Levofloxacin

fluoroquinolone (quinolone antibacterial)

Also sold as Levaquin.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Levofloxacin has no classical depletion machinery. It is almost completely absorbed (oral bioavailability about 99%), undergoes limited metabolism (under 5% of the dose appears as two weakly active metabolites) and is cleared mainly by the kidney, with about 87% recovered unchanged in urine within 48 hours, a half-life of 6 to 8 hours and tubular secretion that cimetidine and probenecid reduce by about 24% and 35% [2][3]. No enzyme-induction or enzyme-inhibition statement appeared in the label text that could be read. The dominant nutrient relationship runs the other way: magnesium and aluminum antacids, sucralfate, iron and zinc-containing multivitamins bind the antibiotic in the gut, and the label separates the doses by 2 hours before or 2 hours after [1]. Human data retrieved for levofloxacin are sparser and smaller than for ciprofloxacin: sucralfate given 2 hours earlier did not change levofloxacin disposition in 24 volunteers, calcium carbonate spaced 2 hours away had no significant effect in healthy volunteers but lowered peak concentration by 19% in 5 adults with cystic fibrosis, and orange juice lowered absorption; no primary levofloxacin trial of iron, zinc or an aluminum or magnesium antacid was retrieved [18][19][20][21]. All of these are nutrient-to-drug timing interactions and sit in the yellow tier under Hard Rule 4; none is a depletion.

fluoroquinolone (quinolone antibacterial) · ATC J01MA12 (WHO ATC/DDD Index [4]) · also sold as Levaquin and others (Cravit and Tavanic) [6] · reviewed 2026-10-09. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Levofloxacin in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe: Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Magnesium and aluminum antacids, sucralfate: label separation of 2 hours; sucralfate given 2 hours earlier did not change levofloxacin exposure in 24 volunteers; magnesium not isolated (nutrient-to-drug timing interaction)

Yellow — Low

See study details

The label names magnesium or aluminum antacids and sucralfate as lowering levofloxacin levels, but the only primary human data retrieved (sucralfate 2 hours before the dose) show no change, so the evidence supports the spacing rule rather than a size of effect; filed as a yellow timing interaction (Hard Rule 4), not a magnesium depletion.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

Null findings: Sucralfate 2 hours before levofloxacin: no change in disposition (Lee 1997) [18]. This supports the 2-hour separation but is not a null for same-time dosing.

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4 (the nutrient affects the drug, so it is a timing interaction with a separation interval, not a depletion). Magnesium (and aluminum, a non-nutrient) bind levofloxacin in the gut. Not magnesium depletion.

Regulatory status

Label 7.1: concurrent administration with antacids containing magnesium or aluminum, or sucralfate, gives "systemic levels considerably lower than desired"; take at least two hours before or two hours after [1]. NIH magnesium fact sheet names levofloxacin (Levaquin) and gives "at least 2 hours before or 4 to 6 hours after a magnesium-containing supplement"; it does not say any fluoroquinolone lowers magnesium status [22].

Population evidence

Lee 1997 [18]: 24 healthy subjects, randomized three-way crossover, levofloxacin 500 mg; sucralfate given 2 hours before did not appear to alter levofloxacin disposition compared with fasting (half-life, clearance, renal clearance and urinary recovery similar); the authors present this as a way to avoid the interaction. AUC values in the reconstructed abstract were garbled and are not quoted. Wiesner 2024 [20]: antacids and mineral supplements mostly lowered quinolone bioavailability, calcium being the exception, and aluminum-containing antacids had a larger effect than calcium, but no levofloxacin-specific antacid values were rendered. Fish and Chow 1997 [21]: aluminum- and magnesium-containing antacids markedly reduce absorption (review). Wikipedia says peak levels "may be reduced by 90% or more" [6]; that figure is Tier D, its source was not opened, and it is not used.

Mechanism

Named: chelation by multivalent cations (label). No magnesium-alone human study with levofloxacin was retrieved.

Separation interval

Label: levofloxacin at least 2 hours before or 2 hours after magnesium or aluminum antacids and sucralfate [1]. The NIH fact sheet allows a longer interval for magnesium supplements (4 to 6 hours after); the label governs. This is the action the entry supports; it is not a nutrient recommendation.

Counter-evidence held on record

Counter-evidence and confounding Abstract-level only; the magnitude of the antacid effect on levofloxacin was not retrieved from a primary source. Framing caution A spacing rule for the antibiotic, not a magnesium deficiency or a reason to change magnesium intake. No magnesium dose is recommended here.

Zinc: multivitamins with zinc are named in the label separation rule; no levofloxacin study isolating zinc was retrieved (nutrient-to-drug timing interaction)

Yellow — Low

See study details

The label lists multivitamins with zinc among agents that lower levofloxacin absorption; no human pharmacokinetic study of zinc with levofloxacin was found, so the evidence is the label rule alone, filed as a yellow timing interaction (Hard Rule 4), not a zinc depletion.

Full detail and limits

Limits on what this shows

Null findings: None retrieved.

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4 (the nutrient affects the drug, so it is a timing interaction with a separation interval, not a depletion). Not zinc depletion.

Regulatory status

Label section 2.4: sucralfate, iron and multivitamins with zinc fall under the same two-hour separation rule [1]. Drugs.com lists supplements containing zinc at 2 hours before or 2 hours after [24]. The NIH zinc fact sheet names Cipro, not levofloxacin, and gives 2 hours before or 4 to 6 hours after [23].

Population evidence

None retrieved for levofloxacin and zinc. The Wiesner 2024 text did not mention zinc or multivitamin results for levofloxacin [20].

Mechanism

Plausible and named: chelation by divalent cations (label grouping). Not shown for zinc alone in a human study retrieved.

Separation interval

Label: levofloxacin at least 2 hours before or 2 hours after multivitamins with zinc [1]. This is the action the entry supports; it is not a nutrient recommendation.

Counter-evidence held on record

Counter-evidence and confounding Multivitamins contain other cations, so zinc may not be the responsible component; no primary study. Framing caution A spacing rule for the antibiotic, not a zinc deficiency. No zinc dose is recommended here.

Calcium, dairy and fortified juice: spacing calcium carbonate by 2 hours left levofloxacin unchanged in healthy volunteers but lowered peak concentration by 19% in 5 adults with cystic fibrosis; orange juice lowers absorption (nutrient-to-drug timing interaction)

Yellow — Low

See study details

Levofloxacin is less sensitive to calcium than the ciprofloxacin data would suggest when doses are spaced, yet a small cystic fibrosis crossover and juice studies show a modest reduction in peak exposure; filed as a yellow timing interaction (Hard Rule 4), and no calcium deficiency is implied.

Full detail and limits

Limits on what this shows

Null findings: Healthy volunteers with calcium carbonate spaced 2 hours: no significant interaction [19]. Thesis: no plasma Cmax difference [16].
At-risk subgroups: Adults with cystic fibrosis (slower intestinal transit was proposed by the authors as a reason the 2-hour spacing was not enough); people taking calcium supplements or calcium-containing antacids near doses.

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4 (the nutrient affects the drug, so it is a timing interaction with a separation interval, not a depletion). Calcium (and dairy or juice) lowers levofloxacin peak levels; not calcium depletion.

Regulatory status

The label text read did not mention calcium or dairy in the cation rule (which names magnesium or aluminum antacids, sucralfate, iron and zinc multivitamins); tablets may be taken without regard to food [1]. This is a summarizer reading and not proof of absence. The NIH calcium fact sheet names ciprofloxacin, gemifloxacin and moxifloxacin, not levofloxacin [23]. GoodRx advises separating levofloxacin from dairy "by a few hours"; Drugs.com does not mention dairy [25][24].

Population evidence

Pai 2006 [19]: open-label randomized crossover, 5 adults with cystic fibrosis and 5 matched healthy volunteers, levofloxacin 750 mg daily for 5 days alone or with calcium carbonate 500 mg three times daily with meals, spaced 2 hours from levofloxacin. Healthy volunteers: no significant interaction. Cystic fibrosis patients: Cmax lower by 19% and time to Cmax later by 37% (P < 0.05); Cmax geometric mean ratio 81.6% (90% CI 71.8% to 91.4%), outside bioequivalence limits. Wiesner 2024 [20]: levofloxacin absorption was compromised by orange juice whether or not calcium-fortified (Wallace 2003 and Sultana 2008, not opened), which suggests chelation may not be the only mechanism; calcium preparations as a group had smaller effects than aluminum antacids; the milk finding for levofloxacin was inconsistent within the review. Thesis abstract [16]: 20 healthy volunteers; fecal levofloxacin activity by MIC higher with calcium carbonate, plasma Cmax and HPLC fecal levels not different (not peer reviewed; not graded). The ciprofloxacin calcium figures (about 40% to 50% lower exposure) are a different drug and are not transferred.

Mechanism

Named for calcium: chelation in the gut. For juice, the review notes comparable effects with and without calcium fortification, so another mechanism may contribute.

Separation interval

Label rule for the listed cations is 2 hours before or 2 hours after [1]; the Pai authors argue multivalent cations should be separated as far as possible in cystic fibrosis [19]. This is the action the entry supports; it is not a nutrient recommendation.

Counter-evidence held on record

Counter-evidence and confounding One small crossover (5 per group), abstract only, and a systematic review rated low quality; no infection outcome was measured. Framing caution A spacing instruction for the antibiotic, not a calcium deficiency. Nothing here advises avoiding dairy in general or changing calcium intake. No calcium dose is recommended.

Blood glucose (hypoglycemia and hyperglycemia): label warning and two large diabetic cohorts with higher odds; a clinical outcome and drug-safety signal, not a nutrient deficiency

Yellow — Low

See study details

The label warns of symptomatic hyper- and hypoglycemia with severe cases leading to coma or death, and both a Taiwanese and a US Veterans Affairs diabetic cohort found significantly higher odds of dysglycemia events with levofloxacin than with comparators.

Full detail and limits

Limits on what this shows

Null findings: None for levofloxacin in these two cohorts (both significant). The class grade was not copied: in the same Veterans Affairs cohort ciprofloxacin was null, so the finding is drug-specific here, not a class assumption.

Direction

Outcome entry. Blood glucose is a clinical measure, not a nutrient, so this is filed as a safety signal, not a deficiency or retention finding (Hard Rule 2).

Regulatory status

Label 5.13 Blood Glucose Disturbances: fluoroquinolones "have been associated with disturbances of blood glucose, including symptomatic hyperglycemia and hypoglycemia"; "Severe cases of hypoglycemia resulting in coma or death have been reported"; careful glucose monitoring is recommended and levofloxacin should be discontinued with immediate treatment if hypoglycemia occurs. Section 6.1 Table 5 lists hypoglycemia, hyperglycemia and hyperkalemia at 0.1 to under 1% (N = 7,537). Section 7 lists antidiabetic agents as needing glucose monitoring [1].

Population evidence

Chou 2013 [26]: population-based inception cohort of 78,433 diabetic outpatients in Taiwan (levofloxacin, ciprofloxacin, moxifloxacin, cephalosporin or macrolide starters), propensity-adjusted, 30-day emergency visit or hospitalization for dysglycemia. Versus macrolides, levofloxacin adjusted OR 1.75 (95% CI 1.12 to 2.73) for hyperglycemia and 1.79 (1.33 to 2.42) for hypoglycemia (ciprofloxacin 1.87 and 1.46; moxifloxacin 2.48 and 2.13). Aspinall 2009 [27]: Veterans Affairs retrospective inception cohort 2000 to 2005, each fluoroquinolone versus azithromycin; among patients with diabetes levofloxacin hypoglycemia OR 2.1 (95% CI 1.4 to 3.3) and hyperglycemia OR 1.8 (1.2 to 2.7), versus ciprofloxacin 1.1 (0.6 to 2.0) and 1.0 (0.6 to 1.8) and gatifloxacin 4.3 and 4.5; crude rates for levofloxacin 0.19 and 0.18 per 1,000 versus azithromycin 0.07 and 0.10. Both read as abstracts; per-drug n not retrieved.

Mechanism

Not established in the sources read; the label gives none for levofloxacin and names interaction with antidiabetic agents [1].

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication (infection itself changes glycemia), different comparators (macrolides versus azithromycin), definitions and populations; both are observational and use hospital or emergency outcomes. Framing caution Safety signal for people with diabetes, especially on insulin or sulfonylureas; discuss glucose monitoring with the prescriber. Not a nutrient finding and no dietary or supplement change is implied.

Magnesium and tendon or cartilage injury: juvenile rat data with ciprofloxacin link quinolone cartilage lesions to magnesium; levofloxacin not tested (CLASS EXTRAPOLATION); no human magnesium measurement

Yellow — Low

See study details

In juvenile rats a magnesium-enriched diet cut ciprofloxacin cartilage lesions by 65%, but levofloxacin was not in that cohort and no levofloxacin tendon-magnesium study was found, so this is a class-level animal hypothesis capped at yellow.

Full detail and limits

Limits on what this shows

Null findings: No human or animal measurement of magnesium in levofloxacin-treated tendon was retrieved. The NIH magnesium fact sheet does not say any fluoroquinolone lowers magnesium status [22].

Direction

Proposed local functional magnesium deficit in cartilage caused by chelation (mechanistic, animal, other quinolone). The tendinopathy itself is a clinical outcome, not a magnesium deficiency (Hard Rule 2). No claim that levofloxacin lowers circulating magnesium.

Regulatory status

Label 5.2 Tendinitis and Tendon Rupture: risk increased over age 60, with corticosteroids, in kidney, heart or lung transplant recipients, with strenuous physical activity, renal failure and previous tendon disorders; magnesium is not named [1].

Population evidence

None in humans, none with levofloxacin. A PubMed listing "levofloxacin tendinopathy magnesium" returned 10 records, none a levofloxacin tendon-magnesium study [39].

Cohort test: CLASS EXTRAPOLATION

Pfister 2007 [38]: ciprofloxacin (not levofloxacin) 600 mg/kg subcutaneously twice in 48 juvenile Wistar rats (4 groups of 12) pre-fed normal, vitamin E, magnesium or both diets for 10 days; knee cartilage lesions 17 (normal diet), 10 (vitamin E, 41% fewer), 6 (magnesium, 65% fewer, P < 0.01) and 3 (both, 82% fewer, P < 0.01). Levofloxacin was NOT in the cohort, so this is Tier C for levofloxacin and capped at yellow. Other juvenile dog and rat studies with ciprofloxacin and ofloxacin described in the sibling ciprofloxacin dossier were not opened here and are not cited as evidence.

Circulating claim

Wikipedia states that a 2011 review in athletes suggested clinicians "consider dietary supplements of magnesium and antioxidants during treatment" [6]; the review was not opened. As a recommendation it fails verification (see that section); the underlying hypothesis is carried here.

Mechanism

Named hypothesis: chelation of magnesium in cartilage and tendon reduces functionally available magnesium; supported only by animal data with other quinolones. Magnesium products also lower levofloxacin absorption (see the Magnesium and aluminum antacids entry).

Counter-evidence held on record

Counter-evidence and confounding Juvenile animals at very high ciprofloxacin doses (600 mg/kg); the human risk factors in the label (age, corticosteroids, transplant, exercise, renal failure) are competing explanations that do not involve magnesium. Framing caution An animal mechanistic hypothesis from another quinolone. Not a recommendation to take magnesium for tendon protection (and magnesium products lower levofloxacin absorption). Report tendon pain to the prescriber promptly.

Potassium and magnesium (QT): label advises avoiding levofloxacin with uncorrected hypokalemia; hyperkalemia is listed in label trial tables; levofloxacin is not shown to lower either (status-to-drug-risk direction)

Yellow — Low

See study details

Low potassium or magnesium raises the arrhythmia risk of QT-prolonging drugs including levofloxacin per the label, and the label trial table lists hyperkalemia at 0.1 to under 1%; no source found shows that levofloxacin lowers potassium or magnesium.

Full detail and limits

Limits on what this shows

Null findings: No source found shows levofloxacin lowering potassium or magnesium; the NIH magnesium fact sheet does not list fluoroquinolones as lowering magnesium [22]; the drug-induced hypomagnesemia review (Liamis 2021) names other antibiotics, not fluoroquinolones [39].

Direction

Pre-existing electrolyte status modifies the drug risk (a safety context flag). It is not depletion of potassium or magnesium by levofloxacin (Hard Rules 2 and 4). The label hyperkalemia listing has no comparator rate and no mechanism, so it is a context flag, not an established retention effect; potassium supplementation would be the hazard, not the remedy (Hard Rule 5).

Regulatory status

Label 5.11 Prolongation of the QT Interval: levofloxacin "should be avoided in patients with known prolongation of the QT interval" and, per the summarized text, those with uncorrected hypokalemia. Table 5 of section 6.1 lists hyperkalemia among less common reactions (0.1 to under 1%, N = 7,537) [1]. GoodRx lists low potassium as a QT risk factor [25].

Population evidence

Moghnieh 2023 [33]: retrospective cohort of 68 transplant recipients on levofloxacin plus a triazole, QTc prolongation in 22%, day-3 hypomagnesemia only a non-significant trend, no serious arrhythmias or deaths. Stahlmann 2003 and 2010 [33]: reviews advising avoidance in uncorrected hypomagnesemia (QT). Case reports [33]: Kushner 2001, seizures after levofloxacin in an older woman who was hypomagnesemic with raised creatinine; Ambhore 2014, long QT worsened by hypomagnesemia and drugs including levofloxacin; two drug-resistant tuberculosis cases with low magnesium, potassium and calcium that resolved after the aminoglycoside was stopped and were attributed to kanamycin, not levofloxacin.

Mechanism

Hypokalemia is named in the label as predisposing; QT prolongation itself is a class pharmacology effect (channel mechanism not retrieved).

Counter-evidence held on record

Counter-evidence and confounding Underlying illness, renal function and co-medication (triazoles, chemotherapy) are competing explanations in each report; the label statement is class-wide. Framing caution A safety context flag. Not a reason to take potassium or magnesium supplements (magnesium products also lower levofloxacin absorption). Any electrolyte correction belongs to the prescriber.

Vitamin K and INR: label advises close INR monitoring with warfarin; cohorts conflict; vitamin K never measured

Yellow — Low

See study details

The label says levofloxacin may enhance warfarin effect and lists prolonged prothrombin time and INR postmarketing, but small cohorts found no consistent INR rise and no study measured vitamin K, PIVKA or menaquinone.

Full detail and limits

Limits on what this shows

Null findings: McCall 2005 and Yamreudeewong 2003 found no significant mean INR change; vitamin K was not measured in any record read (it appears only as treatment in Mathews 2006) [32].

Direction

Drug-drug interaction signal. Not a dietary vitamin K deficiency; supplementing vitamin K would oppose warfarin (Hard Rules 2 and 4).

Regulatory status

Label 7.2: levofloxacin "enhances the effects of warfarin" in postmarketing reports with episodes of bleeding; prothrombin time and INR should be monitored closely; 6.2 lists prothrombin time and INR prolonged [1]. Vitamin K is not mentioned in the label text read.

Population evidence

McCall 2005 [32]: 22 on levofloxacin versus 21 on felodipine, mean INR change 0.31 +/- 0.82 versus 0.21 +/- 0.54 (P = 0.65). Yamreudeewong 2003 [32]: 18 patients, INR 2.61 +/- 0.44 before versus 2.74 +/- 0.83 after (95% CI -0.449 to 0.196, P = 0.419), warfarin dose changed in 7. Mathews 2006 [32]: 54 on levofloxacin versus 38 on gatifloxacin, INR above 4 in 2% versus 21% (P = 0.003), vitamin K administered in 0% versus 11%. Mercadal Orfila 2009 [32]: 21 analyzed, significant INR rise (P = 0.001). Jones 2002 [32]: 4 case reports, INR up to 3.5, 8.12 and 11.5. Carroll 2008 [32]: review of 22 publications, no consistent INR rise across ciprofloxacin, levofloxacin and moxifloxacin.

Mechanism

Not established in the sources read; fewer vitamin K-producing intestinal bacteria is a speculation not tested for levofloxacin, and the gut microbiome entry shows richness loss but no vitamin K change.

Counter-evidence held on record

Counter-evidence and confounding Infection, reduced intake, antibiotic-induced diarrhea and warfarin dose adjustments are competing explanations; the cohorts are small and retrospective. Framing caution Monitoring prompt for anticoagulated patients, not a vitamin K deficiency claim. Do not recommend vitamin K supplements.

Sodium: one case report names levofloxacin as a possible contributor to severe hyponatremia (dilutional/SIADH direction, not a deficiency)

Yellow — Low

See study details

A single case report lists levofloxacin among four possible contributors to SIADH-type hyponatremia; no cohort supports a levofloxacin effect on sodium.

Full detail and limits

Limits on what this shows

Null findings: No cohort shows levofloxacin lowering sodium.

Direction

Disturbance (dilutional/SIADH), not dietary sodium deficiency. Retention of water, not loss of sodium intake, is the proposed mechanism; salt supplementation would be the hazard, not the remedy (Hard Rule 5).

Regulatory status

No hyponatremia statement appeared in the label text read [1].

Population evidence

Mocan 2016 [34]: n = 1, a patient with pneumonia and throat cancer treated with cisplatin; levofloxacin named as one of four possible causes (with throat cancer, cisplatin and pneumonia); the authors call it the first case related to levofloxacin. In the same listing, Moghnieh 2023 (68 transplant recipients) found day-6 hyponatremia not associated with QTc (P = 0.36), and the other records implicated infection (Legionella), SIADH of other causes or levofloxacin only as treatment.

Mechanism

SIADH proposed by the case authors; not established.

Counter-evidence held on record

Counter-evidence and confounding Cisplatin, cancer and pneumonia are each independent causes of hyponatremia; one case cannot show causation. Framing caution A rare-event case signal, not a deficiency. No sodium or salt change is implied; hyponatremia symptoms (confusion, nausea, seizures) need clinical assessment.

B vitamins (thiamine, B6, B12, folate), including B vitamins in tendinopathy

Not graded — disclosed evidence gap

See study details

No evidence was found that levofloxacin alters thiamine, vitamin B6, vitamin B12 or folate status, or that B vitamins change levofloxacin tendon outcomes, and no circulating claim naming these vitamins for levofloxacin was found. (Vitamin K is graded separately.)

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

Why no grade: Dual condition met: no Tier B or C source found to support even a yellow grade, and no circulating consumer claim found to rebut. This is a disclosed gap, not a finding of safety. Re-check with open-web search restored, and with PubMed queries "levofloxacin vitamin B12", "levofloxacin thiamine", "levofloxacin folate" and "fluoroquinolone neuropathy vitamin B".

What was searched

Label text read (no B vitamin mentioned) [1]. PubMed listings run 2026-10-09: "levofloxacin vitamin B6 OR pyridoxine OR cobalamin OR thiamine OR folate" (10 records, all reviews of B vitamins in pain, nervous system, dermatology or migraine, none mentioning levofloxacin); "levofloxacin pyridoxine" (9 records: tuberculosis and other case reports in which pyridoxine was prescribed alongside levofloxacin as part of a regimen, an iron-oxide sensor paper and a guideline; none measured vitamin B6 status or tested B6 as an intervention); "levofloxacin tendinopathy magnesium" (10 records; no B vitamin and no levofloxacin tendon study) [39]. Consumer pages: Drugs.com and GoodRx name no vitamin depletion and recommend no probiotic or supplement [24][25]; Wikipedia pages for levofloxacin and fluoroquinolone toxicity make no B vitamin claim [6][7]. NIH Office of Dietary Supplements fact sheets for B6, B12 and thiamin: the medication interaction sections name no quinolone or levofloxacin [40].

Not retrieved

The PubMed listings "levofloxacin vitamin deficiency" and "levofloxacin cobalamin" and a Crossref B12 query were rate limited (HTTP 429) and not read; separate thiamine and folate listings for levofloxacin were not run. The open-web search budget ran out, so consumer claims were checked only on pages fetched directly. Fluoroquinolone neuropathy and tendinopathy cohorts, where a B vitamin measurement could sit, were not individually searched beyond the tendon-magnesium listing.

Channel outcomes

Mostly a genuine gap: two vitamin-specific listings that opened returned no status measurement, the three NIH fact sheets name no fluoroquinolone and no consumer page asserted a levofloxacin B-vitamin loss. Residual tooling limits: no open-web search and rate-limited PubMed listings.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden: levofloxacin inhibits respiratory chain complexes I and III in cultured cancer cell lines and affects complexes I and IV in human cells; no human tissue measurement

Yellow — Low

See study details

Several in vitro and xenograft studies with levofloxacin report mitochondrial dysfunction, but they used cancer or engineered cell lines, no concentration was retrievable from the abstracts, one 3D human liver model showed no injury, and no cohort measured mitochondrial function in treated people.

Full detail, limits and 1 references

Limits on what this shows

Null findings: Kaden 2023: in a 3D human liver microphysiological model trovafloxacin caused toxicity while levofloxacin caused no tissue injury [29]. Normal breast cells were spared in the Yu 2016 cancer study. No study quantified the effect at plasma concentrations from ordinary dosing.
Dose relevance: Concentrations were not retrievable from the abstracts, so no comparison with clinical plasma levels can be made. The only clinical plasma peak retrieved is 5.1 to 5.9 ug/mL after a single 500 mg oral dose in the Lee 1997 volunteer data [18].

Direction

Drug-to-cell injury (a mechanistic toxicity signal). Not a nutrient deficiency and no supplementation implication (Hard Rule 2).

Regulatory status

No mitochondrial statement appeared in the label text read; tendinitis, peripheral neuropathy and other serious reactions are listed outcomes, not mitochondrial findings [1].

Population evidence

None in humans.

In vitro and animal evidence (Tier B)

Song 2016 [28]: lung cancer cell lines and a xenograft; levofloxacin inhibited electron transport chain complexes I and III, lowering respiration and ATP, and N-acetylcysteine and vitamin C blocked the effects. Reinhardt 2025 [29]: in human cells ciprofloxacin and levofloxacin caused mitochondrial dysfunction, mainly complexes I and IV, through the off-targets AIFM1 and IDH2 (OpenAlex abstract; no numeric values). Yu 2016 [29]: breast cancer cell lines, framed as inhibition of mitochondrial biogenesis, with normal breast cells spared. Hardgrave 2025 [29]: mitochondrial hyperpolarization in macrophages. Huang 2026 [29]: loss of membrane potential and ROS accumulation in colorectal cancer cells when combined with 5-fluorouracil. Concentrations and magnitudes were not in the abstracts read.

Cohort test: Kalghatgi 2013

Kalghatgi et al. (Sci Transl Med 2013; PMID 23825301) tested quinolones, aminoglycosides and beta-lactams in mammalian cells and mice. The abstract names classes, not drugs, and the full text could not be opened (PMC returned a bot-verification page; Science errored), so this review could NOT confirm that levofloxacin was among the drugs tested. It is used only as CLASS EXTRAPOLATION (quinolone class), capped at yellow, and levofloxacin is not claimed to be in the cohort [30].

Mechanism

Named: electron transport chain complexes I, III and IV inhibition and off-target binding of AIFM1 and IDH2 in cell studies [28][29].

Counter-evidence held on record

Counter-evidence and confounding Cancer and engineered cell lines, unknown concentrations, short exposures and no human tissue; the one human liver tissue model with levofloxacin was negative. The sibling ciprofloxacin dossier reports similar in vitro findings for that drug; they are not transferred. Framing caution A mechanistic signal, not a deficiency and not a finding that therapeutic courses damage mitochondria in people. No antioxidant or mitochondrial supplement is recommended by this entry.

Kalghatgi S, Spina CS, Costello JC, et al. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Sci Transl Med 2013;5(192):192ra85. PMID 23825301. — Tier B/C. Abstract read as an OpenAlex reconstruction (paraphrased): clinically relevant doses of quinolones, aminoglycosides and beta-lactams cause mitochondrial dysfunction and ROS overproduction in mammalian cells, oxidative stress markers rose in treated mice, and N-acetyl-L-cysteine alleviated the effects. The abstract names classes, not drugs.Full text NOT opened (PMC returned a bot-verification page, Science errored), so whether levofloxacin was among the drugs tested is UNCONFIRMED. Used as CLASS EXTRAPOLATION only.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress: higher ROS in cultured cancer cells and oxidative injury markers in high-dose rat studies; no human marker data

Yellow — Low

See study details

Cell and animal studies with levofloxacin show higher ROS, malondialdehyde and altered antioxidant enzymes at high exposures, but no human or clinical-dose marker study was found.

Full detail and limits

Limits on what this shows

Null findings: Donmez 2022 found tissue-dependent directions rather than a uniform rise [31]. No human or clinical-dose study was found either way.

Direction

Drug-to-cell and drug-to-tissue redox burden (mechanistic). Not an antioxidant-nutrient deficiency (Hard Rule 2).

Regulatory status

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

Population evidence

None in humans. No trial or cohort measuring MDA, glutathione or antioxidant enzymes in levofloxacin users was found in a PubMed listing ("levofloxacin oxidative stress malondialdehyde"): all ten records were rats, plants or algae [31].

Cell and animal evidence (Tier B)

Song 2016 [28]: lung cancer cells, higher ROS, mitochondrial superoxide and hydrogen peroxide in vitro and higher HEL and 4-HNE in the xenograft in vivo; N-acetylcysteine and vitamin C blocked the effects. Rat toxicity models [31]: levofloxacin 40 mg/kg every other day for 2 months raised testicular MDA (Zaki 2024, 50 rats); 40 mg/kg raised MDA and nitric oxide with liver and kidney injury (Zaki 2025); 50 or 100 mg/kg/day raised creatinine, urea and MDA, with vitamin D lowering them (Mhaibes 2023, 42 rats); 40 mg/kg/day for 2 weeks raised liver enzymes and oxidative markers (Farid 2020); 40 mg/kg/day for 14 days changed SOD, CAT, GPx, MPO, ADA and GSH with tissue-dependent direction (Donmez 2022, 72 rats). These doses are high relative to human dosing.

Cohort test: Kalghatgi 2013

The abstract reports oxidative stress markers in the blood and tissue of mice after bactericidal antibiotics, but levofloxacin was not confirmed to be in the cohort (full text unopened): CLASS EXTRAPOLATION, yellow cap [30].

Counter-evidence held on record

Counter-evidence and confounding Animal models at doses well above human exposure, protective-agent designs whose controls are not general-population controls, and cancer cell lines; the same cell work supplies the mitochondrial and ATP entries. Framing caution A mechanistic signal only. No antioxidant supplement is recommended; the N-acetylcysteine, vitamin C and vitamin D results are cell or rat findings, not treatment advice.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron: iron lowers levofloxacin absorption (nutrient-to-drug timing interaction, not an iron depletion)

Yellow — Low

See study details

The label separates levofloxacin from iron by 2 hours before or 2 hours after and a pharmacokinetics review states ferrous sulfate markedly reduces absorption; the iron affects the antibiotic, so this is a yellow timing interaction (Hard Rule 4) and implies no iron deficiency.

Full detail and limits

Limits on what this shows

Null findings: None found specific to oral iron. No iron-status measurement (ferritin, hemoglobin) in levofloxacin users was found.
At-risk subgroups: People taking iron tablets or iron-containing products near levofloxacin doses.

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4 (the nutrient affects the drug, so it is a timing interaction with a separation interval, not a depletion). Iron salts chelate levofloxacin in the gut and lower its absorption. Levofloxacin is not shown to lower iron status; that drug-to-mineral question is carried in the ungraded entry on systemic mineral status.

Regulatory status

Label sections 2.4 and 7.1: metal cations such as iron fall under the rule that levofloxacin be taken "at least two hours before or two hours after", and combined administration gives "systemic levels considerably lower than desired" [1]. Drugs.com and GoodRx patient pages repeat the 2 hour interval for iron [24][25]. The NIH iron fact sheet does not name any quinolone [23].

Population evidence

No primary levofloxacin-iron crossover study was retrieved. A PubMed listing "levofloxacin ferrous sulfate" returned only the Fish and Chow 1997 pharmacokinetics review, whose abstract says ferrous sulfate and aluminum- or magnesium-containing antacids markedly reduce levofloxacin absorption and advises separating doses by at least 2 hours; no percentage is printed in the abstract [21]. The Wiesner 2024 systematic review text did not mention ferrous sulfate for levofloxacin [20]. The ciprofloxacin iron figures (about 46% to 63% lower exposure) are a different drug and are not transferred.

Mechanism

Named: chelation of the quinolone by multivalent cations in the gut (label wording: antacids and metal cations; Hard Rule 4 treats the nutrient-to-drug direction) [1].

Separation interval

Label: levofloxacin at least 2 hours before or 2 hours after iron products and the other cations listed [1]. This is the action the entry supports; it is not a nutrient recommendation.

Counter-evidence held on record

Counter-evidence and confounding The clinical consequence (treatment failure) is an inference from reduced exposure, not a measured outcome in the sources read. Framing caution This is a timing rule for the antibiotic, not an iron-deficiency finding. Do not stop or start iron because of it; follow the label spacing from the prescriber or pharmacist. No iron dose is recommended here.

Copper: levofloxacin forms a copper(II) complex in the laboratory; no human or animal copper status measurement

Yellow — Low

See study details

A chemistry paper describes a copper(II) levofloxacin ternary complex, but nothing in the sources read measured copper status in a levofloxacin-treated person or animal.

Full detail and limits

Limits on what this shows

Null findings: None needed; no measurement exists to be null.

Direction

Drug-to-copper chelation (chemistry only). Not a copper deficiency or excess finding. Kept separate from the Iron entry (Hard Rule 7).

Regulatory status

The label text read lists magnesium, aluminum, iron and zinc as cations; copper is not named [1].

Population evidence

None. A PubMed listing "levofloxacin copper serum OR ceruloplasmin OR complex" returned ten records on copper and ceruloplasmin biology and diagnostics, none involving levofloxacin [39]. No human copper, ceruloplasmin or urinary copper measurement in levofloxacin users was retrieved.

Chemistry evidence (Tier B)

Sousa 2012 (J Inorg Biochem) is a synthesis, crystal-structure and antibacterial study of a copper(II) levofloxacin ternary complex; only its metadata and index keywords (co-ligand, crystal structure, MIC against E. coli) were retrieved and the abstract was not opened [37]. It concerns copper as a pharmaceutical complex, not body copper.

Mechanism

Named: metal-ion coordination by the quinolone keto-carboxylate group (the same property behind the label cation rule). No copper-handling mechanism in the body was shown.

Counter-evidence held on record

Counter-evidence and confounding The complex was made for antibacterial chemistry; it says nothing about copper status in treated patients, and the abstract was not read. Framing caution No copper supplement or restriction is implied. This is a chemistry note.

Systemic iron, zinc, calcium and magnesium status lowered by levofloxacin (drug-to-mineral direction)

Not graded — disclosed evidence gap

See study details

No human, animal or in vitro source was found showing that levofloxacin lowers body iron, zinc, calcium or magnesium status or raises their excretion, and no circulating claim of that direction was found; the documented direction is the minerals lowering levofloxacin absorption (graded above).

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

Why no grade: Dual condition met: no Tier B or C source found for a systemic mineral status effect, and no circulating claim of that direction found. Not a finding of safety. Re-check with PubMed restored for single-mineral listings ("levofloxacin zinc", "levofloxacin serum iron", "levofloxacin ferritin"), each as its own simple query.

What was searched

Label text read: cations are listed only as agents that lower levofloxacin absorption [1]. NIH fact sheets for magnesium, zinc, calcium and iron: interactions run nutrient-to-drug only and none says a fluoroquinolone lowers mineral status [22][23]. Consumer pages (Drugs.com, GoodRx) and Wikipedia levofloxacin and fluoroquinolone toxicity pages: mineral statements run nutrient-to-drug [24][25][6][7]. PubMed listings run 2026-10-09: "levofloxacin hypomagnesemia" (7 records: two geriatric safety reviews that advise avoiding fluoroquinolones in uncorrected low magnesium, a QTc cohort with a non-significant magnesium trend, a seizure case with pre-existing low magnesium, and two tuberculosis cases with low magnesium, potassium and calcium attributed to kanamycin) [33]; "levofloxacin magnesium deficiency OR hypomagnesemia" (10 general magnesium reviews; the drug-induced hypomagnesemia review does not name fluoroquinolones) [39]; "levofloxacin hypocalcemia" (3 records: the same QTc cohort in which baseline hypocalcemia was not associated with QTc, P = 0.3, and the same two tuberculosis cases, whose low calcium was attributed to the aminoglycoside-class drug, kanamycin or capreomycin, not levofloxacin) [33]; "levofloxacin copper serum OR ceruloplasmin OR complex" (off-topic) [39]; "levofloxacin tendinopathy magnesium" (no levofloxacin study) [39].

Not retrieved

Single-mineral listings for zinc and iron status with levofloxacin (for example "levofloxacin zinc", "levofloxacin ferritin") were not read: the zinc listing was rate limited (HTTP 429) and the iron listing was not run, so the gap is better established for magnesium and calcium than for zinc and iron. The open-web search budget ran out.

Channel outcomes

Mixed. Magnesium is a reasonably established null (the only human records attribute low magnesium to other drugs or give no cause). Calcium now has its own null listing (no record implicates levofloxacin); zinc and iron status are covered only by the label, the NIH fact sheets, consumer pages and the magnesium and copper listings, so those two are partly tooling-limited.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk: transient lower fecal richness after 5 to 7 day courses of levofloxacin, back to baseline richness by about day 19 in healthy volunteers; not seen consistently in leukemia and transplant patients

Orange — Moderate

See study details

Two Tier A human studies with levofloxacin in the cohort report lower fecal richness or diversity after a short course (a 20-volunteer randomized trial of four regimens, and a patient study with a levofloxacin group), but two patient cohorts on levofloxacin prophylaxis report little or no diversity loss; this is a bounded community disturbance risk, not a nutrient deficiency.

Full detail, limits and 1 references

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

Null and contradicting findings: Rashidi 2019 [12]: two patient cohorts (acute leukemia on intensive chemotherapy and allogeneic transplant recipients; 40 patients per the PubMed line), stool about three times weekly, levofloxacin exposure periods versus none: only Parabacteroides (coefficient -0.063) and Blautia (+0.050) changed, other taxa and overall diversity were unaffected, and the authors call the effect mild. Ziegler 2019 (news report only) [13]: in 60 hematologic malignancy patients Shannon diversity was 3.83 with versus 3.32 without levofloxacin (P =.03); primary paper not identified. C. difficile in prophylaxis populations [17]: in children with leukemia, levofloxacin prophylaxis was associated with less C. difficile infection (RR 0.08, 95% CI 0.01 to 0.62), and a second review found OR 0.43 (95% CI 0.00 to 42.30); these populations differ from outpatient use and do not cancel the label warning. Calcium trial [16]: in an unpublished thesis the Shannon index fell with levofloxacin plus calcium carbonate (P = 0.0019); the split between groups and the levofloxacin-only change were not stated and it is not used for grading.
At-risk subgroups: Not defined by these studies. Healthy adults (Anthony) and patients with unspecified indications (Panda) lose richness; patients already on chemotherapy and other antibiotics did not show it (Rashidi). Older adults and repeated courses were not studied in the sources read.

Direction

Disturbance of the gut microbial community (a risk entry). It implies no supplement, probiotic or fiber recommendation.

Regulatory status

Label section 5.10 carries the Clostridium difficile-associated diarrhea warning for levofloxacin, and in the pooled trials nausea occurred in 7% and diarrhea in 5% of 7,537 patients (Table 4) [1].

Population evidence

Anthony 2022 / conference abstract [9][10][11]: 20 healthy volunteers randomized to levofloxacin, azithromycin, cefpodoxime, or azithromycin plus cefpodoxime for 5 days, 15 stool time points. Diversity and richness fell in the first week for all volunteers (P <.01); pooled across all four regimens richness fell by a mean of 11.5 species at day 6 and culturable bacteria by 4.78 log CFU (aerobic) and 2.90 log (anaerobic); the non-azithromycin groups, levofloxacin among them, returned to baseline richness and culturable counts by day 19; the levofloxacin group showed no significant change in resistance burden; the conference abstract states that after all antibiotics except levofloxacin the microbiomes lost diversity and moved toward an intensive-care-like profile, and that about 10% of volunteers did not recover. Arm size and levofloxacin-only indices were not retrieved; read via institutional abstract pages, a conference abstract and two secondary summaries. Panda 2014 [8]: 21 patients on fluoroquinolones or beta-lactams, fecal samples before treatment and one week later; both classes lowered diversity by about 25% and the core microbiota fell from 29 to 12 taxa. The curated levofloxacin experiment (7 days, 8 before versus 8 exposed) reports lower Chao1 and richness with multiple-testing correction, higher Phocaeicola plebeius, Bacteroides, Coprococcus and Oscillospiraceae and lower Blautia. The levofloxacin-only percent change was not retrieved; full text not opened. Supporting, combination regimen [14]: in the 560-patient EAML14 trial of levofloxacin-based quadruple therapy for H. pylori, diversity dipped at week 2 and mostly recovered by 1 year, resistome up at week 2 and baseline by week 8; levofloxacin was given with other drugs, so this is Tier C for levofloxacin alone and does not count toward the grade. Animal [15]: 4-day levofloxacin lowered alpha and beta diversity in mice (Gu 2020), while in another mouse comparison levofloxacin had the smallest effect of four antibiotics (Wang 2022).

Mechanism

Antibacterial activity against susceptible commensal bacteria is the proposed mechanism; no cohort tested a mechanism and the label states only the C. difficile warning [1].

Cohort test

Levofloxacin is named in every study counted above (Anthony 2022 arm, Panda 2014 curated experiment, Rashidi 2019 exposure, Liou 2023 regimen). Dethlefsen 2008 and the Zaura 2015 / Rashid 2015 placebo-controlled trial, which carry the red grade in the sibling ciprofloxacin dossier, studied ciprofloxacin and are Tier C here (CLASS EXTRAPOLATION: levofloxacin NOT in the cohort); I did not open them and do not use them. No Dubourg-group levofloxacin cohort was found: the one Dubourg-group page opened (a 2018 Emerging Infectious Diseases culturomics table) names no fluoroquinolone [41].

Why orange, not red (and its edge)

Orange: at least one Tier A source with levofloxacin in the cohort (a randomized trial with a pre-treatment baseline and P <.01) shows a real, bounded effect (5 to 7 day courses, richness recovering within weeks in non-azithromycin arms). Not red: the second consistent cohort (Panda) gives no levofloxacin-only effect size, the Anthony numbers are pooled across drugs, and two patient cohorts with levofloxacin run the other way (Rashidi, Ziegler), which is substantial contradicting evidence. It could rise to red with levofloxacin-only indices from the Anthony 2022 supplement and an explanation for the leukemia-cohort null.

Counter-evidence held on record

Counter-evidence and confounding Infection itself, diet and co-medication confound patient studies; volunteer arms are small (about 5 per arm if the 20 volunteers split evenly, not stated); the Panda group totals (15) do not match its abstract (21); the strongest levofloxacin-only numbers sit in figures and supplements that were not seen. 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).

Panda S, El khader I, Casellas F, et al. Short-term effect of antibiotics on human gut microbiota. PLoS One 2014;9(4):e95476. PMID 24748167; DOI 10.1371/journal.pone.0095476. — Tier A (longitudinal study of patients; fecal samples before treatment and one week after; 16S pyrosequencing and quantitative PCR). Abstract read as an OpenAlex reconstruction (paraphrased by the fetch tool): 21 patients on broad-spectrum fluoroquinolones or beta-lactams; both classes lowered diversity by about 25% and shrank the core phylogenetic microbiota from 29 to 12 taxa; Bacteroidetes to Firmicutes ratio rose; several Bacteroides taxa increased. Levofloxacin-specific data come from the BugSigDB curation of this paper (Study 376, Experiment 2: levofloxacin for 7 days, 8 before versus 8 exposed, Spain, fecal 16S V4 on Roche 454, ANOVA with multiple-testing correction, Chao1 and richness decreased; increased: Phocaeicola plebeius, unclassified Bacteroides, Coprococcus and Oscillospiraceae; decreased: unclassified Blautia).Full text NOT opened: the PLoS One page and the PubMed record returned HTTP 429, the PMC copy returned a bot-verification page and the printable PDF was rate limited. The curated database is a secondary record. The abstract says 21 patients while the curated groups total 15 (amoxicillin-clavulanate 7, levofloxacin 8), an unexplained mismatch. The conditions of the patients and a levofloxacin-only percent change were not retrieved.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production: lower ATP reported in lung cancer cell lines (abstract only, no value); no human measurement

Yellow — Low

See study details

ATP was reported as reduced in one levofloxacin cell study whose abstract prints no value; no in vivo or human ATP measurement was found.

Full detail and limits

Limits on what this shows

Null findings: None for levofloxacin and ATP specifically; the 3D human liver model with levofloxacin showed no tissue injury (Kaden 2023) but did not report ATP in the listing read [29].

Direction

Drug-to-cell energy effect (mechanistic). Not a nutrient deficiency (Hard Rule 2).

Regulatory status

No ATP statement appeared in the label text read [1].

Population evidence

None in humans.

Cell evidence (Tier B)

Song 2016 [28]: inhibition of complexes I and III lowered mitochondrial respiration and ATP production in lung cancer cell lines; the antioxidants N-acetylcysteine and vitamin C blocked the effects. No percentage or concentration is printed in the abstract. Reinhardt 2025 describes mitochondrial dysfunction in human cells without an ATP value in the abstract [29].

Cohort test

Ciprofloxacin ATP data (for example in a T-cell line) are summarized in the sibling ciprofloxacin dossier; that is a different drug, was not opened here and is not used. Kalghatgi 2013 gives no ATP value in its abstract and levofloxacin cohort membership is unconfirmed [30].

Counter-evidence held on record

Counter-evidence and confounding One cell system, abstract only, no concentration; the same source underlies the mitochondrial and oxidative stress entries. Framing caution A cell-level mechanistic note, not evidence that levofloxacin lowers energy in people. No energy or mitochondrial supplement is recommended.

Oxygen delivery/utilization: label-listed hemolytic and aplastic anemia and pancytopenia; a case report of autoimmune hemolysis; no hemoglobin cohort (adverse outcome, not a nutrient deficiency)

Yellow — Low

See study details

The label lists anemia including hemolytic and aplastic, pancytopenia and anemia at 0.1 to under 1% in pooled trials, and a case report documents Coombs-positive hemolysis, but no cohort measured hemoglobin or red-cell mass in levofloxacin users and the large G6PD database study does not mention levofloxacin.

Full detail and limits

Limits on what this shows

Null findings: None for levofloxacin. The G6PD cohort is a null for two other fluoroquinolones, not for levofloxacin.

Direction

Adverse-outcome entry (hematologic reaction). Anemia is not iron deficiency and this is not an oxygen-delivery nutrient finding (Hard Rule 2). Distinct from the Iron entry, which concerns absorption of the antibiotic.

Regulatory status

Label 5.6 lists "anemia, including hemolytic and aplastic" and pancytopenia among rare serious reactions; 6.2 postmarketing lists hemolytic anemia and pancytopenia; Table 5 of section 6.1 (0.1 to under 1%, N = 7,537) lists anemia, thrombocytopenia and granulocytopenia without a comparator rate [1]. No G6PD text appeared in the label text read.

Population evidence

Sheikh-Taha 2014 [36]: a 32-year-old woman with fatigue, fever and jaundice after levofloxacin for a urinary tract infection; hemoglobin 6.7 g/dL falling to 5 g/dL by day 2, direct Coombs test positive, indirect bilirubin 5.5 mg/dL, LDH 1283 IU/L, other causes excluded, gradual recovery after stopping levofloxacin. Gronich 2024 [35]: 31,962 G6PD-deficient patients, 71 hospitalized major hemolysis cases (0.2%); ciprofloxacin and ofloxacin were among drugs prescribed safely without hemolysis, levofloxacin is not mentioned, so the study gives no levofloxacin-specific data (CLASS context only, Tier C, not graded above yellow).

Mechanism

Immune (Coombs-positive) hemolysis in the case report; no G6PD mechanism established for levofloxacin in the sources read.

Counter-evidence held on record

Counter-evidence and confounding A case report cannot establish frequency; infection in the indication is a competing explanation for anemia; the pooled-trial table has no comparator arm. Framing caution A label-listed adverse reaction. Unexplained pallor, dark urine, jaundice or marked fatigue during a course needs clinical assessment; iron supplements are not the remedy and also lower levofloxacin absorption.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

"Floxing": levofloxacin damages mitochondria and causes a lasting syndrome through oxidative stress and magnesium chelation at ordinary doses
Where it comes from: Wikipedia "Fluoroquinolone toxicity" (Tier D) says some fluoroquinolones inhibit mitochondrial DNA synthesis, links toxicity to oxidative stress and uses the term "floxing", sourced to an unattributed 2023 North Carolina Medical Society piece that was not opened. Levofloxacin is not named in those passages [7].
Why it fails: The stronger clinical claim fails: no human measurement of mitochondrial function, oxidative markers or magnesium in levofloxacin users was found. The mechanistic parts are carried as yellow entries (cultured cancer cell lines, rat toxicity models, unconfirmed class study), none of which gives a concentration comparable with dosing; a 3D human liver model showed no levofloxacin injury [28][29][31]. The label lists tendon, nerve and other serious reactions as outcomes, not mitochondrial or magnesium findings [1].
"Take magnesium and antioxidant supplements during levofloxacin treatment to protect tendons and joints" (recommendation form)
Where it comes from: Wikipedia "Levofloxacin" (Tier D) cites a 2011 review in athletes suggesting clinicians "consider dietary supplements of magnesium and antioxidants during treatment"; the review was not opened [6].
Why it fails: No human trial or levofloxacin animal study of this supplementation was found; the only supporting animal work retrieved used ciprofloxacin in juvenile rats at 600 mg/kg [38]. A magnesium supplement also lowers levofloxacin absorption and must be separated by the label interval [1][22]. The recommendation fails; the underlying hypothesis is carried as a yellow class-extrapolation entry.
"Levofloxacin is blocked by calcium and dairy as strongly as ciprofloxacin; avoid all dairy" (overstated, copied from ciprofloxacin)
Where it comes from: Consumer wording such as GoodRx ("separate levofloxacin from any dairy products ... by a few hours") [25]; the large ciprofloxacin literature on calcium and milk is not levofloxacin data.
Why it fails: For levofloxacin, calcium carbonate spaced 2 hours had no significant effect in healthy volunteers and lowered peak concentration 19% in a small cystic fibrosis crossover; the label allows tablets without regard to food; the NIH calcium fact sheet does not name levofloxacin [19][1][23]. The interaction is real but modest and handled by spacing, not prohibition (see the Calcium, dairy and fortified juice entry).

How the body handles this medication

Metabolism and enzymes: Limited metabolism: only two metabolites identified in humans (desmethyl-levofloxacin and levofloxacin-N-oxide), together under 5% of the dose, with little pharmacological activity; stereochemically stable in plasma and urine. No CYP450 induction or inhibition statement appeared in the label text read, and the label states levofloxacin had no significant effect on theophylline in healthy volunteers.[2]; [3]; [1]
Elimination: Mainly renal: about 87% recovered unchanged in urine within 48 hours (under 4% in feces by 72 hours per Wikipedia, Tier D); terminal half-life about 6 to 8 hours. Renal clearance exceeds glomerular filtration, so tubular secretion occurs; cimetidine and probenecid lower renal clearance by about 24% and 35% and the label says these changes do not warrant dose adjustment.[2]; [3]; [1]; [6]
Absorption and food: Rapid and essentially complete absorption (oral bioavailability about 99%). Tablets may be taken without regard to food; food delays the peak by about 1 hour and lowers peak concentration by about 14%. In 24 healthy volunteers a high-fat meal moved time to peak from 1.0 to 2.0 hours and peak from 5.9 to 5.1 ug/mL without meaningful change in overall exposure. No named absorption transporter was found in the text read.[2]; [1]; [18]
Distribution: Plasma protein binding about 24% to 38%, mainly to albumin. The label notes pediatric patients cleared levofloxacin faster than adults.[2]
Renal and hepatic handling: Clearance is substantially reduced and half-life substantially prolonged in renal impairment; neither hemodialysis nor continuous ambulatory peritoneal dialysis removes levofloxacin effectively; pharmacokinetic studies in hepatic impairment have not been conducted, and the label cites the limited extent of metabolism.[2]; [1]
Interactions of nutritional interest: Section 7.1 and 2.4: antacids containing magnesium or aluminum, sucralfate, metal cations such as iron, and multivitamins with zinc give "systemic levels considerably lower than desired"; take levofloxacin at least 2 hours before or 2 hours after them. Warfarin: effect may be enhanced, monitor closely. Antidiabetic agents: monitor blood glucose. Calcium was not mentioned in the label text read.[1]; [2]

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

Timing / supplements and antacids
Separate from multivalent cations
The label directs levofloxacin at least 2 hours before or 2 hours after magnesium or aluminum antacids, sucralfate, iron and multivitamins with zinc [1]. Calcium carbonate spaced 2 hours had no significant effect in healthy volunteers but lowered peak concentration in a small cystic fibrosis crossover [19]; orange juice lowers absorption [20]. The NIH magnesium fact sheet gives a longer interval (antibiotic at least 2 hours before or 4 to 6 hours after a magnesium supplement) [22]; the label governs. This is a spacing instruction, not a reason to change nutrient intake.
Lab / people with diabetes
Blood glucose
People with diabetes, especially on insulin or sulfonylureas, need careful glucose monitoring; stop and seek care for a hypoglycemic reaction per the label [1]. This is a safety outcome, not a nutrient finding.
Lab / anticoagulated patients
INR check
Close prothrombin time and INR monitoring during and shortly after coadministration with warfarin [1]; cohorts disagree on the size of the effect [32]. Vitamin K supplements are not the remedy.
Lab or ECG / QT risk
Potassium and magnesium
Known QT prolongation, uncorrected low potassium and other QT-prolonging drugs are reasons to avoid levofloxacin per the label [1]. Electrolyte correction belongs to the prescriber; magnesium products also need spacing from the dose.
Symptoms / during and after a course
Tendon, nerve and bowel symptoms
Tendon pain or swelling, new numbness or tingling, and severe or persistent diarrhea warrant prompt clinical assessment (tendinitis and rupture, peripheral neuropathy and C. difficile warnings) [1]. These are clinical outcomes, not nutrient findings.
Lab / unusual symptoms
Complete blood count and sodium
Jaundice, dark urine, new pallor or unexplained fatigue justify a blood count and review for hemolysis (label-listed anemia including hemolytic and aplastic) [1]. Confusion or nausea with low sodium has one case report [34]. Iron indices are not the first test, and iron tablets lower levofloxacin absorption.
Special populations
Pregnancy, renal impairment, children
Renal impairment prolongs half-life and reduces clearance substantially, and dialysis does not remove the drug effectively [2]. Pediatric patients cleared levofloxacin faster than adults [2]. Tendon and cartilage cautions in the label cover children and older adults; the juvenile animal data in the Magnesium and tendon entry are not guidance. No pregnancy-specific nutrient finding was graded in this review.

Overlap map, to prevent double counting

Iron; Magnesium and aluminum antacids, sucralfate; Zinc; Calcium, dairy and fortified juice (all four yellow timing interactions)
Shares evidence with: Each other; Potassium and magnesium; Magnesium and tendon
Note: All four rest on the same mechanism (chelation by multivalent cations) and the same label sentences (sections 2.4 and 7.1). Iron and zinc rest on the label and a review only; the antacid entry rests on the label plus Lee 1997 (sucralfate); the calcium entry rests on Pai 2006, the juice data in Wiesner 2024 and an unpublished thesis. Treat as one mechanism with several cations, not independent confirmations of each other.
Mitochondrial burden
Shares evidence with: Oxidative stress; ATP production
Note: Same cell studies: Song 2016 (complexes I and III, ATP, ROS, HEL and 4-HNE) supplies all three entries; Reinhardt 2025, Yu 2016, Hardgrave 2025 and Huang 2026 add mitochondrial findings; the rat toxicity studies add only to oxidative stress. Kalghatgi 2013 is class extrapolation for both mitochondrial and oxidative entries and levofloxacin cohort membership is unconfirmed. The three entries are one body of in vitro evidence.
Gut microbiome risk
Shares evidence with: Calcium, dairy and fortified juice; Vitamin K and INR; Fails verification: floxing
Note: The unpublished calcium-carbonate thesis reports a Shannon decline and is mentioned in both the microbiome and calcium entries but counted toward neither grade. The vitamin K entry rests on warfarin studies, not on any microbiome finding. Anthony 2022 and Panda 2014 are the two cohorts behind the orange grade; Liou 2023 is a combination regimen and is supporting only.
Magnesium and tendon or cartilage
Shares evidence with: Magnesium and aluminum antacids, sucralfate; Potassium and magnesium; Fails verification: magnesium and antioxidant supplements
Note: The ciprofloxacin juvenile-rat study (Pfister 2007) supports only the tendon hypothesis and the fails-verification row; it is not evidence for the absorption interaction or the QT context flag, which share only the nutrient name.
Potassium and magnesium (QT)
Shares evidence with: Sodium
Note: Moghnieh 2023 appears in both entries (QTc prolongation with a non-significant magnesium trend; hyponatremia not associated with QTc); it is one cohort counted once and supports neither as a depletion.
Oxygen delivery/utilization
Shares evidence with: Iron
Note: No shared source. Hemolytic anemia is a drug-toxicity outcome and is not an iron finding; the Iron entry concerns absorption of the antibiotic.
Copper
Shares evidence with: Iron
Note: No shared source; the copper evidence is chemistry metadata only. The pair is graded separately per Hard Rule 7.
Blood glucose
Shares evidence with: (none)
Note: Chou 2013 and Aspinall 2009 are used only here. The glucose entry is an outcome, not a nutrient, and is independent of every other entry. Both cohorts also report ciprofloxacin and moxifloxacin results that the sibling dossier uses; those are not borrowed here.

All references used above

Levofloxacin

Findings for this medication

What the research found

Magnesium and aluminum antacids, sucralfate: label separation of 2 hours; sucralfate given 2 hours earlier did not change levofloxacin exposure in 24 volunteers; magnesium not isolated (nutrient-to-drug timing interaction)

Zinc: multivitamins with zinc are named in the label separation rule; no levofloxacin study isolating zinc was retrieved (nutrient-to-drug timing interaction)

Calcium, dairy and fortified juice: spacing calcium carbonate by 2 hours left levofloxacin unchanged in healthy volunteers but lowered peak concentration by 19% in 5 adults with cystic fibrosis; orange juice lowers absorption (nutrient-to-drug timing interaction)

Blood glucose (hypoglycemia and hyperglycemia): label warning and two large diabetic cohorts with higher odds; a clinical outcome and drug-safety signal, not a nutrient deficiency

Magnesium and tendon or cartilage injury: juvenile rat data with ciprofloxacin link quinolone cartilage lesions to magnesium; levofloxacin not tested (CLASS EXTRAPOLATION); no human magnesium measurement

Potassium and magnesium (QT): label advises avoiding levofloxacin with uncorrected hypokalemia; hyperkalemia is listed in label trial tables; levofloxacin is not shown to lower either (status-to-drug-risk direction)

Vitamin K and INR: label advises close INR monitoring with warfarin; cohorts conflict; vitamin K never measured

Sodium: one case report names levofloxacin as a possible contributor to severe hyponatremia (dilutional/SIADH direction, not a deficiency)

B vitamins (thiamine, B6, B12, folate), including B vitamins in tendinopathy

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: levofloxacin inhibits respiratory chain complexes I and III in cultured cancer cell lines and affects complexes I and IV in human cells; no human tissue measurement

💥Oxidative Stress

Oxidative stress: higher ROS in cultured cancer cells and oxidative injury markers in high-dose rat studies; no human marker data

⚖️Copper and Iron Balance

Iron: iron lowers levofloxacin absorption (nutrient-to-drug timing interaction, not an iron depletion)

Copper: levofloxacin forms a copper(II) complex in the laboratory; no human or animal copper status measurement

Systemic iron, zinc, calcium and magnesium status lowered by levofloxacin (drug-to-mineral direction)

🌿Gut Microbiome Risk

Gut microbiome risk: transient lower fecal richness after 5 to 7 day courses of levofloxacin, back to baseline richness by about day 19 in healthy volunteers; not seen consistently in leukemia and transplant patients

💨Oxygen and ATP Output

ATP production: lower ATP reported in lung cancer cell lines (abstract only, no value); no human measurement

Oxygen delivery/utilization: label-listed hemolytic and aplastic anemia and pancytopenia; a case report of autoimmune hemolysis; no hemoglobin cohort (adverse outcome, not a nutrient deficiency)

Claims checked and not supported

"Floxing": levofloxacin damages mitochondria and causes a lasting syndrome through oxidative stress and magnesium chelation at ordinary doses

"Take magnesium and antioxidant supplements during levofloxacin treatment to protect tendons and joints" (recommendation form)

"Levofloxacin is blocked by calcium and dairy as strongly as ciprofloxacin; avoid all dairy" (overstated, copied from ciprofloxacin)

How the body handles this medication

What the research says is worth watching

Overlap map, to prevent double counting

Mitochondrial Burden

Oxidative Stress

Copper and Iron Balance

Gut Microbiome Risk

Oxygen and ATP Output