TACROLIMUS - AN UPDATE OF ITS PHARMACOLOGY AND CLINICAL EFFICACY IN THE MANAGEMENT OF ORGAN-TRANSPLANTATION

Tacrolimus (FK 506) has been evaluated as immunosuppressive therapy in patients with a variety of solid organ and other transplants. Extensi ve data have now confirmed its efficacy as primary or rescue therapy i n renal and hepatic transplantation. In prospective and historically c ontrolled studies of primary therapy, tacrolimus generally demonstrate d greater efficacy than the conventional formulation of cyclosporin fo r preventing episodes of acute rejection and allowed reduction of cort icosteroid use. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial. How ever, patient and graft survival rates were similar in both treatment groups (although numerically larger in adults with liver transplants). In children, rejection rates and corticosteroid requirements were usu ally lower with tacrolimus and patient and graft survival were general ly similar with the 2 immunosuppressants. The finding of reduced corti costeroid requirements with tacrolimus may be of particular benefit in prepubertal children, who are still growing. A small amount of eviden ce has also accumulated regarding the use of tacrolimus as primary the rapy in patients who have undergone bone marrow or heart and/or lung t ransplantation. Data are not conclusive, particularly in children, but tacrolimus appears to be useful for treating patients who have underg one these organ transplantations and may be associated with a lower in cidence of obliterative bronchiolitis than cyclosporin in the latter g roup. Potential efficacy has also been shown in a limited number of pa tients with pancreas or pancreas-kidney, pancreatic islet and intestin al or multivisceral transplants, and in children who have undergone he art or heart-lung transplantation. Tacrolimus also has a use as rescue therapy in bone marrow, heart, lung and pancreatic transplantation, b ut data are currently insufficient for conclusions to be made. However , these results support the need for further study in these population s.Adverse effects occurring during tacrolimus therapy are generally of the type common to all immunosuppressive regimens. However, diabetes mellitus, neurotoxicity and nephrotoxicity are more common in tacrolim us than cyclosporin recipients. Hyperlipidaemia, hypertension, hirsuti sm and gingival hyperplasia are more common with cyclosporin. In 2 lar ge multicentre clinical trials (US liver and European renal), tacrolim us was discontinued more frequently during the first year because of a dverse events. However, the tolerability of tacrolimus appears related to dosage, improving as the dose is reduced. Tacrolimus should be con sidered an effective primary immunosuppressant in renal and hepatic tr ansplantation. The drug is also a useful agent for rescue therapy in p atients experiencing rejection or poor tolerability to cyclosporin. Th us, tacrolimus provides the clinician with an effective option for pat ients requiring immunosuppression and, with a different tolerability a nd efficacy profile to cyclosporin, it will better allow the tailoring of therapy to meet the needs of individual patients.