Adult Dosing
Kidney transplant rejection prophylaxis
Low-moderate immunologic risk
- Loading dose: 6 mg PO x 1 as soon as possible after transplant
- Maintenance dose: 2 mg PO daily
- Max: 40 mg/day
Note:
- Use in combination with cyclosporine and steroids x 2-4 months, then taper cyclosporine over 4-8 wks and adjust sirolimus to achieve trough concentrations within target range
- Sirolimus dose adjustments can be made at 7-14 day intervals
High immunologic risk
- Loading dose: 15 mg PO x 1 as soon as possible after transplant
- Maintenance dose: 5 mg PO daily
- Max: 40 mg/day
Note:
- Use in combination with cyclosporine and corticosteroids x 1 yr. Then adjust dosage as per clinical status, as combination therapy not studied >1yr
- Sirolimus dose adjustments can be made at 7-14 day intervals
Pediatric Dosing
Kidney transplant rejection prophylaxis
Low-moderate immunologic risk, (>13 yrs of age and <40 kg)
- Loading dose: 3 mg/m2 PO x 1 as soon as possible after transplant
- Maintenance dose: 1 mg/m2 PO daily
- Max: 40 mg/day
Note:
- Use in combination with cyclosporine and corticosteroids x 1 yr. Then adjust dosage per clinical status as combination therapy not studied >1yr
Low-moderate immunologic risk, (>13 yrs of age and >40 kg)
- Loading dose: Start 6 mg PO x 1 as soon as possible after transplant
- Maintenance dose: 2 mg PO daily
- Max: 40 mg/day
Note:
- Use in combination with cyclosporine and steroids x 2-4 months, then taper cyclosporine over 4-8 wks and adjust sirolimus levels to achieve trough concentrations within target range
- sirolimus dose adjustments can be made at 7-14 day intervals
[Outline]
- Increased risk of lymphomas and other malignancies, particularly of the skin have been reported following immunosuppressive regimen [US Black Box Warning]
- Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should use sirolimus [US Black Box Warning]
- Sirolimus use is not recommended in liver transplantation as safety and efficacy of is not established. Excess mortality, graft loss and hepatic artery thrombosis (HAT) have been reported following sirolimus use in liver transplant [US Black Box Warning]
- Sirolimus use is not recommended in lung transplantation as safety and efficacy is not established [US Black Box Warning]
- Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis and hypersensitivity vasculitis, have been reported with sirolimus use
- Sirolimus can cause development of angioedema, avoid concomitant use with other drugs known to cause angioedema, such as ACE-inhibitors, as it increase the risk
- Impaired or delayed wound healing including lymphocele and wound dehiscence has been reported in patients receiving sirolimus. Patients with BMI >30 kg/m2 are at higher risk. Take appropriate measures to minimize such complication
- Fluid accumulation, including peripheral edema, lymphedema, pleural effusion, ascites, and pericardial effusions have been reported in patients receiving sirolimus
- Hypercholesterolemia and/or hypertriglyceridemia requiring treatment have been observed in patients treated with sirolimus. Monitor the patient for hyperlipidemia and instiute appropriate diet, exercise and lipid lowering agents if detected
- Long-term administration of sirolimus with cyclosporine has been associated with deterioration of renal function, closely monitor the renal function and consider appropriate adjustment of the immunosuppressive regimen
- Proteinuria including nephrotic range proteinuria has been reported 6-24 month post renal transplant in patients treated with sirolimus. Monitor urine protein excretion periodically
- Activation of latent viral infections including progressive multifocal leukoencephalopathy (PML) and BK virus-associated nephropathy (BKVAN) have been observed in patients receiving immunosuppressants. Monitor the patients periodically and consider reduction in immunosuppression
- Interstitial lung disease (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis), some fatal, with no identified infectious etiology have been reported in patients receiving immunosuppressive regimens. Discontinuation or dose reduction of sirolimus resolves the interstitial lung disease
- The safety and efficacy of de novo use of sirolimus without cyclosporine is not established in renal transplant patients
- Increase risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy have been observed with concomitant use of sirolimus with a calcineurin inhibitor
- Administer antimicrobial prophylaxis for Pneumocystis carinii pneumonia for 1 year and Cytomegalovirus (CMV) prophylaxis for 3 months following transplantation
- Patients on immunosuppressive therapy are at increased risk for skin cancer, limit the exposure to sunlight and UV light by wearing protective clothing and using a sunscreen with a high protection factor
- Monitor whole blood sirolimus concentrations in patients receiving concentration-controlled sirolimus
- Do not co-administer sirolimus with strong inhibitors of CYP3A4 and/or P-gp or strong inducers of CYP3A4 and/or P-gp
Cautions: Use cautiously in
- Renal impairment
- Hepatic impairment
- Concomitant neprotoxic agent
- BMI >30 kg/m2
- Hyperlipidimia
- Delayed graft function
Pregnancy Category:C
Breastfeeding: Safety unknown. Alternate drugs might be preferred, especially while nursing a newborn or preterm infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 7 April 2011). Excreted in the milk of rats; Because of the potential for possible serious adverse reactions in nursing infants a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pricing data from www.DrugStore.com in U.S.A.
- Rapamune 0.5 MG TABS [Bottle] (WYETH)
30 mg = $189.98
90 mg = $534.96 - Rapamune 2 MG TABS [Bottle] (WYETH)
100 mg = $2317.87
300 mg = $6789.67 - Rapamune 1 MG TABS [Bottle] (WYETH)
30 mg = $346.99
90 mg = $1019.94 - Rapamune 1 MG/ML SOLN [Bottle] (WYETH)
60 ml = $662.01
120 ml = $1324.02
Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.
