Hydrochlorothiazide and Cyclophosphamide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Hydrochlorothiazide
Cyclophosphamide
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
Increased risk of myelosuppression
Interaction Deep Dive
Concomitant or sequential use of cyclophosphamide and thiazide diuretics may result in increased hematotoxicity and immunosuppression1. During a clinical trial, coadministration of cyclophosphamide, methotrexate, 5-fluorouracil combination and a thiazide diuretic resulted in significant augmentation of granulocytopenia in patients with metastatic breast cancer 3; however, in a retrospective claim analysis in older women with breast cancer, concomitant use resulted in no significant increase in neutropenia-related hospitalization or chemotherapy discontinuation 2. If concurrent therapy is required, monitor closely for excessive myelosuppression.
Why it happens (mechanism)
Unspecified
Literature reports
2 reports — tap to read
a) In a retrospective claim analysis of women (66 years or older) with breast cancer, concomitant use of adjuvant cyclophosphamide-containing chemotherapy and hydrochlorothiazide (n=581) compared with no hydrochlorothiazide (n=1555), showed no significant increase in neutropenia-related hospitalization (10.15% vs 10.8%; RR 0.92 [95% CI, 0.7 to 1.21]) or chemotherapy discontinuation (21.17% vs 20.84%; RR 1 [95% CI, 0.96 to 1.05]) 2.
b) Thiazide diuretics may enhance the myelosuppressive effects of antineoplastic agents. Fourteen patients with metastatic breast cancer treated with cyclophosphamide, methotrexate, 5-fluorouracil combination and a thiazide diuretic experienced significant augmentation of granulocytopenia during treatment cycles as compared with chemotherapy without thiazides 3.
Common questions
Can I take Hydrochlorothiazide and Cyclophosphamide together?
Increased risk of myelosuppression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydrochlorothiazide and Cyclophosphamide interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Hydrochlorothiazide or Cyclophosphamide 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 (3)
- Product Information: cyclophosphamide oral capsules, cyclophosphamide oral capsules. West-Ward Pharmaceuticals Corp. (per DailyMed), Eatontown, NJ, 2016. DailyMed
- Hsu CD, Hinton SP, Reeder-Hayes KE, et al: Association between concomitant use of hydrochlorothiazide and adverse chemotherapy-related events among older women with breast cancer treated with cyclophosphamide. Cancer Epidemiol Biomarkers Prev 2020; 29(2):520-523. PubMed
- Orr LE: Potentiation of myelosuppression from cancer chemotherapy and thiazide diuretics. Drug Intell Clin Pharm 1981; 15:967-970. DOI
Keep reading about Hydrochlorothiazide
Keep reading about Cyclophosphamide
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist