Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron

During late 1991, a series of severe adverse events involving thrombocytopenia, renal insufficiency and thrombotic episodes was observed in patients receiving emetogenic chemotherapy. Two patients died, one of renal failure and one of cerebral haemorrhage in the presence of thrombocytopenia. Other severe side effects included thrombosis of the aorta causing paraplegia and multifocal cerebral infarctions. Common exposure features included the use of ondansetron and dexamethasone as antiemetics, and in most of the cases high dose (100 mg/M2 or more) cisplatin. Retrospective review of a series of patients treated with similar cytotoxic regimens for similar diseases before the use of ondansetron revealed no similar adverse effects, but no substantial differences were observed in renal function or haematologic toxicity in the two groups overall. Sporadic adverse vascular events have been observed before the use of ondansetron. The mechanism remains unknown, and it is not clear whether ondansetron was a factor in the unusual incidence of such events in the present series.