• Rapamune is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants:
  • Patients at low- to moderate-immunologic risk: Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2–4 months after transplantation (1.1).
  • Patients at high-immunologic risk: Use in combination with CsA and corticosteroids for the first 12 months following transplantation (1.1). Safety and efficacy of CsA withdrawal has not been established in high risk patients (1.1, 1.2, 14.3).
• Rapamune is an mTOR inhibitor indicated for the treatment of patients with lymphangioleiomyomatosis (1.3).

Renal Transplant Patients:

• Administer once daily by mouth, consistently with or without food (2).
• Administer the initial dose as soon as possible after transplantation and 4 hours after CsA (2.1, 7.1).
• Adjust the Rapamune maintenance dose to achieve sirolimus trough concentrations within the target-range (2.5).
• Hepatic impairment: Reduce maintenance dose in patients with hepatic impairment (2.7, 8.6, 12.3).

In renal transplant patients at low-to moderate-immunologic risk:

• Rapamune and CsA Combination Therapy: One loading dose of 6 mg on day 1, followed by daily maintenance doses of 2 mg (2.2).
• Rapamune Following CsA Withdrawal: 2–4 months post-transplantation, withdraw CsA over 4–8 weeks (2.2).

In renal transplant patients at high-immunologic risk:

• Rapamune and CsA Combination Therapy (for the first 12 months post-transplantation): One loading dose of up to 15 mg on day 1, followed by daily maintenance doses of 5 mg (2.3).

Lymphangioleiomyomatosis Patients:

• Administer once daily by mouth, consistently with or without food (2).
• Recommended initial Rapamune dose is 2 mg/day (2.4).
• Adjust the Rapamune dose to achieve sirolimus trough concentrations between 5–15 ng/mL (2.4).
• Hepatic impairment: Reduce maintenance dose in patients with hepatic impairment (2.7, 8.6, 12.3).

Therapeutic drug monitoring is recommended for all patients (2.5, 5.17).

• Oral Solution: 60 mg per 60 mL in amber glass bottle (3.1).
• Tablets: 0.5 mg, 1 mg, 2 mg (3.2).

Hypersensitivity to Rapamune (4).

• Hypersensitivity Reactions (5.4)
• Angioedema (5.5)
• Fluid Accumulation and Impairment of Wound Healing (5.6)
• Hyperlipidemia (5.7)
• Decline in Renal Function (5.8)
• Proteinuria (5.9)
• Latent Viral Infections (5.10)
• Interstitial Lung Disease/Non-Infectious Pneumonitis (5.11)
• De Novo Use Without Cyclosporine (5.12)
• Increased Risk of Calcineurin Inhibitor-Induced Hemolytic Uremic Syndrome/ Thrombotic Thrombocytopenic Purpura/ Thrombotic Microangiopathy (5.13)
• Embryo-Fetal Toxicity: Can cause fetal harm. Use of highly effective contraception is recommended for females of reproductive potential during treatment and for 12 weeks after final dose of Rapamune (5.15, 8.1)
• Male Infertility: Azoospermia or oligospermia may occur (5.16, 13.1)
• Immunizations: Avoid live vaccines (5.19)

Prophylaxis of organ rejection in patients receiving renal transplants: Most common adverse reactions (incidence ≥30%) are peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia (6).

Lymphangioleiomyomatosis: Most common adverse reactions (incidence ≥20%) are stomatitis, diarrhea, abdominal pain, nausea, nasopharyngitis, acne, chest pain, peripheral edema, upper respiratory tract infection, headache, dizziness, myalgia, and hypercholesterolemia (6.6).

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Avoid concomitant use with strong CYP3A4/P-gp inducers or strong CYP3A4/P-gp inhibitors that decrease or increase sirolimus concentrations (7.4, 12.3).
• Therapeutic drug monitoring and dose reduction for Rapamune should be considered when Rapamune is co-administered with cannabidiol (5.21, 7.5).
• See full prescribing information for complete list of clinically significant drug interactions (12.3).

• Pregnancy: Based on animal data can cause fetal harm (5.15, 8.1).
• Lactation: Potential for serious adverse effects in breastfed infants based on mechanism of action (8.2).
• Females and Males of Reproductive Potential: May impair fertility (8.1. 8.3, 13.1).