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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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