Irinotecan Injection and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole
Irinotecan 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
Increased irinotecan exposure and an increased irinotecan active metabolite exposure
Interaction Deep Dive
Concomitant use of irinotecan, a CYP3A4 substrate, and ketoconazole, a potent CYP3A4 inhibitor is contraindicated as it may increase irinotecan exposure3. If irinotecan therapy is required for a patient who is already receiving ketoconazole, then it is recommended that ketoconazole therapy be discontinued at least 1 week prior to initiating irinotecan therapy 12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated irinotecan metabolism by ketoconazole
Literature reports
1 report — tap to read
a) Simultaneous administration of irinotecan, a CYP3A4 substrate, and ketoconazole a CYP3A4 inhibitor, resulted in increased formation of SN-38, an active metabolite of irinotecan in a randomized, cross-over study of seven patients with a diagnosis of metastatic colorectal cancer. Treatment consisted of irinotecan 350 mg/m(2) IV for 90 minutes given alone and followed 3 weeks later by irinotecan 100 mg/m(2) in combination with ketoconazole 200 mg orally for 2 days. In the cross-over study arm, patients received these treatment cycles in reverse order. The exposure to the principal oxidative metabolite (APC) was reduced by 87%, whereas the relative exposure to the carboxylesterase-mediated SN-38 was increased by 109% (p=0.004). These metabolic changes occurred without substantial changes in irinotecan clearance and formation of SN-38G, the SN-38 glucuronide metabolite of irinotecan. Hematologic toxicity and non-hematologic toxicity between the treatment courses were similar despite the reduced irinotecan dose in the presence of ketoconazole, which may be explained by the increased exposure to SN-38. Potentially fatal interactions are likely with concomitant use of irinotecan and ketoconazole 4.
Common questions
Can I take Irinotecan Injection and Ketoconazole together?
Increased irinotecan exposure and an increased irinotecan active metabolite exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Irinotecan Injection and Ketoconazole interaction?
It is rated contraindicated. These should generally not be used together.
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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Irinotecan Injection or Ketoconazole 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 (4)
- Product Information: CAMPTOSAR(R) intravenous injection, irinotecan intravenous injection. Pharmacia & Upjohn Co (per FDA), New York, NY, 2022. DailyMed
- Product Information: ONIVYDE(R) intravenous injection, irinotecan liposome intravenous injection. Ipsen Biopharmaceuticals Inc (per FDA), Cambridge, MA, 2024. DailyMed
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Kehrer D, Mathijssen R, Verwei J, et al: Modulation of irinotecan metabolism by ketoconazole. J Clin Oncol 2002; 20(14):3122-3129. PubMed
Keep reading about Ketoconazole
Keep reading about Irinotecan Injection
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