Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ZOFRAN Tablets. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes cannot be clearly determined.
Treatment-related acute myeloid leukemia or myelodysplasia is known to occur in patients treated with anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. AML occurs at a higher frequency when these agents are given in combination with radiation therapy. AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at 5 years in TAX316 was % for TAC-treated patients and % for FAC-treated patients. This risk of AML is comparable to the risk observed for other anthracyclines/cyclophosphamide containing adjuvant breast chemotherapy regimens.
Influenza can be associated with various neurologic and behavioral symptoms (including hallucinations, delirium, abnormal behavior), with fatal outcomes in some cases; such events may occur with encephalitis or encephalopathy but can occur without obvious severe disease. There are postmarketing reports (mostly in Japan) of delirium and abnormal behavior leading to injury, with fatal outcomes in some cases, in influenza patients using this drug. Although frequency is unknown, based on usage, these events appear uncommon. These events were primarily reported in pediatric patients, often with abrupt onset and rapid resolution. The contribution of this drug to such events has not been established.
Side effects with similar or higher incidence among placebo patients included insomnia. [ Ref ]