o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/332133/2016 EM EA/H/C/000680

EPAR summary for the public

Tandemact

pioglitazone and glimepiride

This is a summary of the European public assessment report (EPAR) for Tandemact. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Tandemact.

What is Tandemact?

Tandemact is a medicine that contains two active substances, pioglitazone and glimepiride. It is available as tablets (30 mg pioglitazone and 2 or 4 mg glimepiride, or 45 mg pioglitazone and 4 mg glimepiride).

What is Tandemact used for?

Tandemact is used to treat adult patients who have type 2 diabetes. It is used in patients for whom metformin (a type of diabetes medicine) is not suitable and who are already being treated with a combination of tablets containing the two active substances pioglitazone and glimepiride.

The medicine can only be obtained with a prescription.

How is Tandemact used?

The usual dose of Tandemact is one tablet once a day, taken just before or with the first meal of the day. The tablet should be swallowed whole with a little water. Patients who are receiving pioglitazone together with another medicine in the same class as glimepiride (i.e. another sulphonylurea) should first be switched from this other sulphonylurea to glimepiride before they can transfer to Tandemact. Patients who experience hypoglycaemia (low blood sugar levels) while taking Tandemact may need to use a lower dose of the medicine or to return to using separate tablets.

Tandemact cannot be used in patients who have severe kidney problems, or in patients who have liver problems.

30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact

© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

Treatment with Tandemact should be reviewed after three to six months, and discontinued in patients who are not deriving sufficient benefit. At subsequent reviews prescribers should confirm that benefits to patients are maintained.

How does Tandemact work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose (sugar) in the blood or when the body is unable to use insulin effectively. Tandemact contains two active substances, each of which has a different mode of action. Pioglitazone makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces. Glimepiride is a sulphonylurea: it stimulates the pancreas to produce more insulin. As a result of the action of both active substances, the blood glucose level is reduced and this helps to control type 2 diabetes.

How has Tandemact been studied?

Because pioglitazone has been approved in the European Union (EU) since 2000 under the name Actos, and glimepiride is already used in authorised medicines in the EU, the company presented data obtained in earlier studies and from the published literature. Actos is approved for use with a sulphonylurea in type 2 diabetes patients who are not satisfactorily controlled on metformin alone. The company used three studies to support the use of Tandemact in the same indication.

The studies included 1,390 patients who added pioglitazone to their existing treatment with a sulphonylurea. The studies lasted between four months and two years and measured the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.

These studies used pioglitazone and sulphonylureas given as separate tablets. The company provided evidence that the levels of the active substances in the blood were the same in people taking Tandemact and people taking the separate tablets.

What benefit has Tandemact shown during the studies?

In all three studies, patients who used a combination of pioglitazone and a sulphonylurea had an improvement in the control of their blood glucose. The patients' HbAlc levels fell from a baseline of over 7.5% by between 1.22 and 1.64%. At least 64% of the patients treated were classified as 'responders', since their HbAlc levels either fell by at least 0.6% from the baseline value over the course of the studies, or their HbA1c levels were 6.1% or less at the end of the studies.

What is the risk associated with Tandemact?

The most common side effects with Tandemact (seen in between 1 and 10 patients in 100) are upper respiratory tract infections (such as colds), hypoaesthesia (reduced sense of touch), bone fractures, weight gain, dizziness, flatulence (gas) and oedema (swelling). For the full list of all side effects reported with Tandemact, see the package leaflet.

Tandemact must not be used in patients who have heart failure, problems with their liver or severe problems with their kidneys. It must not be used in patients with type 1 diabetes, patients who have complications of diabetes (diabetic ketoacidosis or diabetic coma), or women who are pregnant or breastfeeding. It must also not be used in patients who have or have had bladder cancer or those with

Tandemact

EMA/332133/2016    Page 2/3

blood in the urine that has not yet been investigated. For the full list of restrictions, see the package leaflet.

Why has Tandemact been approved?

The CHMP concluded that the effectiveness of pioglitazone and glimepiride in type 2 diabetes had been shown, and that Tandemact simplifies treatment and improves the ability of patients to stick to their treatment when a combination of the two active substances is needed. The Committee decided that Tandemact's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Tandemact?

The company that markets Tandemact will produce educational material for doctors prescribing the medicine, which will cover the possible risk of heart failure and bladder cancer with treatments that contain pioglitazone, the criteria for selecting patients and the need to review treatment regularly and stop treatment if patients are no longer benefiting.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Tandemact have also been included in the summary of product characteristics and the package leaflet.

Other information about Tandemact

The European Commission granted a marketing authorisation valid throughout the EU for Tandemact on 8 January 2007.

The full EPAR for Tandemact can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Tandemact, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2016.

Tandemact

EMA/332133/2016