Transplant Immunosuppressants - Common Side Effects

Transplant Immunosuppressants
1.  Calcineurin Inhibitors (Tacrolimus, aka Prograf, and Cyclosporine)  – bind to intracellular recepts and inactivate calcineurin, which inhibits IL-2 production and ultimately blocks T-cell synthesis. 
Side effects:

• Renal toxicity – both acute and chronic.  Acutely, due to dose-related vasoconstriction, and also associated with multiple electrolyte abnormalities (hyperkalemia, hypermagnesemia, etc).  Chronically, due to tubular atrophy, endothelial damage, glomerular ischemia, interstitial fibrosis, and long-term HTN and diabetes.  Chronic calcineurin inhibitor use is a major contributor to chronic kidney disease in these patients.
• Neuro-toxicity – tremor, headache, seizures, paresthesias, and PRES.
• Hypertension 
• Metabolic effects – Diabetes, Obesity.
• Cyclosporine also tends to cause hirsutism and gingival hyperplasia.

2.  MMF (Mycophenolate, aka Cellcept) – inhibits inosine monophosphate dehydrogenase and blocks guanine synthesis, inhibiting T and B cell proliferation.
Side effects:

• Bone marrow suppression
• GI side effects – dyspepsia, peptic ulcer disease, and diarrhea

3.  Rapamycin (Sirolimus) – also inhibits IL-2 signaling, but in a different pathway than calcineurin inhibitors – they can be synergistic together! 
Side effects:

• Bone marrow suppression
• Hyperlipidemia
• Impaired Wound Healing – big problem, especially after big operations to perform the transplant!

(Chanu Rhee MD, 6/3/11)