Fluorouracil receptor antagonists

Prophylactic administration of antiemetics is essential in any patient receiving FOLFOX chemotherapy. The combination of oxaliplatin and 5-fluorouracil results in a moderate level of emetogenicity and requires the administration of 5HT3-receptor antagonists and corticosteroid treatment, generally with a dopamine antagonist such as metoclopramide or domperidone. Severe manifestations may have to be managed by delay and/or dose modification of the patient s next cycle of chemotherapy. 

In a study in 8 patients, cimetidine 400 mg twice daily increased the AUC of epirubicin by 50%. At the same time the AUCs of two metabolites of epirubicin, epirubicinol and 7-deoxydoxorubicinol aglycone, increased by 41% and 357%, respectively. Liver blood flow also increased by 17%. The mechanism is unknown. More study of this interaction is needed but be aware of the possibility of cimetidine inereasing the exposure to epirubicin monitor the patient closely and adjust epirubicin dosage if needed. Cimetidine is available without a preseription in some countries so that patients may unwittingly increase the toxicity of epirubicin. Cimetidine has also increased the levels or toxicity of some other antineoplastics, see Nitrosoureas + Cimetidine , p.655, Cyclophosphamide + H2-receptor antagonists , p.626 and Fluorouracil + H2-reeeptor antagonists , p.633. 

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