RPB

Cyclosporine

Ciclosporin (INN), cyclosporin A, CsA; brands Sandimmune, Sandimmun, Neoral, Gengraf (systemic), Restasis, Cequa, Ikervis, Verkazia, Vevye (eye drops)

Immune & bioregulators
Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates
Note on this profile. Cyclosporine is an approved, powerful immunosuppressant used mostly in organ transplantation and severe autoimmune disease, with eye-drop versions for dry eye. It is a peptide by chemistry but has nothing in common with the research peptides discussed on this site in how it is used. There is no self-directed use and it would be dangerous; this page explains the published science and its monitoring requirements.

1What it is

Cyclosporine was found in 1970 in a soil sample from Norway by Sandoz scientists screening fungi for antibiotics; Jean-François Borel showed it suppressed immunity without killing cells. Roy Calne's team in Cambridge used it in kidney transplant patients from 1978, and it transformed transplantation: one-year kidney graft survival jumped from about 50% to 80–90%, and heart and liver transplantation became routine. It was approved by the FDA in 1983.

Chemically it is a ring of 11 amino acids, but unlike the peptides most readers of this site know it is not made on a ribosome, several of its residues are methylated, and it dissolves in fat rather than water. That is why it can be swallowed and survive digestion, and also why its absorption is erratic — the microemulsion formulation (Neoral, 1995) was developed to fix that, and the two formulations are not interchangeable milligram for milligram. Cyclosporine is included here as a chemically justified cyclic peptide that people search for; it should not be read as a research compound.

2How it's thought to work

Inside T lymphocytes it binds cyclophilin A. The cyclosporine–cyclophilin complex binds and inhibits calcineurin, a phosphatase that normally lets the transcription factor NFAT enter the nucleus.
Without NFAT, the genes for IL-2, IL-4, interferon-γ and other cytokines stay off, so helper T cells are not activated and cytotoxic T cells are not recruited. B cells and innate immunity are relatively spared.
The same calcineurin pathway operates in kidney tubular and vascular cells, which is the basis of its hallmark kidney toxicity and high blood pressure.
In the eye, it reduces T-cell infiltration of the lacrimal gland and conjunctiva and increases tear production over months (dry eye is partly inflammatory).
It also binds cyclophilin D in mitochondria, blocking the mitochondrial permeability transition pore — the reason it has been tested as a cardioprotective drug during heart attack (negative in large trials, below).
Cyclosporine binds cyclophilin first, and it is that pair which blocks calcineurin. Without calcineurin the transcription factor NFAT never reaches the nucleus, so IL-2 is not made and the T cell response does not get started.Schematic — not to scale

3What the research shows

Prevention of organ rejection

Two early established it: the European Multicentre Trial (n=232) and the Canadian Multicentre Transplant Study (n=209) both showed markedly better one-year kidney graft survival with cyclosporine than azathioprine-based regimens (European Multicentre Trial Group 1983, Lancet; Canadian Multicentre Transplant Study Group 1983, NEJM). It later became the comparator against which tacrolimus was shown to give fewer acute rejections (Pirsch 1997, Transplantation; Webster 2005, BMJ meta-analysis), and tacrolimus is now the first-line calcineurin inhibitor in most centres. [3][4][8]

Psoriasis

Dose-ranging RCTs showed clearance in most patients at 3–5 mg/kg/day within 8–12 weeks (Ellis 1991, NEJM). Guidelines limit continuous courses to 1–2 years because of cumulative kidney damage. [5]

Rheumatoid arthritis

RCTs showed benefit alone and with methotrexate (Tugwell 1995, NEJM); largely superseded by biologics.
Graded A/B

Atopic dermatitis, nephrotic syndrome, acute severe ulcerative colitis, uveitis, aplastic anaemia

Systematic reviews support short-term use in severe atopic dermatitis (Schmitt 2007, J Eur Acad Dermatol Venereol); RCTs show efficacy as rescue therapy in steroid-refractory ulcerative colitis (Lichtiger 1994, NEJM) and in steroid-dependent nephrotic syndrome; aplastic anaemia with antithymocyte globulin is standard. Several of these are off-label in the US but licensed in Europe. [6]

Dry eye disease (topical)

Two 6-month Phase 3 trials of 0.05% emulsion (n=877) showed increased Schirmer tear scores and reduced corneal staining (Sall 2000, Ophthalmology); 0.1% (Ikervis) and 0.09% (Cequa) have similar trial support. [7]
Graded A (negative)

Cardioprotection during heart attack

After promising small studies (Piot 2008, NEJM), the CIRCUS trial (n=970) found no reduction in infarct size or clinical events from a single IV dose before PCI (Cung 2015, NEJM). [9]

Community / self-directed use

Essentially none documented. Occasional online discussion of topical cyclosporine for hair loss (based on a 2018 cell study of a cyclosporine-related WNT mechanism) has no human data.

4Reported side effects and interactions

Literature-reported

Nephrotoxicity (acute, reversible vasoconstriction and chronic, irreversible fibrosis — the main dose-limiting problem); hypertension in up to half of transplant patients; tremor, headache, paraesthesia; hirsutism and gum overgrowth (cosmetic but common); hyperkalaemia, hypomagnesaemia, hyperuricaemia and gout, hyperlipidaemia, raised glucose; hepatotoxicity; serious infections (CMV, BK virus, Pneumocystis) from immunosuppression; increased malignancy, especially skin cancer and lymphoma, with duration and intensity of use; rare posterior reversible encephalopathy syndrome and thrombotic microangiopathy. Ophthalmic: burning on instillation (about 17%), redness, blurred vision.

Community-reported

none; no community use.

Theoretical. the mitochondrial pore mechanism and WNT effects have prompted research interest but not human application.

Interactions. this is one of the most interaction-prone drugs in medicine. It is a substrate of CYP3A4 and P-glycoprotein. Levels are raised (toxicity) by azole antifungals, macrolide antibiotics, diltiazem, verapamil, amiodarone, grapefruit juice and ritonavir; lowered (rejection risk) by rifampicin, carbamazepine, phenytoin, St John's wort and some anti-HIV drugs. Cyclosporine itself raises levels of statins (myopathy), colchicine, dabigatran, aliskiren and many others. Additive kidney toxicity with NSAIDs, aminoglycosides and amphotericin. Live vaccines are avoided.

Markers researchers commonly monitor

Cyclosporine has one of the most intensive monitoring schedules of any drug; these follow the label and transplant/dermatology guidelines:

MarkerWhy it's watched
Whole-blood cyclosporine concentration (trough "C0", or 2-hour post-dose "C2")therapeutic drug monitoring is mandatory in transplantation because absorption and metabolism vary several-fold between people; target ranges depend on organ, time since transplant and co-medication.
Serum creatinine and eGFRthe key toxicity; a sustained rise of more than about 30% from baseline triggers dose reduction (dermatology guidelines).
Blood pressurehypertension is expected and treated; calcium-channel blockers that do not raise cyclosporine levels (amlodipine, nifedipine) are preferred.
Potassium and magnesiumhyperkalaemia and hypomagnesaemia are common and can cause arrhythmia or tremor.
Fasting lipids, glucose, uric acidmetabolic effects accumulate over months.
Liver enzymes and bilirubinhepatotoxicity.
CBCinfection and marrow effects; in combination regimens.
Skin examination (annual or more)skin cancer risk rises with duration; sun protection is advised.
Viral surveillance (CMV, EBV, BK) in transplant recipientsstandard immunosuppression monitoring.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Oral dose forms only outside hospital: soft gelatin capsules 10, 25, 50 and 100 mg (Neoral/Gengraf microemulsion; Sandimmune is a different, non-equivalent formulation) and 100 mg/mL oral solution, which is diluted in orange or apple juice (not grapefruit) in a glass, not plastic, cup and taken at once. Doses are taken at the same times each day, consistently with or without food, because absorption varies. Intravenous formulation (hospital) contains polyoxyethylated castor oil and has caused anaphylaxis. Eye drops are single-use or multidose emulsions; shake before use. Not injectable at home; the site calculator is not applicable.

6Commonly studied alongside

Corticosteroids, mycophenolate, azathioprine and sirolimus/everolimus in transplant regimens; tacrolimus as the main comparator; methotrexate (RA, psoriasis combinations); antithymocyte globulin (aplastic anaemia). It has no peptide-community pairings. The related immune peptides on this site — thymosin alpha-1 and thymalin (earlier profiles) — act in the opposite direction, as immune stimulants, and have never been studied in combination.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

RegionStatus (checked —)
United StatesFDA-approved: Sandimmune (1983), Neoral (1995), Gengraf and generics for transplant, RA and psoriasis; Restasis (2003), Cequa (2018) and Vevye (2023) ophthalmic for dry eye. Boxed warnings for immunosuppression, infection, malignancy, nephrotoxicity and hypertension; specialist prescribing
European UnionNationally authorised in all member states (Sandimmun, Sandimmun Neoral and generics) for transplantation, severe psoriasis, severe atopic dermatitis, RA, nephrotic syndrome, endogenous uveitis; Ikervis (2015) and Verkazia (2018) centrally authorised eye drops
United KingdomMHRA-licensed (same indications as EU); brands must be prescribed by name because formulations differ
AustraliaTGA-registered (Neoral, Sandimmun, generics; Ikervis, Cequa)
South AfricaRegistered with SAHPRA (Sandimmun Neoral and generics) †
SportNot prohibited by WADA

8Open questions

  • Whether lower-exposure or calcineurin-sparing regimens can keep grafts while limiting kidney damage; the long-term trade-off is still being optimised.
  • Why some patients develop chronic nephrotoxicity at the same blood levels others tolerate; pharmacogenetics (CYP3A5, ABCB1) explain only part.
  • Whether topical or local delivery systems can bring its anti-inflammatory effect to skin and hair without systemic exposure.

9References

  1. 1Borel JF et al. (1976). Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. PubMed · DOI
  2. 2Calne RY et al. (1978). Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet. PubMed · DOI
  3. 3European Multicentre Trial Group (1983). Cyclosporin in cadaveric renal transplantation: one-year follow-up of a multicentre trial. Lancet. DOI
  4. 4Canadian Multicentre Transplant Study Group (1983). A randomized clinical trial of cyclosporine in cadaveric renal transplantation. NEJM. PubMed
  5. 5Ellis CN et al. (1991). Cyclosporine for plaque-type psoriasis: results of a multidose, double-blind trial. NEJM. PubMed · DOI
  6. 6Lichtiger S et al. (1994). Cyclosporine in severe ulcerative colitis refractory to steroid therapy. NEJM. PubMed · DOI
  7. 7Sall K et al. (2000). Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. Ophthalmology. PubMed · DOI
  8. 8Webster AC et al. (2005). Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ. PubMed · DOI
  9. 9Cung TT et al. (2015). Cyclosporine before PCI in patients with acute myocardial infarction (CIRCUS). NEJM. PubMed · DOI
  10. 10Novartis. Neoral / Sandimmun Neoral prescribing information and Summary of Product Characteristics (current). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

30 Oct 2026Profile published — awaiting medical review

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