Cyclosporine
Also known as: CsA, Cyclosporin A, Gengraf, Neoral, Restasis, Sandimmun, Sandimmune
Source Cyclosporine at Peptiology
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Summary
Cyclosporine is a cyclic non‑ribosomal peptide that acts as a calcineurin inhibitor. It is an approved prescription drug given orally, intravenously, ophthalmically, or topically. Clinically it prevents organ‑allograft rejection and treats immune‑mediated kidney disease, severe ulcerative colitis, atopic dermatitis and certain dermatologic conditions. Its immunosuppressive properties stem from inhibition of T‑cell activation, making it a cornerstone in transplantation and a therapeutic option for refractory inflammatory disorders.
Mechanism of Action
Cyclosporine binds intracellular cyclophilin A, forming a complex that blocks calcineurin phosphatase activity. Calcineurin normally dephosphorylates NF‑AT, permitting NF‑AT to enter the nucleus and drive transcription of interleukin‑2 and other cytokines essential for T‑cell proliferation. By preventing NF‑AT activation, cyclosporine reduces IL‑2 production, dampening helper T‑cell activation and downstream immune responses, which underlies its efficacy in graft protection and autoimmune inflammation.
What the Research Shows
Randomised trials in renal transplantation (ELITE‑Symphony, 1645 patients) compared low‑dose cyclosporine with standard‑dose and with low‑dose tacrolimus; graft survival with low‑dose cyclosporine was comparable to tacrolimus, though tacrolimus yielded higher GFR. In membranous nephropathy, a phase‑III trial (130 patients) showed oral cyclosporine achieved complete or partial remission in 52 % at 12 months, meeting non‑inferiority to rituximab, but remission fell to 20 % by 24 months. A 2025 meta‑analysis of acute severe ulcerative colitis found infliximab superior to cyclosporine for colectomy avoidance, yet cyclosporine remained an effective non‑biologic option. Systematic reviews of atopic dermatitis and of psoriasis/urticaria placed cyclosporine among agents with moderate efficacy but lower certainty compared with newer biologics and JAK inhibitors. Across studies, cyclosporine’s benefits are balanced by notable adverse‑event rates.
Reported Benefits
Cyclosporine provides reliable immunosuppression for organ‑transplant recipients, preserving graft function with acceptable survival rates. In membranous nephropathy it can induce remission of proteinuria in about half of patients within a year. For acute severe ulcerative colitis, it offers a non‑biologic intravenous option that can avert early colectomy. Dermatologic reviews cite it as an effective oral agent for refractory atopic dermatitis and certain forms of psoriasis when other therapies fail. Its multiple routes allow use in ocular surface disease and topical inflammation.
Limitations of the Evidence
Evidence for cyclosporine is often limited to short‑term trials; long‑term remission after discontinuation is uncommon, especially in membranous nephropathy where rates dropped by 24 months. Comparative trials frequently favour newer agents such as tacrolimus, infliximab, or JAK inhibitors, leaving cyclosporine’s relative efficacy uncertain. Many systematic reviews rate its benefit as low‑certainty due to heterogeneous study designs and small sample sizes. Renal toxicity and drug‑interaction potential restrict dose escalation. Consequently, cyclosporine is generally reserved for patients who cannot access or tolerate newer therapies.
Safety Considerations
Cyclosporine is associated with nephrotoxicity, hypertension, hyperlipidaemia, gingival hyperplasia, hirsutism and increased infection risk. In the membranous nephropathy trial, serious adverse events occurred in 31 % of cyclosporine‑treated patients versus 17 % with rituximab. Renal transplant studies reported similar overall adverse‑event rates across regimens, but monitoring of serum creatinine and drug levels is essential. Drug interactions via CYP3A4 can amplify toxicity. Patients should be screened for baseline renal function, blood pressure and lipid profile, and monitored regularly during therapy.
How It Is Administered
Cyclosporine is formulated for oral capsules, intravenous infusion, ophthalmic eye‑drops (e.g., Restasis) and topical ointments (e.g., Sandimmune). Systemic use (oral or IV) requires individualized dosing and therapeutic drug monitoring to maintain target trough concentrations. Ophthalmic and topical preparations are applied directly to the eye or skin as directed. Choice of route depends on the clinical indication and patient tolerance.
Routes of Administration
Goals & Uses
- Dry eye diseaseOphthalmologyHigh
- Plaque psoriasisDermatologyHigh
- Dry eye disease (topical)OphthalmologyHigh
- Nephrotic syndromeNephrologyModerate
- Rheumatoid arthritisAutoimmune DiseaseModerate
- Severe plaque psoriasisDermatologyModerate
- Organ transplant prophylaxisImmunosuppressionHigh
- Prevention of solid organ transplant rejectionImmunosuppressionHigh
- Atopic dermatitisDermatologyModerate
Contraindications
- Concurrent use of potassium-sparing diureticsDrug InteractionModerate
- Hypersensitivity to cyclosporineAllergyHigh
- Live vaccinesVaccinationModerate
- Active malignancy or history of malignancy (for non-transplant use)OncologyHigh
- Renal impairment (for non-transplant indications)RenalHigh
- Severe renal impairment (CrCl <30 mL/min)RenalHigh
- Hypersensitivity to cyclosporine or polyoxyethylated castor oil (IV formulation)AllergyHigh
- Uncontrolled hypertensionCardiovascularModerate
Adverse Effects
- HypertensionCardiovascularCommonHigh blood pressure
- HirsutismDermatologicCommon
- TremorNeurologicCommonInvoluntary shaking
- Increased infection riskImmunologicCommon
- Gingival hyperplasiaOralCommon
- Neurotoxicity (tremor, headache, paresthesia)NeurologicalCommon
- Increased risk of infection and malignancyImmunologicCommon
- NephrotoxicityRenalCommon
- HyperlipidemiaMetabolicCommon
Drug Interactions
- RifampinModerate
- CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's Wort)High
- CYP3A4 inhibitors (e.g., ketoconazole, diltiazem, erythromycin)High
- KetoconazoleHigh
- Potassium-sparing diuretics / ACE inhibitors / ARBsModerate
- Statins (HMG-CoA reductase inhibitors)High
- AzithromycinModerate
- NSAIDsModerateMay increase renal risk in susceptible patients
- MethotrexateModerate
- TacrolimusHigh
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- ElderlyAgeRelative
- Patients with hepatic impairmentOrgan FunctionRelative
- Elderly patientsAgeRelative
- BreastfeedingReproductiveRelative
Regulatory Status
- European UnionApprovedApproved: organ transplantation prophylaxis, psoriasis, rheumatoid arthritis, dry eye diseaseApproved under EMA with similar indications
- United StatesApprovedApproved: organ transplantation prophylaxis, psoriasis, rheumatoid arthritis, dry eye diseaseMultiple formulations (oral, IV, ophthalmic)
- United KingdomApprovedApproved: organ transplantation prophylaxis, psoriasis, rheumatoid arthritis, dry eye diseaseRegulated by MHRA
Requires therapeutic drug monitoring due to narrow therapeutic index; contraindicated in uncontrolled hypertension and severe renal impairment.
Evidence & Sources
- Journal ArticleModerateEkberg H, et al.2007-01-01T00:00:00.000000Z
- Journal ArticleModerateFervenza FC, et al.2019-01-01T00:00:00.000000Z
- Journal ArticleHighVuyyuru SK, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleHighChu AWL, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleHighSpencer RK, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleHighChu AWL, et al.2025-01-01T00:00:00.000000Z
Frequently Asked Questions
How does cyclosporine differ from tacrolimus?
Both inhibit calcineurin, but cyclosporine binds cyclophilin while tacrolimus binds FKBP‑12. Clinical trials suggest tacrolimus may provide higher glomerular filtration rates in transplant patients, although both achieve comparable graft‑survival rates.
Is cyclosporine curative for membranous nephropathy?
It can induce remission in about half of patients within a year, but remission often declines after treatment stops, and long‑term cure has not been demonstrated.
What monitoring is required during systemic therapy?
Regular measurement of serum creatinine, blood pressure, lipid profile, and cyclosporine trough levels is recommended to detect nephrotoxicity, hypertension and drug interactions, allowing dose adjustments as needed.
Can cyclosporine be used long‑term for skin disease?
It is effective for refractory atopic dermatitis and psoriasis, but long‑term systemic use is limited by toxicity. Clinicians often limit duration or transition to newer agents when possible.
What is Cyclosporine?
Cyclosporine is a cyclic non‑ribosomal peptide that acts as a calcineurin inhibitor. It is an approved prescription drug given orally, intravenously, ophthalmically, or topically. Clinically it prevents organ‑allograft rejection and treats immune‑mediated kidney disease, severe ulcerative colitis, atopic dermatitis and certain dermatologic conditions. Its immunosuppressive properties stem from inhibition of T‑cell activation, making it a cornerstone in transplantation and a therapeutic option for refractory inflammatory disorders.
What is Cyclosporine used for?
Cyclosporine is educationally associated with: Dry eye disease, Plaque psoriasis, Dry eye disease (topical), Nephrotic syndrome, Rheumatoid arthritis, Severe plaque psoriasis, Organ transplant prophylaxis, Prevention of solid organ transplant rejection, Atopic dermatitis. Educational only — not medical advice.
How is Cyclosporine administered?
Recorded routes of administration: Intravenous, Ophthalmic, Oral, Topical.
What are the potential side effects of Cyclosporine?
Reported adverse effects include: Hypertension, Hirsutism, Tremor, Increased infection risk, Gingival hyperplasia, Neurotoxicity (tremor, headache, paresthesia), Increased risk of infection and malignancy, Nephrotoxicity, Hyperlipidemia. This list is not exhaustive — consult a qualified clinician.
Who should avoid Cyclosporine?
Recorded contraindications: Concurrent use of potassium-sparing diuretics, Hypersensitivity to cyclosporine, Live vaccines, Active malignancy or history of malignancy (for non-transplant use), Renal impairment (for non-transplant indications), Severe renal impairment (CrCl <30 mL/min), Hypersensitivity to cyclosporine or polyoxyethylated castor oil (IV formulation), Uncontrolled hypertension. Consult a qualified clinician before use.