Prolonged-release hard capsule.

Gelatin capsules imprinted in red with “0.5 mg” on the light yellow capsule cap and “ 647” on the orange capsule body, containing white powder.

Advagraf 1 mg prolonged-release hard capsules

Prolonged-release hard capsule.

Gelatin capsules imprinted in red with “1 mg” on the white capsule cap and “ 677” on the orange capsule body, containing white powder.

Advagraf 3 mg prolonged-release hard capsules

Prolonged-release hard capsule.

Gelatin capsules imprinted in red with “3 mg” on the orange capsule cap and “ 637” on the orange capsule body, containing white powder.

Advagraf 5 mg prolonged-release hard capsules

Prolonged-release hard capsule.

Gelatin capsules imprinted in red with “5 mg” on the greyish red capsule cap and ” 687” on the orange capsule body, containing white powder.

Go to top of the page4. Clinical particulars

Go to top of the page4.1 Therapeutic indications
 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.

Go to top of the page4.2 Posology and method of administration
 Advagraf is a once-a-day oral formulation of tacrolimus. Advagraf therapy requires careful monitoring by adequately qualified and equipped personnel. This medicinal product should only be prescribed, and changes in immunosuppressive therapy initiated, by physicians experienced in immunosuppressive therapy and the management of transplant patients.

Inadvertent, unintentional or unsupervised switching of immediate- or prolonged-release formulations of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of adverse reactions, including under- or overimmunosuppression, due to clinically relevant differences in systemic exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.4 and 4.8). Following conversion to any alternative formulation, therapeutic drug monitoring must be performed and dose adjustments made to ensure that systemic exposure to tacrolimus is maintained.

Posology

The recommended initial doses presented below are intended to act solely as a guideline. Advagraf is routinely administered in conjunction with other immunosuppressive agents in the initial post-operative period. The dose may vary depending upon the immunosuppressive regimen chosen. Advagraf dosing should primarily be based on clinical assessments of rejection and tolerability in each patient individually aided by blood level monitoring (see below under “Therapeutic drug monitoring”). If clinical signs of rejection are apparent, alteration of the immunosuppressive regimen should be considered.

In de novo kidney and liver transplant patients AUC0-24 of tacrolimus for Advagraf on Day 1 was 30% and 50% lower respectively, when compared with that for the immediate release capsules (Prograf) at equivalent doses. By Day 4, systemic exposure as measured by trough levels is similar for both kidn