Nitrofurantoin

Evidence Level: L5

Predicted Indications: 10

Nitrofurantoin

Pharmacist Assessment Report

Nitrofurantoin: From Urinary Tract Infection (Presumed) to Rheumatoid Arthritis

One-Sentence Summary

Nitrofurantoin is an oral antibacterial; the registered indication text was not available in the data compiled for this report, but its established clinical use is for urinary tract infection (UTI). The TxGNN model predicts it may be effective for rheumatoid arthritis, but there are no registered clinical trials and the 9 publications retrieved mostly describe adverse events, not therapeutic benefit.

Quick Overview

Item	Content
Original Indication	Not stated in the data compiled for this report (nitrofurantoin is an antibacterial generally used for UTI)
Predicted New Indication	Rheumatoid arthritis
TxGNN Prediction Score	0.9989
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on general pharmacology, nitrofurantoin is a nitrofuran antibacterial whose metabolites damage bacterial DNA and ribosomal proteins. It has no known anti-inflammatory or immunomodulatory action relevant to rheumatoid arthritis (RA).

The prediction is therefore not mechanistically supported. The high TxGNN score (0.9989) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence of benefit. The retrieved literature concerns drug-induced pulmonary fibrosis, a methotrexate-nitrofurantoin interaction causing irreversible lung fibrosis in an RA patient, RA-associated interstitial lung disease, and antibiotic exposure as a possible trigger of RA flares. The safety signal points in the opposite direction to a therapeutic effect.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15195196	2004	Review	Saudi Med J	Drug-induced pulmonary fibrosis; nitrofurantoin is a recognised cause, and RA is a predisposing disease
25362778	2014	Review	Rev Prat	Drug-induced interstitial lung disease; nitrofurantoin listed among implicated antibiotics
31222078	2019	Self-controlled case series	Sci Rep	Association between antibiotic use and RA flares in a UK primary care cohort (n = 31,992)
35145797	2022	Case report	Cureus	Methotrexate and nitrofurantoin interaction causing irreversible pulmonary fibrosis in a 94-year-old woman with RA
3335140	1988	Cohort	Chest	Poor prognosis in RA patients hospitalised for interstitial lung fibrosis (not specific to nitrofurantoin)
41635325	2026	Case report	Cureus	Autoimmune hepatitis versus drug-induced liver injury; nitrofurantoin named as a cause to rule out
8104358	1993	Case report	Rev Pneumol Clin	Gold salt-induced pneumonitis in an RA-treated patient (nitrofurantoin not the focus)
11937933	2002	Case report	Ann Dermatol Venereol	Phenylbutazone-induced sialadenitis; nitrofurantoin mentioned as a rare cause
899886	1977	Screening/treatment study	Acta Med Scand	Short-term nitrofurantoin for bacteriuria in middle-aged women; not related to RA

None of these publications reports a therapeutic benefit of nitrofurantoin in RA.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 1692C	Nitrofurantoin BNM	Capsule 50 mg	Not stated in the data compiled for this report

Safety Considerations

Disease associations flagged in the knowledge graph (not label text): diabetes mellitus, diabetic ketoacidosis, anuria, impaired renal function, peripheral neuropathy and other peripheral nervous system disease, interstitial lung disease, pulmonary fibrosis, G6PD deficiency, drug-induced liver injury, hepatitis, obstructive jaundice, biliary tract disease, vitamin B12 and other B-vitamin deficiency, optic neuritis, Clostridium difficile colitis, cystinuria, galactosemia and glycogen storage disease.
Literature-based safety signals: pulmonary fibrosis (including a severe interaction with methotrexate, a drug commonly used in RA), hepatotoxicity including autoimmune-like hepatitis, and haemolysis or methaemoglobinaemia, particularly in G6PD deficiency.
Drug interactions: 100 interactions were identified. The main moderate ones include metronidazole, balsalazide, picosulfuric acid, naltrexone, rosuvastatin and simvastatin. Anticholinergics (for example atropine, hyoscyamine, glycopyrronium) and magnesium-containing antacids are listed as minor.

Please also refer to the TGA-approved Product Information (PI) for full warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction is supported only by a model score, with no clinical trials, no plausible mechanism, and literature that points to harm (pulmonary, hepatic and haematological toxicity, and a dangerous interaction with methotrexate) rather than benefit in RA.

To proceed, the following is needed:

Mechanism of action data and any biological rationale for an anti-inflammatory or immunomodulatory effect in RA
The approved indication text and the Product Information (warnings and contraindications) for the ARTG entry
Preclinical or early clinical evidence of benefit in RA
A safety assessment covering concurrent methotrexate use, lung and liver risk, and renal function in the RA population

Other predicted indications (for example autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, brain small vessel disease, diabetic nephropathy, sclerosing cholangitis, methaemoglobinaemia and gout) are likewise supported by prediction only, or by adverse-effect literature, and are also on Hold.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.