Ciclosporin is a potent, lipophilic, cyclic undecapeptide immunosuppressant agent derived from the fungus Tolypocladium inflatum. It is a cornerstone drug in solid organ transplantation and autoimmune diseases. It acts primarily by selectively inhibiting T-lymphocyte activation and proliferation, thereby suppressing cell-mediated immunity. In the Indian context, it is widely used for renal, liver, and cardiac transplants, as well as for severe autoimmune conditions like psoriasis and rheumatoid arthritis, where conventional therapy has failed. It requires meticulous therapeutic drug monitoring (TDM) due to its narrow therapeutic index and significant inter- and intra-patient pharmacokinetic variability.
Adult: HIGHLY INDICATION-SPECIFIC AND MUST BE INDIVIDUALIZED. Initial doses: Transplant: 10-15 mg/kg/day orally, 1-2 days pre-transplant, then tapered. Rheumatoid Arthritis: 2.5-5 mg/kg/day in two divided doses. Psoriasis: 2.5-5 mg/kg/day in two divided doses. Dose adjustments are based on TDM and clinical response.
Note: Administer in two divided doses, 12 hours apart. Take consistently with respect to meals (either always with food or always on an empty stomach) to minimize variability. The microemulsion formulation (Neoral) is less affected by food. Swallow capsule whole with a full glass of water. Do not crush or chew. Grapefruit juice must be avoided.
Ciclosporin is a calcineurin inhibitor. It forms a complex with the intracellular immunophilin, cyclophilin. This drug-cyclophilin complex binds to and inhibits the calcium/calmodulin-dependent serine-threonine phosphatase, calcineurin. Inhibition of calcineurin prevents the dephosphorylation and subsequent nuclear translocation of the cytosolic component of the nuclear factor of activated T-cells (NF-AT). This blocks the transcription of early T-cell activation genes, including those for interleukin-2 (IL-2), interferon-gamma, and other cytokines.
Pregnancy: Pregnancy Category C (US FDA). Animal studies show fetotoxicity. Use only if potential benefit justifies potential fetal risk. Increased risk of prematurity and low birth weight. Register pregnant patients in a pregnancy registry.
Driving: May cause visual disturbances, dizziness, or tremors. Patients should be cautioned about driving or operating machinery until they know how the drug affects them.
| Ketoconazole, Fluconazole, Itraconazole, Voriconazole | Inhibit CYP3A4, markedly INCREASE ciclosporin levels (up to 5-fold). Risk of severe toxicity. | Major |
| Rifampicin, Rifabutin, Phenytoin, Carbamazepine, Phenobarbital | Induce CYP3A4, DECREASE ciclosporin levels significantly. Risk of graft rejection. | Major |
| NSAIDs (e.g., Diclofenac, Ibuprofen), Aminoglycosides, Amphotericin B | Additive nephrotoxicity. | Major |
| Potassium-sparing diuretics (Spironolactone), ACE Inhibitors (Ramipril) | Increased risk of hyperkalemia. | Moderate |
| Statins (Atorvastatin, Simvastatin) | Increased risk of myopathy/rhabdomyolysis. | Moderate |
| Digoxin | Increased digoxin levels (reduced renal clearance). | Moderate |
| Metoclopramide | May increase absorption of ciclosporin. | Moderate |
Same composition (Ciclosporin (100mg)), different brands: