Ondansetron Cyclophosphamide

Ondansetron antagonizes the action of serotonin at receptors in the upper gastrointestinal tract and in the chemoreceptor trigger zone of the central nervous system. Given intravenously (IV), it prevents vomiting completely for 24 h in 40% of patients treated with high doses (>100 mg/m2) of cisplatin and in 70 to 80% of patients treated with 50 to 100 mg/m2 of cisplatin or a combination of cyclophosphamide and doxorubicin. 

Ondansetron is also available in an oral formulation, which can be used for mildly or moderately emetogenic chemotherapy. In one double-blind trial in 318 patients taking combinations of cyclophosphamide with methotrexate and/or doxorubicin, oral ondansetron 1, 4, or 8 mg t.i.d. for 3 d was completely effective in preventing emesis in 57,65, and 66% of patients, respectively, compared to 19% who did not vomit with placebo. 

When used in combination with corticosteroids, cyclophosphamide is dosed at 1-3 mg/kg for oral therapy and 0.5-1.0 g/m of body surface area for intravenous therapy. The most common route of cyclophosphamide administration is intravenous, although there is little evidence that this is better than oral administration. Likewise, there is no evidence to suggest the optimal duration of treatment. Based on empirical experience, cyclophosphamide generally is dosed monthly for 6 months and then every 3 months for a period of either 2 years or for 1 year after the nephritis is in remission." " Of course, cyclophosphamide therapy is not without risk. Serious toxic effects include suppression of hematopoiesis, opportunistic infections, bladder complications (e.g., hemorrhagic cystitis and cancer), sterility, and teratogenesis. White blood cell counts must be monitored during cyclophosphamide therapy, and if the nadir is less than 1500/mm, the dose must be adjusted to keep the white cell count above 1500/mm. Nausea and vomiting associated with cyclophosphamide can be controlled with oral ondansetron plus dexamethasone. ... 

Yarboro CH, Wesley R, Amantea MA, et al. Modifled oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis. Ann Pharmacother 1996 30 752-755. 

Acetaminophen, arachidonic acid, benzo[a]pyrene, clozapine, cyclophosphamide, dapsone, dorzolamide, (i2)-fluoxetine, hexobarbital,(S)- and (f2)-ibuprofen, lauric acid, losartan, (S)- and (i )-naproxen, N-nitrosodimethylamine,ondansetron, phenylbutazone, piroxicam, 9-cis-retinoic acid, sulfadiazine, sulfamethoxazole, tetrahydrocannabinol, torasemide, trimethoprim,... 

Cyclophosphamide produces severe nausea and is often used with a 5HT3 antagonist, ondansetron. Cyclophosphamide is metabolized to a toxic metabolite called acrolein, which can cause haemorrhagic cystitis, a rare but serious complication. This effect can be counteracted by a high intake of fiuid and by using a drug called mesna. Otherwise,... 

Fleming, R.A. Olsen, D.J. Savage, RD. Fox, J.L. Stability of ondansetron hydrochloride and cyclophosphamide in injectable solutions. Am.J.Health-Syst.Pharm., 1995, 52, 514-516... 

Some evidence su ests ondansetron may modestly affect the pharmacokinetics of cyclophosphamide and cisplatin but it does not appear to affect those of carmustine. Ondansetron did not affect the in vitro activity of epirubicin, bleomycin, cisplatin or es-tramustine. Cisplatin and fluorouracil do not affect the pharmacokinetics of ondansetron. In in vitro studies granisetron potentiated the cytotoxic effects of epirubicin, had an additive effect on bleomycin and estramustine activity and appeared not to affect the metabolism of docetaxel and paclitaxel. 

The pharmacokinetics of high-dose cyclophosphamide, cisplatin and carmustine in 23 patients given ondansetron, lorazepam and diphenhydramine as antiemetics were compared with those in 129 patients who received prochlorperazine instead of ondansetron. It was found that the AUCs of cyclophosphamide and cisplatin, but not that of carmustine, were significantly lower (by 15% and 19%, respectively) in the ondansetron group. Similarly, in another study, the pharmacokinetics of antineoplastics were analysed in 54 patients with breast cancer who were receiving high-dose cyclophosphamide, cisplatin and carmustine with lorazepam and ondansetron with or without prochlorperazine and com-... 

Gilbert CJ, Petros WP, Vredenburgh J, Hussein A, Ross M, Rubin P, Fehdrau R, Cavanaugh C, Berry D, McKinstry C, Peters WP. Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer. Cancer Chemoffier Pharmacol (1998) 42,497-503. 

Lorenz C, Eickhoff C, BaumarmF, Sehouli J, PreissR, SchunackW, JaehdeU. Does ondansetron affect the metabolism of cyclophosphamide /wfJC/iwP/ranwaco/ 772er(2000) 38,143-4. 

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