Cyclosporine (CsA)| | | | | | Calcineurin: a phosphatase activated in the presence of calmodulin and calcium by cyclophilin | | | | | |
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- Inhibits T-cell activity by binding to cyclophilin, which subsequently blocks cyclophilin’s ability to activate calcineurin; calcineurin regulates NFAT and IL-12, which results in overall inability to produce/release IL-12
- Treatment for psoriasis, pyoderma gangrenosum, severe atopic dermatitis, autoimmune bullous disorders
- SE: nephrotoxicity, reversible hypertension (HTN), gingival hyperplasia, hyperlipidema, ↑ K and ↓ Mg, ↑ uric acid, paresthesias, hypertrichosis, lymphoma
- Metabolized by cytochrome p450 3A4: inhibitors of cytochrome cause ↑ CsA levels (i.e., diltiazem, nicardipine, verapamil, ketoconazole, fluconazole, itraconazole, erythromycin); inducers of p450 enzymes result in ↓ CsA levels (rifampin, phenobarbital, phenytoin, carbamazepine)
- Check BP regularly; if renal creatinine above 30% of baseline, dose should be reduced
- ↑ Risk for renal toxicity: aminoglycosides, NSAIDs, amphotericin B and vancomycin
- Pregnancy category C
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