Interaction between methotrexate and omeprazole in an adolescent with leukemia: a case report

Bauters, Tieneke; Verlooy, Joris; Robays, Hugo; Laureys, Geneviève

doi:10.1007/s11096-008-9204-9

Cited by 23 publications

(21 citation statements)

References 6 publications

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“…Recently, the delayed elimination of MTX associated with serious side effects was described in three retrospective clinical studies of patients treated with high doses of MTX and PPIs (Joerger et al, 2006;Suzuki et al, 2009;Santucci et al, 2010;Leveque et al, 2011) and one prospective study of low dose MTX (Vakily et al, 2005). Although conflicting data were reported in some case reports for either omeprazole or pantoprazole (Whelan et al, 1999;Beorlegui et al, 2000;Troger et al, 2002;Bauters et al, 2008), recent clinical studies are in line with our results suggesting that PPIs might decrease MTX renal clearance via OAT3-mediated inhibition. In the first study, Joerger et al (2006) described 76 patients who received high-dose MTX, 13 of whom received omeprazole or lansoprazole.…”

Section: Discussionmentioning

confidence: 99%

“…Over the past few years, several case reports in oncology (Reid et al, 1993;Beorlegui et al, 2000;Troger et al, 2002;Bauters et al, 2008) and two retrospective cohort studies (Suzuki et al, 2009;Santucci et al, 2010) have suggested that the coadministration of proton pump inhibitors (PPIs), including omeprazole, pantoprazole, lansoprazole, and rabeprazole, decreased the renal clearance of MTX. The elimination of MTX was significantly delayed during cycles with one PPI but normalized during subsequent cycles after PPI discontinuation or substitution with ranitidine.…”

Section: Introductionmentioning

confidence: 99%

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Proton Pump Inhibitors Inhibit Methotrexate Transport by Renal Basolateral Organic Anion Transporter hOAT3

et al. 2014

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The coadministration of methotrexate (MTX) and proton pump inhibitors (PPIs) can result in a pharmacokinetic interaction that delays MTX elimination and subsequently increases the MTX blood concentrations. Human organic anion transporters (hOATs) are responsible for the renal tubular secretion of MTX and are thought to be involved in this drug interaction. The aim of this study was to evaluate the inhibitory potencies of PPIs on hOAT1 and hOAT3, which are the two isoforms of OATs predominantly expressed in kidney proximal tubules. Using stably transfected cell systems that express the uptake transporters human embryonic kidney (HEK)-hOAT1 and HEK-hOAT3, we analyzed the inhibitory potencies of omeprazole, lansoprazole, and pantoprazole on OAT-mediated [

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proton Pump Inhibitors Inhibit Methotrexate Transport by Renal Basolateral Organic Anion Transporter hOAT3

et al. 2014

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“…Drug-drug interaction with valaciclovir and fluoxetine treatment is unlikely due to their metabolism pathways and the lack of drug interaction reported in the literature. However, as it has already been described with other PPI, alteration in methotrexate renal elimination might be understood by drug interaction with pantoprazole [8,9,10,11]. In opposition with Whelan et al [24] who suggested that there was no alteration in plasma methotrexate clearance in a single patient treated with omeprazole, recent studies consistently showed that PPI coadministration could reduce methotrexate clearance, resulting in significantly higher plasma methotrexate concentrations [15,25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Different elimination pathways of methotrexate and its main metabolite 7-hydroxymethotrexate are mediated by membrane cell transporters such as breast cancer resistance protein (BCRP), expressed on the apical membranes of renal epithelial cells, and hydrogen-potassium adenosine triphosphatase enzyme (H + /K + /ATPase pump) in the distal nephron [11,25,27]. A possible decrease in hepatobiliary elimination of high-dose methotrexate should also be taken into account because BCRP is present in the bile canalicular membrane of human liver hepatocytes [29].…”

Section: Discussionmentioning

confidence: 99%

“…In cancer patients, drug interactions have also been reported between methotrexate, or its main metabolite 7-hydroxymethotrexate, and benzimidazoles (omeprazole and pantoprazole), resulting in clinically relevant myelosuppression with systemic infections and severe mucositis. These reports suggested that proton pump inhibitors (PPI) might have delayed plasma elimination of methotrexate, resulting in a higher risk of methotrexate toxicity [8,9,10,11]. PPI are widely used to reduce the frequency of epigastric pain, stress ulcer and heartburn that occur in cancer patients receiving antineoplastic chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Suspicion of Drug-Drug Interaction between High-Dose Methotrexate and Proton Pump Inhibitors: A Case Report – Should the Practice Be Changed?

Ranchon¹,

Vantard²,

Gouraud

et al. 2011

Chemotherapy

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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.

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Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug–drug interactions mediated by organic anion transporter 3

Narumi

Sato

Kobayashi

et al. 2017

Biopharm & Drug Disp

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Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyse the potential drug-drug interactions between MTX and gastric antisecretory drugs in high-dose MTX (HD-MTX) therapy. The impact of PPIs on the plasma MTX concentration on 73 cycles of HD-MTX therapy was analysed retrospectively in 43 patients. Also investigated was the involvement of OAT3 in PPI-MTX drug interaction in an in vitro study using human OAT3 expressing HEK293 cells. In a retrospective study, patients who received a PPI had significantly higher MTX levels at 48 h (0.38 vs. 0.15 μmol l , respectively, p = 0.000018) and 72 h (0.13 vs. 0.05 μmol l , respectively, p = 0.0002) compared with patients who did not receive a PPI (but received famotidine). Moreover, in vitro experiments demonstrated that PPIs (esomeprazole, lansoprazole, omeprazole and rabeprazole) inhibited hOAT3-mediated uptake of MTX in a concentration-dependent manner (IC values of 0.40-5.5 μ m), with a rank order of lansoprazole > esomeprazole > rabeprazole > omeprazole. In contrast to PPIs, famotidine showed little inhibitory effect on hOAT3-mediated MTX uptake. These results demonstrated that co-administration of PPI, but not famotidine, could result in a pharmacokinetic interaction that increases the plasma MTX levels, at least in part, via hOAT3 inhibition.

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Interaction between methotrexate and omeprazole in an adolescent with leukemia: a case report

Cited by 23 publications

References 6 publications

Proton Pump Inhibitors Inhibit Methotrexate Transport by Renal Basolateral Organic Anion Transporter hOAT3

Proton Pump Inhibitors Inhibit Methotrexate Transport by Renal Basolateral Organic Anion Transporter hOAT3

Suspicion of Drug-Drug Interaction between High-Dose Methotrexate and Proton Pump Inhibitors: A Case Report – Should the Practice Be Changed?

Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug–drug interactions mediated by organic anion transporter 3

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