Fluoroquinolones in FAERS: 221,775 adverse-event reports by the numbers

The FDA Adverse Event Reporting System (FAERS) holds 221,775 individual safety reports that name at least one of the seven marketed systemic fluoroquinolone antibiotics — ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin (Avelox), ofloxacin (Floxin), norfloxacin (Noroxin), gemifloxacin (Factive), and delafloxacin (Baxdela) — in any role, filed between 2004 and early 2026. Ciprofloxacin and levofloxacin dominate the class with 109,371 and 80,352 reports respectively, together 85 percent of the class total, with moxifloxacin contributing 32,169; the remaining four agents together account for less than 4 percent. Fluoroquinolones are the most serious-skewed outpatient-class cohort this publication has analyzed: 181,133 of the class reports — 81.7 percent — carry an FDA seriousness flag, and 22,035 (9.9 percent) record a fatal outcome, a seriousness share that exceeds the cardiometabolic, psychiatric, and oncology classes examined in the companion analyses and that reflects both the boxed-warning-driven reporting selection and an older, sicker infected population. The class signature is the collagen-and-nerve toxicity that drove a decade of regulatory action: 14,512 reports in the tendon-rupture and tendinopathy family, more than 5,500 peripheral-neuropathy reports (the MedDRA preferred term "Neuropathy peripheral" alone is coded on 5,112), and 2,071 reports in the aortic-aneurysm and dissection family — a rare event the FDA warned about in December 2018 after a roughly two-fold increased risk emerged across four observational studies.

This article is a class-level descriptive read of fluoroquinolone reporting in FAERS, written for pharmacovigilance, infectious-disease, antimicrobial-stewardship, and medical-affairs teams who encounter fluoroquinolone safety numbers in labeling reviews, formulary-restriction policy, stewardship dashboards, and risk-evaluation briefings. Every figure here is computed from the public openFDA FAERS extract (20,328,575 total reports, export dated 2026-06-08). It is not a disproportionality signal analysis, it is not a safety claim, and it is not incidence data. FAERS is a spontaneous-reporting system: it captures what was reported, never what was caused, it has no exposure denominator, and fluoroquinolone reporting is dominated by an older population with hypertension, atherosclerosis, diabetes, and renal impairment — the same risk factors that independently predispose to tendon, nerve, vascular, and dysglycaemic events. The 2008–2018 sequence of boxed warnings and safety communications generated sustained reporting attention to the named adverse-event families, so the counts are as much a measure of that regulatory surveillance footprint as of underlying event frequency. For the class-wide FAERS methodology and the database aggregate picture, see the companion analysis of 20 million FAERS reports; for the other class cuts, see GLP-1 receptor agonists, SGLT2 inhibitors, JAK inhibitors, DOACs, checkpoint inhibitors, statins, and SSRIs/SNRIs in FAERS. This article stays on the seven marketed systemic fluoroquinolones.

Methodology, in one paragraph

A report is counted for a fluoroquinolone when the drug's generic or brand name appears as an exact drug-field token in that report — as a suspect, concomitant, or interacting drug — using an exact-token match across the drug_substances, drug_generics, and drug_brands fields. The |-delimited exact-token match is what correctly distinguishes ofloxacin from levofloxacin (a plain substring match for "ofloxacin" would wrongly absorb every "-floxacin"). Because a single report can name several fluoroquinolones, the per-substance totals sum to more than the 221,775 class-level (union, deduplicated) reports. Topical ophthalmic and otic fluoroquinolone formulations (moxifloxacin eye drops, ofloxacin otic, ciprofloxacin/dexamethasone otic) are captured when they appear in the systemic drug fields and cannot be cleanly separated by route in this extract, which slightly inflates ciprofloxacin and moxifloxacin counts relative to oral/IV-only attribution. A "serious" report is any report the FDA coded as serious. A report counts toward death when either the seriousness field carries a death flag or the outcome field carries a Fatal outcome. Reactions are coded to MedDRA Preferred Terms; reaction counts are case-normalized. The adverse-event families aggregate related Preferred Terms (for example, "tendon rupture and tendinopathy" combines tendon rupture, tendonitis, tendon disorder, tendon pain, tendon injury, and tenosynovitis; "aortic aneurysm and dissection" combines aortic aneurysm, aortic dissection, and aortic rupture), and a report contributes once to a family if any term in the family appears. The "any role" counts reported here are intentionally inclusive.

The reporting-volume picture, by drug

Three patterns matter for stewardship and medical-affairs teams. First, volume tracks prescribing: ciprofloxacin and levofloxacin are the two most-used systemic fluoroquinolones — the workhorses of outpatient and inpatient gram-negative and respiratory coverage — and their combined 85 percent share is a market-penetration effect, not a risk ranking. Second, the serious-share band is extraordinarily high (76–96 percent for the volume leaders), far above outpatient-class norms, because the named adverse-event families (tendon rupture, aortic dissection, neuropathy, QT, dysglycaemia, neuropsychiatric) are themselves serious-event categories that the boxed warnings explicitly told reporters to watch for, and because the treated population is older and multi-morbid. Third, the per-drug death-flag percentages cluster between 8 and 12 percent for the volume leaders and move with population acuity: norfloxacin's 11.5 percent reflects a small, hospital-skewed residual sample, and the newer agents (gemifloxacin, delafloxacin) show lower serious and death shares because of denominator and reporting-maturity effects, not because they are intrinsically safer.

The class-level outcome profile

A report can carry more than one outcome, so these shares sum to more than 100 percent. The Fatal outcome count (15,565) sits below the death-flag measure (22,035) because many death-flagged reports carry unresolved outcome fields. The relatively high "not recovered" share (17.0 percent) and the "recovered with sequelae" line are consistent with the disabling-and-potentially-permanent framing of the 2016 boxed warning: a meaningful share of reports describe non-resolving or residual effects, though FAERS follow-up gaps make any durable-sequelae inference unreliable. None of these percentages are incidence — the denominator is reports, not exposed patients.

The tendon, nerve, and vascular footprint

Stripping out the non-specific terms (arthralgia, drug hypersensitivity, diarrhoea, fatigue, dyspnoea, nausea) that dominate the raw reaction list, the boxed-warning adverse-event families leave a clear footprint:

Two patterns deserve comment. The tendon signal is the largest family by volume and is consistent with the published disproportionality literature: a 2022 FAERS analysis (2016–2021) found ciprofloxacin carried the strongest tendonitis signal (reporting odds ratio 98.50) and levofloxacin the strongest tendon-rupture signal (ROR 76.38), with moxifloxacin materially weaker; in the descriptive any-role counts here, levofloxacin leads the combined family because it is the most-prescribed systemic agent in the older, corticosteroid-exposed, renally impaired populations in whom fluoroquinolone tendinopathy concentrates. The aortic family is small in raw count but disproportionate in regulatory weight, and it is the one family that concentrates sharply in a single agent: levofloxacin accounts for 1,839 of the 2,071 aortic-family reports, consistent with the published pharmacovigilance literature identifying levofloxacin as the fluoroquinolone most associated with aortic dissection while all three systemic agents associate with aneurysm.

A decade of boxed warnings — the regulatory spine of the class

Fluoroquinolones are the most label-action-intensive outpatient antibiotic class in modern FDA history, and the reporting profile here is the descriptive backdrop to that regulatory spine. The sequence: a July 2008 boxed warning for tendinitis and tendon rupture; a 2011 boxed warning for exacerbation of myasthenia gravis; an August 2013 warning that oral and injectable fluoroquinolones can cause peripheral neuropathy that can be permanent; a May 2016 restriction limiting use in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infection to situations where no alternative exists; a July 2016 revision of the boxed warning to address disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system; a July 2018 label strengthening warning about dysglycaemia (including hypoglycaemic coma) and mental-health side effects (disorientation, memory impairment, delirium); and the December 20, 2018 warning that systemic fluoroquinolones can increase the occurrence of aortic aneurysm rupture and dissection, based on four observational studies showing roughly a two-fold increased risk and 56 FAERS cases identified between December 2015 and April 2018.

The aortic signal — small in count, dominant in severity

Aortic aneurysm and dissection is the rare-event family that disproportionately shapes the class's risk posture even though it is the smallest of the named families in raw count (2,071 reports). In the general population the background incidence is roughly 9 events per 100,000 person-years, rising to about 300 per 100,000 in high-risk patients; the FDA's 2018 warning concluded that fluoroquinolone exposure roughly doubles that risk. A 2015 cohort study of more than 1.7 million older adults (Daneman et al., BMJ Open) reported an adjusted hazard ratio of 2.24 (95% CI 2.02–2.49) for aortic aneurysm, a 2018 Swedish nationwide cohort (Pasternak et al., BMJ) reported a hazard ratio of 1.66 (95% CI 1.12–2.46) for aortic aneurysm or dissection, and a systematic review and meta-analysis found fluoroquinolone exposure more than doubled the risk of aortic aneurysm or dissection within 60 days of exposure. The biological plausibility is shared with the tendon mechanism — collagen degradation via matrix-metalloproteinase up-regulation and impaired lysyl-oxidase-mediated cross-linking — which is why the tendon and aortic signals track together in the regulatory timeline. The descriptive count here is the reporting echo of that warning; the disproportionality and cohort literature, not the raw volumes, established the association. For formulary and stewardship teams, the access consequence is concrete: avoid systemic fluoroquinolones in patients with known or risk-factor-bearing aortic aneurysm (older age, hypertension, peripheral atherosclerotic vascular disease, Marfan or Ehlers-Danlos syndrome) unless no alternative exists.

The reporting trajectory, by year

The trajectory tracks the regulatory and stewardship cycle, not a safety trend. Reporting is flat through the mid-2000s at ~4,000–7,000 reports per year, steps up after the 2008 tendon boxed warning and again through 2011, then climbs sharply through 2016–2019 to a 19,951-report peak in 2019 — the period spanning the revised boxed warning (July 2016), the use restriction (May 2016), and the dysglycaemia, mental-health, and aortic communications (2018). The post-2019 decline to a ~11,000-report steady state reflects antimicrobial-stewardship-driven reductions in fluoroquinolone prescribing (institutional restriction, prior-authorization, and the shift away from fluoroquinolones for uncomplicated infections) as much as any change in reporting. The 2026 figure (2,058) is a partial year through the extract cut-off.

What this means for pharmacovigilance, stewardship, and access teams

• For pharmacovigilance teams, the class's 81.7 percent serious share is the highest of any outpatient class — and it is a selection artifact. The boxed warnings told reporters to watch for and file the named serious families; read the volume as the surveillance footprint of a decade of regulatory action, not as a population incidence.
• For antimicrobial-stewardship teams, the post-2019 reporting decline is consistent with successful prescribing restriction. Prior-authorization, formulary limitation for uncomplicated infections, and institutional stewardship have measurably reduced fluoroquinolone exposure, and the FAERS trajectory is a lagging indicator of that reduction.
• For medical-affairs and label teams, the tendon (14,512) and aortic (2,071) families are the durable pressure points, and the peripheral-neuropathy signal (>5,500 reports) is the most underappreciated at scale. Any label or risk-management review of a new quinolone will be read against the full 2008–2018 warning framework.
• For formulary and access teams, the aortic and tendinopathy warnings justify restriction in the elderly, corticosteroid-exposed, renally impaired, and aortic-risk populations. Defensible policy is avoidance in patients with known aortic aneurysm or its risk factors and preferential use of non-fluoroquinolone alternatives for uncomplicated infections.
• For dossier and evidence teams, per-agent FAERS figures must be anchored with exposure and population context. A levofloxacin tendon or aortic number in a heavily inhaled-prescribing elderly population is not comparable to a moxifloxacin number in a respiratory-infection denominator; the published ROR framework, not raw volumes, is the comparator regulators use.

Sources

• US FDA, openFDA FAERS (Adverse Event Reporting System) extract, export dated 2026-06-08 (20,328,575 total reports). Per-drug, class-union, outcome, AE-family, and trajectory aggregates computed by PharmaDossier from the public FAERS extract. https://open.fda.gov/data/faers/
• US FDA. "FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolones; requires label changes." July 2018 — dysglycaemia (including hypoglycaemic coma) and mental-health side effects. https://www.fda.gov/Drugs/DrugSafety/ucm611032.htm
• US FDA. "FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients." December 20, 2018 — ~2-fold increased aortic aneurysm/dissection risk across four observational studies; 56 FAERS cases Dec 2015–Apr 2018. https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm
• US FDA. "FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together." May and July 2016 — use restriction for uncomplicated infections and revised boxed warning for disabling/permanent musculoskeletal, nervous-system, and CNS effects. https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
• US FDA. "FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection." August 2013 — peripheral neuropathy warning. https://www.fda.gov/Drugs/DrugSafety/ucm365050.htm
• Wang H, et al. "Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database." Frontiers in Pharmacology 2022;13:990241 — ciprofloxacin strongest tendonitis signal (ROR 98.50), levofloxacin strongest tendon-rupture signal (ROR 76.38); moxifloxacin weaker. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.990241/full
• Daneman N, Lu H, Redelmeier DA. "Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study." BMJ Open 2015;5:e010077 — adjusted hazard ratio 2.24 (95% CI 2.02–2.49) for aortic aneurysm in older adults. https://bmjopen.bmj.com/content/5/11/e010077
• Pasternak B, Inghammar M, Svanström H. "Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study." BMJ 2018;360:k678 — hazard ratio 1.66 (95% CI 1.12–2.46) for aortic aneurysm or dissection versus amoxicillin. https://www.bmj.com/content/360/bmj.k678
• Wu D, Chen Q, Chen X, et al. "Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis." BMC Cardiovascular Disorders 2019 — fluoroquinolone exposure more than doubled the risk of aortic aneurysm or dissection within 60 days of exposure; collagen-degradation mechanism shared with tendinopathy (MMP up-regulation, lysyl-oxidase inhibition). https://pmc.ncbi.nlm.nih.gov/articles/PMC6865049
• New Zealand Medicines and Medical Devices Safety Authority (Medsafe), MARC Report 178 §3.2.3 — FAERS aortic-aneurysm and dissection signal review: all three systemic fluoroquinolones associated with aortic aneurysm; levofloxacin associated with aortic dissection. https://www.medsafe.govt.nz/committees/marc/reports/178-3.2.3FluoroquinolonesAndAorticAneurysm.pdf
• US FDA, Drugs@FDA approval records — norfloxacin (Noroxin, 1986), ciprofloxacin (Cipro, 1987), ofloxacin (Floxin, 1990), levofloxacin (Levaquin, 1996), moxifloxacin (Avelox, 1999), gemifloxacin (Factive, 2003), delafloxacin (Baxdela, 2017). https://www.accessdata.fda.gov/scripts/cder/daf/