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approvedImmune & Inflammation

Cyclosporine

Also known as: Ciclosporin, Cyclosporin A, Sandimmune, Neoral, Gengraf, Restasis, CsA

Cyclosporine is a cyclic undecapeptide (11 amino acids) isolated from the fungus Tolypocladium inflatum that revolutionized organ transplantation when introduced in the 1980s. As the first calcineurin inhibitor, it selectively suppresses T-cell activation without destroying lymphocytes, enabling transplant survival rates to increase from approximately 50% to over 80%. FDA-approved for prevention of organ rejection in kidney, liver, and heart transplants, as well as for rheumatoid arthritis, psoriasis, and dry eye disease (Restasis), cyclosporine remains one of the most important immunosuppressants in clinical medicine.

3 cited references·6 researched benefits

Quick Answer

Cyclosporine is a cyclic 11-amino acid peptide immunosuppressant isolated from a soil fungus that transformed organ transplantation. It inhibits calcineurin in T-cells, blocking IL-2 production and T-cell activation without destroying lymphocytes. FDA-approved for transplant rejection prevention, rheumatoid arthritis, psoriasis, and dry eye disease (Restasis), it remains a cornerstone of immunosuppressive therapy. Its introduction in the 1980s doubled organ transplant survival rates and earned its discoverers lasting recognition in medicine.

Key Facts

Mechanism
Cyclosporine enters T-cells and binds to the cytoplasmic immunophilin cyclophilin A, forming a complex that inhibits the serine/threonine phosphatase calcineurin. Calcineurin normally dephosphorylates NFAT (nuclear factor of activated T-cells), allowing it to translocate to the nucleus and activate transcription of IL-2 and other cytokines essential for T-cell proliferation and differentiation. By blocking this pathway, cyclosporine selectively suppresses T-helper cell activation and IL-2 production without affecting other immune cells at therapeutic doses. The molecule contains several unusual amino acids including D-alanine and the novel amino acid (4R)-4-[(E)-2-butenyl]-N,4-dimethyl-L-threonine (MeBmt), which is critical for calcineurin binding. Its cyclic structure and N-methylated backbone confer oral bioavailability despite its large size.
Research Status
approved
Half-Life
~6-24 hours (formulation-dependent)
Molecular Formula
C₆₂H₁₁₁N₁₁O₁₂
Primary Use
Immune & Inflammation
Table of Contents

Benefits

  • Prevents organ transplant rejection — transformed transplantation medicine; kidney graft survival improved from ~50% to >80% at one yearstrong
  • Treats severe psoriasis — FDA-approved for recalcitrant plaque psoriasis unresponsive to other therapies; rapid improvement in 80-90% of patientsstrong
  • Rheumatoid arthritis disease control — slows joint destruction and improves symptoms in moderate-to-severe RA refractory to methotrexatestrong
  • Dry eye disease treatment — Restasis (0.05% ophthalmic emulsion) FDA-approved for chronic dry eye; increases tear productionstrong
  • Steroid-sparing agent — allows reduction in corticosteroid doses in autoimmune and inflammatory conditionsmoderate
  • Treats aplastic anemia — part of standard immunosuppressive therapy (with ATG) for severe aplastic anemia in non-transplant candidatesstrong

Dosage Protocols

RouteDosage RangeFrequencyNotes
Oral (transplant — Neoral/modified)4-12 mg/kg/day (initial); 2-6 mg/kg/day (maintenance)Twice daily (divided doses 12 hours apart)Neoral (microemulsion) formulation preferred over Sandimmune (original) due to more predictable absorption. Dose adjusted based on trough blood levels (target varies by organ: typically 150-300 ng/mL early post-transplant, 100-200 ng/mL maintenance). Grapefruit juice contraindicated (CYP3A4 inhibition increases levels).
Oral (autoimmune — psoriasis/RA)2.5-5 mg/kg/dayTwice dailyStart at 2.5 mg/kg/day and increase by 0.5-0.75 mg/kg/day every 2-4 weeks if needed. Maximum 5 mg/kg/day. Continuous use limited to 1-2 years due to cumulative nephrotoxicity. Monitor creatinine biweekly for first 3 months, then monthly.
Ophthalmic emulsion (Restasis)0.05% (one drop per eye)Twice daily (12 hours apart)For chronic dry eye disease. Onset of benefit may take 3-6 months. Single-use vials; invert before use. May cause initial stinging/burning. Can be used with artificial tears (separate by 15 minutes).
Intravenous infusion3-5 mg/kg/dayContinuous infusion or divided over 2-6 hoursReserved for patients unable to take oral formulation (immediate post-surgery). Convert to oral as soon as possible (IV:oral ratio approximately 1:3). Anaphylactoid reactions can occur with IV due to Cremophor EL vehicle.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nephrotoxicity — the most significant limitation; dose-dependent renal vasoconstriction and chronic tubulointerstitial fibrosis affects 15-40% of patientsserious
  • Hypertension — occurs in 25-50% of patients due to renal vasoconstriction and sodium retention; often requires antihypertensive therapycommon
  • Tremor and headache — neurotoxic effects in 10-25% of patients, usually dose-related and reversiblecommon
  • Gingival hyperplasia — overgrowth of gum tissue in 10-30% of patients; improved by switching to tacrolimus or dose reductioncommon
  • Increased infection risk — opportunistic infections due to T-cell suppression, particularly viral (CMV, EBV) and fungalserious
  • Increased malignancy risk — long-term immunosuppression raises risk of lymphoma and skin cancers; sun protection essentialserious
  • Hyperlipidemia — elevated cholesterol and triglycerides in 15-20% of patients, contributing to cardiovascular riskcommon

Frequently Asked Questions

How did cyclosporine transform organ transplantation?
Before cyclosporine (introduced clinically in 1983), organ transplant recipients relied on non-specific immunosuppressants like azathioprine and high-dose corticosteroids, with one-year kidney graft survival around 50% and heart transplantation barely viable. Cyclosporine selectively targets T-cells without destroying other immune components, dramatically improving graft survival to over 80%. It made heart, liver, and pancreas transplantation routinely feasible and earned the 1996 Gairdner Award for its discoverers. It remains part of standard transplant immunosuppression, though tacrolimus has become preferred in many centers.
What is the difference between Sandimmune and Neoral?
Sandimmune is the original cyclosporine formulation (oil-based) with erratic, bile-dependent absorption that varied widely between patients and meals. Neoral (introduced 1995) is a microemulsion pre-concentrate that forms a fine emulsion on contact with GI fluid, providing more consistent and predictable absorption independent of bile and food. Neoral has approximately 30% higher bioavailability and much less inter-patient variability. The two formulations are NOT interchangeable — switching requires dose adjustment and increased blood level monitoring.
Why does cyclosporine damage the kidneys?
Cyclosporine causes both acute and chronic nephrotoxicity through distinct mechanisms. Acutely, it causes afferent arteriolar vasoconstriction (via endothelin and thromboxane A2 upregulation and nitric oxide suppression), reducing renal blood flow and GFR reversibly. Chronically, sustained vasoconstriction leads to ischemia-driven interstitial fibrosis, tubular atrophy, and arteriolar hyalinosis (the characteristic "striped fibrosis" pattern on biopsy). This chronic damage is largely irreversible and dose/duration dependent, which is why careful blood level monitoring and dose minimization are essential.
Is cyclosporine a peptide or a drug?
Cyclosporine is both — it is a naturally occurring cyclic peptide (11 amino acids) produced by the fungus Tolypocladium inflatum, and also a widely prescribed pharmaceutical drug. Its peptide nature is unusual: it contains several non-standard amino acids, N-methylated backbone amides (making it membrane-permeable despite its size), and a cyclic structure. These features give it the rare property of oral bioavailability in a molecule of ~1,200 daltons, well above the traditional "rule of 5" limit for oral drugs. It is one of the most commercially successful peptide drugs in history.

References

  1. 1
    Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers(1984)PubMed ↗
  2. 2
    Calcineurin inhibitors in the treatment of transplant rejection: pharmacology and clinical aspects(2004)PubMed ↗
  3. 3
    Cyclosporine microemulsion (Neoral) versus conventional cyclosporine (Sandimmune): a systematic review of efficacy and safety(2001)PubMed ↗

Latest Research

Last updated: 2026-02-19