Pentostatin Injection and Cyclophosphamide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclophosphamide
Pentostatin Injection
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
Cardiac toxicity
Interaction Deep Dive
Fatal cardiac toxicity has been reported with concurrent use of pentostatin and cyclophosphamide in two bone marrow transplant patients1. Animal studies in the rat also suggest increased toxicity with this combination. This early evidence suggests that these agents are not safe to be used concurrently.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Two cases of fatal cardiac toxicity have been reported in association with the use of cyclophosphamide (total dose 6.4 grams/m(2) over 4 days) and pentostatin (4 mg/m(2) over 4 hours on day 3) 1. Both patients had normal cardiac histories and evaluations prior to treatment and within 48 hours suffered profuse pulmonary edema, hypotension, and refractory ventricular fibrillation. Etoposide and BCNU were also given in the protocol. An animal model in the rat demonstrated an increased early mortality with the pentostatin/cyclophosphamide combination compared to cyclophosphamide alone (no mortality seen with pentostatin alone). Further study of this interaction is needed.
Common questions
Can I take Pentostatin Injection and Cyclophosphamide together?
Cardiac toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Pentostatin Injection and Cyclophosphamide interaction?
It is rated major. Potentially serious — often needs a change or close 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.
Questions for your pharmacist
- Does my dose of Pentostatin Injection 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 a safer alternative to one of these medications for me?
References (1)
- Gryn J, Gordon R, Bapat A, et al: Pentostatin increases the acute toxicity of high dose cyclophosphamide. Bone Marrow Transplant 1993; 12:217-220.
Keep reading about Cyclophosphamide
Keep reading about Pentostatin Injection
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