Drug Interactions between lansoprazole / naproxen and pembrolizumab

GENERALLY AVOID: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered.

MANAGEMENT: Concomitant use of these drugs is generally not recommended.

MONITOR: Use of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (P-CABs) concurrently with or in close proximity to immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and/or inhibitors of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) may result in reduced clinical efficacy of the ICI. The exact mechanism of this interaction has not been fully characterized, but may be related to alterations in the gut microbiota by the PPI/P-CAB, potentially resulting in immune dysregulation and a decreased response to the ICI. Evidence of this interaction is limited and conflicting. One retrospective analysis of patients with advanced cancer treated with ICIs found that PPI use (n=239/635) was associated with shorter median overall survival (9 months vs. 26.5 months), shorter median progression-free survival (3.5 months vs. 8 months), as well as less frequent tumor response (61% vs. 72%). A retrospective analysis of pooled data from clinical trials of atezolizumab in patients with advanced urothelial carcinoma, identified PPI use during the 30 days before and 30 days after atezolizumab as a negative prognostic marker associated with reductions in overall survival and progression-free survival, which was not observed in the outcomes of patients receiving chemotherapy (docetaxel, paclitaxel, or vinflunine). This association has also been noted in the literature for PPI use during atezolizumab treatment for non-small cell lung cancer. In a separate retrospective study of Japanese patients (n=133) using pembrolizumab (200 mg every 3 weeks or 400 mg every 6 weeks) as second-line therapy or beyond for metastatic urothelial carcinoma, patients using P-CABs were grouped together and analyzed with those using PPIs. Similar to other studies, when grouped together, patients on a PPI or P-CAB within 30 days before or after treatment with pembrolizumab had shorter PFS and OS than those who were not on a PPI or P-CAB. However, when PPI users and P-CAB users were examined as separate groups, multivariate analysis revealed that only PPI use was significantly associated with disease progression. In contrast, a retrospective cohort study of advanced cancer adult patients (n=233) who received nivolumab or pembrolizumab, treatment with a PPI 30 days before or after the ICI revealed no significant effect on overall survival or progression free survival. Data are not available for every ICI.

MANAGEMENT: Until more information is available, caution and clinical monitoring for reduced efficacy of immune checkpoint inhibitors (ICIs) are advised if therapy with a proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) is required, particularly during the 30 days before or after the ICI is initiated. PPI or P-CAB use should be limited to clinically appropriate indications and durations. Clinicians should consult relevant literature, local and national treatment guidelines, and package labeling for further guidance.