Glubrava

pioglitazone / metformin

This is a summary of the European public assessment report (EPAR) for Glubrava. 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 Glubrava.

What is Glubrava?

Glubrava is a medicine that is available as white, oblong tablets containing two active substances, pioglitazone (15 mg) and metformin hydrochloride (850 mg).

This medicine is the same as Competact, which is already authorised in the European Union (EU). The company that makes Competact has agreed that its scientific data can be used for Glubrava (‘informed consent’).

What is Glubrava used for?

Glubrava is used in adults (particularly those who are overweight) who have type-2 diabetes. Glubrava is used in patients who are not satisfactorily controlled on metformin (an antidiabetes medicine) used on its own and at the maximum possible dose.

The medicine can only be obtained with a prescription.

How is Glubrava used?

The usual dose of Glubrava is one tablet taken twice a day. Patients changing from metformin only to Glubrava may need to introduce pioglitazone slowly until a dose of 30 mg per day is reached. It is possible to change to Glubrava directly from metformin if appropriate. Taking Glubrava with or just after food may reduce any stomach problems caused by metformin. Elderly patients should have their kidney function monitored regularly.

How does Glubrava work?

Type-2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. Glubrava contains two active substances which each have 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. Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut. As a result of the action of both active substances, the blood glucose is reduced and this helps to control type-2 diabetes.

Treatment with Glubrava 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 has Glubrava been studied?

Pioglitazone on its own has been approved by the EU under the name Actos, and can be used with metformin in type-2 diabetes patients who are not satisfactorily controlled on metformin alone. Three studies of Actos used with metformin as separate tablets were used to support the use of Glubrava in the same indication. The studies lasted from four months to two years and involved 1,305 patients who took the combination. They measured the level in the blood of a substance (HbA1c), which gives an indication of how well the blood glucose is controlled.

What benefit has Glubrava shown during the studies?

In all studies, adding pioglitazone 30 mg to metformin gave an improvement in the control of blood glucose, with levels of HbA1c which were further decreased by 0.64 to 0.89% compared to the levels on metformin alone.

What is the risk associated with Glubrava?

At the start of treatment, abdominal pain (stomach ache), diarrhoea, loss of appetite, nausea (feeling sick) and vomiting may occur. These side effects are very common but disappear on their own in most cases. Lactic acidosis (a build-up of lactic acid in the body) is a side effect which may occur in less than 1 in 10,000 patients. Other side effects such as bone fracture, increased weight and oedema (swelling) may occur in less than 1 in 10 patients. For the full list of all side effects reported with Glubrava, see the package leaflet.

Glubrava should not be used in people who may be hypersensitive (allergic) to pioglitazone, metformin or any of the other ingredients, and in patients who have heart failure, or problems with their liver or their kidneys. Glubrava should not be used in patients who have a disease that causes lack of oxygen to the tissues such as a recent heart attack or shock. Glubrava should not be used where there is alcohol intoxication, diabetic ketoacidosis (high levels of ketones), conditions that may affect the kidneys, and during breast-feeding. It must also not be used in patients who have or have had bladder cancer or those with blood in the urine that has not yet been investigated. For the full list of restrictions, see the package leaflet.

Why has Glubrava been approved?

The CHMP concluded that the effectiveness of pioglitazone and metformin in type-2 diabetes had been shown, and that Glubrava simplifies treatment and improves compliance when a combination of the active substances is required. The Committee decided that Glubrava’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Glubrava

The European Commission granted a marketing authorisation valid throughout the European Union, for Glubrava on 11 December 2007.

For more information about treatment with Glubrava, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 16/05/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

29/04/2013  Glubrava -EMEA/H/C/000893 -T/0026

Contents

• 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.

Pharmacotherapeutic group

Drugs used in diabetes

Therapeutic indication

Glubrava is indicated as second line treatment of type-2-diabetes-mellitus adult patients, particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.

After initiation of therapy with pioglitazone, patients should be reviewed after three to six months to assess adequacy of response to treatment (e.g. reduction in HbA1c). In patients who fail to show an adequate response, pioglitazone should be discontinued. In light of potential risks with prolonged therapy, prescribers should confirm at subsequent routine reviews that the benefit of pioglitazone is maintained.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents