Clinical Oncology, Department of Pharmacy, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
Chemotherapy. 2011;57(3):225-9. doi: 10.1159/000327372. Epub 2011 May 18.
We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate.
我们报告了一例女性患者在接受高剂量甲氨蝶呤治疗 T 淋巴细胞性淋巴瘤的首次注射时发生药物-药物相互作用的情况。同时给予伐昔洛韦、氟西汀和泮托拉唑。输注后 36 小时显示甲氨蝶呤过量，伴有严重肾衰竭。给予碱化水化、亚叶酸和羧肽酶 G2。通过药剂师的处方分析和文献研究，我们建议甲氨蝶呤和质子泵抑制剂 (PPI) 之间的药物相互作用是导致这种肾衰竭的原因。提出了几种相互作用机制，可能与 PPI 抑制肾脏中甲氨蝶呤转运蛋白、PPI 通过上调多药耐药蛋白 3 增加甲氨蝶呤向血液中的流出或遗传多态性有关。该病例表明，药剂师可以帮助医生优化患者治疗：当患者接受高剂量甲氨蝶呤治疗时，他们一致决定系统停用 PPI 或改用雷尼替丁。
