**5. Concluding remarks**

Although success of organ transplantation is continuously improving, several short- and long-term complications can adversely affect the outcome. One of the most significant factors influencing the long-term graft and patient survival is the appropriate immunosuppressive therapy. Subtherapeutic blood concentrations of immunosuppressive drugs can evoke acute or chronic graft injury mediated by immunological mechanisms, whereas overdosing leads to over-suppression of the immune system that consequently develops serious infections, as well as adverse and even life-threatening side effects. Because of the narrow therapeutic indexes, dosing of most of the immunosuppressive agents is applied under careful monitoring of their blood concentrations. The knowledge of the potential factors that can modify immunosuppressive therapy, as well as pharmacokinetic and metabolic drug interactions, can decrease the fluctuation of immunosuppressant blood concentrations, can facilitate to avoid the serious adverse events, can improve the therapeutic outcome for transplant patients, and can reduce the medical costs.

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The appropriate and tailored immunosuppressive medication is a great challenge and requires careful and continuous attention, because unrecognized simple interactions can induce serious complications. As such during administratrion of clarithromycin or antifungal agents without dose reduction of calcineurin inhibitors or mTOR inhibitors, blood concentrations of immunosuppressants can substantially exceed the therapeutic range within some days. Without dose modification, a reverse outcome is expected during comedication with anticonvulsants (valproic acid and carbamazepine) or with rifampicin resulting in subtherapeutic blood concentrations of immunosuppressants and increasing the risk of organ rejection. The lack of mycophenolate dose reduction during cessation of ciclosporin or replacement of ciclosporin to another immunosuppressant can also evolve development of serious adverse reactions. It is anticipated that the special attention and the knowledge of potential drug interactions can prevent the majority of misdosing-induced adverse events.
