FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS

1 INDICATIONS AND USAGE

1.1 Prophylaxis of Organ Rejection in Renal Transplantation

1.2 Limitations of Use in Renal Transplantation

1.3 Treatment of Patients with Lymphangioleiomyomatosis

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Guidance for Renal Transplant Patients

2.2 Renal Transplant Patients at Low- to Moderate-Immunologic Risk

2.3 Renal Transplant Patients at High-Immunologic Risk

2.4 Dosing in Patients with Lymphangioleiomyomatosis

2.5 Therapeutic Drug Monitoring

2.6 Patients with Low Body Weight

2.7 Patients with Hepatic Impairment

2.8 Patients with Renal Impairment

2.9 Instructions for Dilution and Administration of Rapamune Oral Solution

3 DOSAGE FORMS AND STRENGTHS

3.1 Rapamune Oral Solution

3.2 Rapamune Tablets

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Increased Susceptibility to Infection and the Possible Development of Lymphoma

5.2 Liver Transplantation – Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis

5.3 Lung Transplantation – Bronchial Anastomotic Dehiscence

5.4 Hypersensitivity Reactions

5.5 Angioedema

5.6 Fluid Accumulation and Impairment of Wound Healing

5.7 Hyperlipidemia

5.8 Decline in Renal Function

5.9 Proteinuria

5.10 Latent Viral Infections

5.11 Interstitial Lung Disease/Non-Infectious Pneumonitis

5.12 De Novo Use Without Cyclosporine

5.13 Increased Risk of Calcineurin Inhibitor-Induced Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura/Thrombotic Microangiopathy

5.14 Antimicrobial Prophylaxis

5.15 Embryo-Fetal Toxicity

5.16 Male Infertility

5.17 Different Sirolimus Trough Concentration Reported between Chromatographic and Immunoassay Methodologies

5.18 Skin Cancer Events

5.19 Immunizations

5.20 Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp

5.21 Cannabidiol Drug Interactions

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience in Prophylaxis of Organ Rejection Following Renal Transplantation

6.2 Rapamune Following Cyclosporine Withdrawal

6.3 High-Immunologic Risk Renal Transplant Patients

6.4 Conversion from Calcineurin Inhibitors to Rapamune in Maintenance Renal Transplant Population

6.5 Pediatric Renal Transplant Patients

6.6 Patients with Lymphangioleiomyomatosis

6.7 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Use with Cyclosporine

7.2 Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp

7.3 Grapefruit Juice

7.4 Weak and Moderate Inducers or Inhibitors of CYP3A4 and P-gp

7.5 Cannabidiol

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Patients with Hepatic Impairment

8.7 Patients with Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Prophylaxis of Organ Rejection in Renal Transplant Patients

14.2 Cyclosporine Withdrawal Study in Renal Transplant Patients

14.3 High-Immunologic Risk Renal Transplant Patients

14.4 Conversion from Calcineurin Inhibitors to Rapamune in Maintenance Renal Transplant Patients

14.5 Conversion from a CNI-based Regimen to a Sirolimus-based Regimen in Liver Transplant Patients

14.6 Pediatric Renal Transplant Patients

14.7 Lymphangioleiomyomatosis Patients

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Rapamune Oral Solution

16.2 Rapamune Tablets

17 PATIENT COUNSELING INFORMATION

17.1 Dosage

17.2 Skin Cancer Events

17.3 Pregnancy and Lactation

17.4 Infertility

*

Sections or subsections omitted from the full prescribing information are not listed.