Delayed elimination of methotrexate associated with co-administration of proton pump inhibitors.

AIM

We conducted a retrospective non-interventional cohort study to analyze the impact of proton pump inhibitors co-administration on methotrexate elimination in cancer patients receiving treatment protocol with the antifolate at high dose (>1 g/m(2) intravenously).

PATIENTS AND METHODS

Between 2005 and 2008, 79 patients (mean age: 48.8 years; range: 16-76 years) were treated by high dose methotrexate for 197 cycles.

RESULTS

Delayed methotrexate elimination (i.e., plasma concentration >15 μmol/l at 24 h, >1.5 μmol/l at 48 h and/or >0.15 μmol/l at 72 h) occurred in 16% (32/197) of the cycles. The co-prescription of a proton pump inhibitor (pantoprazole, lansoprazole, omeprazole, esomeprazole) was found in 53% (17/32) of the courses with delayed elimination and in 15% (24/165) of the cycles without delayed elimination. We identified co-administration of proton pump inhibitors as a major risk factor for delayed elimination (odds ratio 6.66, 95% confidence interval 3.13, 14.17).

CONCLUSION

Proton pump inhibitors should not be administered during methotrexate treatment.