Number of patients analysed, N (%) 126 (100,0) 128 (100,0) 112 (100,0) 112 (100,0) Patients with endpoint, N (%) 0 (0,0) 0 (0,0) 0 (0,0) 3 (2,7)

During controlled clinical trials in healthy subjects, single doses of up to 800 mg empagliflozin, equivalent to 32 times the daily recommended dose, were well tolerated. During controlled clinical trials in healthy subjects, single doses of up to 600 mg linagliptin (equivalent to 120 times the recommended dose) were well tolerated. There is no experience with doses above 600 mg in humans.

Treatment
In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g. remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring and institute clinical measures as required. The removal of empagliflozin by haemodialysis has not been studied.