Rabeprazole and Nivolumab Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nivolumab Injection
Rabeprazole
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
Reduced efficacy of nivolumab
Interaction Deep Dive
Concomitant use of proton pump inhibitors (PPI) was associated with decreased progression-free survival and overall survival in patients with metastatic renal cell carcinoma (MRCC)1 and gastric cancer (GC) 2 treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs with nivolumab in patients with MRCC 1 and GC 2.
Why it happens (mechanism)
Modified gastrointestinal microbiota by proton pump inhibitors; disruption of immune system physiological function; detrimental effect on cytotoxic activity of natural killer cells and neutrophil functions
Literature reports
2 reports — tap to read
a) In a single-center, retrospective study of 80 adult patients with advanced or recurrent gastric or gastroesophageal junction cancer receiving nivolumab monotherapy, concomitant use of proton pump inhibitors (PPIs; n=33) was associated with a significantly shorter median progression-free survival (PFS) compared with patients not taking PPIs (3.61 vs 9.43 months; HR, 2.21 [95% CI, 1.2 to 4.06]), as well as a significantly shorter median overall survival (OS) on univariate analysis (4.83 vs 16.4 months; HR, 2.24 [95% CI, 1.24 to 4.05]). In subgroup analysis of patients receiving PPIs, patients with a previous gastrectomy had a significantly longer median PFS (10.2 vs 3.65 months; HR, 0.51 [95% CI, 0.28 to 0.93]) and OS (22.2 vs 6.4 months; HR, 0.43 [95% CI, 0.24 to 0.78]) than those without gastrectomy. The authors theorized that a change in the gut microbiome and increased gastrin levels leading to tumor progression from PPI use could contribute to the interaction 2.
b) In a multicenter retrospective study of 109 patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy, 59 patients were not using a concomitant proton pump inhibitor (PPI) and 50 were using a PPI. Median progression-free survival (PFS) was 6.37 (5.2 to 7.5) months in the concomitant PPI group and 9.7 (4.5 to 15) months in the non-PPI group (no PPI vs PPI, HR 0.44; 95% CI 0.28 to 0.96). Median overall survival (OS) was 14.6 (7.1 to 22.1) months in patients receiving PPI and 29.9 (17.1 to 42.7) months in the non-users (no PPI vs PPI, HR 0.68; 95% CI 0.22 to 0.88). PPIs used were pantoprazole 40 mg, esomeprazole 40 mg, lansoprazole 30 mg, or omeprazole 40 mg. The mean duration of PPI use was 3.95 months, and the median follow-up period was 14.5 months. Other variables evaluated included best response to nivolumab, any grade side effects, and grade 3/4 side effects; no difference between concomitant PPI users and non-users was noted. PFS and OS were determined to be independent risk factors 1.
Common questions
Can I take Rabeprazole and Nivolumab Injection together?
Reduced efficacy of nivolumab Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rabeprazole and Nivolumab Injection interaction?
It is rated major. Potentially serious — often needs a change or close 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Rabeprazole or Nivolumab Injection 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 (2)
- Ugrakli M, Kocak MZ, Dinc G, et al: The effect of concomitant proton pump inhibitor use on survival outcomes of nivolumab-treated renal cell carcinoma patients: a multicenter study. J Cancer Res Clin Oncol 2023; 149(11):9183-9189. PubMed
- Shibano M, Takahashi M, Nakatsukasa H, et al: Proton pump inhibitors reduce nivolumab efficacy in unresectable advanced or recurrent gastric cancer. Immunotherapy 2025; 17(5):331-338. DOI
Keep reading about Nivolumab Injection
Keep reading about Rabeprazole
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