METHOTREXATE AND PROTON PUMP INHIBITORS: ARE THERE ANY NEGATIVE PHARMACOLOGIAL EFFECTS?

Abstract

Methotrexate (MTX) is the first-line medication to treat rheumatoid arthritis (RA). However, it may have serious adverse effects (AE) on liver, kidneys, hematopoietic system, etc., thus requiring meticulous control over patient’s condition and the dynamics of laboratory indicators. A number of drugs may affect MT pharmacokinetics and increase its toxicity. In theory, proton pump inhibitors (PPIs) may have this effect. Objective. To assess the relationship between the coadministration of MT and PPIs and the risk for developing drug-induced complications.Material and Methods. A retrospective analysis of clinical symptoms and laboratory indicators in 539 RA patients (median age, 52.5±14.6 years; 86.8% females and 13.2% males) who received MTX in 2009–2011 was carried out. Fifty-two patients who received PPIs on a regular basis were included in the study. The control group consisted of 104 PPI-naive patients comparable in terms of gender, age, and therapy. The numbers of patients with increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase (ALP); anemia (hemoglobin level < 110 g/l in females and <120 g/l in males), leukopenia (<4.0•109/l), elevated creatinine level, and proteinurea (qualitative and quantitative values) were compared.Results. No significant intergroup differences were revealed. MTX showed no clinically manifested AE. The odds ratio (OR) and 95% confidence interval (CI) for changes in laboratory indicators were as follows: ALT 1.35 (95% CI 0.22–8.32), AST 0.66 (95% CI 0.13–3.38), ALP 0.98 (95% CI 0.955–1.01), anemia 1.19 (95% CI 0.517–2.71), and proteinurea 1.95 (95% CI 0.83–4.59; р=0.17). A small increase in the creatinine level was observed in one case for each group.Conclusions. The results showed no significant increase in toxicity when low doses of MTX and PPIs were coadministered in RA patients. There was a trend towards more frequent proteinurea in patients who received both drugs. This fact requires further research.

Keywords

• methotrexate
• proton pump inhibitors
• drug–drug interaction