Delayed Elimination of High Dose Methotrexate due to Co-Administration of Omeprazole: A Case Report

Abstract

Methotrexate High Doses (HD-MTX) is indicated for the treatment of cancer diseases and its use requires strict precautions to prevent toxic side effects. It has also numerous drug interactions, the most known are interaction with trimethoprim - sulfamethoxazole (TMP-SMX) and Non Steroidal Anti-Inflammatory drugs (NSAIDs), which can exacerbate toxicity of MTX. We report herein a case of delayed elimination of HD-MTX due to co-administraion of omeprazole. B.A, a 17-year-old female having acute lymphoblastic leukemia (ALL). She is treated since September 2011 by HD-MTX every month for 6 months. The elimination of MTX was usually averaged at H₇₂. Because of epigastralgia, the sixth cycle of HD-MTX was associated this time to omeprazole 20 mg/d during the entire cycle. MTX monitoring showed a high concentration at H₃₆ (23 mol/L) and a delayed elimination. In fact, MTX remained above 0.2 mol/L until H₁₆₄. The patient's serum creatinin was normal but the liver function was altered marked by transaminases increase observed at H₄₈ (AST = 2N, ALT = 5N). Delayed elimination of MTX was not observed in every patient receiving PPIs and the reason remains unclear. Mechanisms may include the H+/K+ ATPase pump. It seems also that inhibition of renal transporters of MTX is involved in this interaction. Genetic factors may be associated with an accentuated risk of toxicity. Because of the severity of this type of drug interaction and the frequent ambulatory use of PPIs, it is important to mention such drug-drug interaction and to find an alternative for omeprazole during HD-MTX cycles.




doi: http://dx.doi.org/10.4021/jh71w