Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
CellCept (Roche Products)
250 mg capsules
500 mg tablets
Indication: renal transplantation
Acute rejection of an allogeneic renal transplant can occur in up to 60% of patients. As this can reduce the survival of the allograft, there is a need to try to prevent acute rejection. Mycophenolate mofetil has been studied because it inhibits guanosine nucleotide synthesis and hence the proliferation of T and B lymphocytes.
A study of 491 patients compared mycophenolate with placeboin patients who were also given cyclosporin and corticosteroids to prevent rejection. In the first 6 months after surgery, significantly fewer rejections occurred in the patients receiving mycophenolate. Whereas 46% of patients given placebo developed biopsy-proven rejections, only 17% of those given 2 g of mycophenolate had a rejection. A 3 g dose gave a better response rate, but was less well tolerated.1
Mycophenolate has been compared with azathioprine in patients also given cyclosporin and corticosteroids. The combination containing mycophenolate was more effective in preventing rejection.
Treatment is taken twice a day starting within 72 hours of the transplant. Plasma level monitoring is not required in the prevention of toxicity. The drug is completely converted to an active metabolite. This metaboliteis further metabolised and then excreted mainly in the urine. Extra caution is needed if there is severe renal impairment.
The patients need regular blood tests during the first year of treatment as anaemia and leucopenia can develop. Other adverse effects include vomiting, diarrhoea and infections. Opportunistic infections include Herpes simplex, Herpes zoster, cytomegalovirus and, rarely, candida and Pneumocystiscarinii. The treatment of Pneumocystis carinii may be complicated by the possibility, suggested by animal studies, that there is an interaction with trimethoprim/sulfamethoxazole. Other potential interactions include acyclovir, antacids and cholestyramine.
Although mycophenolate has a proven benefit in the first 6months after transplantation, its long-term safety and effectiveness will need to be confirmed. The studies of mycophenolate have revealed an increased incidence of skin carcinoma and lymphoma/lymphoproliferative disease compared to placebo.
- European Mycophenolate Mofetil Co-operative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 1995;345:1321-5.