How has it 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 benefits has it 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?
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 it 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.

Further information
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.

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Name

Advagraf 3 mg prolonged-release hard capsules

Composition

Each prolonged-release hard capsule contains 3 mg tacrolimus (as monohydrate).

Excipients:
Each capsule contains 321.84 mg lactose monohydrate.
The printing ink used to mark the capsule contains trace amounts of soya lecithin (0.48% of total printing ink composition).

For a full list of ex