Jardiance

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Jardiance 10 mg film-coated tablets
Jardiance 25 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Jardiance 10 mg film-coated tablets
Each tablet contains 10 mg empagliflozin.

Excipients with known effect
Each tablet contains lactose monohydrate equivalent to 154.3 mg lactose anhydrous.
Each tablet contains less than 1 mmol sodium (23 mg), that is to say essentially ‘sodium free’.

Jardiance 25 mg film-coated tablets
Each tablet contains 25 mg empagliflozin.

Excipients with known effect
Each tablet contains lactose monohydrate equivalent to 107.4 mg lactose anhydrous.
Each tablet contains less than 1 mmol sodium (23 mg), that is to say essentially ‘sodium free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Jardiance 10 mg film-coated tablets
Round, pale yellow, biconvex, bevel-edged film-coated tablet debossed with “S10” on one side and 
the Boehringer Ingelheim logo on the other (tablet diameter: 9.1 mm).

Jardiance 25 mg film-coated tablets
Oval, pale yellow, biconvex film-coated tablet debossed with “S25” on one side and the Boehringer 
Ingelheim logo on the other (tablet length: 11.1 mm, tablet width: 5.6 mm).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus 
as an adjunct to diet and exercise
- as monotherapy when metformin is considered inappropriate due to intolerance
- in addition to other medicinal products for the treatment of diabetes

For study results with respect to combinations, effects on glycaemic control and cardiovascular events, 
and the populations studied, see sections 4.4, 4.5 and 5.1.

4.2 Posology and method of administration

Posology

The recommended starting dose is 10 mg empagliflozin once daily for monotherapy and add-on 
combination therapy with other medicinal products for the treatment of diabetes. In patients tolerating 
empagliflozin 10 mg once daily who have an eGFR ≥60 ml/min/1.73 m2 and need tighter glycaemic 



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control, the dose can be increased to 25 mg once daily. The maximum daily dose is 25 mg (see below 
and section 4.4).

When empagliflozin 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).

Special populations
Renal impairment
Due to the mechanism of action, the glycaemic efficacy of empagliflozin is dependent on renal 
function. No dose adjustment is required for patients with an eGFR ≥60 ml/min/1.73 m2 or 
CrCl ≥60 ml/min.

Empagliflozin should not be initiated in patients with an eGFR <60 ml/min/1.73 m2 or 
CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR falls persistently below 
60 ml/min/1.73 m2 or CrCl below 60 ml/min, the dose of empagliflozin should be adjusted to or 
maintained at 10 mg once daily. Empagliflozin should be discontinued when eGFR is persistently 
below 45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min (see sections 4.4, 4.8, 5.1, and 5.2).

Empagliflozin should not be used in patients with end stage renal disease (ESRD) or in patients on 
dialysis as it is not expected to be effective in these patients (see sections 4.4 and 5.2).

Hepatic impairment
No dose adjustment is required for patients with hepatic impairment. Empagliflozin exposure is 
increased in patients with severe hepatic impairment. Therapeutic experience in patients with severe 
hepatic impairment is limited and therefore not recommended for use in this population (see section 
5.2).

Elderly 
No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for 
volume depletion should be taken into account (see sections 4.4 and 4.8). In patients aged 85 years and 
older, initiation of empagliflozin therapy is not recommended due to the limited therapeutic experience 
(see section 4.4).

Paediatric population
The safety and efficacy of empagliflozin in children and adolescents has not yet been established. No 
data are available.

Method of administration

The tablets can be taken with or without food, swallowed whole with water. If a dose is missed, it 
should be taken as soon as the patient remembers; however, a double dose should not be taken on the 
same day.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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.



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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.

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 SGLT-2 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.

Renal impairment
Jardiance should not be initiated in patients with an eGFR below 60 ml/min/1.73 m2 or 
CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR is persistently below 
60 ml/min/1.73 m2 or CrCl <60 ml/min, the dose of empagliflozin should be adjusted to or maintained 
at 10 mg once daily. Empagliflozin should be discontinued when eGFR is persistently below 
45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min. Empagliflozin should not be used in patients 
with ESRD or in patients on dialysis as it is not expected to be effective in these patients (see sections
4.2 and 5.2).

Monitoring of renal function
Due to the mechanism of action, the glycaemic efficacy of empagliflozin is dependent on renal 
function. Therefore 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, 5.1 and 5.2).
- Prior to initiation of any concomitant medicinal product that may have a negative impact on 

renal function.

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.

Elevated haematocrit
Haematocrit increase was observed with empagliflozin treatment (see section 4.8).



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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 (see section 5.1). 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.

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.

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). 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 in patients aged 85 years 
and older is limited. Initiation of empagliflozin therapy in this population is not recommended (see 
section 4.2).

Urinary tract infections
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 section 4.8). 
Post-marketing cases of complicated urinary tract infections including pyelonephritis and urosepsis 
have been reported in patients treated with empagliflozin. Temporary interruption of empagliflozin 
should be considered in patients with complicated urinary tract infections.

Necrotising fasciitis of the perineum (Fournier’s gangrene)
Post-marketing cases of necrotising fasciitis of the perineum, (also known as Fournier’s gangrene), 
have been reported in female and male patients taking SGLT2 inhibitors. This is a rare but serious and 
potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment.

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.

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.

Cardiac failure
Experience 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 its mechanism of action, patients taking Jardiance will test positive for glucose in their urine.



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Lactose
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.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

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).

Insulin and insulin secretagogues
Insulin and insulin secretagogues, such as sulphonylureas, may increase the risk of hypoglycaemia. 
Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of 
hypoglycaemia when used in combination with empagliflozin (see sections 4.2 and 4.8).

Pharmacokinetic interactions

Effects of other medicinal products on empagliflozin
In vitro data suggest that the primary route of metabolism of empagliflozin in humans is 
glucuronidation by uridine 5'-diphosphoglucuronosyltransferases UGT1A3, UGT1A8, UGT1A9, and 
UGT2B7. Empagliflozin is a substrate of the human uptake transporters OAT3, OATP1B1, and 
OATP1B3, but not OAT1 and OCT2. Empagliflozin is a substrate of P-glycoprotein (P-gp) and breast 
cancer resistance protein (BCRP).

Co-administration of empagliflozin with probenecid, an inhibitor of UGT enzymes and OAT3, 
resulted in a 26% increase in peak empagliflozin plasma concentrations (Cmax) and a 53% increase in 
area under the concentration-time curve (AUC). These changes were not considered to be clinically 
meaningful. 

The effect of UGT induction on empagliflozin has not been studied. Co-treatment with known 
inducers of UGT enzymes should be avoided due to a potential risk of decreased efficacy.

An interaction study with gemfibrozil, an in vitro inhibitor of OAT3 and OATP1B1/1B3 transporters, 
showed that empagliflozin Cmax increased by 15% and AUC increased by 59% following co-
administration. These changes were not considered to be clinically meaningful.

Inhibition of OATP1B1/1B3 transporters by co-administration with rifampicin resulted in a 75% 
increase in Cmax and a 35% increase in AUC of empagliflozin. These changes were not considered to 
be clinically meaningful.

Empagliflozin exposure was similar with and without co-administration with verapamil, a P-gp 
inhibitor, indicating that inhibition of P-gp does not have any clinically relevant effect on 
empagliflozin.

Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by co-
administration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, 
ramipril, simvastatin, torasemide and hydrochlorothiazide.

Effects of empagliflozin on other medicinal products
Based on in vitro studies, empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. 
Empagliflozin does not inhibit UGT1A1, UGT1A3, UGT1A8, UGT1A9, or UGT2B7. Drug-drug 
interactions involving the major CYP450 and UGT isoforms with empagliflozin and concomitantly 
administered substrates of these enzymes are therefore considered unlikely. 
Empagliflozin does not inhibit P-gp at therapeutic doses. Based on in vitro studies, empagliflozin is 
considered unlikely to cause interactions with active substances that are P-gp substrates. Co-



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administration of digoxin, a P-gp substrate, with empagliflozin resulted in a 6% increase in AUC and 
14% increase in Cmax of digoxin. These changes were not considered to be clinically meaningful.

Empagliflozin does not inhibit human uptake transporters such as OAT3, OATP1B1, and OATP1B3 
in vitro at clinically relevant plasma concentrations and, as such, drug-drug interactions with
substrates of these uptake transporters are considered unlikely.

Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically 
relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, 
linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of empagliflozin in pregnant women. Animal studies show that 
empagliflozin crosses the placenta during late gestation to a very limited extent but do not indicate 
direct or indirect harmful effects with respect to early embryonic development. However, animal 
studies have shown adverse effects on postnatal development (see section 5.3). As a precautionary 
measure, it is preferable to avoid the use of Jardiance during pregnancy. 

Breast-feeding

No data in humans are available on excretion of empagliflozin into milk. Available toxicological data 
in animals have shown excretion of empagliflozin in milk. A risk to the newborns/infants cannot be 
excluded. Jardiance should not be used during breast-feeding.

Fertility

No studies on the effect on human fertility have been conducted for Jardiance. Animal studies do not 
indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

Jardiance 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 
Jardiance is used in combination with a sulphonylurea and/or insulin.

4.8 Undesirable effects

Summary of the safety profile

A total of 15,582 patients with type 2 diabetes were included in clinical studies to evaluate the safety 
of empagliflozin, of which 10,004 patients received empagliflozin, either alone or in combination with 
metformin, a sulphonylurea, pioglitazone, DPP-4 inhibitors, or insulin.

In 6 placebo-controlled trials of 18 to 24 weeks duration, 3,534 patients were included of which 1,183 
were treated with placebo and 2,351 with empagliflozin. The overall incidence of adverse events in 
patients treated with empagliflozin was similar to placebo. The most frequently reported adverse 
reaction was hypoglycaemia when used with sulphonylurea or insulin (see description of selected 
adverse reactions).

Tabulated list of adverse reactions

Adverse reactions classified by system organ class and MedDRA preferred terms reported in patients 
who received empagliflozin in placebo-controlled studies are presented in the table below (Table 1).



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The adverse reactions are listed by absolute frequency. Frequencies are defined as very common 
(≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥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: Tabulated list of adverse reactions (MedDRA) from reported placebo-controlled studies and 
from post-marketing experience

System organ 
class

Very common Common Uncommon Rare Not known

Infections and 
infestations

Vaginal 
moniliasis, 
vulvovaginitis, 
balanitis and 
other genital 
infectiona

Urinary tract 
infection
(including 
pyelonephritis 
and urosepsis)a

Necrotising 
fasciitis of 
the perineum 
(Fournier´s 
gangrene)*

Metabolism 
and nutrition 
disorders

Hypoglycaemia 
(when used with 
sulphonylurea or 
insulin)a

Thirst Diabetic
ketoacidosis*

Skin and 
subcutaneous 
tissue 
disorders

Pruritus 
(generalised)
Rash

Urticaria Angioedema

Vascular 
disorders

Volume 
depletiona

Renal and 
urinary 
disorders

Increased 
urinationa

Dysuria

Investigations Serum lipids 
increasedb

Blood creatinine 
increased/
Glomerular 
filtration rate
decreaseda

Haematocrit 
increasedc

a see subsections below for additional information
b Mean percent increases from baseline for empagliflozin 10 mg and 25 mg versus placebo, respectively, were 

total cholesterol 4.9% and 5.7% versus 3.5%; HDL-cholesterol 3.3% and 3.6% versus 0.4 %; LDL-cholesterol 
9.5% and 10.0% versus 7.5%; triglycerides 9.2% and 9.9% versus 10.5%.
c Mean changes from baseline in haematocrit were 3.4% and 3.6% for empagliflozin 10 mg and 25 mg, 
respectively, compared to 0.1% for placebo. In the EMPA-REG Outcome study, haematocrit values returned 
towards baseline values after a follow-up period of 30 days after treatment stop.
* see section 4.4

Description of selected adverse reactions

Hypoglycaemia
The frequency of hypoglycaemia depended on the background therapy in the respective studies and 
was similar for empagliflozin and placebo as monotherapy, add-on to metformin, add-on to 
pioglitazone with or without metformin, as add-on to linagliptin and metformin, and as adjunct to 
standard care therapy and for the combination of empagliflozin with metformin in drug-naïve patients 
compared to those treated with empagliflozin and metformin as individual components. An increased 
frequency was noted when given as add-on to metformin and a sulfonylurea (empagliflozin 10 mg: 



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16.1%, empagliflozin 25 mg: 11.5%, placebo: 8.4%), add-on to basal insulin with or without 
metformin and with or without a sulphonylurea (empagliflozin 10 mg: 19.5%, empagliflozin 25 mg: 
28.4%, placebo: 20.6% during initial 18 weeks treatment when insulin could not be adjusted; 
empagliflozin 10 mg and 25 mg: 36.1%, placebo 35.3% over the 78-week trial), and add-on to MDI 
insulin with or without metformin (empagliflozin 10 mg: 39.8%, empagliflozin 25 mg: 41.3%, 
placebo: 37.2% during initial 18 weeks treatment when insulin could not be adjusted; empagliflozin 
10 mg: 51.1%, empagliflozin 25 mg: 57.7%, placebo: 58% over the 52-week trial).

Major hypoglycaemia (events requiring assistance)
No increase in major hypoglycaemia was observed with empagliflozin compared to placebo as 
monotherapy, add-on to metformin, add-on to metformin and a sulfonylurea, add-on to pioglitazone 
with or without metformin, add-on to linagliptin and metformin, as adjunct to standard care therapy 
and for the combination of empagliflozin with metformin in drug-naïve patients compared to those 
treated with empagliflozin and metformin as individual components. An increased frequency was 
noted when given as add-on to basal insulin with or without metformin and with or without a 
sulfonylurea (empagliflozin 10 mg: 0%, empagliflozin 25 mg: 1.3%, placebo: 0% during initial 
18 weeks treatment when insulin could not be adjusted; empagliflozin 10 mg: 0%, empagliflozin 
25 mg: 1.3%, placebo 0% over the 78-week trial), and add-on to MDI insulin with or without 
metformin (empagliflozin 10 mg: 0.5%, empagliflozin 25 mg: 0.5%, placebo: 0.5% during initial 
18 weeks treatment when insulin could not be adjusted; empagliflozin 10 mg: 1.6%, empagliflozin
25 mg: 0.5%, placebo: 1.6% over the 52-week trial).

Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection
Vaginal moniliasis, vulvovaginitis, balanitis and other genital infections were reported more 
frequently in patients treated with empagliflozin (empagliflozin 10 mg: 4.0%, empagliflozin 25 mg: 
3.9%) compared to placebo (1.0%). These infections were reported more frequently in females treated 
with empagliflozin compared to placebo, and the difference in frequency was less pronounced in 
males. The genital tract infections were mild or moderate in intensity.

Increased urination
Increased urination (including the predefined terms pollakiuria, polyuria, and nocturia) was observed 
at higher frequencies in patients treated with empagliflozin (empagliflozin 10 mg: 3.5%, empagliflozin 
25 mg: 3.3%) compared to placebo (1.4%). Increased urination was mostly mild or moderate in 
intensity. The frequency of reported nocturia was similar for placebo and empagliflozin (<1%).

Urinary tract infection
The overall frequency of urinary tract infection reported as adverse event was similar in patients 
treated with empagliflozin 25 mg and placebo (7.0% and 7.2%) and higher in empagliflozin 10 mg 
(8.8%). Similar to placebo, urinary tract infection was reported more frequently for empagliflozin in 
patients with a history of chronic or recurrent urinary tract infections. The intensity (mild, moderate, 
severe) of urinary tract infection was similar in patients treated with empagliflozin and placebo. 
Urinary tract infection was reported more frequently in females treated with empagliflozin compared 
to placebo; there was no difference in males. 

Volume depletion
The overall frequency of volume depletion (including the predefined terms blood pressure 
(ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolaemia, 
orthostatic hypotension, and syncope) was similar in patients treated with empagliflozin 
(empagliflozin 10 mg: 0.6%, empagliflozin 25 mg: 0.4%) and placebo (0.3%). The frequency of 
volume depletion events was increased in patients 75 years and older treated with empagliflozin 10 mg 
(2.3%) or empagliflozin 25 mg (4.3%) compared to placebo (2.1%).

Blood creatinine increased/Glomerular filtration rate decreased 
The overall frequency of patients with increased blood creatinine and decreased glomerular filtration 
rate were similar between empagliflozin and placebo (blood creatinine increased: empagliflozin 10 mg 
0.6%, empagliflozin 25 mg 0.1%, placebo 0.5%; glomerular filtration rate decreased: empagliflozin 
10 mg 0.1%, empagliflozin 25 mg 0%, placebo 0.3%).



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Initial increases in creatinine and initial decreases in estimated glomerular filtration rates in patients 
treated with empagliflozin were generally transient during continuous treatment or reversible after 
drug discontinuation of treatment.
Consistently, in the EMPA-REG OUTCOME study, patients treated with empagliflozin experienced 
an initial fall in eGFR (mean: 3 ml/min/1.73 m2). Thereafter, eGFR was maintained during continued 
treatment. Mean eGFR returned to baseline after treatment discontinuation suggesting acute 
haemodynamic changes may play a role in these renal function changes.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Symptoms

In controlled clinical studies single doses of up to 800 mg empagliflozin (equivalent to 32 times the 
highest recommended daily dose) in healthy volunteers and multiple daily doses of up to 100 mg 
empagliflozin (equivalent to 4 times the highest recommended daily dose) in patients with type 2 
diabetes did not show any toxicity. Empagliflozin increased urine glucose excretion leading to an 
increase in urine volume. The observed increase in urine volume was not dose-dependent and is not 
clinically meaningful. There is no experience with doses above 800 mg in humans.

Therapy

In the event of an overdose, treatment should be initiated as appropriate to the patient‘s clinical status. 
The removal of empagliflozin by haemodialysis has not been studied.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes, Other blood glucose lowering drugs, excl. 
insulins, ATC code: A10BK03

Mechanism of action

Empagliflozin is a reversible, highly potent (IC50 of 1.3 nmol) and selective competitive inhibitor of 
sodium-glucose co-transporter 2 (SGLT2). Empagliflozin does not inhibit other glucose transporters 
important for glucose transport into peripheral tissues and is 5000 times more selective for SGLT2 
versus SGLT1, the major transporter responsible for glucose absorption in the gut. SGLT2 is highly 
expressed in the kidney, whereas expression in other tissues is absent or very low. It is responsible, as 
the predominant transporter, for the reabsorption of glucose from the glomerular filtrate back into the 
circulation. In patients with type 2 diabetes and hyperglycaemia a higher amount of glucose is filtered 
and reabsorbed.

Empagliflozin improves glycaemic control in patients with type 2 diabetes by reducing renal glucose 
reabsorption. The amount of glucose removed by the kidney through this glucuretic mechanism is 
dependent on blood glucose concentration and GFR. Inhibition of SGLT2 in patients with type 2 
diabetes and hyperglycaemia leads to excess glucose excretion in the urine. In addition, initiation of 
empagliflozin increases excretion of sodium resulting in osmotic diuresis and reduced intravascular 
volume.

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In patients with type 2 diabetes, urinary glucose excretion increased immediately following the first 
dose of empagliflozin and is continuous over the 24 hour dosing interval. Increased urinary glucose 
excretion was maintained at the end of the 4-week treatment period, averaging approximately 
78 g/day. Increased urinary glucose excretion resulted in an immediate reduction in plasma glucose 
levels in patients with type 2 diabetes. 

Empagliflozin improves both fasting and post-prandial plasma glucose levels. The mechanism of 
action of empagliflozin is independent of beta cell function and insulin pathway and this contributes to 
a low risk of hypoglycaemia. Improvement of surrogate markers of beta cell function including 
Homeostasis Model Assessment-β (HOMA-β) was noted. In addition, urinary glucose excretion 
triggers calorie loss, associated with body fat loss and body weight reduction. The glucosuria observed 
with empagliflozin is accompanied by diuresis which may contribute to sustained and moderate 
reduction of blood pressure. The glucosuria, natriuresis and osmotic diuresis observed with 
empagliflozin may contribute to the improvement in cardiovascular outcomes.

Clinical efficacy and safety

Both improvement of glycaemic control and reduction of cardiovascular morbidity and mortality are 
an integral part of the treatment of type 2 diabetes.

Glycaemic efficacy and cardiovascular outcomes have been assessed in a total of 14,663 patients with 
type 2 diabetes who were treated in 12 double-blind, placebo- and active-controlled clinical studies, of 
which 9,295 received empagliflozin (empagliflozin 10 mg: 4,165 patients; empagliflozin 25 mg: 5,130
patients). Five studies had treatment durations of 24 weeks; extensions of those and other studies had 
patients exposed to empagliflozin for up to 102 weeks.

Treatment with empagliflozin as monotherapy and in combination with metformin, pioglitazone, a 
sulphonylurea, DPP-4 inhibitors, and insulin lead to clinically relevant improvements in HbA1c, 
fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure. Administration 
of empagliflozin 25 mg resulted in a higher proportion of patients achieving HbA1c goal of less than 
7% and fewer patients needing glycaemic rescue compared to empagliflozin 10 mg and placebo. 
Higher baseline HbA1c was associated with a greater reduction in HbA1c. In addition, empagliflozin 
as adjunct to standard care therapy reduced cardiovascular mortality in patients with type 2 diabetes 
and established cardiovascular disease.

Monotherapy

The efficacy and safety of empagliflozin as monotherapy was evaluated in a double-blind, 
placebo- and active-controlled study of 24 weeks duration in treatment-naïve patients. Treatment with 
empagliflozin resulted in a statistically significant (p<0.0001) reduction in HbA1c compared to 
placebo (Table 2) and a clinically meaningful decrease in FPG.
In a prespecified analysis of patients (N=201) with a baseline HbA1c ≥8.5%, treatment resulted in a 
reduction in HbA1c from baseline of -1.44% for empagliflozin 10 mg, -1.43% for empagliflozin
25 mg, -1.04% for sitagliptin, and an increase of 0.01% for placebo. 
In the double-blind placebo-controlled extension of this study, reductions of HbA1c, body weight and 
blood pressure were sustained up to Week 76.



12

Table 2: Efficacy results of a 24 week placebo-controlled study of empagliflozin as monotherapya

Placebo
Jardiance Sitagliptin

10 mg 25 mg 100 mg
N 228 224 224 223
HbA1c (%)

Baseline (mean) 7.91 7.87 7.86 7.85
Change from baseline1 0.08 -0.66 -0.78 -0.66
Difference from placebo1

(97.5% CI)
-0.74*

(-0.90, -0.57)
-0.85*

(-1.01, -0.69)
-0.73

(-0.88, -0.59)3

N 208 204 202 200
Patients (%) achieving 
HbA1c <7% with 
baseline HbA1c ≥7%2

12.0 35.3 43.6 37.5

N 228 224 224 223
Body Weight (kg)

Baseline (mean) 78.23 78.35 77.80 79.31
Change from baseline1 -0.33 -2.26 -2.48 0.18
Difference from placebo1

(97.5% CI)
-1.93*

(-2.48, -1.38)
-2.15*

(-2.70,-1.60)
0.52

(-0.04, 1.00)3

N 228 224 224 223
SBP (mmHg)4

Baseline (mean) 130.4 133.0 129.9 132.5
Change from baseline1 -0.3 -2.9 -3.7 0.5
Difference from placebo1

(97.5% CI)
-2.6* (-5.2, -0.0)

-3.4* (-6.0, 
-0.9)

0.8 (-1.4, 3.1)3

a Full analysis set (FAS) using last observation carried forward (LOCF) prior to glycaemic rescue 
therapy

1 Mean adjusted for baseline value
2 Not evaluated for statistical significance as a result of the sequential confirmatory testing procedure
3 95% CI
4 LOCF, values after antihypertensive rescue censored
*p-value <0.0001

Combination therapy

Empagliflozin as add-on to metformin, sulphonylurea, pioglitazone
Empagliflozin as add-on to metformin, metformin and a sulphonylurea, or pioglitazone with or 
without metformin resulted in statistically significant (p<0.0001) reductions in HbA1c and body 
weight compared to placebo (Table 3). In addition it resulted in a clinically meaningful reduction in 
FPG, systolic and diastolic blood pressure compared to placebo.
In the double-blind placebo-controlled extension of these studies, reduction of HbA1c, body weight 
and blood pressure were sustained up to Week 76.



13

Table 3: Efficacy results of 24 week placebo-controlled studiesa

Add-on to metformin therapy

Placebo
Jardiance

10 mg 25 mg
N 207 217 213

HbA1c (%)
Baseline (mean) 7.90 7.94 7.86
Change from baseline1 -0.13 -0.70 -0.77
Difference from placebo1

(97.5% CI)
-0.57* (-0.72, -0.42) -0.64* (-0.79, -0.48)

N 184 199 191
Patients (%) achieving 
HbA1c <7% with baseline 
HbA1c ≥7%2

12.5 37.7 38.7

N 207 217 213
Body Weight (kg)

Baseline (mean) 79.73 81.59 82.21
Change from baseline1 -0.45 -2.08 -2.46
Difference from placebo1

(97.5% CI)
-1.63* (-2.17, -1.08) -2.01* (-2.56, -1.46)

N 207 217 213
SBP (mmHg)2

Baseline (mean) 128.6 129.6 130.0
Change from baseline1 -0.4 -4.5 -5.2
Difference from placebo1

(95% CI)
-4.1* (-6.2, -2.1) -4.8* (-6.9, -2.7)

Add-on to metformin and a sulphonylurea therapy

Placebo
Jardiance

10 mg 25 mg
N 225 225 216

HbA1c (%)
Baseline (mean) 8.15 8.07 8.10
Change from baseline1 -0.17 -0.82 -0.77
Difference from placebo1

(97.5% CI)
-0.64* (-0.79, -0.49) -0.59* (-0.74, -0.44)

N 216 209 202
Patients (%) achieving 
HbA1c <7% with baseline 
HbA1c ≥7%2

9.3 26.3 32.2

N 225 225 216
Body Weight (kg)

Baseline (mean) 76.23 77.08 77.50
Change from baseline1 -0.39 -2.16 -2.39
Difference from placebo1

(97.5% CI)
-1.76* (-2.25, -1.28) -1.99* (-2.48, -1.50)

N 225 225 216
SBP (mmHg)2

Baseline (mean) 128.8 128.7 129.3
Change from baseline1 -1.4 -4.1 -3.5
Difference from placebo1

(95% CI)
-2.7 (-4.6, -0.8) -2.1 (-4.0, -0.2)



14

Add-on to pioglitazone +/- metformin therapy

Placebo
Jardiance

10 mg 25 mg
N 165 165 168
HbA1c (%)

Baseline (mean) 8.16 8.07 8.06
Change from baseline1 -0.11 -0.59 -0.72
Difference from placebo1

(97.5% CI)
-0.48* (-0.69, -0.27) -0.61* (-0.82, -0.40)

N 155 151 160
Patients (%) achieving 
HbA1c <7% with baseline 
HbA1c ≥7%2

7.7 24 30

N 165 165 168
Body Weight (kg)

Baseline (mean) 78.1 77.97 78.93
Change from baseline1 0.34 -1.62 -1.47
Difference from placebo1

(97.5% CI)
-1.95* (-2.64, -1.27) -1.81* (-2.49, -1.13)

N 165 165 168
SBP (mmHg)3

Baseline (mean) 125.7 126.5 126
Change from baseline1 0.7 -3.1 -4.0
Difference from placebo1

(95% CI)
-3.9 (-6.23, -1.50) -4.7 (-7.08, -2.37)

a Full analysis set (FAS) using last observation carried forward (LOCF) prior to glycaemic rescue 
therapy

1 Mean adjusted for baseline value
2 Not evaluated for statistical significance as a result of the sequential confirmatory testing procedure
3 LOCF, values after antihypertensive rescue censored
* p-value <0.0001

In combination with metformin in drug-naïve patients
A factorial design study of 24 weeks duration was conducted to evaluate the efficacy and safety of 
empagliflozin in drug-naïve patients. Treatment with empagliflozin in combination with metformin 
(5 mg and 500 mg; 5 mg and 1000 mg; 12.5 mg and 500 mg, and 12.5 mg and 1000 mg given twice 
daily) provided statistically significant improvements in HbA1c (Table 4) and led to greater reductions 
in FPG (compared to the individual components) and body weight (compared to metformin).



15

Table 4: Efficacy results at 24 week comparing empagliflozin in combination with metformin to the 
individual componentsa

Empagliflozin 10 mgb Empagliflozin 25 mgb Metformin
c

+ Met 
1000 mgc

+ Met 
2000 mgc

No 
Met

+ Met 
1000 mgc

+ Met 
2000 mgc

No 
Met

1000
mg

2000
mg

N 161 167 169 165 169 163 167 162
HbA1c (%)

Baseline 
(mean)

8.68 8.65 8.62 8.84 8.66 8.86 8.69 8.55

Change from 
baseline1

-1.98 -2.07 -1.35 -1.93 -2.08 -1.36 -1.18 -1.75

Comparison 
vs. empa 
(95% CI)1

-0.63*
(-0.86,
-0.40)

-0.72*
(-0.96,
-0.49)

-0.57*
(-0.81,
-0.34)

-0.72*
(-0.95,
-0.48)

Comparison 
vs. met (95% 
CI)1

-0.79*
(-1.03,
-0.56)

-0.33*
(-0.56,
-0.09)

-0.75*
(-0.98
-0.51)

-0.33*
(-0.56,
-0.10)

Met = metformin; empa = empagliflozin
1 mean adjusted for baseline value
a Analyses were performed on the full analysis set (FAS) using an observed cases (OC) approach
b Given in two equally divided doses per day when given together with metformin
c Given in two equally divided doses per day
*p≤0.0062 for HbA1c

Empagliflozin in patients inadequately controlled with metformin and linagliptin
In patients inadequately controlled with metformin and linagliptin 5 mg, treatment with both 
empagliflozin 10 mg or 25 mg resulted in statistically significant (p<0.0001) reductions in HbA1c and 
body weight compared to placebo (Table 5). In addition it resulted in clinically meaningful reductions 
in FPG, systolic and diastolic blood pressure compared to placebo.



16

Table 5: Efficacy results of a 24 week placebo-controlled study in patients inadequately controlled 
with metformin and linagliptin 5 mg

Add-on to metformin and linagliptin 5 mg
Placebo5 Empagliflozin6

10 mg 25 mg
N 106 109 110

HbA1c (%)3

Baseline (mean) 7.96 7.97 7.97
Change from baseline1 0.14 -0.65 -0.56
Difference from placebo
(95% CI)

-0.79* (-1.02, -0.55) -0.70* (-0.93, -0.46)

N 100 100 107
Patients (%) achieving 
HbA1c <7% with baseline 
HbA1c ≥7%2

17.0 37.0 32.7

N 106 109 110
Body Weight (kg)3

Baseline (mean) 82.3 88.4 84.4
Change from baseline1 -0.3 -3.1 -2.5
Difference from placebo
(95% CI)

-2.8* (-3.5, -2.1) -2.2* (-2.9, -1.5)

N 106 109 110
SBP (mmHg)4

Baseline (mean) 130.1 130.4 131.0
Change from baseline1 -1.7 -3.0 -4.3
Difference from placebo 
(95% CI)

-1.3 (-4.2, 1.7) -2.6 (-5.5, 0.4)

1 Mean adjusted for baseline value
2 Not evaluated for statistical significance; not part of sequential testing procedure for the secondary 
endpoints
3 MMRM model on FAS (OC) included baseline HbA1c, baseline eGFR (MDRD), geographical 
region, visit, treatment, and treatment by visit interaction. For weight, baseline weight was included.
4 MMRM model included baseline SBP and baseline HbA1c as linear covariate(s), and baseline eGFR, 
geographical region, treatment, visit, and visit by treatment interaction as fixed effects.
5 Patients randomized to the placebo group were receiving the placebo plus linagliptin 5 mg with 
background metformin
6 Patients randomized to the empagliflozin 10 mg or 25 mg groups were receiving empagliflozin 
10 mg or 25 mg and linagliptin 5 mg with background metformin
* p-value <0.0001

In a prespecified subgroup of patients with baseline HbA1c greater or equal than 8.5% the reduction 
from baseline in HbA1c was -1.3% with empagliflozin 10 mg or 25 mg at 24 weeks (p<0.0001) 
compared to placebo.

Empagliflozin 24 months data, as add-on to metformin in comparison to glimepiride
In a study comparing the efficacy and safety of empagliflozin 25 mg versus glimepiride (up to 4 mg
per day) in patients with inadequate glycaemic control on metformin alone, treatment with 
empagliflozin daily resulted in superior reduction in HbA1c (Table 6), and a clinically meaningful 
reduction in FPG, compared to glimepiride. Empagliflozin daily resulted in a statistically significant 
reduction in body weight, systolic and diastolic blood pressure and a statistically significantly lower 
proportion of patients with hypoglycaemic events compared to glimepiride (2.5% for empagliflozin, 
24.2% for glimepiride, p<0.0001).



17

Table 6: Efficacy results at 104 week in an active controlled study comparing empagliflozin to 
glimepiride as add-on to metformina

Empagliflozin 25 mg Glimepirideb

N 765 780
HbA1c (%)

Baseline (mean) 7.92 7.92
Change from baseline1 -0.66 -0.55
Difference from glimepiride1 (97.5% CI) -0.11* (-0.20, -0.01)

N 690 715
Patients (%) achieving HbA1c <7% with 
baseline HbA1c ≥7%2

33.6 30.9

N 765 780
Body Weight (kg)

Baseline (mean) 82.52 83.03
Change from baseline1 -3.12 1.34
Difference from glimepiride1 (97.5% CI) -4.46** (-4.87, -4.05)

N 765 780
SBP (mmHg)2

Baseline (mean) 133.4 133.5
Change from baseline1 -3.1 2.5
Difference from glimepiride1 (97.5% CI) -5.6** (-7.0,-4.2)

a Full analysis set (FAS) using last observation carried forward (LOCF) prior to glycaemic rescue 
therapy

b Up to 4 mg glimepiride
1 Mean adjusted for baseline value
2 LOCF, values after antihypertensive rescue censored 
* p-value <0.0001 for non-inferiority, and p-value = 0.0153 for superiority
** p-value <0.0001

Add-on to insulin therapy
Empagliflozin as add-on to multiple daily insulin
The efficacy and safety of empagliflozin as add-on to multiple daily insulin with or without 
concomitant metformin therapy was evaluated in a double-blind, placebo-controlled trial of 52 weeks 
duration. During the initial 18 weeks and the last 12 weeks, the insulin dose was kept stable, but was 
adjusted to achieve pre-prandial glucose levels <100 mg/dl [5.5 mmol/l], and post-prandial glucose 
levels <140 mg/dl [7.8 mmol/l] between Weeks 19 and 40. 
At Week 18, empagliflozin provided statistically significant improvement in HbA1c compared with 
placebo (Table 7). 
At Week 52, treatment with empagliflozin resulted in a statistically significant decrease in HbA1c and 
insulin sparing compared with placebo and a reduction in FPG and body weight.



18

Table 7: Efficacy results at 18 and 52 weeks in a placebo-controlled study of empagliflozin as add
on to multiple daily doses of insulin with or without metformin

Placebo
Jardiance

10 mg 25 mg
N 188 186 189
HbA1c (%) at week 18

Baseline (mean) 8.33 8.39 8.29
Change from baseline1 -0.50 -0.94 -1.02
Difference from placebo1

(97.5% CI)
-0.44* (-0.61, -0.27) -0.52* (-0.69, -0.35)

N 115 119 118
HbA1c (%) at week 522

Baseline (mean) 8.25 8.40 8.37
Change from baseline1 -0.81 -1.18 -1.27
Difference from placebo1 

(97.5% CI)
-0.38*** (-0.62, -0.13) -0.46* (-0.70, -0.22)

N 113 118 118
Patients (%) achieving 
HbA1c <7% with 
baseline HbA1c ≥7% at 
week 52

26.5 39.8 45.8

N 115 118 117
Insulin dose (IU/day)
at week 522

Baseline (mean) 89.94 88.57 90.38
Change from baseline1 10.16 1.33 -1.06
Difference from placebo1

(97.5% CI)
-8.83# (-15.69, -1.97) -11.22** (-18.09, -4.36)

N 115 119 118
Body Weight (kg)
at week 522

Baseline (mean) 96.34 96.47 95.37
Change from baseline1 0.44 -1.95 -2.04
Difference from placebo1

(97.5% CI)
-2.39* (-3.54, -1.24) -2.48* (-3.63, -1.33)

1 Mean adjusted for baseline value
2 Week 19-40: treat-to-target regimen for insulin dose adjustment to achieve pre-defined glucose target 

levels (pre-prandial <100 mg/dl (5.5 mmol/l), post-prandial <140 mg/dl (7.8 mmol/l)
* p-value <0.0001
** p-value = 0.0003
*** p-value = 0.0005
# p-value = 0.0040

Empagliflozin as add-on to basal insulin
The efficacy and safety of empagliflozin as add-on to basal insulin with or without metformin and/or a 
sulphonylurea was evaluated in a double-blind, placebo-controlled trial of 78 weeks duration. During 
the initial 18 weeks the insulin dose was kept stable, but was adjusted to achieve a FPG <110 mg/dl in 
the following 60 weeks. 
At week 18, empagliflozin provided statistically significant improvement in HbA1c (Table 8).
At 78 weeks, empagliflozin resulted in a statistically significant decrease in HbA1c and insulin sparing 
compared to placebo. Furthermore, empagliflozin resulted in a reduction in FPG, body weight, and 
blood pressure.



19

Table 8: Efficacy results at 18 and 78 weeks in a placebo-controlled study of empagliflozin as add-on 
to basal insulin with or without metformin or a sulphonylureaa

Placebo
Empagliflozin

10 mg
Empagliflozin

25 mg
N 125 132 117
HbA1c (%) at week 18

Baseline (mean) 8.10 8.26 8.34
Change from baseline1 -0.01 -0.57 -0.71
Difference from placebo1

(97.5% CI)
-0.56* (-0.78, -0.33) -0.70* (-0.93, -0.47)

N 112 127 110
HbA1c (%) at week 78

Baseline (mean) 8.09 8.27 8.29
Change from baseline1 -0.02 -0.48 -0.64
Difference from placebo1 

(97.5% CI)
-0.46* (-0.73, -0.19) -0.62* (-0.90, -0.34)

N 112 127 110
Basal insulin dose (IU/day) at 
week 78

Baseline (mean) 47.84 45.13 48.43
Change from baseline1 5.45 -1.21 -0.47
Difference from placebo1

(97.5% CI)
-6.66** (-11.56, -1.77) -5.92** (-11.00, -0.85)

a Full analysis set (FAS) - Completers using last observation carried forward (LOCF) prior to 
glycaemic rescue therapy

1 mean adjusted for baseline value
* p-value <0.0001
** p-value <0.025

Patients with renal impairment, 52 week placebo controlled data
The efficacy and safety of empagliflozin as add-on to antidiabetic therapy was evaluated in patients 
with renal impairment in a double-blind, placebo-controlled study for 52 weeks. Treatment with 
empagliflozin led to a statistically significant reduction of HbA1c (Table 9) and clinically meaningful 
improvement in FPG compared to placebo at Week 24. The improvement in HbA1c, body weight, and 
blood pressure was sustained up to 52 weeks.



20

Table 9: Results at 24 week in a placebo-controlled study of empagliflozin in renally impaired type 2 
diabetes patientsa

Placebo
Empagliflozin 

10 mg
Empagliflozin 

25 mg
Placebo

Empagliflozin 
25 mg

eGFR ≥60 to <90 ml/min/1.73 m²
eGFR ≥30 to 

<60 ml/min/1.73 m²
N 95 98 97 187 187
HbA1c (%)

Baseline (mean) 8.09 8.02 7.96 8.04 8.03
Change from 
baseline1

0.06 -0.46 -0.63 0.05 -0.37

Difference from 
placebo1 (95% CI)

-0.52*
(-0.72, -0.32)

-0.68*
(-0.88, -0.49)

-0.42*
(-0.56, -0.28)

N 89 94 91 178 175
Patients (%) 
achieving HbA1c 
<7% with baseline 
HbA1c ≥7%2

6.7 17.0 24.2 7.9 12.0

N 95 98 97 187 187
Body Weight (kg)2

Baseline (mean) 86.00 92.05 88.06 82.49 83.22
Change from 
baseline1

-0.33 -1.76 -2.33 -0.08 -0.98

Difference from 
placebo1 (95% CI)

-1.43
(-2.09, -0.77)

-2.00
(-2.66, -1.34)

-0.91
(-1.41, -0.41)

N 95 98 97 187 187
SBP (mmHg)2

Baseline (mean) 134.69 137.37 133.68 136.38 136.64
Change from 
baseline1

0.65 -2.92 -4.47 0.40 -3.88

Difference from 
placebo1 (95% CI)

-3.57
(-6.86, -0.29)

-5.12
(-8.41, -1.82)

-4.28
(-6.88, -1.68)

a Full analysis set (FAS) using last observation carried forward (LOCF) prior to glycaemic rescue 
therapy

1 Mean adjusted for baseline value
2 Not evaluated for statistical significance as a result of the sequential confirmatory testing procedure
* p<0.0001

Cardiovascular outcome
The double-blind, placebo-controlled EMPA-REG OUTCOME study compared pooled doses of 
empagliflozin 10 mg and 25 mg with placebo as adjunct to standard care therapy in patients with 
type 2 diabetes and established cardiovascular disease. A total of 7020 patients were treated 
(empagliflozin 10 mg: 2345, empagliflozin 25 mg: 2342, placebo: 2333) and followed for a median of 
3.1 years. The mean age was 63 years, the mean HbA1c was 8.1%, and 71.5% were male. At baseline,
74% of patients were being treated with metformin, 48% with insulin, and 43% with a sulfonylurea. 
About half of the patients (52.2%) had an eGFR of 60-90 ml/min/1.73 m2, 17.8% of 
45-60 ml/min/1.73 m2 and 7.7% of 30-45 ml/min/1.73 m2.

At week 12, an adjusted mean (SE) improvement in HbA1c when compared to baseline of 0.11% 
(0.02) in the placebo group, 0.65% (0.02) and 0.71% (0.02) in the empagliflozin 10 and 25 mg groups 
was observed. After the first 12 weeks glycaemic control was optimized independent of investigative 
treatment. Therefore the effect was attenuated at week 94, with an adjusted mean (SE) improvement in 
HbA1c of 0.08% (0.02) in the placebo group, 0.50% (0.02) and 0.55% (0.02) in the empagliflozin 
10 and 25 mg groups.



21

Empagliflozin was superior in preventing the primary combined endpoint of cardiovascular death, 
non-fatal myocardial infarction, or non-fatal stroke, as compared with placebo. The treatment effect 
was driven by a significant reduction in cardiovascular death with no significant change in non-fatal 
myocardial infarction, or non-fatal stroke. The reduction of cardiovascular death was comparable for 
empagliflozin 10 mg and 25 mg (Figure 1) and confirmed by an improved overall survival (Table 10).

The efficacy for preventing cardiovascular mortality has not been conclusively established in patients 
using empagliflozin concomitantly with DPP-4 inhibitors or in Black patients because the 
representation of these groups in the EMPA-REG OUTCOME study was limited.

Table 10:Treatment effect for the primary composite endpoint, its components and mortalitya

Placebo Empagliflozinb

N 2333 4687
Time to first event of CV death, non-fatal 
MI, or non-fatal stroke N (%)

282 (12.1) 490 (10.5)

Hazard ratio vs. placebo (95.02% CI)* 0.86 (0.74, 0.99)
p−value for superiority 0.0382

CV Death N (%) 137 (5.9) 172 (3.7)
Hazard ratio vs. placebo (95% CI) 0.62 (0.49, 0.77)
p-value <0.0001

Non-fatal MI N (%) 121 (5.2) 213 (4.5)
Hazard ratio vs. placebo (95% CI) 0.87 (0.70, 1.09)
p−value 0.2189

Non-fatal stroke N (%) 60 (2.6) 150 (3.2)
Hazard ratio vs. placebo (95% CI) 1.24 (0.92, 1.67)
p−value 0.1638

All-cause mortality N (%) 194 (8.3) 269 (5.7)
Hazard ratio vs. placebo (95% CI) 0.68 (0.57, 0.82)
p-value <0.0001

Non-CV mortality N (%) 57 (2.4) 97 (2.1)
Hazard ratio vs. placebo (95% CI) 0.84 (0.60, 1.16)

CV = cardiovascular, MI = myocardial infarction
a Treated set (TS), i.e. patients who had received at least one dose of study drug
b Pooled doses of empagliflozin 10 mg and 25 mg
* Since data from the trial were included in an interim analysis, a two-sided 95.02% confidence 
interval applied which corresponds to a p-value of less than 0.0498 for significance.



22

Figure 1 Time to occurrence of cardiovascular death in the EMPA-REG OUTCOME study

Heart failure requiring hospitalization 
In the EMPA-REG OUTCOME study, empagliflozin reduced the risk of heart failure requiring 
hospitalization compared with placebo (empagliflozin 2.7 %; placebo 4.1 %; HR 0.65, 95 % CI 0.50, 
0.85).

Nephropathy
In the EMPA-REG OUTCOME study, for time to first nephropathy event, the HR was 0.61 (95 % CI 
0.53, 0.70) for empagliflozin (12.7 %) vs placebo (18.8 %).

In addition, empagliflozin showed a higher (HR 1.82, 95 % CI 1.40, 2.37) occurrence of sustained 
normo- or micro-albuminuria (49.7 %) in patients with baseline macro-albuminuria compared with 
placebo (28.8 %).

Fasting plasma glucose
In four placebo-controlled studies, treatment with empagliflozin as monotherapy or add-on therapy to 
metformin, pioglitazone, or metformin plus a sulfonylurea resulted in mean changes from baseline in 
FPG of -20.5 mg/dl [-1.14 mmol/l] for empagliflozin 10 mg and -23.2 mg/dl [-1.29 mmol/l] for 
empagliflozin 25 mg compared to placebo (7.4 mg/dl [0.41 mmol/l]). This effect was observed after 
24 weeks and maintained for 76 weeks.

2-hour post-prandial glucose
Treatment with empagliflozin as add-on to metformin or metformin and a sulphonylurea resulted in a 
clinically meaningful reduction of 2-hour post-prandial glucose (meal tolerance test) at 24 weeks 
(add-on to metformin: placebo +5.9 mg/dl, empagliflozin 10 mg: -46.0 mg/dl, empagliflozin
25 mg: -44.6 mg/dl, add-on to metformin and a sulphonylurea: placebo -2.3 mg/dl, empagliflozin 
10 mg: -35.7 mg/dl, empagliflozin 25 mg: -36.6 mg/dl).

Patients with high baseline HbA1c >10%
In a pre-specified pooled analysis of three phase 3 studies, treatment with open-label empagliflozin 
25 mg in patients with severe hyperglycaemia (N=184, mean baseline HbA1c 11.15%) resulted in a 
clinically meaningful reduction in HbA1c from baseline of 3.27% at week 24; no placebo or 
empagliflozin 10 mg arms were included in these studies.



23

Body weight
In a pre-specified pooled analysis of 4 placebo controlled studies, treatment with empagliflozin 
resulted in body weight reduction (-0.24 kg for placebo, -2.04 kg for empagliflozin 10 mg
and -2.26 kg for empagliflozin 25 mg) at week 24 that was maintained up to week 52 (-0.16 kg for 
placebo, -1.96 kg for empagliflozin 10 mg and -2.25 kg for empagliflozin 25 mg).

Blood pressure
The efficacy and safety of empagliflozin was evaluated in a double-blind, placebo controlled study of 
12 weeks duration in patients with type 2 diabetes and high blood pressure on different antidiabetic 
and up to 2 antihypertensive therapies. Treatment with empagliflozin once daily resulted in 
statistically significant improvement in HbA1c, and 24 hour mean systolic and diastolic blood pressure 
as determined by ambulatory blood pressure monitoring (Table 11). Treatment with empagliflozin 
provided reductions in seated SBP and DBP.

Table 11:Efficacy results at 12 week in a placebo-controlled study of empagliflozin in patients with 
type 2 diabetes and uncontrolled blood pressurea

Placebo
Jardiance

10 mg 25 mg
N 271 276 276
HbA1c (%) at week 121

Baseline (mean) 7.90 7.87 7.92
Change from baseline2 0.03 -0.59 -0.62
Difference from placebo2

(95% CI)
-0.62* (-0.72, -0.52) -0.65* (-0.75, -0.55)

24 hour SBP at week 123

Baseline (mean) 131.72 131.34 131.18
Change from baseline4 0.48 -2.95 -3.68
Difference from placebo4

(95% CI)
-3.44* (-4.78, -2.09) -4.16* (-5.50, -2.83)

24 hour DBP at week 123

Baseline (mean) 75.16 75.13 74.64
Change from baseline5 0.32 -1.04 -1.40
Difference from placebo5

(95% CI)
-1.36** (-2.15, -0.56) -1.72* (-2.51, -0.93)

a Full analysis set (FAS)
1 LOCF, values after taking antidiabetic rescue therapy censored
2 Mean adjusted for baseline HbA1c, baseline eGFR, geographical region and number of 

antihypertensive medicinal products
3 LOCF, values after taking antidiabetic rescue therapy or changing antihypertensive rescue therapy

censored
4 Mean adjusted for baseline SBP, baseline HbA1c, baseline eGFR, geographical region and number 

of antihypertensive medicinal products
5 Mean adjusted for baseline DBP, baseline HbA1c, baseline eGFR, geographical region and number 

of antihypertensive medicinal products
* p-value <0.0001
** p-value <0.001

In a pre-specified pooled analysis of 4 placebo-controlled studies, treatment with empagliflozin 
resulted in a reduction in systolic blood pressure (empagliflozin 10 mg: -3.9 mmHg; empagliflozin 
25 mg: -4.3 mmHg) compared with placebo (-0.5 mmHg) and in diastolic blood pressure 
(empagliflozin 10 mg: -1.8 mmHg; empagliflozin 25 mg: -2.0 mmHg) compared with placebo 
(-0.5 mmHg) at week 24 that were maintained up to week 52.



24

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with 
Jardiance in one or more subsets of the paediatric population in type 2 diabetes mellitus (see section 
4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Absorption

The pharmacokinetics of empagliflozin have been extensively characterised in healthy volunteers and 
patients with type 2 diabetes. After oral administration, empagliflozin was rapidly absorbed with peak 
plasma concentrations occurring at a median tmax of 1.5 hours post-dose. Thereafter, plasma 
concentrations declined in a biphasic manner with a rapid distribution phase and a relatively slow 
terminal phase. The steady state mean plasma AUC and Cmax were 1870 nmol.h/l and 259 nmol/l with 
empagliflozin 10 mg and 4740 nmol.h/l and 687 nmol/l with empagliflozin 25 mg once daily. 
Systemic exposure of empagliflozin increased in a dose-proportional manner. The single-dose and 
steady-state pharmacokinetic parameters of empagliflozin were similar suggesting linear 
pharmacokinetics with respect to time. There were no clinically relevant differences in empagliflozin 
pharmacokinetics between healthy volunteers and patients with type 2 diabetes.

Administration of empagliflozin 25 mg after intake of a high-fat and high calorie meal resulted in 
slightly lower exposure; AUC decreased by approximately 16% and Cmax by approximately 37% 
compared to fasted condition. The observed effect of food on empagliflozin pharmacokinetics was not 
considered clinically relevant and empagliflozin may be administered with or without food.

Distribution

The apparent steady-state volume of distribution was estimated to be 73.8 l based on the population 
pharmacokinetic analysis. Following administration of an oral [14C]-empagliflozin solution to healthy 
volunteers, the red blood cell partitioning was approximately 37% and plasma protein binding was 
86%.

Biotransformation

No major metabolites of empagliflozin were detected in human plasma and the most abundant 
metabolites were three glucuronide conjugates (2-, 3-, and 6-O glucuronide). Systemic exposure of 
each metabolite was less than 10% of total drug-related material. In vitro studies suggested that the 
primary route of metabolism of empagliflozin in humans is glucuronidation by the uridine 
5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9.

Elimination

Based on the population pharmacokinetic analysis, the apparent terminal elimination half-life of 
empagliflozin was estimated to be 12.4 hours and apparent oral clearance was 10.6 l/hour. The 
inter-subject and residual variabilities for empagliflozin oral clearance were 39.1% and 35.8%, 
respectively. With once-daily dosing, steady-state plasma concentrations of empagliflozin were 
reached by the fifth dose. Consistent with the half-life, up to 22% accumulation, with respect to 
plasma AUC, was observed at steady-state. Following administration of an oral [14C]-empagliflozin 
solution to healthy volunteers, approximately 96% of the drug-related radioactivity was eliminated in 
faeces (41%) or urine (54%). The majority of drug-related radioactivity recovered in faeces was 
unchanged parent drug and approximately half of drug related radioactivity excreted in urine was 
unchanged parent drug.



25

Special populations
Renal impairment
In patients with mild, moderate or severe renal impairment (eGFR <30 - <90 ml/min/1.73 m2) and 
patients with kidney failure/end stage renal disease (ESRD), AUC of empagliflozin increased by 
approximately 18%, 20%, 66%, and 48%, respectively compared to subjects with normal renal 
function. Peak plasma levels of empagliflozin were similar in subjects with moderate renal impairment 
and kidney failure/ESRD compared to patients with normal renal function. Peak plasma levels of 
empagliflozin were roughly 20% higher in subjects with mild and severe renal impairment as 
compared to subjects with normal renal function. The population pharmacokinetic analysis showed 
that the apparent oral clearance of empagliflozin decreased with a decrease in eGFR leading to an 
increase in drug exposure.

Hepatic impairment
In subjects with mild, moderate, and severe hepatic impairment according to the Child-Pugh 
classification, AUC of empagliflozin increased approximately by 23%, 47%, and 75% and Cmax by 
approximately 4%, 23%, and 48%, respectively, compared to subjects with normal hepatic function.

Body Mass Index
Body mass index had no clinically relevant effect on the pharmacokinetics of empagliflozin based on 
the population pharmacokinetic analysis. In this analysis, AUC was estimated to be 5.82%, 10.4%, and 
17.3% lower in subjects with BMI of 30, 35, and 45 kg/m2, respectively, compared to subjects with a 
body mass index of 25 kg/m2.

Gender
Gender had no clinically relevant effect on the pharmacokinetics of empagliflozin based on the 
population pharmacokinetic analysis.

Race
In the population pharmacokinetic analysis, AUC was estimated to be 13.5% higher in Asians with a 
body mass index of 25 kg/m2 compared to non-Asians with a body mass index of 25 kg/m2.

Elderly 
Age did not have a clinically meaningful impact on the pharmacokinetics of empagliflozin based on 
the population pharmacokinetic analysis.

Paediatric population
A paediatric Phase 1 study examined the pharmacokinetics and pharmacodynamics of empagliflozin 
(5 mg, 10 mg and 25 mg) in children and adolescents ≥10 to <18 years of age with type 2 diabetes 
mellitus. The observed pharmacokinetic and pharmacodynamic responses were consistent with those 
found in adult subjects.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, genotoxicity, fertility and early embryonic development. 

In long term toxicity studies in rodents and dogs, signs of toxicity were observed at exposures greater 
than or equal to 10-times the clinical dose of empagliflozin. Most toxicity was consistent with 
secondary pharmacology related to urinary glucose loss and electrolyte imbalances including
decreased body weight and body fat, increased food consumption, diarrhoea, dehydration, decreased 
serum glucose and increases in other serum parameters reflective of increased protein metabolism and
gluconeogenesis, urinary changes such as polyuria and glucosuria, and microscopic changes including 
mineralisation in kidney and some soft and vascular tissues. Microscopic evidence of the effects of 
exaggerated pharmacology on the kidney observed in some species included tubular dilatation, and 
tubular and pelvic mineralisation at approximately 4-times the clinical AUC exposure of empagliflozin 
associated with the 25 mg dose.



26

Empagliflozin is not genotoxic.

In a 2 year carcinogenicity study, empagliflozin did not increase the incidence of tumours in female 
rats up to the highest dose of 700 mg/kg/day, which corresponds to approximately 72-times the 
maximal clinical AUC exposure to empagliflozin. In male rats, treatment-related benign vascular 
proliferative lesions (haemangiomas) of the mesenteric lymph node were observed at the highest dose, 
but not at 300 mg/kg/day, which corresponds to approximately 26-times the maximal clinical exposure 
to empagliflozin. Interstitial cell tumours in the testes were observed with a higher incidence in rats at 
300 mg/kg/day and above, but not at 100 mg/kg/day which corresponds to approximately 18-times the 
maximal clinical exposure to empagliflozin. Both tumours are common in rats and are unlikely to be 
relevant to humans.

Empagliflozin did not increase the incidence of tumours in female mice at doses up to 
1000 mg/kg/day, which corresponds to approximately 62-times the maximal clinical exposure to 
empagliflozin. Empagliflozin induced renal tumours in male mice at 1000 mg/kg/day, but not at 300 
mg/kg/day, which corresponds to approximately 11-times the maximal clinical exposure to 
empagliflozin. The mode of action for these tumours is dependent on the natural predisposition of the 
male mouse to renal pathology and a metabolic pathway not reflective of humans. The male mouse 
renal tumours are considered not relevant to humans.

At exposures sufficiently in excess of exposure in humans after therapeutic doses, empagliflozin had 
no adverse effects on fertility or early embryonic development. Empagliflozin administered during the 
period of organogenesis was not teratogenic. Only at maternally toxic doses, empagliflozin also 
caused bent limb bones in the rat and increased embryofetal loss in the rabbit.

In pre- and postnatal toxicity studies in rats, reduced weight gain of offspring was observed at 
maternal exposures approximately 4-times the maximal clinical exposure to empagliflozin. No such 
effect was seen at systemic exposure equal to the maximal clinical exposure to empagliflozin. The 
relevance of this finding to humans is unclear.

In a juvenile toxicity study in the rat, when empagliflozin was administered from postnatal day 21 
until postnatal day 90, non-adverse, minimal to mild renal tubular and pelvic dilation in juvenile rats 
was seen only at 100 mg/kg/day, which approximates 11-times the maximum clinical dose of 25 mg. 
These findings were absent after a 13 weeks drug-free recovery period.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Lactose monohydrate
Microcrystalline cellulose
Hydroxypropylcellulose
Croscarmellose sodium
Colloidal anhydrous silica
Magnesium stearate

Film coating
Hypromellose
Titanium dioxide (E171)
Talc
Macrogol (400)



27

Iron oxide yellow (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/aluminium perforated unit dose blisters.
Pack sizes of 7 x 1, 10 x 1, 14 x 1, 28 x 1, 30 x 1, 60 x 1, 70 x 1, 90 x 1, and 100 x 1 film-coated 
tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

8. MARKETING AUTHORISATION NUMBER(S) 

Jardiance 10 mg film-coated tablets
EU/1/14/930/010
EU/1/14/930/011
EU/1/14/930/012
EU/1/14/930/013
EU/1/14/930/014
EU/1/14/930/015
EU/1/14/930/016
EU/1/14/930/017
EU/1/14/930/018

Jardiance 25 mg film-coated tablets
EU/1/14/930/001
EU/1/14/930/002
EU/1/14/930/003
EU/1/14/930/004
EU/1/14/930/005
EU/1/14/930/006
EU/1/14/930/007



28

EU/1/14/930/008
EU/1/14/930/009

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 May 2014
Date of latest renewal: 14 February 2019

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

http://www.ema.europa.eu


29

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



30

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Strasse 173
55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Ellas A.E.
5th km Paiania – Markopoulo
Koropi Attiki, 19400
Greece

Rottendorf Pharma GmbH
Ostenfelder Strasse 51 – 61
59320 Ennigerloh
Germany

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC
and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT  

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



31

ANNEX III

LABELLING AND PACKAGE LEAFLET



32

A. LABELLING



33

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Jardiance 10 mg film-coated tablets
empagliflozin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 10 mg of empagliflozin.

3. LIST OF EXCIPIENTS

Contains lactose, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

7 x 1 film-coated tablets
10 x 1 film-coated tablets
14 x 1 film-coated tablets
28 x 1 film-coated tablets
30 x 1 film-coated tablets
60 x 1 film-coated tablets
70 x 1 film-coated tablets
90 x 1 film-coated tablets
100 x 1 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



34

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/930/010 7 tablets
EU/1/14/930/011 10 tablets
EU/1/14/930/012 14 tablets
EU/1/14/930/013 28 tablets
EU/1/14/930/014 30 tablets
EU/1/14/930/015 60 tablets
EU/1/14/930/016 70 tablets
EU/1/14/930/017 90 tablets
EU/1/14/930/018 100 tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Jardiance 10 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



35

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blisters (perforated)

1. NAME OF THE MEDICINAL PRODUCT

Jardiance 10 mg tablets
empagliflozin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



36

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Jardiance 25 mg film-coated tablets
empagliflozin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 25 mg of empagliflozin.

3. LIST OF EXCIPIENTS

Contains lactose, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

7 x 1 film-coated tablets
10 x 1 film-coated tablets
14 x 1 film-coated tablets
28 x 1 film-coated tablets
30 x 1 film-coated tablets
60 x 1 film-coated tablets
70 x 1 film-coated tablets
90 x 1 film-coated tablets
100 x 1 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



37

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/930/001 7 tablets
EU/1/14/930/002 10 tablets
EU/1/14/930/003 14 tablets
EU/1/14/930/004 28 tablets
EU/1/14/930/005 30 tablets
EU/1/14/930/006 60 tablets
EU/1/14/930/007 70 tablets
EU/1/14/930/008 90 tablets
EU/1/14/930/009 100 tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Jardiance 25 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



38

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blisters (perforated)

1. NAME OF THE MEDICINAL PRODUCT

Jardiance 25 mg tablets
empagliflozin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



39

B. PACKAGE LEAFLET



40

Package leaflet: Information for the patient

Jardiance 10 mg film-coated tablets
Jardiance 25 mg film-coated tablets

empagliflozin

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Jardiance is and what it is used for
2. What you need to know before you take Jardiance
3. How to take Jardiance
4. Possible side effects
5. How to store Jardiance
6. Contents of the pack and other information

1. What Jardiance is and what it is used for

What Jardiance is
Jardiance contains the active substance empagliflozin.

Jardiance is a member of a group of medicines called sodium glucose co-transporter-2 (SGLT2)
inhibitors.

What Jardiance is used for
 Jardiance is used to treat type 2 diabetes in adult patients (aged 18 years and older) that cannot 

be controlled by diet and exercise alone. 
 Jardiance can be used without other medicines in patients who cannot take metformin (another 

diabetes medicine).
 Jardiance can also be used with other medicines for the treatment of diabetes. These may be 

medicines taken by mouth or given by injection such as insulin.

It is important that you continue with your diet and exercise plan as told by your doctor, pharmacist or 
nurse.

How Jardiance works
Jardiance works by blocking the SGLT2 protein in your kidneys. This causes blood sugar (glucose) to 
be removed in your urine. Thereby Jardiance lowers the amount of sugar in your blood.

This medicine can also help prevent heart disease.

What is type 2 diabetes?
Type 2 diabetes is a disease that comes from both your genes and your lifestyle. If you have type 2 
diabetes, your pancreas does not make enough insulin to control the level of glucose in your blood, 
and your body is unable to use its own insulin effectively. This results in high levels of glucose in your 
blood which can lead to medical problems like heart disease, kidney disease, blindness, and poor 
circulation in your limbs.



41

2. What you need to know before you take Jardiance

Do not take Jardiance
- if you are allergic to empagliflozin or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking this medicine, and during treatment:
 if you have “type 1 diabetes”. This type usually starts when you are young and your body does 

not produce any insulin.
 if you experience rapid weight loss, feeling sick or being sick, stomach pain, excessive thirst, 

fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to your breath, 
a sweet or metallic taste in your mouth, or a different odour to your urine or sweat, contact a 
doctor or the nearest hospital straight away. These symptoms could be a sign of “diabetic 
ketoacidosis” – a rare, but serious, sometimes life-threatening problem you can get with 
diabetes because of increased levels of “ketone bodies” in your urine or blood, seen in tests. The 
risk of developing diabetic ketoacidosis may be increased with prolonged fasting, excessive 
alcohol consumption, dehydration, sudden reductions in insulin dose, or a higher need of insulin 
due to major surgery or serious illness.

 if you have serious kidney or liver problems – your doctor may ask you to take a different 
medicine.

 might be at risk of dehydration, for example:
o if you are being sick, have diarrhoea or fever, or if you are not able to eat or drink
o if you are taking medicines that increase urine production [diuretics] or lower blood 

pressure
o if you are over 75 years old.

Possible signs are listed in section 4 under ‘dehydration’. Your doctor may ask you to stop 
taking Jardiance until you recover to prevent loss of too much body fluid. Ask about ways to 
prevent dehydration.

 if you are 85 years old or older as you should not start taking Jardiance.
 if you have a serious infection of the kidney or the urinary tract with fever. Your doctor may ask 

you to stop taking Jardiance until you have recovered.

Talk to your doctor immediately if you develop a combination of symptoms of pain, tenderness, 
redness, or swelling of the genitals or the area between the genitals and the anus with fever or feeling 
generally unwell. These symptoms could be a sign of a rare but serious or even life-threatening 
infection, called necrotising fasciitis of the perineum or Fournier´s gangrene which destroys the tissue 
under the skin. Fournier’s gangrene has to be treated immediately.

Foot care
Like for all diabetic patients it is important to check your feet regularly and adhere to any other advice 
regarding foot care given by your health care professional.

Urine glucose
Because of how this medicine works, your urine will test positive for sugar while you are taking this 
medicine.

Children and adolescents
Jardiance is not recommended for children and adolescents under 18 years, because it has not been 
studied in these patients.

Other medicines and Jardiance
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.
It is important to tell your doctor:



42

 if you are taking medicines that increase urine production (diuretics). Your doctor may ask you 
to stop taking Jardiance. Possible signs of losing too much fluid from your body are listed in 
section 4.

 if you are taking other medicines that lower the amount of sugar in your blood such as insulin or 
a “sulphonylurea” medicine. Your doctor may want to lower the dose of these other medicines, 
to prevent your blood sugar levels from getting too low (hypoglycaemia).

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Do not use Jardiance if you are 
pregnant. It is unknown if Jardiance is harmful to the unborn child. Do not use Jardiance if you are 
breast-feeding. It is not known if Jardiance passes into human breast milk.

Driving and using machines
Jardiance has minor influence on the ability to drive and use machines.

Taking this medicine in combination with medicines called sulphonylureas or with insulin can cause 
blood sugar levels to drop too low (hypoglycaemia), which may cause symptoms such as shaking, 
sweating and change in vision, and may affect your ability to drive and use machines. Do not drive or 
use any tools or machines, if you feel dizzy while taking Jardiance.

Jardiance contains lactose
Jardiance contains lactose (milk sugar). If you have been told by your doctor that you have an 
intolerance to some sugars, contact your doctor before taking this medicine.

Jardiance contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium 
free’.

3. How to take Jardiance

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.

How much to take
 The starting dose of Jardiance is one 10 mg tablet once a day. Your doctor will decide whether 

to increase your dose to 25 mg once a day.
 Your doctor may limit your dose to 10 mg once a day if you have a kidney problem.
 Your doctor will prescribe the strength that is right for you. Do not change your dose unless 

your doctor has told you to.

Taking this medicine
 Swallow the tablet whole with water
 You can take the tablet with or without food
 You can take the tablet at any time of the day. However, try to take it at the same time each day. 

This will help you to remember to take it.

Your doctor may prescribe Jardiance together with another diabetes medicine. Remember to take all 
medicines as directed by your doctor to achieve the best results for your health.

Appropriate diet and exercise help your body use its blood sugar better. It is important to stay on the 
diet and exercise program recommended by your doctor while taking Jardiance.

If you take more Jardiance than you should
If you take more Jardiance than you should, talk to a doctor immediately or go to a hospital 
immediately. Take the medicine pack with you.



43

If you forget to take Jardiance
What to do if you forget to take a tablet depends on how long it is until your next dose.
 If it is 12 hours or more until your next dose, take Jardiance as soon as you remember. Then 

take your next dose at the usual time.
 If it is less than 12 hours until your next dose, skip the missed dose. Then take your next dose at 

the usual time.
 Do not take a double dose of Jardiance to make up for a forgotten dose.

If you stop taking Jardiance
Do not stop taking Jardiance without first consulting your doctor. Your blood sugar levels may 
increase when you stop taking Jardiance.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor or the nearest hospital straight away if you have any of the following side 
effects:

Severe allergic reaction, seen with unknown frequency (frequency cannot be estimated from the 
available data )
Possible signs of severe allergic reaction may include:
 swelling of the face, lips, mouth, tongue, or throat that may lead to difficulty breathing or 

swallowing)

Diabetic ketoacidosis, seen rarely (may affect up to 1 in 1,000 people)
These are the signs of diabetic ketoacidosis (see also section 2, ‘Warnings and precautions’):
 increased levels of “ketone bodies” in your urine or blood
 rapid weight loss
 feeling sick or being sick
 stomach pain
 excessive thirst
 fast and deep breathing
 confusion
 unusual sleepiness or tiredness
 a sweet smell to your breath, a sweet or metallic taste in your mouth or a different odour to your 

urine or sweat.

This may occur regardless of blood glucose level. Your doctor may decide to temporarily or 
permanently stop your treatment with Jardiance.

Contact your doctor as soon as possible if you notice the following side effects:

Low blood sugar (hypoglycaemia), seen very commonly (may affect more than 1 in 10 people)
If you take Jardiance with another medicine that can cause low blood sugar, such as a sulfonylurea or 
insulin, your risk of getting low blood sugar is higher. The signs of low blood sugar may include:
 shaking, sweating, feeling very anxious or confused, fast heart beat
 excessive hunger, headache

Your doctor will tell you how to treat low blood sugar levels and what to do if you get any of the signs 
above. If you have symptoms of low blood sugar, eat glucose tablets, a high sugar snack or drink fruit 
juice. Measure your blood sugar if possible and rest.



44

Urinary tract infection, seen commonly (may affect up to 1 in 10 people)
The signs of urinary tract infection are:
 burning sensation when passing urine
 urine that appears cloudy
 pain in the pelvis, or mid-back pain (when kidneys are infected)

An urge to pass urine or more frequent urination may be due to the way Jardiance works, but they can 
also be signs of urinary tract infection. If you note an increase in such symptoms, you should also 
contact your doctor.

Dehydration, seen uncommonly (may affect up to 1 in 100 people)
The signs of dehydration are not specific, but may include:
 unusual thirst
 lightheadedness or dizziness upon standing
 fainting or loss of consciousness

Other side effects while taking Jardiance:
Common
 genital yeast infection (thrush)
 passing more urine than usual or needing to pass urine more often
 itching
 rash or red skin – this may be itchy and include raised bumps, oozing fluid or blisters
 thirst
 blood tests may show an increase in blood fat (cholesterol) levels in your blood

Uncommon
 hives
 straining or pain when emptying the bladder
 blood tests may show a decrease in kidney function (creatinine or urea)
 blood tests may show increases in the amount of red blood cells in your blood (haematocrit)

Not known
 necrotising fasciitis of the perineum or Fournier´s gangrene, a serious soft tissue infection of the 

genitals or the area between the genitals and the anus

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Jardiance

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and the carton after ‘EXP’. 
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


45

6. Contents of the pack and other information

What Jardiance contains 
- The active substance is empagliflozin.

- Each tablet contains 10 mg or 25 mg empagliflozin.

- The other ingredients are:
- tablet core: lactose monohydrate (see end of section 2 under ‘Jardiance contains 

lactose’), microcrystalline cellulose, hydroxypropylcellulose, croscarmellose sodium
(see end of section 2 under ‘Jardiance contains sodium’), colloidal anhydrous silica, 
magnesium stearate

- film-coating: hypromellose, titanium dioxide (E171), talc, macrogol (400), iron oxide 
yellow (E172)

What Jardiance looks like and contents of the pack
Jardiance 10 mg film-coated tablets are round, pale yellow, biconvex and bevel-edged. They have 
“S10” on one side and the Boehringer Ingelheim logo on the other side. The tablets are 9.1 mm in 
diameter.
Jardiance 25 mg film-coated tablets are oval, pale yellow and biconvex. They have “S25” on one side 
and the Boehringer Ingelheim logo on the other side. The tablet is 11.1 mm long and has a width of 
5.6 mm.

Jardiance tablets are available in PVC/aluminium perforated unit dose blisters. The pack sizes are 
7 x 1, 10 x 1, 14 x 1, 28 x 1, 30 x 1, 60 x 1, 70 x 1, 90 x 1, and 100 x 1 film-coated tablets.

Not all pack sizes may be marketed in your country.

Marketing Authorisation Holder
Boehringer Ingelheim International GmbH
Binger Strasse 173
55216 Ingelheim am Rhein
Germany

Manufacturer
Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Strasse 173
55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Ellas A.E.
5th km Paiania – Markopoulo
Koropi Attiki, 19400
Greece

Rottendorf Pharma GmbH
Ostenfelder Strasse 51 – 61
59320 Ennigerloh
Germany



46

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG
Lietuvos filialas
Tel: +370 37 473922

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко. КГ -
клон България
Тел: +359 2 958 79 98

Luxembourg/Luxemburg
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. s r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG 
Magyarországi Fióktelepe
Tel: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim b.v.
Tel: +31 (0) 800 22 55 889

Lilly Deutschland GmbH
Tel. +49 (0) 6172 273 2222

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Norway KS
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp. z o.o.
Tel: +48 22 699 0 699

Lilly S.A.
Tel: +34 91 663 50 00

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim, Unipessoal, Lda.
Tel: +351 21 313 53 00

Lilly France SAS
Tél: +33 1 55 49 34 34

Lilly Portugal Produtos Farmacêuticos, Lda
Tel: +351 21 412 66 00



47

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG 
Viena - Sucursala Bucureşti
Tel: +40 21 302 28 00

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG 
Podružnica Ljubljana
Tel: +386 1 586 40 00

Eli Lilly and Company (Ireland) Limited
Tel: +353 1 661 4377

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG 
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Eli Lilly Italia S.p.A.
Tel: +39 05 5425 71

Κύπρος
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom
Boehringer Ingelheim Ltd.
Tel: +44 1344 424 600

Eli Lilly and Company Limited
Tel: +44 1256 315 000

This leaflet was last revised in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

http://www.ema.europa.eu

	SUMMARY OF PRODUCT CHARACTERISTICS
	A.	MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B.	CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.	OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D.	CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET