Drug interactions
Methotrexate + Nitrofurantoin
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Overview
Additive risk of pulmonary toxicity (eg, interstitial pneumonitis/fibrosis) and hepatotoxicity when used together; serious lung injury has been reported with either agent and rare cases are described with concomitant use.
Mechanism of action
Pharmacodynamic: overlapping pulmonary and hepatic toxicity profiles; no well-established pharmacokinetic interaction.
Clinical management
Prefer alternative antibiotics in patients on methotrexate, especially avoiding chronic nitrofurantoin. If nitrofurantoin must be used, use the shortest effective course, counsel patients to report new cough, dyspnea, or fever immediately, and monitor liver enzymes if therapy exceeds a few days or symptoms arise; discontinue and evaluate promptly if pulmonary or hepatic toxicity is suspected.
Drug reference
References
- Macrobid (nitrofurantoin monohydrate/macrocrystals) — US Prescribing Information (Pulmonary and Hepatic Warnings) — FDA Label
- Methotrexate — US Prescribing Information (Pulmonary and Hepatic Warnings) — FDA Label
- Nitrofurantoin: Drug information — Lexicomp
- Methotrexate (systemic): Drug information — Lexicomp
Frequently asked questions
Can I take Methotrexate with Nitrofurantoin?
The interaction is rated: Moderate. Additive risk of pulmonary toxicity (eg, interstitial pneumonitis/fibrosis) and hepatotoxicity when used together; serious lung injury has been reported with either agent and rare cases are described with concomitant use.
How serious is the interaction between Methotrexate and Nitrofurantoin?
The interaction is rated: Moderate. Evidence level: Low.
How is the interaction between Methotrexate and Nitrofurantoin managed?
Prefer alternative antibiotics in patients on methotrexate, especially avoiding chronic nitrofurantoin. If nitrofurantoin must be used, use the shortest effective course, counsel patients to report new cough, dyspnea, or fever immediately, and monitor liver enzymes if therapy exceeds a few days or symptoms arise; discontinue and evaluate promptly if pulmonary or hepatic toxicity is suspected.
Why do Methotrexate and Nitrofurantoin interact?
Pharmacodynamic: overlapping pulmonary and hepatic toxicity profiles; no well-established pharmacokinetic interaction.
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