Nitrofurantoin and Macrocrystals side effects: what 16,610 FDA adverse event reports show
Drug class
Nitrofuran antibacterial
Label matched
Nitrofurantoin (Nitrofurantoin)
Who reports
16,610 reports · 80% serious · 1,041 with death outcome · 84% female
Used for
Nitrofurantoin oral suspension is indicated in adults and pediatric patients 1 month of age and older for the treatment of urinary tract infections due to susceptible strains of Escherichia coli, Enterococcus species , Staphylococcus aureus, Klebsiella species and Enterobacter species.
What it is
Nitrofurantoin oral suspension, USP contains nitrofurantoin, a synthetic nitrofuran antibacterial agent specific for urinary tract infections.
Boxed warning
None in the current label
Causality screen of the 40 strongest signals
What the badges mean
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 903 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Tubulointerstitial nephritis | 223 | 15.2 13.3–17.3ROR 15.4 · χ² 2,911 / p <1e-300 | 15.0 EB05 13.4 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 10.8 · ♀ 52% (drug 84%) · 93% clinician | not reported in cached trials |
| Cystitis | 367 | 14.7 13.2–16.2ROR 15.0 · χ² 4,608 / p <1e-300 | 14.5 EB05 13.3 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 12.0 | not reported in cached trials |
| Swollen tongue | 312 | 12.7 11.4–14.2ROR 12.9 · χ² 3,327 / p <1e-300 | 12.6 EB05 11.4 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 12.5 | not reported in cached trials |
| Flank pain | 89 | 12.1 9.8–14.9ROR 12.2 · χ² 888 / p 2e-195 | 11.9 EB05 9.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 11.0 | not reported in cached trials |
| Impaired quality of life | 126 | 11.1 9.4–13.3ROR 11.2 · χ² 1,144 / p 5e-251 | 10.9 EB05 9.4 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 11.6 · ♀ 33% (drug 84%) | not reported in cached trials |
| Drug-induced liver injury | 265 | 10.9 9.7–12.3ROR 11.1 · χ² 2,364 / p <1e-300 | 10.8 EB05 9.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 · 96% clinician | not reported in cached trials |
| Urosepsis | 76 | 10.5 8.4–13.1ROR 10.5 · χ² 638 / p 6e-141 | 10.2 EB05 8.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | NCT04187144: 1/798 (0.1%) on Nitrofurantoin and Macrocrystals (serious AE) |
| Urinary tract infection (bladder infection) | 1,375 | 10.3 9.8–10.8ROR 11.1 · χ² 11,511 / p <1e-300 | 10.2 EB05 9.7 · IC025 +3.3 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 7.8 | NCT04187144: 15/798 (1.9%) on Nitrofurantoin and Macrocrystals |
| Pulmonary fibrosis | 150 | 10.0 8.5–11.7ROR 10.1 · χ² 1,194 / p 5e-262 | 9.8 EB05 8.5 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.0 | not reported in cached trials |
| Bladder disorder | 78 | 10.0 8.0–12.4ROR 10.0 · χ² 616 / p 3e-136 | 9.6 EB05 7.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=67 | not reported in cached trials |
| Chronic kidney disease | 591 | 9.8 9.1–10.6ROR 10.1 · χ² 4,643 / p <1e-300 | 9.7 EB05 9.1 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 7.1 | not reported in cached trials |
| End stage renal disease | 139 | 9.6 8.1–11.3ROR 9.7 · χ² 1,054 / p 2e-231 | 9.4 EB05 8.1 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | not reported in cached trials |
| Jaundice (yellowing of skin/eyes) | 192 | 9.0 7.8–10.4ROR 9.1 · χ² 1,357 / p 3e-297 | 8.9 EB05 7.9 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.6 | not reported in cached trials |
| Sleep apnoea syndrome | 127 | 8.4 7.1–10.0ROR 8.5 · χ² 820 / p 1e-180 | 8.2 EB05 7.1 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.0 | not reported in cached trials |
| Impaired work ability | 139 | 8.2 7.0–9.7ROR 8.3 · χ² 871 / p 1e-191 | 8.0 EB05 7.0 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.4 · ♀ 33% (drug 84%) | not reported in cached trials |
| Tinnitus (ringing in the ears) | 269 | 7.4 6.6–8.4ROR 7.5 · χ² 1,481 / p <1e-300 | 7.3 EB05 6.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 · ♀ 59% (drug 84%) | not reported in cached trials |
| Peripheral coldness | 79 | 7.3 5.8–9.1ROR 7.3 · χ² 419 / p 2e-93 | 7.0 EB05 5.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.3 | not reported in cached trials |
| Frequent bowel movements | 143 | 6.7 5.7–7.9ROR 6.8 · χ² 690 / p 2e-152 | 6.6 EB05 5.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 · ♀ 28% (drug 84%) | not reported in cached trials |
| Mass | 74 | 6.7 5.3–8.4ROR 6.7 · χ² 351 / p 1e-78 | 6.4 EB05 5.3 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 6.9 | not reported in cached trials |
| Acute hepatic failure | 69 | 6.4 5.1–8.1ROR 6.5 · χ² 310 / p 1e-69 | 6.2 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 · 94% clinician | not reported in cached trials |
| Nightmare | 176 | 6.4 5.5–7.4ROR 6.5 · χ² 797 / p 1e-175 | 6.3 EB05 5.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.4 · ♀ 41% (drug 84%) | not reported in cached trials |
| Economic problem | 78 | 6.4 5.1–8.0ROR 6.4 · χ² 350 / p 3e-78 | 6.2 EB05 5.1 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious PRR 5.0 | not reported in cached trials |
| Lip swelling | 168 | 6.4 5.5–7.5ROR 6.5 · χ² 759 / p 2e-167 | 6.3 EB05 5.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | not reported in cached trials |
| Drug reaction with eosinophilia and systemic symptoms | 129 | 6.4 5.4–7.6ROR 6.4 · χ² 580 / p 2e-128 | 6.2 EB05 5.4 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.6 · 97% clinician | not reported in cached trials |
| Loss of personal independence in daily activities | 236 | 6.3 5.5–7.1ROR 6.4 · χ² 1,042 / p 7e-229 | 6.2 EB05 5.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 · ♀ 51% (drug 84%) | not reported in cached trials |
| Gallbladder disorder | 88 | 6.2 5.1–7.7ROR 6.3 · χ² 380 / p 8e-85 | 6.0 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.7 | not reported in cached trials |
| Eosinophilia | 82 | 5.9 4.8–7.4ROR 6.0 · χ² 331 / p 3e-74 | 5.7 EB05 4.8 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.4 · 100% clinician | not reported in cached trials |
| Fibromyalgia | 113 | 5.9 4.9–7.1ROR 5.9 · χ² 453 / p 8e-101 | 5.7 EB05 4.9 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.4 | not reported in cached trials |
| Dysuria (painful urination) | 171 | 5.9 5.1–6.8ROR 5.9 · χ² 686 / p 2e-151 | 5.8 EB05 5.1 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 | not reported in cached trials |
| Chromaturia | 104 | 5.8 4.8–7.1ROR 5.9 · χ² 410 / p 2e-91 | 5.7 EB05 4.8 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 | not reported in cached trials |
| Tendonitis | 69 | 5.6 4.4–7.1ROR 5.6 · χ² 256 / p 5e-58 | 5.4 EB05 4.4 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.0 · ♀ 57% (drug 84%) | not reported in cached trials |
| Kidney infection | 87 | 5.6 4.6–6.9ROR 5.6 · χ² 325 / p 7e-73 | 5.4 EB05 4.5 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.4 | not reported in cached trials |
| Liver function test abnormal | 128 | 5.5 4.7–6.6ROR 5.6 · χ² 470 / p 1e-104 | 5.4 EB05 4.7 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 4.7 | not reported in cached trials |
| Sleep disorder due to a general medical condition | 70 | 5.5 4.3–6.9ROR 5.5 · χ² 251 / p 7e-57 | 5.3 EB05 4.3 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 7.0 | not reported in cached trials |
| Muscle spasticity | 53 | 5.4 4.1–7.1ROR 5.4 · χ² 186 / p 1e-42 | 5.2 EB05 4.1 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 | not reported in cached trials |
| Swelling face | 277 | 5.4 4.8–6.1ROR 5.5 · χ² 986 / p 8e-217 | 5.3 EB05 4.8 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | not reported in cached trials |
| Stress | 302 | 5.3 4.8–5.9ROR 5.4 · χ² 1,054 / p 2e-231 | 5.3 EB05 4.8 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | not reported in cached trials |
| Urinary incontinence | 124 | 5.3 4.4–6.3ROR 5.3 · χ² 428 / p 3e-95 | 5.2 EB05 4.5 · IC025 +2.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 4.3 | not reported in cached trials |
| Accidental overdose | 152 | 5.3 4.5–6.2ROR 5.3 · χ² 520 / p 2e-115 | 5.2 EB05 4.5 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 6.0 · ♀ 33% (drug 84%) | not reported in cached trials |
| Systemic lupus erythematosus | 145 | 5.2 4.4–6.1ROR 5.2 · χ² 485 / p 8e-108 | 5.1 EB05 4.4 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.8 · ♀ 30% (drug 84%) | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Nitrofurantoin and Macrocrystals as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (2 of 40 signal terms matched).
- NCT04187144 — Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicat (N=1606, PHASE3; 21 AE terms posted; arms: Gepotidacin; Nitrofurantoin)
- NCT04020341 — A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infecti (N=1531, PHASE3; 17 AE terms posted; arms: Gepotidacin; Nitrofurantoin)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Urinary tract infection (bladder infection) | 1,375 | 10.3 9.8–10.8ROR 11.1 · χ² 11,511 / p <1e-300 | 10.2 EB05 9.7 · IC025 +3.3 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 7.8 | NCT04187144: 15/798 (1.9%) on Nitrofurantoin and Macrocrystals |
| Fatigue (tiredness) | 1,281 | 2.1 2.0–2.2ROR 2.2 · χ² 747 / p 8e-165 | 2.1 EB05 2.0 · IC025 +1.0 | Labeled (related wording) related wording | serious PRR 2.3 | NCT04187144: 8/798 (1.0%) on Nitrofurantoin and Macrocrystals |
| Nausea | 1,244 | 2.0 1.9–2.1ROR 2.1 · χ² 637 / p 9e-141 | 2.0 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.2 | NCT04187144: 35/798 (4.4%) on Nitrofurantoin and Macrocrystals |
| Headache | 1,156 | 2.3 2.2–2.5ROR 2.4 · χ² 905 / p 5e-199 | 2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 | NCT04187144: 22/798 (2.8%) on Nitrofurantoin and Macrocrystals |
| Dyspnoea (shortness of breath) | 1,013 | 2.3 2.1–2.4ROR 2.3 · χ² 731 / p 2e-161 | 2.3 EB05 2.1 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.1 | not reported in cached trials |
| Pain | 1,001 | 2.1 1.9–2.2ROR 2.1 · χ² 557 / p 2e-123 | 2.1 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.1 | NCT04187144: 1/804 (0.1%) on Nitrofurantoin and Macrocrystals (serious AE) |
| Diarrhoea (diarrhea) | 916 | 1.8 1.7–1.9ROR 1.8 · χ² 334 / p 7e-75 | 1.8 EB05 1.7 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.8 | NCT04187144: 24/798 (3.0%) on Nitrofurantoin and Macrocrystals |
| Rash | 890 | 2.6 2.4–2.8ROR 2.7 · χ² 887 / p 3e-195 | 2.6 EB05 2.4 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 | not reported in cached trials |
| Malaise (feeling unwell) | 872 | 2.5 2.4–2.7ROR 2.6 · χ² 804 / p 4e-177 | 2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | not reported in cached trials |
| Vomiting | 858 | 2.3 2.2–2.5ROR 2.4 · χ² 651 / p 6e-144 | 2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.2 | NCT04187144: 7/798 (0.9%) on Nitrofurantoin and Macrocrystals |
| Pyrexia (fever) | 844 | 3.1 2.9–3.3ROR 3.2 · χ² 1,202 / p 1e-263 | 3.1 EB05 2.9 · IC025 +1.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.6 | not reported in cached trials |
| Dizziness | 820 | 2.1 1.9–2.2ROR 2.1 · χ² 470 / p 2e-104 | 2.1 EB05 2.0 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.2 | NCT04187144: 11/798 (1.4%) on Nitrofurantoin and Macrocrystals |
| Drug ineffective (drug did not work) | 791 | 0.8 0.7–0.8ROR 0.7 · χ² 65 / p 4e-16 | 0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.1 | not reported in cached trials |
| Off label use (used outside approved label) | 733 | 1.1 1.0–1.1ROR 1.1 · χ² 3 / p 0.040 | 1.1 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.2 | not reported in cached trials |
| Fall | 604 | 2.3 2.1–2.5ROR 2.3 · χ² 447 / p 2e-99 | 2.3 EB05 2.1 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.7 | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Tubulointerstitial nephritis — n=223, PRR 15.2
- Cystitis — n=367, PRR 14.7
- Swollen tongue — n=312, PRR 12.7
- Flank pain — n=89, PRR 12.1
- Impaired quality of life — n=126, PRR 11.1
- Drug-induced liver injury — n=265, PRR 10.9
- Urosepsis — n=76, PRR 10.5 (also seen in trial arm)
- Bladder disorder — n=78, PRR 10.0
- Chronic kidney disease — n=591, PRR 9.8
- End stage renal disease — n=139, PRR 9.6
✓ A hand-written Bradford Hill causality assessment exists for this drug: Nitrofurantoin ↔ Pulmonary fibrosis / interstitial lung disease.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Nitrofurantoin and Macrocrystals?
In FDA FAERS, the most frequently co-reported reaction terms for Nitrofurantoin and Macrocrystals are urinary tract infection, fatigue, nausea, headache, dyspnoea, pain. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Nitrofurantoin and Macrocrystals have an FDA boxed warning?
No. The FDA label retrieved for Nitrofurantoin and Macrocrystals has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Nitrofurantoin and Macrocrystals causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 11e700aa-66f9-4939-8a6b-a23240ae1a0b, effective 20240516; matched on
openfda.generic_name.exact:"NITROFURANTOIN") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 943 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
NITROFURANTOIN, results-bearing studies sorted by enrollment)
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.