What drugs do post-transplant patients require, and what are their side effects? How should I follow up such patients?

Following successful cardiac, cardiopulmonary or pulmonary transplantation, patients require life-long immunosuppressive therapy. Routine immunosuppression consists of cyclosporin-A and azathioprine, occasionally supplemented by corticosteroids.

Episodes of acute allograft rejection are treated with intravenous methylprednisolone therapy or occasionally antithymocyte globulin or OKT3. Other drugs used include tacrolimus, mycophenolate mofetil and cyclophosphamide. Early evidence suggests that mycophenolate mofetil (an antimetabolite drug) may be a useful alternative to azathioprine as maintenance postoperative immunosuppression. OKT3 is a monoclonal antibody raised in mice, which is directed against the lymphocyte CD3 complex. Although it is sometimes used for induction following transplantation it is now more frequently employed in the management of severe episodes of acute cardiac rejection.

Common complications following transplantation include allograft rejection and infection. It is of paramount importance to immunosuppress the patient to minimise the risk of allograft rejection, without over-immunosuppressing and thereby increasing susceptibility to opportunistic infection. For this reason, cyclosporin-A blood levels are regularly monitored postoperatively. Side effects include renal failure, hypertension, hyperkalaemia, hirsutism, gum hypertrophy and increased susceptibility to opportunistic infection and to lymphoproliferative disorders. Tacrolimus acts in a similar way to cyclosporin-A although it may be a more potent immunosuppressive agent. Although its side effect profile is similar, diabetes mellitus can be a complication. Azathioprine is an antimetabolite whose major side effects include bone marrow suppression and hepatic cholestasis. Occasionally pancreatitis can occur. Some patients who are intolerant of azathioprine are prescribed mycophenolate mofetil (which is less likely to cause bone marrow suppression) or cyclophosphamide. At the present time the precise role of tacrolimus and mycophenolate in post-cardiac and pulmonary transplant immunosuppression is unclear and requires further study. The side effect profile of corticosteroid therapy is well documented.

In addition to regular monitoring of drug levels and haematological (full blood count) and biochemical (renal and hepatic function, blood glucose) indices, one should be aware of drug interactions which may reduce or increase the levels or effectiveness of immunosuppressive agents. For example drugs which promote hepatic enzyme induction (e.g. anticonvulsants, antituberculous therapy) will reduce cyclosporin-A levels. Certain antibiotics (e.g. erythromycin) and calcium channel blockers (e.g. diltiazem) will increase cyclosporin-A levels. Similar interactions apply to tacrolimus. Non-steroidal antiinflammatory agents can potentiate nephrotoxicity when given with cyclosporin-A or tacrolimus. The dose of azathioprine has to be reduced by 70% if patients are also prescribed allopurinol.