title: Sirolimus: new preparation. No tangible advance in renal transplantation.
abstract: (1) Sirolimus, an immunosuppressant, is chemically related to tacrolimus but has a different mechanism of action. (2) In a double-blind trial in patients also treated with ciclosporin and a steroid, sirolimus was more effective than azathioprine at preventing acute rejection during the first three months, but caused more adverse effects (especially renal). (3) An unblinded trial compared ciclosporin + steroid + sirolimus with steroid + sirolimus for maintenance treatment. Ciclosporin was withdrawn gradually from the steroid + sirolimus group. Side effects from ciclosporin were therefore reduced (mainly nephrotoxicity and arterial hypertension), but rates of acute rejection, hepatotoxicity, and thrombocytopenia went up. (4) Sirolimus has numerous adverse effects, including hyperlipidemia, thrombocytopenia, hepatic disorders and opportunistic infections. The adverse effects of long term treatment are unknown. Sirolimus is metabolised by the cytochrome P450 isoenzyme CYP3A4, so may induce drug interactions. (5) In practice, sirolimus offers no advantage over existing immunosuppressive treatments for people with renal transplants.
mesh_terms: D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D017277:Drug Approval; D004359:Drug Therapy, Combination; D005060:Europe; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D007008:Hypokalemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D020123:Sirolimus