Cyclosporin A

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Cyclosporin A


Class

  • immunosuppressant
  • cyclic hydrophobic decapeptide

Uses

  • Immunosuppression for solid organ transplantation
  • Refractory psoriasis

Route and dosage

  • A high dose is given 4-12h before transplantation
  • Safer to start 14mg/kg/day orally reducing over 3 months to a maintenance dose of 6mg/kg/day
  • In graft-vs.-host disease and bone marrow transplantation iv treatment 3-5mg/kg/day used initially, followed by oral administration for 6-9 months

Mechanism of action

  • T-lymphocyte suppresser, primarily acting on T-helper cells
  • Inhibits transcription of IL-2 production and pro-inflammatory cytokines by T-lymphocytes

Adverse effects

  • Nephrotoxicity
  • Nausea and GI disturbances
  • Hyperkalaemia
  • Hepatotoxicity
  • Hypertension
  • Hirsuitism
  • Gingival hypertrophy
  • Tremor
  • Anaphylaxis
  • Malignancy (Lymphoma)

Pharmacokinetics

  • Given orally/iv shows variable absorption and hepatic metabolism (cytochrome P4503A4) to many inactive metabolites
  • Bioavailability is 30%.
  • Peak plasma concentration occur within 1-4h
  • Renal dysfunction does not affect its clearance but beware of nephrotoxicity, hence monitor serum urea and cretonne clearance.
  • Reduce dose in patients with hepatic impairment.

Therapeutic Drug monitoring

  • Assayed by radioimmunoassay
  • Trough plasma concentration of 100-300 ug/L if iv infusion
  • Effective immunosuppression at 60-300 ug/L if orally given
  • Monitor plasma concentration in all, especially
    • in GI disturbances,
    • hepatic impairment
    • if patient is receiving nephrotoxic drugs

Drug interactions

  • Many,
  • include Azoles
  • macrolides
  • and Calcium channel blockers (dilitiazem),
  • Anabolic steroids.
 

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