Cyclosporine

CYCLOSPORINE

Mechanism of Action

Cyclosporine is a peptide antibiotic but is considered a nonbiologic DMARD. Through regulation of gene transcription, it inhibits interleukin-1 and interleukin-2 receptor production and second-arily inhibits macrophage–T-cell interaction and T-cell responsive-ness . T-cell-dependent B-cell function is also affected.

Pharmacokinetics

Cyclosporine absorption is incomplete and somewhat erratic, although a microemulsion formulation improves its consistency and provides 20–30% bioavailability. Grapefruit juice increases cyclosporine bioavailability by as much as 62%. Cyclosporine is metabolized by CYP3A and consequently is subject to a large number of drug interactions.

Indications

Cyclosporine is approved for use in rheumatoid arthritis and retards the appearance of new bony erosions. Its usual dosage is 3–5 mg/kg/d divided into two doses. Anecdotal reports suggest that it may be useful in systemic lupus erythematosus, polymyosi-tis and dermatomyositis, Wegener’s granulomatosis, and juvenile chronic arthritis.

Adverse Effects

Leukopenia, thrombocytopenia, and to a lesser extent, anemia, are predictable. High doses can be cardiotoxic and sterilty may occur after chronic dosing at anti-rheumatic doses, especially in women. Bladder cancer is very rare but must be looked for, even 5 years after cessation of use.