What is cyclosporine (Cyclosporin, CsA)?

From the Guidelines

Cyclosporine A is a potent immunosuppressive agent used to reduce T-cell activity, widely used in organ transplantation and autoimmune disorders, with a usual starting dose of 3 to 6 mg/kg per day. The medication works by binding to the protein cyclophilin, and the complex inhibits calcineurin, a protein vital for T-cell activation 1. Key points about cyclosporine A include:

• It is a natural product, a cyclic peptide of 11 amino acids, initially identified in the fungus Tolypocladium inflatum 1.
• The response rate at 1 month ranges from 37.8% to 56.7%, with durable response rates ranging from 23.3% to 44% 1.
• Major adverse effects include gingival hyperplasia (6.6%), hypertension (11.6%), nephrotoxicity (6.7%), and nausea 1.
• It is not recommended for use during pregnancy or lactation 1.
• Dose adjustment is necessary, with monitoring of trough drug levels to avoid toxicity 1.
• The maximum dose is 200 mg for both adults and children 1. Overall, cyclosporine A is a valuable immunosuppressant therapy, but its use requires careful management due to its potential for significant side effects and interactions 1.

From the FDA Drug Label

Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung Cyclosporine has been demonstrated to suppress some humoral immunity and to a greater extent, cell-mediated immune reactions such as allograft rejection, delayed hypersensitivity, experimental allergic encephalomyelitis, Freund's adjuvant arthritis, and graft vs. host disease in many animal species for a variety of organs The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G0- and G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2

Cyclosporine is a potent immunosuppressive agent that suppresses humoral immunity and cell-mediated immune reactions. It works by inhibiting immunocompetent lymphocytes, specifically T-lymphocytes, and suppressing the production and release of lymphokines, including interleukin-2 2.

From the Research

Definition and Mechanism of Action

• Cyclosporine is an immunosuppressant used to prevent the rejection of transplanted kidneys, hearts, and livers 3.
• It suppresses T-lymphocyte function without causing myelosuppression 3, 4.
• Cyclosporine acts by blocking T-lymphocyte function, primarily through reversible inhibition of T-lymphocytes, without myelotoxicity 5.
• It inhibits primary activation of helper cells and decreases the production of lymphokines by these cells 5.

Clinical Efficacy and Usage

• Cyclosporine has contributed to the improved success of transplantation and the recognition of transplantation as a new therapeutic option for several diseases 3.
• It has been used in human renal, cardiac, liver, bone marrow, and pancreatic transplantation, as well as in other experimental animal models 5.
• The dosage of cyclosporine must be individualized based on the clinical status of the patient as well as blood concentrations of the drug 3, 4.
• Monitoring cyclosporine blood concentrations is necessary in the postoperative management of transplant patients 3.

Adverse Effects and Toxicity

• The adverse effects of cyclosporine include nephrotoxicity, hepatotoxicity, malignancies, hirsutism, and minor neurologic complications 3.
• Cyclosporine has a narrow therapeutic index, with major complications arising from nephrotoxicity, hypertension, and hepatotoxicity 5.
• The long-term survival of renal allografts is still less prevalent, and an in-depth analysis has led to the belief that there is a chronic irreversible component to the drug that causes toxicity 6.
• Strategies to avoid toxic side effects include gastrointestinal decontamination, supporting the airway, monitoring for signs of respiratory insufficiency, and avoiding the administration of drugs that increase the blood levels of cyclosporine 6.