Cyclosporine Side Effects: What Studies Report

What cyclosporine is

Cyclosporine (also spelled ciclosporin) is an approved prescription immunosuppressant that inhibits calcineurin, a calcium- and calmodulin-dependent phosphatase involved in T-cell activation. A 2022 review in Developmental Neurobiology described how calcineurin signalling is modulated across developmental contexts and how pharmacological calcineurin inhibition has been used experimentally to probe that pathway (PMID 35785416). Because the same pathway is active in many tissues beyond lymphocytes, much of the published safety literature concerns effects outside the immune system.

Formulations differ substantially. Systemic oral and intravenous products have been studied in transplantation and immune-mediated disease, while a water-free topical ophthalmic solution has been studied in dry eye disease. Adverse-event profiles reported in those settings are not interchangeable, and this page keeps them separate.

Evidence tier and how to read this page

Evidence tier: Established. Cyclosporine is a long-marketed, regulator-approved medicine with decades of randomised trials, registry data and post-marketing surveillance behind it. That places it in a different category from compounds studied only in early laboratory work. An "established" tier describes the maturity of the evidence base — it does not mean every reported adverse event applies to every person, every formulation or every dose, and it does not substitute for a prescriber's judgement.

Each claim below is attributed in the same sentence to the publication that reported it. Where a finding came from an animal or cell model, that is stated. PeptideU's separate cyclosporine learning module covers pharmacology and mechanism in more depth; this page stays focused on what the safety and tolerability literature reported.

Systemic Adverse Events in Clinical Use: What Studies Report

Pharmacovigilance signal mining

A 2024 real-world disproportionality analysis published in the Brazilian Journal of Medical and Biological Research mined the United States FDA Adverse Event Reporting System (FAERS) for reports naming cyclosporine and ranked adverse-event terms by disproportionality, an approach researchers use to flag potential associations for further study (PMID 39082578). Disproportionality methods identify statistical signals in spontaneously submitted reports; as that analysis is framed, such signals describe reporting patterns rather than confirmed causation, because reporting databases lack denominators and are subject to reporting bias.

Transplantation experience

A 2004 Transplantation Proceedings paper summarised accumulated clinical experience with cyclosporine in transplantation, the setting in which the drug's long-term use and monitoring requirements were first characterised (PMID 15041307). Transplant literature of this kind typically addresses the balance between graft outcomes and drug-related toxicity, which is why blood-level monitoring became standard practice with systemic cyclosporine regimens.

Kidney and haematologic findings in experimental models

A 2022 study in Kidney International reported that cyclosporine A administration in an experimental model was associated with anemia and peritubular capillary loss, and that the prolyl hydroxylase inhibitor daprodustat prevented both changes in that model (PMID 35643373). The researchers framed peritubular capillary rarefaction as a mechanism linking calcineurin-inhibitor exposure to chronic kidney injury. Findings from an experimental model do not automatically translate to people, but they illustrate why renal parameters feature prominently in cyclosporine monitoring literature.

Combination regimens in kidney disease

A 2025 randomised controlled trial in BMC Medicine evaluated the safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy, reporting both treatment outcomes and adverse events in the randomised population (PMID 40442735). Trials of this design are informative because adverse events are collected prospectively and compared between arms, rather than reported voluntarily after the fact.

Dermatology Use and Monitoring: What Studies Report

A 2020 practical compendium in Dermatologic Therapy reviewed cyclosporine in dermatology, covering the conditions in which it has been used and the safety monitoring that accompanies systemic courses (PMID 32602210). Reviews of this type consolidate scattered clinical reports into one reference; the authors of that compendium addressed practical management issues that arise when systemic cyclosporine is prescribed for skin disease, including the monitoring parameters clinicians track during treatment.

Rare and Case-Report Findings: What Studies Report

A 2023 report in Practical Neurology described cyclosporine-induced erythromelalgia — a painful condition characterised by redness, warmth and burning discomfort in the extremities — in a patient receiving the drug (PMID 37391230). Single case reports cannot establish incidence or causation; they document that a presentation occurred and was considered drug-related by the reporting clinicians, which is how uncommon reactions typically enter the literature before larger series confirm or refute them.

Topical Ophthalmic Cyclosporine Tolerability: What Studies Report

The ESSENCE-2 randomised clinical trial, published in JAMA Ophthalmology in 2023, assessed the efficacy and safety of a water-free topical cyclosporine 0.1% solution in moderate to severe dry eye disease and reported both effectiveness endpoints and treatment-emergent adverse events for the randomised participants (PMID 37022717). A 2024 open-label extension of that programme, published in Cornea, reported longer-term safety and efficacy data for the same water-free cyclosporine 0.1% ophthalmic solution (PMID 38771801).

Topical ocular exposure differs fundamentally from systemic dosing, and the tolerability questions researchers examined in the ESSENCE-2 programme concerned the ocular surface rather than the systemic organ toxicities studied in transplantation (PMID 38771801). Readers comparing sources should note which formulation a given publication studied before generalising any adverse-event list.

Drug Interactions and Combination Safety: What Studies Report

Cyclosporine is a substrate and inhibitor of transport and metabolic pathways that many co-administered drugs also use, so interaction studies form a distinct branch of its safety literature. A 2018 study in Clinical Pharmacology in Drug Development characterised the pharmacokinetics and safety of letermovir coadministered with cyclosporine A or tacrolimus in healthy subjects (PMID 28967706). A 2026 pharmacovigilance analysis in Transplantation and Cellular Therapy mined real-world data for safety signals associated with letermovir drug combinations, an approach the researchers used to surface combination-specific patterns that single-drug analyses can miss (PMID 41043774).

Preclinical combination work

A 2025 paper in the International Journal of Molecular Sciences reported that cannabidiol enhanced the therapeutic efficacy of olsalazine and cyclosporine in a murine model of colitis (PMID 40869234). That work was conducted in mice and addressed efficacy in an animal disease model; it does not describe human tolerability, and the study authors positioned it as mechanistic rather than clinical.

Summary of the cited literature

What this literature does not settle

• Incidence. Case reports such as the erythromelalgia description (PMID 37391230) document that an event occurred, not how often it occurs.
• Causation from databases. Disproportionality findings from FAERS reflect reporting patterns rather than established causal relationships (PMID 39082578).
• Species translation. Anemia and capillary loss observed in an experimental model (PMID 35643373) and efficacy signals in murine colitis (PMID 40869234) are preclinical results.
• Formulation transfer. Ocular tolerability data from the ESSENCE-2 programme (PMID 37022717) do not describe systemic exposure.

Regulatory and naming notes

Cyclosporine is the nonproprietary (generic) name of the molecule. Several branded oral, injectable and ophthalmic products contain cyclosporine; each brand name is a trademark of its owner, and PeptideU is not affiliated with or endorsed by any manufacturer, marketing authorisation holder or distributor of any cyclosporine product. Prescribing information, indications and contraindications are set by the relevant national regulator and by the approved product labelling, which supersedes any summary of individual studies.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medicine, symptom or treatment decision. Nothing here describes how cyclosporine should be prescribed, monitored, combined or discontinued, and no comparison of products is intended or implied.

References

• Cyclosporine-induced erythromelalgia (Practical Neurology, 2023)
• Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial (JAMA Ophthalmology, 2023)
• Experience with cyclosporine (Transplantation Proceedings, 2004)
• Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial (BMC Medicine, 2025)
• Modulation of calcineurin signaling during development (Developmental Neurobiology, 2022)
• Daprodustat prevents cyclosporine-A-mediated anemia and peritubular capillary loss (Kidney International, 2022)
• Long-Term Safety and Efficacy of a Water-Free Cyclosporine 0.1% Ophthalmic Solution for Treatment of Dry Eye Disease: ESSENCE-2 OLE (Cornea, 2024)
• Cyclosporin in dermatology: A practical compendium (Dermatologic Therapy, 2020)
• Cannabidiol Enhances the Therapeutic Efficacy of Olsalazine and Cyclosporine in a Murine Model of Colitis (International Journal of Molecular Sciences, 2025)
• A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database (Brazilian Journal of Medical and Biological Research, 2024)
• Mining Safety Signals of Letermovir Drug Combinations: Real-World Pharmacovigilance Analysis (Transplantation and Cellular Therapy, 2026)
• Pharmacokinetics and Safety of Letermovir Coadministered With Cyclosporine A or Tacrolimus in Healthy Subjects (Clinical Pharmacology in Drug Development, 2018)