Moxifloxacin

Limits on what this shows

• Key null findings: No human tissue, muscle or blood mitochondrial DNA, respiration or lactate measurement after moxifloxacin was found. Islet fission/fusion changes were absent for moxifloxacin [21].
• At-risk subgroups: Not defined. The tendon cell work is proposed by its authors as relevant to fluoroquinolone tendinopathy, an outcome not graded here.
• Counter-evidence on record: Concentrations used were mostly well above plasma peak; some of the cytotoxicity work (melanoma, glioma cells) was framed by its authors as anti-cancer research, not as a safety signal.

Direction

Excess burden on mitochondrial function (drug toxicity in vitro); not a nutrient deficiency (Hard Rule 2).

Regulatory status

No mitochondrial statement in the label text read [1][2].

Population evidence

All Tier B (moxifloxacin used, cells or animals). Human Achilles tendon cells [20]: 0 to 0.3 mM moxifloxacin or ciprofloxacin for 24 h and 7 days; dichlorodihydrofluorescein oxidation up to 3-fold (p < 0.0001) and loss of mitochondrial membrane function (p < 0.001); the mitochondria-targeted antioxidant MitoQ (1 uM) reduced both. Mouse islets [21]: 100 uM moxifloxacin abolished the 20 mM glucose-induced NAD(P)H rise and reduced the FAD and ATP/ADP responses; in 20 h culture, moxifloxacin did not cause the fission/fusion changes seen with gatifloxacin and ciprofloxacin. Human PBMC from 3 healthy donors [23]: 10 ug/mL for 24 h; single-cell sequencing showed marked NK cell loss and severely depleted mitochondrial genes. Neutrophils [24]: reduced maximal mitochondrial respiration and inhibited complex I (concentrations and sizes not in the abstract). U87MG glioma cells [22]: EC50 0.48, 0.22 and 0.15 umol/mL at 24, 48 and 72 h, with loss of mitochondrial membrane potential. Concentration context (calculated here with molecular weight about 401.4, not from a retrieved source): the label multiple-dose Cmax is 4.5 mg/L, about 11 uM [1], so 10 ug/mL is about 2 times, 100 uM about 9 times and 0.3 mM about 27 times that peak. Tenocyte, islet and PBMC abstracts read through PubMed listing summaries or OpenAlex reconstructions.

Mechanism

Named in the source abstracts: loss of mitochondrial membrane potential, respiratory chain (complex I) inhibition and reactive oxygen species generation [20][21][24]. CLASS EXTRAPOLATION flag: the bactericidal-antibiotic paper (Sci Transl Med 2013) reports mitochondrial dysfunction and ROS with "quinolones", aminoglycosides and beta-lactams in mammalian cells and mice, but the abstract names classes only; whether moxifloxacin was among the quinolones tested was not established, so it is Tier C, was not used to raise this grade and moxifloxacin is not confirmed in its cohort [25].

Counter-evidence held on record

Framing caution This is mechanistic laboratory evidence at high concentrations; it does not show a lasting energy or mitochondrial deficit in patients and recommends no supplement (including no antioxidant or CoQ10).

Limits on what this shows

• Key null findings: No human study measured MDA, glutathione, SOD or total antioxidant capacity after moxifloxacin.
• At-risk subgroups: Not defined.
• Counter-evidence on record: Rat results conflict in direction and doses (8 to 50 mg/kg/day i.p.) are not clinical doses; the lung injury model is a disease model where inflammation confounds.

Direction

Mixed. Pro-oxidant in vitro and in some rat studies; lower malondialdehyde in a rat acute lung injury model and after 14 days in one rat comparison. Not a nutrient deficiency (Hard Rule 2). A reverse-direction (protective) finding is carried in the evidence below.

Regulatory status

No oxidative stress statement in the label text read [1][2].

Population evidence

Tier B only. Human tenocytes [20]: ROS up to 3-fold, reduced by MitoQ. Glioma cells [22]: glutathione depletion at the cytotoxic EC50s above. Rats (listing summaries [26]): moxifloxacin 50 mg/kg/day intraperitoneal for 7 of 28 days raised malondialdehyde in kidney, liver and brain and lowered serum total antioxidant status (resveratrol reduced this; PMID 42745652); 8 mg/kg/day for 7 days with royal jelly and Echinacea protective against renal and hepatic malondialdehyde and glutathione changes (PMID 36322409). Opposite direction: a 14-day rat comparison of ciprofloxacin, levofloxacin and moxifloxacin (40 mg/kg/day) found moxifloxacin lowered MDA together with GSH, CAT and GPx (PMID 34601990); in HCl-induced rat lung injury, moxifloxacin lowered lung MDA and raised GSH (PMID 31872097). Non-mammalian toxicology records (algae, onion) were not used.

Mechanism

Mitochondrial ROS generation (MitoQ-reversible in tenocytes) [20]; none named for the animal results.

Counter-evidence held on record

Framing caution Do not read this as a reason for antioxidant supplements. The evidence is laboratory and animal only and runs in both directions.

Limits on what this shows

• Key null findings: No measurement of serum iron, ferritin, hemoglobin or iron absorption after moxifloxacin exists in the records found [28][31]. The iron-related moxifloxacin items found were bacterial (a rise in the labile iron pool of Mycobacterium tuberculosis, an in vitro mechanism of killing) and formulation chemistry, not host status [28].
• At-risk subgroups: People taking oral iron, multivitamin-mineral products or antacids with moxifloxacin. A hospital cross-sectional study of 47 patients co-given oral antibiotics and cation products included 12 on moxifloxacin, with 74.5% getting both at the same time (listing line only) [28].
• Counter-evidence on record: Absorption slowed (Tmax about 2.8 h) in addition to lower total exposure; the authors suggested staggering doses [11]. Single dose in healthy men; the effect at steady state was not tested.

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4. Iron chelates moxifloxacin in the gut. Moxifloxacin is not shown here to lower iron status: no study measured host iron after moxifloxacin (Hard Rules 2 and 4).

Regulatory status

Label section 2.2 and 7: moxifloxacin at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron or zinc; section 12.3 reports iron AUC -39% and Cmax -59% [1][2].

Population evidence

Clin Pharmacokinet 2001 [11]: single-center, nonblinded, randomized two-way crossover, 12 healthy men aged 19 to 41, single moxifloxacin 400 mg alone or with ferrous sulfate (100 mg Fe2+), 1-week washout. AUC geometric mean 34.0 to 20.7 mg/L.h (relative bioavailability 61%, 90% CI 54 to 69%); Cmax 2.86 to 1.17 mg/L (41%, 90% CI 34 to 49%); median Tmax 1.0 to 2.79 h. Abstract only, via a PubMed listing summary. The label repeats this result, so label and paper are one data point, not two [1].

Mechanism

Named by the authors: chelation with polyvalent cations in the gut lumen [11].

Counter-evidence held on record

Framing caution The documented effect is iron lowering the antibiotic, not the antibiotic lowering iron. Do not take extra iron because of moxifloxacin; space the doses as the label states (a prescriber or pharmacist decides on any change).

Limits on what this shows

• Key null findings: No serum copper, ceruloplasmin or tissue copper after moxifloxacin was found.
• At-risk subgroups: Not defined.
• Counter-evidence on record: The study itself concludes unlikely mobilization.

Direction

Neutral to minimal (mechanistic, in silico). No evidence of copper depletion. Never merged with Iron (Hard Rule 7).

Regulatory status

Copper is not mentioned in the label text read [1][2].

Population evidence

Molecules 2014 [27]: moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin against Cu(II), Ni(II) and Zn(II) in modeled human plasma; the main low-molecular-weight copper complex was only slightly affected; ciprofloxacin had the highest calculated copper-mobilizing power; the authors judged essential metal mobilization unlikely. Tier B (moxifloxacin in the study, in silico and in vitro chemistry). Abstract only; moxifloxacin-specific values not retrieved. A listing search for moxifloxacin with copper, iron or metal complexes (10 records on the page, 37 total) found only metal-complex formulation and catalyst chemistry and no host copper measurement [28].

Mechanism

Complex formation with Cu(II) shown in vitro; competing equilibria with plasma ligands limit effect [27].

Counter-evidence held on record

Framing caution There is no evidence that moxifloxacin lowers copper; no copper supplement is implied.

Limits on what this shows

• Key null and contradicting findings: Ayele 2025 [15]: randomized phase 1 trial in healthy adults aged 18 to 40, moxifloxacin or oral vancomycin for 10 days, 16S sequencing and bile acids; the abstract states moxifloxacin "caused minimal microbial disruption", with Clostridiales species changing during therapy and secondary bile acids falling from day 0 to day 7, for a shorter period than vancomycin. Sample size, diversity indices and dose were not in the abstract, but the abstract states the trial is registered as NCT06030219, whose protocol lists moxifloxacin 400 mg once daily for 10 days and 8 volunteers per arm (the protocol is titled as an omadacycline study; the published enrollment was not retrieved) [16]. This is a Tier A source with moxifloxacin in the cohort pointing to a smaller community effect than [12][13]; the two cannot be reconciled from abstracts. Different methods (16S versus shotgun), course length (10 versus 5 days) and endpoints may explain it.
• At-risk subgroups: Not defined: the moxifloxacin cohorts are healthy adults. Hospitalized older patients on fluoroquinolones lost diversity in a 243-patient trial (less loss with the adsorbent DAV132, P = 0.003), but that abstract does not name moxifloxacin, so it is Tier C here [17].

Direction

Disturbance of the gut microbial community (a risk entry). It implies no probiotic, fiber, vitamin or other supplement, and no recommendation to avoid or change the antibiotic.

Regulatory status

Label section 5.10: "Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile"; CDAD "must be considered in all patients who present with diarrhea following antibacterial use" [1][2]. Section 12.4 lists activity against anaerobes such as Bacteroides fragilis and Clostridium perfringens [2]. Table 2 (N = 14,981): nausea 7%, diarrhea 6%, without comparator rates [1]. The label text read does not describe fecal flora changes [1][2].

Population evidence

de Gunzburg 2018 [12]: randomized controlled trial (NCT02176005), 44 healthy adult volunteers completed: moxifloxacin alone 14, moxifloxacin plus DAV132 14, DAV132 alone 8, untreated control 8; moxifloxacin 400 mg orally once daily on days 1 to 5; shotgun quantitative metagenomics. Gene richness "was strongly decreased to 54.6% of baseline value at day 6"; AUC (day 0 to 16) medians 11.63 for moxifloxacin versus 15.59 for control (an unchanged baseline would be 16); pairwise q about 1e-5 (superscript lost in the text read); baseline-species composition correlation at day 6 was 0.44 for moxifloxacin versus 0.65 for control; 86 of 252 baseline metagenomic species were affected. Decreased taxa included Alistipes, Bilophila, Butyricimonas, Coprobacillus, Faecalibacterium, Odoribacter, Oscillibacter, Parasutterella, Roseburia and Sutterella; Bacteroides, Paraprevotella and Lachnoclostridium were unaffected. Free fecal moxifloxacin peaked at 136.2 ug/g; richness in the moxifloxacin-alone group "failed to return to the initial value even at day 37". Read from the OUP article page through a summarizing fetch tool, plus the OpenAlex abstract and a BugSigDB curation page (secondary, "Needs review"). Same trial, 16S analysis [13]: 22 volunteers (14 moxifloxacin, 8 untreated), 142 fecal samples (90 treated, 52 control); baseline Shannon index 4.75 and 163 OTUs; median maximal loss 27.5% of Shannon (range 17.5 to 27.7%) and 47.4% of OTUs (range 30.4 to 48.3%), that is 1.2 Shannon units and 77 OTUs; median time to return to 95% of baseline 16.3 days (Shannon) and 21.3 days (OTUs); diversity loss tracked fecal concentration (median 130.4 ug/g by day 5; EC50 about 0.13 ug/g, 95% CI 0.01 to 2). Read through a PMC summarizer and the OpenAlex abstract. Four-antibiotic modeling paper [14]: 5-day courses of ceftriaxone, ceftazidime/avibactam, piperacillin/tazobactam or moxifloxacin 400 mg orally in healthy volunteers; moxifloxacin had the longest perturbation (median 13.2 days after the last dose, IQR 8.3 to 19.1, to return to 95% of baseline) and "the highest global impact"; diversity AUC from day 0 to 42 of -13.2 Shannon unit.day (-20.4 to -7.9). Abstract only; the trial of origin and the moxifloxacin sample size were not retrieved, and the identical dose and duration suggest it reuses the CL-1002 volunteers (not confirmed).

Mechanism

Named: antibacterial activity against susceptible commensal anaerobes and others, sustained by high colonic exposure (about a quarter of the dose is excreted in feces [1]; fecal free drug 130 to 136 ug/g [12][13]). In vitro gut-model and mouse listing lines point the same way: about 4 log10 CFU/mL drops in enterococci and the Bacteroides fragilis group and about 3 log10 in bifidobacteria and lactobacilli (chemostat, listing line only), and "extensive dysbiosis" in mice [18].

Why orange, not red

CLASS EXTRAPOLATION is not used to set this grade. Tier A with moxifloxacin: [12] (shotgun, richness to 54.6%, no recovery by day 37) and [13] (16S, Shannon -27.5%, OTUs -47.4%) appear to be the same trial (inferred from the identical dose and 14 and 8 group sizes), and [14] very likely reuses it, so they count once. [15] is an independent trial that reports minimal disruption. One real, clinically interpretable but bounded effect meets orange; the absence of a second independent concordant cohort, plus the contradicting abstract, keeps it from red.

Cohort test (excluded sources)

Edlund 1987 (enoxacin, norfloxacin), Edlund 2000 (telithromycin, clarithromycin) and Lidbeck 1988 (enoxacin, clindamycin) were opened and do not include moxifloxacin, so they are not used [33][34][35]. Ciprofloxacin volunteer cohorts exist in the sibling dossier for that drug; they were not opened here and fail the cohort test for moxifloxacin, so they are not cited.

Counter-evidence held on record

Framing caution This is a disturbance risk, not a deficiency. No probiotic, fiber or vitamin supplement is recommended by this entry. New severe or persistent diarrhea during or after a course needs clinical assessment (the label carries a C. difficile warning).

Limits on what this shows

• Key null findings: No cellular ATP content or lactate in humans after moxifloxacin was found. Ciprofloxacin did not reduce the islet NAD(P)H response at 100 uM [21].
• At-risk subgroups: Not defined.
• Counter-evidence on record: Concentrations are above clinical peak (100 uM is about 9 times the label Cmax, calculated here); species are mouse and in vitro human cells.

Direction

Reduced energy-output signal in vitro; not a nutrient deficiency and not a clinical outcome (Hard Rule 2).

Regulatory status

No ATP or energy statement in the label text read [1][2].

Population evidence

Mouse islets [21]: 100 uM moxifloxacin reduced the glucose-induced ATP/ADP rise and partially blocked glucose-induced mitochondrial hyperpolarization (gatifloxacin and ciprofloxacin showed different patterns; ciprofloxacin had no significant effect on NAD(P)H). Neutrophils (mouse model plus in vitro) [24]: reduced maximal respiration and complex I activity. PBMC [23]: mitochondrial gene depletion linked to impaired oxidative phosphorylation (10 ug/mL, 3 donors). Abstracts only.

Mechanism

Named: inhibition of mitochondrial respiratory chain components (NAD(P)H, complex I) [21][24].

Counter-evidence held on record

Framing caution This is not evidence of low energy in people taking moxifloxacin, and no supplement is implied.

Limits on what this shows

• Key null findings: No hemoglobin or oxygen-carrying measurement after moxifloxacin was found; the 1% anemia rate has no comparator and may reflect the infections treated.
• At-risk subgroups: Not defined. The G6PD association sometimes circulated for quinolones is not in the label text read.
• Counter-evidence on record: Confounding by indication (infection, comorbidity) is presumed (Hard Rule 6).

Direction

Outcome (adverse event). Anemia is not iron deficiency and a hemolytic reaction is not a nutrient deficiency (Hard Rule 2).

Regulatory status

Section 5.7 (serious adverse reactions): "Anemia, including hemolytic and aplastic"; Table 2 (N = 14,981): anemia 1%, no comparator [1][2]. G6PD deficiency is not mentioned in the label text read [1][2].

Population evidence

A PubMed listing for moxifloxacin with hemolytic anemia, methemoglobinemia or G6PD (6 records) found case reports in which hemolysis was attributed to other causes (rituximab, hemoplasma infection, G6PD deficiency in a leprosy patient treated with a moxifloxacin-containing regimen); none reports moxifloxacin-induced hemolysis, methemoglobinemia or hemoglobin values [31].

Mechanism

Absent in the sources read.

Counter-evidence held on record

Framing caution Anemia reported in a label adverse-event table is not evidence that moxifloxacin lowers iron or oxygen delivery. No iron or other supplement is implied; unexplained fatigue, dark urine or jaundice needs clinical review.