Section 07 · Monograph

Cyclosporine

Reviewed Nov 2026FDA label

Neoral / SandimmuneCalcineurin inhibitor

Black Box Warning

Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe cyclosporine
Increased susceptibility to infection and possible development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression
Can cause nephrotoxicity; risk increases with higher doses/prolonged use and requires frequent monitoring of renal function
Sandimmune and Neoral (and generic formulations) are NOT bioequivalent and cannot be used interchangeably without medical supervision
Increased risk of infection and lymphoma when used with other immunosuppressive agents; combination with PUVA, UVB, methotrexate, coal tar, or radiation therapy increases malignancy risk

Prophylaxis of organ rejection in kidney, liver, and heart transplantation, used with corticosteroidsFDA-labeled
Treatment of chronic rejection in patients previously treated with other immunosuppressive agentsFDA-labeled
Severe active rheumatoid arthritis (Neoral, in patients who have not responded to methotrexate)FDA-labeled
Severe recalcitrant plaque psoriasis (Neoral, in non-immunocompromised adults who failed other systemic therapy)FDA-labeled

Steroid-sparing immunosuppressant for myasthenia gravis, typically reserved for patients who fail or cannot tolerate other agents given nephrotoxicity burden; typical MG dosing 3-6 mg/kg/day divided twice daily, titrated to trough levels and renal toleranceOff-label
MG benefit may occur within 1-2 months, faster than mycophenolate or azathioprine, but nephrotoxicity/hypertension often limit long-term useOff-label

Calcineurin inhibitor that binds to the intracellular protein cyclophilin
The cyclosporine-cyclophilin complex inhibits calcineurin, a calcium/calmodulin-dependent phosphatase
Calcineurin inhibition prevents dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells)
Blocks transcription of IL-2 and other cytokine genes, producing specific and reversible inhibition of T lymphocytes in the G0/G1 phase
Reduces both cell-mediated and antibody-mediated (T-cell-dependent) immune responses relevant to MG autoantibody production

Transplant (Sandimmune, initial): 15 mg/kg PO given 4-12 hours before transplant, continued 1-2 weeks postoperatively, then tapered ~5%/week to maintenance of 5-10 mg/kg/day
Neoral (modified microemulsion) has higher, more consistent bioavailability than Sandimmune — not interchangeable mg-per-mg without monitoring
Rheumatoid arthritis (Neoral): initiate 2.5 mg/kg/day divided twice daily; may increase to max 4 mg/kg/day
Psoriasis (Neoral): initiate 2.5 mg/kg/day divided twice daily; may increase to max 4 mg/kg/day; discontinue if no response by 6 weeks at max dose
MG off-label: commonly 3-6 mg/kg/day divided twice daily; lower target range than transplant to balance efficacy against nephrotoxicity

Dose must be individualized and adjusted based on trough blood concentrations, renal function, and clinical response

Hypersensitivity to cyclosporine or to any component of the formulation
Hypersensitivity to polyoxyethylated castor oil (relevant to injectable formulation)
Concomitant use with live vaccines should be avoided
Psoriasis/RA indication: abnormal renal function, uncontrolled hypertension, or malignancy are contraindications for Neoral in these populations

CYP3A4 inhibitors (azole antifungals, macrolides, diltiazem, verapamil, protease inhibitors, grapefruit juice) increase cyclosporine levels — risk of nephrotoxicity
CYP3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) decrease cyclosporine levels — risk of rejection/loss of efficacy
Increases levels of statins (risk of myopathy/rhabdomyolysis), digoxin, colchicine, repaglinide, and dabigatran
Nephrotoxic drugs increase risk of additive renal toxicity
Potassium-sparing diuretics/ACE inhibitors/ARBs increase risk of hyperkalemia
Grapefruit and grapefruit juice increase cyclosporine blood levels and should be avoided

Nephrotoxicity — very common, dose-related
Hypertension — occurs in roughly half of transplant patients
Tremor, headache, paresthesias
Hirsutism and gingival hyperplasia
Hyperlipidemia, hyperkalemia, hyperuricemia/gout, hypomagnesemia
Increased risk of infection and malignancy due to immunosuppression
Hepatotoxicity
Posterior reversible encephalopathy syndrome (PRES) and other neurotoxicity, including seizures
Thrombotic microangiopathy/hemolytic-uremic syndrome (rare but serious)

Cyclosporine whole-blood trough concentration regularly
Renal function: serum creatinine and BUN frequently, especially during dose titration
Blood pressure at every visit
Liver function tests periodically
Serum potassium, magnesium, uric acid, and lipid panel periodically
CBC and surveillance for infection
Periodic skin examinations for malignancy given prolonged immunosuppression

Pregnancy registry data have not shown increased major birth defects, but adverse maternal/fetal outcomes (hypertension, preeclampsia, preterm birth, low birth weight) occur more frequently in cyclosporine-treated pregnancies
Animal studies show embryo-fetal toxicity at maternally toxic doses
Use during pregnancy only if potential benefit justifies potential risk; close obstetric monitoring recommended
Present in human breast milk
Decision should be made whether to discontinue breastfeeding or the drug, considering importance of the drug to the mother