Advagraf

tacrolimus

  • Email
  • Help

About

This is a summary of the European public assessment report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach its recommendations on how to use the medicine.

If you need more information about your medical condition or your treatment, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the scientific discussion (also part of the EPAR).

What is Advagraf?

Advagraf is a medicine containing the active substance tacrolimus. It is available as prolonged-released capsules containing tacrolimus (0.5 mg: yellow and orange; 1 mg: white and orange; 5 mg: greyish-red and orange). ‘Prolonged-release’ means that tacrolimus is released slowly from the capsule over a few hours.

What is Advagraf used for?

Advagraf is used in adult patients who have had a kidney or liver transplant, to prevent rejection (when the immune system attacks the transplanted organ). Advagraf can also be used to treat organ rejection in adult patients when other immunosuppressive medicines are not effective.

The medicine can only be obtained with a prescription.

How is Advagraf used?

Treatment with Advagraf should only be prescribed by doctors who have experience in the management of transplant patients.

Advagraf is for long-term use. Doses are calculated based on the patient’s weight. Doctors should monitor the levels of tacrolimus in the blood to check that they stay within predefined ranges.

In the prevention of rejection, the dose of Advagraf to use depends on the type of transplant the patient has received. In kidney transplant, the starting dose is 0.20 to 0.30 mg per kilogram body weight. In liver transplant, the starting dose is 0.10 to 0.20 mg/kg.

When treating rejection, these same doses may be used in kidney and liver transplants. Starting doses are 0.10 to 0.30 mg/kg in other types of transplant (heart, lung, pancreas or intestine).

Advagraf is given once a day, in the morning, at least one hour before or two to three hours after food.

How does Advagraf work?

Tacrolimus, the active substance in Advagraf, is an immunosuppressive agent. This means that it reduces the activity of the immune system (the body’s natural defences). Tacrolimus acts on some special cells in the immune system called T-cells that are primarily responsible for attacking the transplanted organ (organ rejection).

Tacrolimus has been used since the mid-1990s. In the European Union (EU), it has been available as capsules under the name Prograf or Prograft (depending on the country). Advagraf is very similar to Prograf / Prograft, but the way the medicine is made has been changed so that the active substance is released more slowly from the capsule than it is in Prograf / Prograft. This allows Advagraf to be given once a day, whereas Prograf / Prograft is given twice a day. This can help the patients stick to their treatment.

How has Advagraf been studied?

Because tacrolimus and Prograf / Prograft have already been used in the EU, the company presented the results of studies that had been carried out with Prograf / Prograft previously, as well as data from the published literature. It also presented the results of a clinical study in 668 kidney transplant patients comparing the use of Advagraf with that of Prograf / Prograft or ciclosporin (another immunosuppressive medicine used in the prevention of rejection). Patients also received mycophenolate mofetil (another medicine used in the prevention of rejection). The main measure of effectiveness was the number of patients in whom the transplant failed (as measured by looking at, for example, the need for a repeat transplant or a return to dialysis) after one year’s treatment. Further shorter studies were also carried out in 119 kidney transplant patients and 129 liver transplant patients, looking at how Advagraf is absorbed by the body in comparison to Prograf / Prograft.

What benefit has Advagraf shown during the studies?

Advagraf was as effective as both comparator medicines. After one year, 14% of the patients receiving Advagraf had experienced organ failure. The percentages were 15% in the patients treated with Prograf / Prograft, and 17% in those treated with ciclosporin. The shorter studies in kidney and liver transplant patients showed that Advagraf and Prograf / Prograft have comparable absorption in the body.

What is the risk associated with Advagraf?

The most common side effects with Advagraf (seen in more than 1 patient in 10) are tremor (shaking), headache, nausea (feeling sick), diarrhoea, kidney problems, hyperglycaemia (raised blood glucose levels), diabetes, hyperkalaemia (raised blood potassium levels), hypertension (high blood pressure) and insomnia (difficulty sleeping). For the full list of all side effects reported with Advagraf, see the package leaflet.

Advagraf should not be used in people who may be hypersensitive (allergic) to tacrolimus, to macrolide antibiotics (such as erythromycin) or to any of the other ingredients.

Patients and doctors must be careful when other medicines (including some herbal remedies) are taken at the same time as Advagraf, as there may be a need to adjust the dose of Advagraf or the dose of the medicine it is taken with. See the package leaflet for details.

Why has Advagraf been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Advagraf’s benefits are greater than its risks for the prophylaxis of transplant rejection in adult kidney and liver allograft recipients, and in the treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients. The Committee recommended that Advagraf be given marketing authorisation.

Other information about Advagraf

The European Commission granted a marketing authorisation valid throughout the EU for Advagraf on 23 April 2007. The marketing authorisation holder is Astellas Pharma Europe B.V.

Name Language First published Last updated
Advagraf : EPAR - Summary for the public BG = bălgarski 2008-03-31  
Advagraf : EPAR - Summary for the public ES = español 2008-03-31  
Advagraf : EPAR - Summary for the public CS = čeština 2008-03-31  
Advagraf : EPAR - Summary for the public DA = dansk 2008-03-31  
Advagraf : EPAR - Summary for the public DE = Deutsch 2008-03-31  
Advagraf : EPAR - Summary for the public ET = eesti keel 2008-03-31  
Advagraf : EPAR - Summary for the public EL = elliniká 2008-03-31  
Advagraf : EPAR - Summary for the public EN = English 2008-03-31  
Advagraf : EPAR - Summary for the public FR = français 2008-03-31  
Advagraf : EPAR - Summary for the public IT = italiano 2008-03-31  
Advagraf : EPAR - Summary for the public LV = latviešu valoda 2008-03-31  
Advagraf : EPAR - Summary for the public LT = lietuvių kalba 2008-03-31  
Advagraf : EPAR - Summary for the public HU = magyar 2008-03-31  
Advagraf : EPAR - Summary for the public MT = Malti 2008-03-31  
Advagraf : EPAR - Summary for the public NL = Nederlands 2008-03-31  
Advagraf : EPAR - Summary for the public PL = polski 2008-03-31  
Advagraf : EPAR - Summary for the public PT = português 2008-03-31  
Advagraf : EPAR - Summary for the public RO = română 2008-03-31  
Advagraf : EPAR - Summary for the public SK = slovenčina 2008-03-31  
Advagraf : EPAR - Summary for the public SL = slovenščina 2008-03-31  
Advagraf : EPAR - Summary for the public FI = suomi 2008-03-31  
Advagraf : EPAR - Summary for the public SV = svenska 2008-03-31  

This EPAR was last updated on 14/09/2015 .

Authorisation details

Product details

Product details for Advagraf
NameAdvagraf
Agency product numberEMEA/H/C/000712
Active substance

tacrolimus

International non-proprietary name (INN) or common name

tacrolimus

Therapeutic area Graft Rejection
Anatomical therapeutic chemical (ATC) code L04AD02

Publication details

Publication details for Advagraf
Marketing-authorisation holder

Astellas Pharma Europe B.V.

Revision15
Date of issue of marketing authorisation valid throughout the European Union23/04/2007

Contact address:

Astellas Pharma Europe B.V.
Regulatory Affairs Europe
Elisabethhof 19
NL-2353 EW Leiderdorp
The Netherlands

Product information

Product information

25/06/2015  Advagraf -EMEA/H/C/000712 -WS/0721

Name Language First published Last updated
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14
Advagraf : EPAR - Product Information SV = svenska 2009-05-19 2015-09-14

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.


Name Language First published Last updated
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08
Advagraf : EPAR - All Authorised presentations SV = svenska 2009-05-19 2010-10-08

Pharmacotherapeutic group

Immunosuppressants

Therapeutic indication

Prophylaxis of transplant rejection in adult kidney or liver allograft recipients.

Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Advagraf : EPAR - Procedural steps taken and scientific information after authorisation SV = svenska 2009-05-19 2015-09-14

Initial marketing-authorisation documents

Name Language First published Last updated
Advagraf : EPAR - Scientific Discussion SV = svenska 2007-05-30  
Advagraf : EPAR - Procedural steps taken before authorisation SV = svenska 2007-05-15  

Authorised

This medicine is approved for use in the European Union

More information on Advagraf