Sirolimus Dosage
This dosage information may not include all the information needed to use Sirolimus safely and effectively. See additional information for Sirolimus.
The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.
Usual Adult Dose for:
Usual Pediatric Dose for:
Additional dosage information:
Usual Adult Dose for Organ Transplant - Rejection Prophylaxis
For the prophylaxis of organ rejection in patients receiving renal transplants:
For patients at low to moderate immunologic risk:
Dosing by body weight:
Less than 40 kg:
Loading dose: 3 mg/m2 on day 1
Maintenance: 1 mg/m2 once daily
Greater than or equal to 40 kg:
Loading dose: 6 mg orally on day 1
Maintenance: 2 mg orally once daily
It is recommended that sirolimus be used in a regimen with cyclosporine and corticosteroids.
In patients at high immunologic risk (defined as Black transplant recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high-panel reactive antibodies [PRA; peak PRA level greater than 80%]):
For patients receiving sirolimus with cyclosporine:
Loading Dose: up to 15 mg on day one post-transplantation.
Maintenance Dose: Beginning on day 2, an initial maintenance dose of 5 mg/day should be given. A trough level should be obtained between days 5 and 7, and the daily dose of sirolimus should be adjusted thereafter.
Antibody induction therapy may be used.
Intestinal transplant:
Initial loading dose: 2 to 3 orally mg/m2
Maintenance dose: 1 mg/m2 orally once daily to achieve blood levels of 8 to 10 ng/mL
Maintenance therapy after withdrawal of cyclosporine:
Cyclosporine withdrawal is not recommended in high-immunological risk patients. Following two to four months of combined therapy, withdrawal of cyclosporine may be considered in low-to-moderate risk patients. Cyclosporine should be discontinued over four to eight weeks, and a necessary increase in the dosage of sirolimus (up to fourfold) should be anticipated due to removal of metabolic inhibition by cyclosporine and to maintain adequate immunosuppressive effects. Dose-adjusted trough target concentrations are typically 16 to 24 ng/mL for the first year post-transplant and 12 to 20 ng/mL thereafter (measured by chromatographic methodology).
Usual Pediatric Dose for Organ Transplant - Rejection Prophylaxis
Greater than or equal to 13 years who weigh less than 40 kg:
Loading dose: 3 mg/m2
Initial maintenance dose: 1 mg/m2/day divided every 12 hours or once daily; adjust dose to achieve target sirolimus trough blood concentration
Renal Dose Adjustments
No dosage adjustment is necessary in loading or maintenance dose. However, adjustment of the regimen (including discontinuation of therapy) should be considered when used concurrently with cyclosporine and elevated or increasing serum creatinine is noted.
Liver Dose Adjustments
Loading dose: No adjustment is required.
Maintenance dose:
Mild-to-moderate hepatic impairment: Reduce maintenance dose by approximately 33%.
Severe hepatic impairment: Reduce maintenance dose by approximately 50%.
Dose Adjustments
Sirolimus dosages should be adjusted to maintain trough concentrations within the desired range based on risk and concomitant therapy. Maximum daily dose: 40 mg. The dosage should be adjusted at intervals of 7 to 14 days to account for the long half-life of sirolimus. In general, dose proportionality may be assumed. The new sirolimus dose equals current dose multiplied by (target concentration/current concentration).
If a large dose increase is required, consider loading dose calculated as:
Loading dose equals (new maintenance dose minus current maintenance dose) multiplied by 3
Maximum dose in one day: 40 mg
If the required dose is greater than 40 mg (due to loading dose), then the dose should be divided over 2 days. Serum concentrations should not be used as the sole basis for dosage adjustment. Clinical signs/symptoms, tissue biopsy, and laboratory parameters should also be monitored.
Precautions
The safety and efficacy of conversion from calcineurin inhibitors to sirolimus in maintenance renal transplant population has not been established.
The safety and efficacy of sirolimus have been established in children aged 13 years or older who are judged to be at low to moderate risk. Safety and efficacy information from a controlled clinical trial in children less than 18 years of age who were renal transplant recipients judged to be at high immunologic risk (defined as a history of one or more acute rejection episodes and/or the presence of chronic allograft nephropathy) do not support the chronic use of sirolimus in combination with calcineurin inhibitors and corticosteroids, due to the increased risk of lipid abnormalities and deterioration of renal function associated with these immunosuppressive regimens, without increased benefit with respect to acute rejection, graft survival, or patient survival.
Dialysis
Data not available
Other Comments
The initial dose of sirolimus should be administered as soon as possible after transplantation.
To minimize the variability of exposure to sirolimus, the drug should be taken consistently with or without food.
It is recommended that sirolimus be taken 4 hours after administration of cyclosporine oral solution and/or cyclosporine capsules.
Blood sirolimus levels should be monitored in pediatric patients, patients with hepatic impairment, and/or if cyclosporine dosing is markedly reduced or discontinued.
Sirolimus tablets and oral solution are not bioequivalent due to differences in absorption. However, clinical equivalence has been demonstrated at the 2 mg dose level.
