Rejection therapy – adults and children

Increased Prograf doses, supplemental corticosteroid therapy, and introduction of short courses of mono-/polyclonal antibodies have all been used to manage rejection episodes.

In adult patients converted to Prograf, an initial oral dose of 0.15 mg/kg/day should be administered in two divided doses (e.g. morning and evening).

In paediatric patients converted to Prograf, an initial oral dose of 0.20 - 0.30 mg/kg/day should be administered in two divided doses (e.g. morning and evening).

For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in specific patient populations”.

Dosage recommendations - Rejection therapy, other allografts

The dose recommendations for lung, pancreas and intestinal transplantation are based on limited prospective clinical trial data. In lung-transplanted patients Prograf has been used at an initial oral dose of 0.10 - 0.15 mg/kg/day, in pancreas-transplanted patients at an initial oral dose of 0.2 mg/kg/day and in intestinal transplantation at an initial oral dose of 0.3 mg/kg/day.

Dosage adjustments in specific patient populations

Patients with liver impairment

Dose reduction may be necessary in patients with severe liver impairment in order to maintain the blood trough levels within the recommended target range.

Patients with kidney impairment

As the pharmacokinetics of tacrolimus are unaffected by renal function, no dose adjustment should be required. However, owing to the nephrotoxic potential of tacrolimus careful monitoring of renal function is recommended (including serial serum creatinine concentrations, calculation of creatinine clearance and monitoring of urine output).

Paediatric patients

In general, paediatric patients require doses 1½ - 2 times higher than the adult doses to achieve similar blood levels.

Older people

There is no evidence currently available to indicate that dosing should be adjusted in older people.

Conversion from ciclosporin

Care should be taken when converting patients from ciclosporin-based to Prograf-based therapy (see sections 4.4 and 4.5). Prograf therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient. Dosing should be delayed in the presence of elevated ciclosporin blood levels. In practice, Prograf therapy has been initiated 12 - 24 hours after discontinuation of ciclosporin. Monitoring of ciclosporin blood levels should be continued following conversion as the clearance of ciclosporin might be affected.

Target whole blood trough concentration recommendations

Dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient.

As an aid to optimise dosing, several immunoassays are available for determining tacrolimus concentrations in whole blood including a semi-automated microparticle enzyme immunoassay (MEIA). Comparisons of concentrations from the published literature to individual values in clinical practice should be assessed with care and knowledge of the assay methods employed. In current clinical practice, whole b