MOA: Cyclosporine binds to cyclophilin (immunophilin) to form cyclosporine+cyclophilin complex which binds and blocks the function of enzyme calcineurin resulting in T cell inhibition. T cell activation is thus inhibited and in turn the production of pro-inflammatory cytokine IL-2 is inhibited.

Uses:

• Effective in treatment of MG. Therapeutic latency: 1 - 3 months.

• In psoriasis, the time of onset is reported to be 6 weeks.

• It has steroid sparing effect in 95% of patients; able to reduce or discontinue their corticosteroid use.

• May be beneficial in systemic vasculitis, non-systemic vasculitic neuropathy, sarcoid neuropathy, LEMS, DM, PM. CIDP benefit is anecdotal. MMN benefit is suspect.

AE:

• 1/4 of patients develop renal toxicity. Monitor creatinine, trough levels of cyclosporine frequently.

• Patients may get calcineurin inhibition syndrome which includes prominent and debilitating tremor, needing dose reductions.

• MG patients who are refractory to prednisone and AZA may benefit from cyclosporine use.

Brand name drugs: Neoral and Sandimmune is preferable to generic counterparts.

Dose regimens:

• 3 - 4 mg/kg/day in 2 divided doses; increase to 6 mg/kg/day dose titrated to maintain serum cyclosporine levels of 100 - 200 ng/mL qmo.

• Check BP, electrolytes, renal function.

• Dose adjustment or lowering depending on creatinine level with aim to maintain trough levels in the therapeutic range.

• After maximal improvement, dose is lowered to minimum dose needed for therapeutic response.

• Avoid NSAIDs and elevation of serum K+ levels.

Cyclosporine

Dose: Initial: 100 mg twice daily, increase by 0.5 mg/kg/d every 4-8 wk as needed maintenance: 3-6 mg/kg/d split into 2 daily doses

Onset of Action: 1-3 mo

Adverse events: Nephrotoxicity, hypertension, infection, hepatoxicity, hirsutism, tremor, gum hyperplasia, malignancy, teratogenicity

Monitoring parameter: BP; monthly: CBC, BUN/Cr, LFTs, trough level (aim <300 ng/mL); consider skin cancer screening exam annually