Posology : מינונים

4.2    Posology and method of administration

Grafalon should be prescribed only by physicians who are experienced in the use of immunosuppressive therapies. Grafalon must be administered under qualified medical supervision.

Posology
The dose of Grafalon is dependent on the indication. Dose recommendations are based on body weight (BW).

Prevention of acute transplant rejection in patients receiving allogeneic solid organ transplants The recommended dose range is 2 to 5 mg/kg BW/d Grafalon. The most common doses are in the range of 3 to 4 mg/kg BW/d. Therapy should commence on the day of transplantation pre-, intra-, or immediately post-operatively. Depending on the patient's condition, selected daily dose and the concomitant immunosuppressive regimen, the recommended duration of therapy is in the range of 5 to 14 days.

Therapy of acute corticosteroid-resistant rejection after allogeneic solid organ transplantation The recommended dose range is 3 to 5 mg/kg BW/d Grafalon. The most common dosages are in the range of 3 to 4 mg/kg BW/d. Duration of therapy will vary according to the condition of the grafted organ and clinical response, usually between 5 to 14 days.

Prevention of graft-versus-host disease (GVHD) in adults after allogeneic stem cell transplantation (SCT) As part of myeloablative conditioning regimens for stem cell transplantation, the recommended dose is 20 mg/kg BW/d of Grafalon, usually starting from day -3 to day -1 prior to SCT.

Method of administration
Intravenous use (after dilution)
Grafalon is a hypotonic concentrate for solution for infusion with pH 3.7 ± 0.3 and is not for direct injection.
It has to be diluted in sodium chloride 9 mg/ml (0.9%) solution before intravenous administration to the patient. A dilution ratio of 1:7 is recommended (per 1 ml Grafalon 6 ml sodium chloride solution should be added) to maintain the required level of osmolality. Higher dilution ratios, with attendant higher pH levels of the infusion solution, may result in particle formation. Solutions containing visible particles must not be used.

The standard infusion time in organ transplantation is 4 hours while in stem cell transplantation, 4 to 12 hours infusion times are recommended. In case of intra-operative administration, infusion time of 0.5 to 2 hours has been usually used.

During administration, the patient shall be closely monitored for symptoms of hypersensitivity or anaphylaxis. The first dose of Grafalon should be administered at a reduced infusion rate for the first 30 minutes. If no symptoms of intolerance occur, the infusion rate may be increased. In case of anaphylactic or anaphylactoid reactions, the responsible physician must be prepared to deal promptly with such an event and appropriate medical treatment has to be implemented.

Alternatively to infusion via central venous catheter, a peripheral vein with high flow rate and large diameter can be chosen. The administration of methylprednisolone and/or antihistamines prior to infusion is recommended in order to improve systemic and local tolerance. Apart from standard hygienic precautions at the injection site, reduction of the infusion speed and/or change of the venous access site are to be considered.

Sodium heparin must not be added to the Grafalon infusion solution or administered via the same infusion set, see section 6.2.