Makindo Medical Notes

⚠️ Key toxicity: Ciclosporin commonly causes renal impairment and hypertension. Unlike many other immunosuppressants, it does not cause bone marrow suppression. Close monitoring of renal function, BP, and drug levels is essential.

📖 About

• Ciclosporin is an oral calcineurin inhibitor, a cyclic polypeptide of 11 amino acids, highly lipophilic.
• Originally derived from the fungus Tolypocladium inflatum.
• One of the landmark drugs enabling successful solid organ transplantation.
• Always check the BNF for up-to-date prescribing guidance.

⚙️ Mode of Action

• Ciclosporin binds to cyclophilin in T lymphocytes.
• This complex inhibits calcineurin, preventing dephosphorylation of NFAT (nuclear factor of activated T cells).
• ↓ IL-2 transcription → ↓ T-cell activation and proliferation.
• Suppresses cell-mediated immunity; has little effect on acute inflammation.
• No direct bone marrow suppression.

🩺 Indications (BNF/UK practice)

• Transplant medicine: Prevention of rejection after renal, hepatic, and cardiac transplantation.
• Graft-versus-host disease: Following bone marrow transplantation.
• Autoimmune/inflammatory disease:
  • Severe psoriasis
  • Atopic dermatitis (short-term use)
  • Nephrotic syndrome (steroid-resistant)
  • Rheumatoid arthritis (specialist use)
  • Uveitis (sight-threatening)
  • Inflammatory bowel disease (specialist-directed)

🚫 Contraindications

• Concomitant use with tacrolimus (↑ risk of nephrotoxicity).
• Uncontrolled hypertension.
• Significant renal impairment (unless being treated for nephrotic syndrome).
• Uncontrolled infections or known malignancy (due to immunosuppressive risk).

⚠️ Side Effects

• Renal toxicity (dose-dependent, early functional and later structural injury).
• Hypertension.
• Neurotoxicity: tremor, seizures (especially if IV, low magnesium, or low cholesterol).
• Cosmetic: hirsutism, gum hypertrophy.
• GI disturbance: nausea, diarrhoea.
• Hepatotoxicity.
• Dyslipidaemia, hyperuricaemia.
• ↑ Malignancy risk (esp. lymphoproliferative disorders, skin cancers).
• ↑ Opportunistic infection risk.

🧪 Monitoring

• Baseline: FBC, U&E, LFTs, lipids, uric acid, magnesium, BP, weight.
• After initiation: FBC, U&E/creatinine, LFTs, BP, and drug levels every 2 weeks for 3 months, then monthly if stable.
• Long-term: monitor renal function, BP, and lipids regularly; annual skin check for malignancy.
• Measure trough ciclosporin levels (therapeutic drug monitoring essential in transplants).

🔄 Interactions

• ↑ Ciclosporin levels: macrolides (erythromycin, clarithromycin), azole antifungals (ketoconazole, itraconazole, fluconazole >200 mg/day), diltiazem, verapamil, amiodarone, protease inhibitors, grapefruit juice.
• ↓ Ciclosporin levels: rifampicin, carbamazepine, phenytoin, phenobarbital, griseofulvin, primidone.
• ↑ Nephrotoxicity when combined with: aminoglycosides, NSAIDs, amphotericin, trimethoprim.

💊 Dose (BNF ranges – check indication)

📚 References

• BNF: Ciclosporin
• Summary of Product Characteristics