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

• Published in: Anticancer research Vol. 30; no. 9; pp. 3807 - 3810
• Main Authors: Santucci, R, Levêque, D, Lescoute, A, Kemmel, V, Herbrecht, R
• Format: Journal Article
• Language: English
• Published: Greece 01.09.2010
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - metabolism; Drug Interactions; Humans; Methotrexate - administration & dosage; Methotrexate - metabolism; Middle Aged; Neoplasms - drug therapy; Proton Pump Inhibitors - administration & dosage; Retrospective Studies; Young Adult
• ISSN: 1791-7530

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). Between 2005 and 2008, 79 patients (mean age: 48.8 years; range: 16-76 years) were treated by high dose methotrexate for 197 cycles. 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). Proton pump inhibitors should not be administered during methotrexate treatment.