Cyclosporine

Summary

Cyclosporine is a cyclic peptide immunosuppressant derived from the fungus Tolypocladium inflatum. It is widely used to prevent organ transplant rejection and to treat autoimmune conditions such as rheumatoid arthritis, psoriasis, and nephrotic syndrome. It selectively inhibits T-lymphocyte activity without broadly suppressing bone marrow function.

Mechanism of Action

Binds cyclophilin in T-lymphocytes, forming a complex that inhibits calcineurin, thereby blocking the transcription of interleukin-2 (IL-2) and other cytokines, suppressing T-cell activation and proliferation

Routes of Administration

Goals & Uses

• Dry eye diseaseOphthalmologyHigh
• Plaque psoriasisDermatologyHigh
• Nephrotic syndromeNephrologyModerate
• Rheumatoid arthritisAutoimmune DiseaseHigh
• Prevention of solid organ transplant rejectionImmunosuppressionHigh
• Atopic dermatitisDermatologyModerate

Contraindications

• Concurrent use of potassium-sparing diureticsDrug InteractionModerate
• Live vaccinesVaccinationModerate
• Active malignancy or history of malignancy (for non-transplant use)OncologyHigh
• Renal impairment (for non-transplant indications)RenalHigh
• Hypersensitivity to cyclosporine or polyoxyethylated castor oil (IV formulation)AllergyHigh
• Uncontrolled hypertensionCardiovascularHigh

Adverse Effects

• HypertensionCardiovascularCommonHigh blood pressure
• HirsutismDermatologicCommon
• Gingival hyperplasiaOralCommon
• Neurotoxicity (tremor, headache, paresthesia)NeurologicalCommon
• Increased risk of infection and malignancyImmunologicCommon
• NephrotoxicityRenalCommon

Drug Interactions

• CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's Wort)High
• CYP3A4 inhibitors (e.g., ketoconazole, diltiazem, erythromycin)High
• Potassium-sparing diuretics / ACE inhibitors / ARBsModerate
• Statins (HMG-CoA reductase inhibitors)High
• NSAIDsModerateMay increase renal risk in susceptible patients
• MethotrexateModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Elderly patientsAgeRelative
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Organ transplant rejection prophylaxis, Bone marrow transplantation, Severe autoimmune diseases (psoriasis, RA, atopic dermatitis, nephrotic syndrome), Dry eye disease (ophthalmic)Approved across EU member states; atopic dermatitis is an approved indication in many EU countries unlike the US
• United StatesApprovedApproved: Prophylaxis of organ rejection in kidney, liver, and heart transplants, Rheumatoid arthritis (moderate to severe), Plaque psoriasis (severe, recalcitrant), Dry eye disease (ophthalmic emulsion)Multiple formulations approved (Sandimmune, Neoral/Gengraf microemulsion, Restasis ophthalmic); not bioequivalent between oil and microemulsion formulations
• United KingdomApprovedApproved: Organ and bone marrow transplantation, Severe psoriasis, Atopic dermatitis, Rheumatoid arthritis, Nephrotic syndromeMHRA-approved; therapeutic drug monitoring guidelines provided by NHS; generic formulations available

FDA-approved for prevention of organ rejection (kidney, liver, heart), rheumatoid arthritis, and plaque psoriasis. Also approved as an ophthalmic emulsion (Restasis) for dry eye disease. Multiple generic formulations exist. Neoral (microemulsion) and Sandimmune (oil-based) are NOT bioequivalent and require separate therapeutic drug monitoring.

Evidence & Sources

No sources recorded yet.