PROGRAF CAPSULES 1 mg

THERAPEUTIC INDICATION

Primary immunosuppression in liver and kidney allograft recipients and liver and kidney allograft rejection resistant to conventional immunosuppressive agents.

CONTRAINDICATIONS

• Known hypersensitivity to tacrolimus or other macrolides.
• Prograf Capsules 1 mg and Prograf Capsules 5 mg in addition; known hypersensitivity to other ingredients.
• Prograf Concentration for Infusion 5 mg/ml in addition; known hypersensitivity to polyoxyethylated castor oil (HCO-60) or structurally related compounds.

POSOLOGY AND METHOD OF ADMINISTRATION

Only physicians experienced in immunosuppressive therapy and the management of organ transplant patients should prescribe Prograf. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow up of the patient.

The dosage recommendations given below for oral and intravenous administration are intended to act as a guideline. Prograf doses should be adjusted according to individual patient requirements.

Dosing should commence orally, if necessary via an intranasal gastric tube. If the clinical condition of the patient does not allow oral therapy, initial intravenous dosing may be necessary.

Dosage recommendations

Primary Immunosuppression Dose Levels – Adults

Liver and kidney transplantation: Oral tacrolimus therapy should commence at 0.10 – 0.20 mg/kg/day for liver transplantation and at 0.15 – 0.30 mg/kg/day for kidney transplantation administered as two divided doses. Administration should start approximately 6 hours after the completion of liver transplant surgery and within 24 hours after completion of kidney transplant surgery. If clinical condition of the patient does not allow oral dosing, then intravenous tacrolimus therapy should be initiated as a continuous 24 hours infusion at 0.01 to 0.05 mg/kg for liver transplant and 0.05 to 0.10 mg/kg for kidney transplant.

Primary Immunosuppression Dose Levels – Paediatric Patients

Paediatric patients generally require doses 1.5 to 2 times higher than the recommended adult doses to achieve the same blood levels.

Liver and kidney transplantation: An initial dose of 0.3 mg/kg/day for liver and kidney transplantation should be administered in two divided doses. If the dose cannot be given orally, an initial intravenous dose of 0.05 mg/kg/day for the liver transplantation or 0.1 mg/kg/day for kidney transplantation should be administered as a continuous 24 hours infusion.

Maintenance Therapy Dose Levels

It is necessary to continue immunosuppression with oral Prograf to maintain graft survival. Dose can frequently be reduced during maintenance therapy. Dosing should be primarily based on clinical assessments of rejection and tolerability of the patient.

If progression of disease occurs (e.g. signs of acute rejection) alteration of the immunosuppressive regimen should be considered. Increase the amount of corticosteroids, introduction of short courses of mono/polyclonal antibodies and increase in the dose of Prograf have been used to manage rejection episodes.

If signs of toxicity (e.g. pronounced adverse event) are noted, the dose of Prograf should be reduced.

When Prograf is administered in combination with a corticosteroid these may often be reduced and in rare cases the treatment has continued as monotherapy.

Therapy Dose Levels for Liver and Kidney Allograft Rejection Resistant to Conventional Immunosuppressive Regimens

In patients experiencing rejections episodes which are unresponsive to conventional immunosuppressive therapy, Prograf treatment should begin with the initial dose recommended for primary immunosuppression in that particular allograft.

Prograf should be initiated after considering cyclosporin blood concentrations and the clinical condition of the patient. In practice, Prograf therapy has been initiated 12–24 hours after discontinuation of cyclosporin. Monitoring of cyclosporin blood levels should be continued following conversion as the clearance of cyclosporin may be affected.

Duration of dosing

For oral dosing, the capsules normally have to be taken continuously to suppress graft rejection and no limit for therapy duration can be given. Patients should be converted from intravenous to oral medication as soon as individual circumstances permit. Intravenous therapy should not be continued for more than 7 days.

Mode of Intake

Capsules should generally be administered on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal, to achieve maximal absorption (see Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Monitoring of Whole Blood Concentrations

Drug level monitoring is recommended during the early post-transplantation period, following dose adjustment of Prograf therapy after switching from another immunosuppressive regimen or following co-administration of drugs which are likely to lead to a drug interaction. Trough blood levels of Prograf should also be monitored periodically during maintenance therapy. The frequency of blood level monitoring should be based on clinical needs. As tacrolimus has a long half-life, it can take several days for adjustments in Prograf dosing to be reflected in changes in blood levels.

Patient with Liver Impairment

A dose reduction is necessary.

Patient with Renal Impairment

Careful monitoring of renal function including serial creatinine estimations, calculations of creatinine clearance and monitoring urine output is recommended.

Elderly Patients

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