FDA
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- Use caution when administering high-dose methotrexate to patients
receiving proton pump inhibitor (PPI) therapy.
- Concomitant use of some PPIs with methotrexate (primarily at high
dose), may elevate and prolong serum levels of methotrexate and/or its
metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.
- Delayed methotrexate elimination was observed when high-dose
methotrexate was co-administered with PPIs, but was not observed when
methotrexate was co-administered with ranitidine.
- No formal drug interaction
studies of methotrexate with ranitidine have been conducted.
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Lexicomp
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- Severity :Moderate (clinical
significance pf the interaction may be lower with typically lower
methotrexate dose )
- Mechanism :MTX is actively secreted in distal renal tubule with
hydrogen ions produced via hydrogen/potassium ATPase pump, PPI by inhibiting
renal elimication of hydrogen ion may inhibit MTX elimination.
- Management: Monitor increased MTX toxicity (mucositis, myalgias, etc)
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BC Cancer Agency Cancer Drug Manual
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Management of concomitant use
- Monitor for methotrexate toxicity
- for high-dose methotrexate - consider discontinuing
PPI one day prior to methotrexate
- consider an H2 antagonist (e.g., ranitidine) instead
of PPI
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Bezabeh et al, 2012
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- The
majority of the reported cases occurred with the administration of high-dose
methotrexate.
- Although
the product label describes high-dose therapy as 12 g/m2 as a 4-hour infusion, doses ≥500
mg/m2 are frequently cited as “high dose”
in the literature, and the majority of the above case reports and series were
reported from patients receiving doses of 300 mg/m2 to 12 g/m2.
- It
appears the risk is greatest in the high-dose setting; however, there were
also cases of patients taking a PPI and experiencing toxicity at doses as low
as 15 mg of methotrexate per week.
- Clinicians
should consider substituting H2 blockers
for PPIs when acid suppression is clinically indicated during methotrexate
therapy.
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