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Neuromuscular

Tacrolimus

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.

  • Lymphopenia is amongst one of the most common adverse events, which usually does not lead to treatment discontinuation. Other side effects include renal insufficiency, neuropathy, hypomagnesemia, etc.

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 × 6 months, then less frequently

Developed and maintained by Abbas Jowkar, M.D
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