Mechanism of action:
Blinds FK506 binding protein (FKB), forming tacrolimus+FKB complex, which also binds to and blocks calcineurin.
It is a calcineurin inhibitor.
Cyclosporine and tacrolimus to bind to different target molecules. However T-cell inhibition occurs in the same manner.
Reduces inflammatory cytokine: IL-2
Uses:
Tacrolimus may be beneficial in myasthenia gravis patients who fail cyclosporine.
Myasthenia gravis as monotherapy or with thymectomy.
Dermatomyositis/polymyositis reportedly effective.
CIDP, vasculitic neuropathy.
Isaac syndrome and Lambert-Eaton myasthenia syndrome.
Treatment regimen:
Myasthenia gravis -0.1 mg/kg/day in 2 divided doses. Plasma concentration is adjusted between 7 to 8 mg/mL.
Adverse events:
Less nephrotoxic than cyclosporine. Hyperglycemia.
Sirolimus has less renal toxicity than tacrolimus or cyclosporine. However it has no apparent benefit in myasthenia gravis.
Initial: 0.1 mg/kg/d divided in 2 doses; can increase up to 5 mg/d following trough levels
1-3 mo
Nephrotoxicity, hypertension, electrolyte imbalance, diabetes, infection, hepatotoxicity, diarrhea, abdominal pain, tremor, teratogenicity
BP, BUN/Cr, glucose, potassium, trough level (aim 5-15 ng/mL) monthly Ă— 6 months, then less frequently