Immunosuppressant agents for transplants

There are 4categories of maintenance immunosuppressive medications for transplant recipients.

Immunosuppressive medications include: calcineurin inhibitors, anti-metabolites, mammalian target of rapamycin (m-TOR) inhibitors and glucocorticoids.

Presently the most commonly used combination for maintenance immunosuppression consists of tacrolimus and mycophenolate with or without low-dose prednisone.

Tacrolimus and mycophenolate are stronger immunosuppressives than cyclosporine and azathioprine, respectively.

m-TOR inhibitors are not use for primary immunosuppression because they impair wound healing, suppress bone marrow activity, increase lymphcele formation during the postoperative period.

In patients with calcineurin inhibitor kidney or neuro toxicity, or post transplant malignancies the use of m-TOR inhibitors may be implemented.

In kidney transplant recipients changing from calcineurin inhibitors to m-TOR inhibitors is associated with a higher GFR, fewer skin cancers and cytomegalic infections.

mTOR inhibitors have higher rates of acute rejection approximately 1.7% versus 1% with calcineurin inhibitors, and drug withdrawal due to side effects of 21.6% versus 9.6%.

mTOR inhibitors potentiate calcineurin inhibitor nephrotoxicity and lthese drugs are rarely used together.

Trough levels of cyclosporine, tacrolimus, sirolimus, and everolimus correlate well with the area under the time concentration curve and should be monitored periodically.

Mycophenolate trough levels do not correlate well with the area under the time concentration curve.

Mycophenolate dosage is frequently determined by the degree of bone marrow suppression, G.I. side effects, and infection complications, particularly BK viremia.

Azothioprine is metabolizing into several metabolites and monitoring such metabolites is not useful.

For azathioprine periodic measurement of blood counts and liver functions are needed.

Calcineurin and mTOR inhibitors are metabolized ny cytochrome P450 system (CYP3A4).

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