What are the uses of rapamycin (sirolimus)?

Uses of Rapamycin (Sirolimus)

Rapamycin (sirolimus) is primarily used for prophylaxis of organ rejection in patients receiving renal transplants, with additional applications in treating lymphangioleiomyomatosis (LAM), drug-eluting stents, and various mTOR pathway-related conditions. 1

Primary FDA-Approved Indications

• Organ Transplantation

  • Prophylaxis of organ rejection in patients aged 13 years and older receiving renal transplants 1
  • Used as part of an immunosuppressive regimen, often in combination with other agents

• Lymphangioleiomyomatosis (LAM)

  • Treatment of pulmonary complications of LAM, including chylothorax 1

Mechanism of Action

Rapamycin works through a unique mechanism compared to other immunosuppressants:

• Binds to FK-binding protein to form a complex that inhibits mammalian target of rapamycin (mTOR) 1
• Blocks IL-2-mediated T-cell proliferation pathways
• Arrests T-cell proliferation in the G1 phase of the cell cycle 1
• Exhibits antiproliferative and antiangiogenic effects 1

Additional Clinical Applications

Established Uses

• Cardiac Stents

  • Used in drug-eluting stents to prevent restenosis due to antiproliferative properties 1

• Liver Transplantation

  • Alternative immunosuppressant in liver transplant recipients 1
  • May be equivalent to calcineurin inhibitors in preventing graft rejection

Emerging Applications

• mTOR Pathway-Related Conditions 1

  • Tuberous sclerosis
  • PTEN (Cowden disease)
  • LKB1 (Peutz-Jeghers syndrome)
  • Neurofibromatosis (NF1)

• Other Potential Uses 1, 2

  • Treatment of certain cancers (antiproliferative effects)
  • Autoimmune diseases
  • Graft-versus-host disease
  • Pulmonary fibrosis
  • Hepatic fibrosis
  • Autosomal-dominant polycystic kidney disease

Important Side Effects and Monitoring

Common Adverse Effects

• Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) 1, 2
• Hematologic effects (anemia, thrombocytopenia, leukopenia) 1
• Impaired wound healing 1, 2
• Increased risk of infections 2
• Gastrointestinal symptoms (diarrhea, nausea, vomiting) 1

Monitoring Requirements

• Regular monitoring of blood levels
• Complete blood count
• Lipid profile
• Renal function
• Blood pressure 2
• Drug interactions (especially with CYP3A4 inhibitors/inducers) 1

Clinical Considerations

Advantages Over Other Immunosuppressants

• Absence of nephrotoxicity when used as monotherapy 3
• No gingival hyperplasia 4
• Less tremor compared to calcineurin inhibitors 4
• Potentially less hypertension 4

Important Precautions

• Avoid in patients with active infections 2
• Consider temporary discontinuation during surgical procedures due to poor wound healing risk 2
• Use caution in patients with renal insufficiency 2
• Monitor for pulmonary toxicity and new respiratory symptoms 2

Drug Interactions

• Metabolized through CYP3A4 system, with numerous potential drug interactions 1
• Can inhibit clearance of other medications including digoxin, colchicine, and HMG-CoA reductase inhibitors 1

Rapamycin represents an important immunosuppressive agent with a unique mechanism of action that continues to find new applications in medicine beyond its original approval for renal transplantation.