💊 Ciclosporin

Ciclosporin is a calcineurin inhibitor, classified as an immunosuppressant. It is a cyclic polypeptide.

Ciclosporin binds to cyclophilin, forming a complex that inhibits calcineurin. Calcineurin is essential for the activation of nuclear factor of activated T-cells (NFAT), which in turn is crucial for the transcription of interleukin-2 (IL-2) and other pro-inflammatory cytokines, thereby suppressing T-cell activation.

In the UK, its primary use is for the prophylaxis of organ transplant rejection (kidney, liver, heart, lung). It is also indicated for severe, active rheumatoid arthritis, severe psoriasis, severe atopic dermatitis, and nephrotic syndrome.

Absolute contraindications include hypersensitivity to ciclosporin. It is generally contraindicated in uncontrolled hypertension, uncontrolled infections, and malignancy. Caution is required in patients with renal impairment, hyperkalaemia, or gout.

Common and dose-dependent side effects include nephrotoxicity, hypertension, hirsutism, gingival hyperplasia, and tremor. Other serious effects include increased risk of infections, malignancy (especially skin cancers and lymphoproliferative disorders), hepatotoxicity, and hyperkalaemia.

Regular monitoring of ciclosporin blood trough levels is essential to ensure therapeutic efficacy and minimise toxicity. Renal function (U&Es), blood pressure, liver function tests (LFTs), and potassium levels must be closely monitored.

Always check for drug interactions, especially with CYP3A4 inhibitors/inducers which can significantly alter ciclosporin levels. Counsel patients on the importance of adherence, regular blood tests, and reporting any signs of infection. Advise on sun protection.

A potent immunosuppressant, remember its mechanism via calcineurin inhibition. High yield for its narrow therapeutic index, requiring TDM, and its significant nephrotoxicity and hypertension. Often used in combination with other immunosuppressants in transplant.

SBAs frequently test the key adverse effects, particularly nephrotoxicity and hypertension, and the need for therapeutic drug monitoring (TDM) of blood levels. Questions may also focus on its role in transplant medicine and the increased risk of infection and malignancy.