Cyclosporin

1. CYCLOSPORIN
Class: Immunosuppressants
Mechanism of Action:
It complexes with cyclophilin to inhibit
calcineurin which normally activates the
transcription of interleukin-2 (IL-2).
DOSE AND DOSAGE FORM
Solid Organ Transplantation- oral 4-12 hr pre-
transplant: 15 mg/kg PO for 1 dose
Rheumatoid Arthritis -1.25 mg/kg PO BID; may
increase by 0.5-0.75 mg/kg/day after 8 weeks and
again after 12 wk if needed, not to exceed 4
mg/kg/day
Psoriasis -1.25 mg/kg PO BID.
PHARMACOKINETICS
Absorption: Bioavailability: Neoral >Sandimmune,Peak plasma time: Neoral 1.5-2 hr;
Sandimmune 3.5 hr
Distribution: Protein Bound: 90%,Vd: 13 L/kg
Metabolism: via hepatic CYP3A4,Metabolites: AM1, AM9, AM4N,Enzymes inhibited:
CYP3A4 and P-gp.
Excretion: Half-Life: 8.4-27 hr,Clearance: 5-7 mL/min/kg, Mainly bile and feces; 6%
urine.
MONITORING PARAMETERS
Patient BUN/SCr, Mg++, and blood pressure require
monitoring while on therapy. Uric acid monitoring
is debatable.
Therapeutic monitoring of cyclosporine in
transplant patients is a valuable tool in adjusting
drug dosage to prevent acute rejection,
nephrotoxicity, and predictable dose-dependent
adverse reactions.
INDICATIONS (FDA & Non-FDA)
FDA approved indications include: In solid
organ transplantation, it has clinical use for the
treatment of organ rejection in kidney, liver,
and rheumatoid arthritis,psoriasis.
Non-FDA approved indications include:Allergic
conjunctivitis, ocular graft vs. host disease and
Duchenne muscular dystrophy.
.
MAJOR SIDE EFFECTS
Hirsutism (21%),Hypertrichosis (5-19%),Female reproductive disorder (5-19%)
Gum hyperplasia (2-16%),Triglycerides increased (15%).
MAJOR DRUG INTERACTIONS
 Amphotericin B deoxycholate-
Amphotericin B deoxycholate and
cyclosporine both increase nephrotoxicity
and/or ototoxicity. Contraindicated.
 Atorvastatin-cyclosporine increases
toxicity of atorvastatin by Other
(bosentan.
VVVVVVII
CONTRAINDICATIONS
BCG,Attenuated vaccine,Hypersensitivity to
cyclosporine or any of the ingredients of the
formulation (such as polyoxyethylated castor
oil),Patients with impaired renal
function,Asthma and History of blood
dyscrasias.
- CHAITHANYA K.J