Synjardy

empagliflozin / metformin

Overview
Authorisation details
Product information
Assessment history

Authorised

This medicine is authorised for use in the European Union.

Overview

This is a summary of the European public assessment report (EPAR) for Synjardy. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Synjardy.

For practical information about using Synjardy, patients should read the package leaflet or contact their doctor or pharmacist.

Synjardy is a diabetes medicine used with diet and exercise to treat adults with type 2 diabetes. It contains the active substances empagliflozin and metformin. Synjardy is used:

in patients whose diabetes is not sufficiently controlled by metformin alone;
in combination with other diabetes medicines in patients whose diabetes is not sufficiently controlled on these medicines plus metformin;
in patients who are already taking metformin and empagliflozin as separate tablets.

: Synjardy is available as tablets containing 5 or 12.5 mg of empagliflozin with 850 or 1,000 mg of metformin, and can only be obtained with a prescription.
The recommended dose of Synjardy is one tablet twice a day with meals, and treatment is normally started with a tablet that supplies the dose of metformin the patient is already taking, together with the lowest dose (5 mg) of empagliflozin. Doses are adjusted as necessary.
If Synjardy is used in combination with insulin or a sulphonylurea (a medicine that increases the body’s production of insulin), the doses of these medicines may need to be lowered to avoid hypoglycaemia (low blood sugar levels).
For further information, see the package leaflet.

: In type 2 diabetes the body does not make enough insulin to control the level of glucose (sugar) in the blood or the body is unable to use insulin effectively. This leads to a high level of glucose in the blood. The two active substances in Synjardy, empagliflozin and metformin, work in different ways to lower blood glucose, and thus to control symptoms of the disease.
Empagliflozin works by blocking a protein in the kidneys (called sodium-glucose co-transporter 2 or SGLT2). As blood is filtered by the kidneys, SGLT2 stops glucose in the bloodstream from being passed out into the urine. By blocking the action of SGLT2, empagliflozin causes more glucose to be removed in the urine, thereby reducing the levels of glucose in the blood. Empagliflozin has been authorised in the EU under the trade name Jardiance since 2014.
Metformin works mainly by reducing the production of glucose in the body and reducing its absorption from the gut. Metformin has been available in the EU since the 1950s.

: The benefits of empagliflozin in combination with metformin have been shown in 3 main studies involving 1,679 patients with type 2 diabetes whose blood sugar was not adequately controlled by metformin, alone or combined with other diabetes medicines (such as pioglitazone or a type of diabetes medicine called a sulphonylurea). The studies compared the effect of empagliflozin plus metformin versus placebo (a dummy treatment) with metformin. The main measure of effectiveness was the reduction in the level of a substance in the blood called glycosylated haemoglobin (HbA1c) after 24 weeks of treatment. HbA1c gives an indication of how well the blood glucose is controlled.
The studies showed a greater reduction in HbA1c when empagliflozin plus metformin was given, compared with placebo plus metformin. Overall, the additional reduction was 0.58 percentage points with a combination providing 5 mg of empagliflozin twice daily, and 0.62 percentage points with the 12.5 mg dose, and these reductions were considered clinically relevant. Similar benefits were seen in the studies regardless of the other diabetes medicines being taken. In addition, the results indicated that the combination was associated with a beneficial decrease in body weight and blood pressure.
Supportive evidence was provided from several further studies. Some of these were continuations of the main studies that suggested the benefits of the combination continued with longer therapy. Studies also indicated Synjardy was as effective as empagliflozin and metformin taken separately, and that the combination helped reduce HbA1c when added to treatment including insulin.
Another main study showed that adding empagliflozin (one of the active substances of Synjardy) to usual treatment reduced adverse cardiovascular (heart and blood vessels) effects. The study involved patients with type 2 diabetes who already had cardiovascular disease (such as angina, heart attack and stroke). The main measure of effectiveness was the occurrence of one of three major cardiovascular events: stroke, heart attack or death caused by cardiovascular disease. On average, patients in the study were followed up for 3.1 years. In those receiving empagliflozin, cardiovascular events occurred in 10.5% (490 out of 4,687) of patients compared with 12.1% (282 out of 2,333) of patients receiving placebo. Among these, in patients who were also taking metformin (the other active substance in Synjardy), the three major cardiovascular events occurred in 9.9% (344 out of 3,459) of patients receiving empagliflozin and in 10.9% (189 out of 1,734) of patients receiving placebo.

The most common side effects with Synjardy are hypoglycaemia (low blood sugar levels) when the medicine is taken with a sulphonylurea or insulin, infections of the urinary tract and genitals, and increased urination. For the full list of all side effects reported with Synjardy, see the package leaflet.

Synjardy must not be used in patients with:

metabolic acidosis (when the body produces more acid than it gets rid of) or diabetic pre-coma (dangerous complications of diabetes);
severely reduced kidney function or conditions that could affect the kidneys such as dehydration, severe infection or a steep fall in blood pressure;
a condition that could reduce the supply of oxygen to body tissues (such as in patients with worsening heart failure, recent heart attack, breathing difficulty or a steep fall in blood pressure);
liver impairment, or problems with alcoholism or alcohol intoxication.

For the full list of restrictions, see the package leaflet.

: The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Synjardy’s benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded that the medicine could help produce a clinically meaningful reduction in blood glucose in patients with type 2 diabetes, and the benefits and risks were in line with those of the individual active substances. Synjardy was also shown to reduce cardiovascular events in patients with type 2 diabetes who already had cardiovascular disease. Because of concerns about the balance of benefit and risk in patients with reduced kidney function taking the fixed-dose combination, the CHMP recommended restricting its use in these patients.

: Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Synjardy have been included in the summary of product characteristics and the package leaflet.
Further information can be found in the summary of the risk management plan .

: The European Commission granted a marketing authorisation valid throughout the European Union for Synjardy on 27 May 2015.
For more information about treatment with Synjardy, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

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Synjardy : EPAR - Summary for the public (PDF/86.41 KB)

First published: 12/06/2015
Last updated: 05/07/2017
EMA/355552/2015
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Synjardy : EPAR - Risk-management-plan summary (PDF/56.45 KB)

First published: 12/06/2015
Last updated: 12/06/2015
EMA/217413/2015

More detail is available in the summary of product characteristics

This EPAR was last updated on 05/06/2019

Authorisation details

Product details
Name	Synjardy
Agency product number	EMEA/H/C/003770
Active substance	empagliflozin metformin
International non-proprietary name (INN) or common name	empagliflozin / metformin
Therapeutic area (MeSH)	Diabetes Mellitus, Type 2
Anatomical therapeutic chemical (ATC) code	A10BD20
Additional monitoring	This medicine is under additional monitoring, meaning that it is monitored even more intensively than other medicines. For more information, see Medicines under additional monitoring.

Publication details
Marketing-authorisation holder	Boehringer Ingelheim GmbH
Revision	14
Date of issue of marketing authorisation valid throughout the European Union	27/05/2015
Contact address	Binger Strasse 173 55216 Ingelheim am Rhein Germany

Product information

22/02/2019 Synjardy - EMEA/H/C/003770 - IAIN/0038

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Synjardy : EPAR - Product Information (PDF/395.62 KB) (updated)

First published: 12/06/2015
Last updated: 05/06/2019
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Annex I - Summary of product characteristics
Annex IIA - Manufacturing-authorisation holder responsible for batch release
Annex IIB - Conditions of the marketing authorisation
Annex IIIA - Labelling
Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

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Synjardy : EPAR - All Authorised presentations (PDF/38.13 KB)

First published: 12/06/2015
Last updated: 20/11/2015
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Pharmacotherapeutic group

Drugs used in diabetes

Therapeutic indication

Synjardy is indicated in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control:

in patients inadequately controlled on their maximally tolerated dose of metformin alone;
in patients inadequately controlled with metformin in combination with other glucose-lowering medicinal products, including insulin;
in patients already being treated with the combination of empagliflozin and metformin as separate tablets.

Assessment history

Changes since initial authorisation of medicine

List item

Synjardy : EPAR - Procedural steps taken and scientific information after authorisation (PDF/190.9 KB) (updated)

First published: 20/11/2015
Last updated: 05/06/2019
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Synjardy-H-C-PSUSA-00010388-201704 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/69.69 KB)

First published: 11/01/2018
Last updated: 11/01/2018
EMA/19599/2018
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Synjardy-H-C-PSUSA-00010388-201610 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/108.79 KB)

First published: 03/08/2017
Last updated: 03/08/2017
EMA/493961/2017
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Synjardy-H-A20-1442-C-3770-0022 : EPAR - Assessment Report - Article 20 (PDF/254.07 KB)

Adopted

First published: 05/07/2017
Last updated: 05/07/2017
EMA/PRAC/637349/2016
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Synjardy-H-A20-1442-C-3770-0022 : EPAR - Scientific Conclusion - Article 20 (PDF/41.36 KB)

First published: 05/07/2017
Last updated: 05/07/2017
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  (PDF/41.68 KB)
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Synjardy-H-C-3770-II-0015 : EPAR - Assessment Report - Variation (PDF/1.06 MB)

Adopted

First published: 10/05/2017
Last updated: 10/05/2017
EMA/173251/2017
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CHMP post-authorisation summary of positive opinion for Synjardy (PDF/73.55 KB)

First published: 27/01/2017
Last updated: 27/01/2017
EMA/CHMP/44144/2017
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Synjardy : EPAR - Scientific Conclusion (PDF/32.54 KB)

First published: 09/01/2017
Last updated: 09/01/2017
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Synjardy-H-C-PSUSA-00010388-201510 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisations (PDF/108.16 KB)

Adopted

First published: 20/07/2016
Last updated: 20/07/2016
EMA/342499/2016
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Synjardy-H-C-3770-A20-1419-0001 : EPAR - Assessment Report - Article 20 (PDF/264.09 KB)

Adopted

First published: 19/05/2016
Last updated: 19/05/2016
EMA/PRAC/50218/2016
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Synjardy : EPAR - Scientific Conclusion (PDF/44.81 KB)

First published: 19/05/2016
Last updated: 19/05/2016
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Synjardy

Table of contents

Overview

Synjardy : EPAR - Summary for the public (PDF/86.41 KB)

Synjardy : EPAR - Risk-management-plan summary (PDF/56.45 KB)

Authorisation details

Product information

Synjardy : EPAR - Product Information (PDF/395.62 KB) (updated)

Contents

Synjardy : EPAR - All Authorised presentations (PDF/38.13 KB)

Pharmacotherapeutic group

Therapeutic indication

Assessment history

Changes since initial authorisation of medicine

Synjardy : EPAR - Procedural steps taken and scientific information after authorisation (PDF/190.9 KB) (updated)

Synjardy-H-C-PSUSA-00010388-201704 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/69.69 KB)

Synjardy-H-C-PSUSA-00010388-201610 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/108.79 KB)

Synjardy-H-A20-1442-C-3770-0022 : EPAR - Assessment Report - Article 20 (PDF/254.07 KB)

Synjardy-H-A20-1442-C-3770-0022 : EPAR - Scientific Conclusion - Article 20 (PDF/41.36 KB)

Synjardy-H-C-3770-II-0015 : EPAR - Assessment Report - Variation (PDF/1.06 MB)

CHMP post-authorisation summary of positive opinion for Synjardy (PDF/73.55 KB)

Synjardy : EPAR - Scientific Conclusion (PDF/32.54 KB)

Synjardy-H-C-PSUSA-00010388-201510 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisations (PDF/108.16 KB)

Synjardy-H-C-3770-A20-1419-0001 : EPAR - Assessment Report - Article 20 (PDF/264.09 KB)

Synjardy : EPAR - Scientific Conclusion (PDF/44.81 KB)

Initial marketing-authorisation documents

Synjardy : EPAR - Public assessment report (PDF/1.53 MB)

CHMP summary of positive opinion for Synjardy (PDF/74.92 KB)

News

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Synjardy

Table of contents

Overview

Synjardy : EPAR - Summary for the public (PDF/86.41 KB)

Synjardy : EPAR - Risk-management-plan summary (PDF/56.45 KB)

Authorisation details

Product information

Synjardy : EPAR - Product Information (PDF/395.62 KB) (updated)

Contents

Synjardy : EPAR - All Authorised presentations (PDF/38.13 KB)

Pharmacotherapeutic group

Therapeutic indication

Assessment history

Changes since initial authorisation of medicine

Synjardy : EPAR - Procedural steps taken and scientific information after authorisation (PDF/190.9 KB) (updated)

Synjardy-H-C-PSUSA-00010388-201704 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/69.69 KB)

Synjardy-H-C-PSUSA-00010388-201610 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisation (PDF/108.79 KB)

Synjardy-H-A20-1442-C-3770-0022 : EPAR - Assessment Report - Article 20 (PDF/254.07 KB)

Synjardy-H-A20-1442-C-3770-0022 : EPAR - Scientific Conclusion - Article 20 (PDF/41.36 KB)

Synjardy-H-C-3770-II-0015 : EPAR - Assessment Report - Variation (PDF/1.06 MB)

CHMP post-authorisation summary of positive opinion for Synjardy (PDF/73.55 KB)

Synjardy : EPAR - Scientific Conclusion (PDF/32.54 KB)

Synjardy-H-C-PSUSA-00010388-201510 : EPAR - Scientific conclusions and grounds for the variation to the terms of the marketing authorisations (PDF/108.16 KB)

Synjardy-H-C-3770-A20-1419-0001 : EPAR - Assessment Report - Article 20 (PDF/264.09 KB)

Synjardy : EPAR - Scientific Conclusion (PDF/44.81 KB)

Initial marketing-authorisation documents

Synjardy : EPAR - Public assessment report (PDF/1.53 MB)

CHMP summary of positive opinion for Synjardy (PDF/74.92 KB)

News

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