Cyclophosphamide and Ondansetron: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ondansetron
No brand names on recordCyclophosphamide
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Decreased cyclophosphamide systemic exposure
Interaction Deep Dive
Two studies have shown that ondansetron decreases the systemic exposure of cyclophosphamide in cancer patients. Although a statistical analysis of toxicity and/or response has not been performed, even a small difference in drug exposure could have major implications in terms of response and toxicity because of the narrow therapeutic index of chemotherapeutic agents12.
Why it happens (mechanism)
Unknown
Literature reports
2 reports — tap to read
a) Ondansetron decreased the systemic exposure to cyclophosphamide when these agents were coadministered to breast cancer patients. A total of 54 patients receiving high-dose cyclophosphamide, cisplatin, and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II were given continuous infusions of ondansetron and prochlorperazine, while cohorts III and IV received ondansetron alone. The area under the concentration-time curve (AUC) of cyclophosphamide was less in patients receiving ondansetron alone or with prochlorperazine (73.6 mg/mL/min) when compared to controls (88.3 mg/mL/min). Overall, the clearance of cyclophosphamide was increased by 17% in the presence of ondansetron continuous infusion 1.
b) The pharmacokinetics of ondansetron were evaluated in 23 patients receiving ondansetron (8 mg intravenous bolus, followed by 1 mg/hr continuous infusion) with high-dose chemotherapy consisting of cyclophosphamide, cisplatin, and carmustine. These results were compared with 129 contemporaneously treated patients who received an identical high-dose chemotherapy regimen but with prochlorperazine (1 mg/m2/hr as a continuous intravenous infusion) instead of ondansetron as the antiemetic. The mean area under the concentration-time curve (AUC) of cyclophosphamide was 76,600 mcg/mL/min in the ondansetron group and 90,600 mcg/mL/min in the prochlorperazine group. Additionally, the half-life of cyclophosphamide on day 2 of administration and the maximum concentration of cyclophosphamide on day 3 of administration were significantly lower for the ondansetron group. The small number of patients, together with the fact that this was a heterogenous group, precluded meaningful statistical analysis of toxicity and/or response, although it does not rule out potential differences 2.
Common questions
Can I take Cyclophosphamide and Ondansetron together?
Decreased cyclophosphamide systemic exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclophosphamide and Ondansetron interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cyclophosphamide or Ondansetron need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (2)
- Gilbert CJ, Petros WP, Vredenburgh J, et al: Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer. Cancer Chemother Pharmacol 1998; 42:497-503. DOI
- Cagnoni PJ, Matthes S, Day TC, et al: Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. Bone Marrow Transplant 1999; 24:1-4. PubMed
Keep reading about Ondansetron
Keep reading about Cyclophosphamide
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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