Severe intoxication with methotrexate possibly associated with concomitant use of proton pump inhibitors.

Abstract:

BACKGROUND:Delayed elimination of methotrexate associated with serious side-effects has been attributed to the co-administration of benzimidazole proton pump inhibitors. PATIENTS AND METHODS:We have retrospectively analyzed the causes of delayed methotrexate elimination in patients who had received the rescue agent glucarpidase to evaluate the potential implication of benzimidazoles. RESULTS:Between 2002 and 2008, six patients (mean age: 30 years; range: 4-74 years) were treated with glucarpidase. Delayed elimination associated with impaired renal function occured after the first cycle except in 2 patients (2nd and 8th administration of high-dose methotrexate). The possible causes of delayed elimination identified were: insufficient hydration (n=1) and drug-drug interactions (n=5). The potential drug-drug interactions included the co-administration of piperacillin/tazobactam (n=1) and proton pump inhibitors (omeprazole, n=3; esomeprazole, n=2). Impaired elimination of methotrexate was not observed either in the 3 patients who were treated further or during the previous cycles of the 2 pretreated patients in relation to the absence of co-prescription of proton pump inhibitors. CONCLUSION:In line with the recent literature and given the prohibitive cost of glucarpidase, we have advocated the cessation of proton pump inhibitors administration during methotrexate treatment.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Santucci R,Levêque D,Kemmel V,Lutz P,Gérout AC,N'guyen A,Lescoute A,Schneider F,Bergerat JP,Herbrecht R

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

963-5

issue

3

eissn

0250-7005

issn

1791-7530

pii

30/3/963

journal_volume

30

pub_type

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