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