Ciclosporin (Cyclosporine A)

Overview

Genuinely a peptide — a cyclic eleven-residue peptide made by a soil fungus — and arguably the most consequential one in medicine. It made organ transplantation routine. Its ophthalmic form is the reason chronic dry eye became a treatable inflammatory disease rather than something you managed with drops.

How it works

Binds cyclophilin; the complex inhibits calcineurin, blocking dephosphorylation of NFAT and preventing transcription of IL-2 and other cytokines required for T-cell activation. On the ocular surface this interrupts the self-sustaining inflammatory cycle that damages lacrimal tissue.

Evidence base

Rated 5 of 5 — Very strong. Multiple phase 3 randomized trials plus regulatory approval in a major market.

• One of the most thoroughly studied drugs in medicine, across transplantation, rheumatology, dermatology and ophthalmology.
• Ophthalmic and systemic risk profiles are almost entirely separate — do not transfer one to the other.

Benefits & potential uses

Bars indicate how well each claim is supported: three = strong human evidence, two = moderate, one = preliminary or preclinical.

• Treats the cause of dry eye, not just symptoms Strong evidence

  Randomized trials showed increased tear production by Schirmer testing — restored function rather than lubrication alone.

• Made modern transplantation possible Strong evidence

  Systemic ciclosporin transformed graft survival rates and is among the most consequential drugs of the twentieth century.

• Negligible systemic exposure ophthalmically Strong evidence

  Blood levels after topical ocular use are generally undetectable, so systemic toxicities do not apply.

• Steroid-sparing on the ocular surface Strong evidence

  Avoids the cataract and intraocular pressure risks of long-term topical steroids.

• Effective in several autoimmune diseases Strong evidence

  Systemic use has randomized evidence in severe psoriasis, rheumatoid arthritis and nephrotic syndrome.

Risks, cons & cautions

Bars indicate seriousness: three = serious or common, two = moderate, one = minor.

• Systemic use is nephrotoxic Serious

  Dose-related and often progressive renal impairment is the principal limitation of oral ciclosporin, requiring level monitoring throughout.

• Systemic use raises malignancy and infection risk Serious

  Sustained T-cell suppression increases lymphoma, skin cancer and opportunistic infection risk. None of this applies to eye drops.

• Ocular burning on instillation Moderate evidence

  The most common complaint with the emulsion and a frequent reason for stopping.

• Slow onset ophthalmically Moderate evidence

  Benefit typically takes 3–6 months, and many patients abandon treatment before it appears.

• Systemic hypertension and gum hyperplasia Moderate evidence

  Common with oral therapy; irrelevant to ophthalmic use.

• Extensive systemic drug interactions Serious

  A CYP3A4 substrate with a long and clinically important interaction list.

Who should avoid it

• Ocular infection — do not use the emulsion during active infection
• Systemic use: uncontrolled hypertension, significant renal impairment, active malignancy
• Contact lenses should be removed before instillation and reinserted after 15 minutes

If used under medical supervision, monitor

• Ophthalmic: symptom and Schirmer response at 3–6 months
• Systemic: trough levels, serum creatinine, blood pressure, potassium, lipids
• Systemic: skin surveillance for malignancy

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

• Systemic: CYP3A4 inhibitors (ketoconazole, macrolides, grapefruit) raise levels sharply
• Systemic: CYP3A4 inducers (rifampicin, phenytoin, St John's wort) cause graft-threatening drops
• Systemic: statins — increased rhabdomyolysis risk
• Systemic: NSAIDs and aminoglycosides — additive nephrotoxicity
• Ophthalmic: minimal, given negligible absorption

Regulatory & legal status

Prescription drug in both ophthalmic and systemic forms.

Infographic

Ciclosporin (Cyclosporine A) — benefits & risks at a glance Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

• PubMed — all published literature on Ciclosporin (Cyclosporine A)
• PubMed — randomized controlled trials only
• ClinicalTrials.gov — registered human trials
• DailyMed — official FDA prescribing information

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