Immunosuppression With Sirolimus After Solid Organ Transplantation in Children

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2006;12(2) 

In This Article

Dosing Recommendations and Availability

The recommended dosing regimen for sirolimus in adult renal transplant patients is a loading dose of 6 mg followed by a maintenance dose of 2 mg given once daily.[2,3] In pediatric patients, a loading dose of 3 mg/m2 may be given, with a maintenance dose of 1 mg/m2/day.[2,3,4,5,6,7,8,9,10,11,12,13,14,15,16] Dosage adjustments should be made to maintain whole blood sirolimus trough concentrations within the desired range. For patients receiving sirolimus with a calcineurin inhibitor and a corticosteroid, a therapeutic range of 5-12 ng/mL is recommended. If the regimen does not include a calcineurin inhibitor, a higher range (12-24 ng/mL) should be used.[1,2]

Once a dose adjustment has been made, patients should remain on the new dose for 7 to 14 days until steady-state has been reached before making further changes. In patients for whom a considerable increase in sirolimus concentration is needed, a loading dose may be calculated by the following equation[2]:

sirolimus loading dose = 3 × (new maintenance dose-current maintenance dose)

Sirolimus (Rapamune®, Wyeth Pharmaceuticals) is available in 1 and 2 mg tablets, as well as a 1 mg/mL oral solution. The oral solution is provided in 60 mL amber glass bottles with disposable amber oral syringes and caps. The solution should be refrigerated at 2-8º C. Once opened, the bottle should be used within one month. If necessary, the solution may be stored at room temperature for a period of no more than 15 days.[2]

To prepare a dose of the oral solution, the desired volume should be drawn up in the amber oral syringe and emptied into a glass or plastic cup. It should then be mixed with at least 60 mL (2 oz) of water or orange juice, stirred, and given. The cup should then be rinsed with another 120 mL (4 oz) of water or orange juice and the patient given the rinse solution. Sirolimus should not be mixed with any other liquids. Neither the tablets nor the oral solution should be administered with grapefruit juice. Because of the variability in absorption when given with food, it is recommended that sirolimus be administered at consistent times in relation to meals.[2]

Sirolimus may provide a useful addition or alternative to the calcineurin inhibitors for chronic immunosuppression in children with solid organ transplants. While small case series have shown it to be effective and produce less nephrotoxicity, it has been associated with a wide range of adverse effects. Additional prospective studies are needed to establish its role in transplant management.

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