Metaxalone

centrally acting skeletal muscle relaxant (oxazolidinone) [5]

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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.

Metaxalone has no recognized classical depletion machinery. It is metabolized in the liver, mainly by CYP1A2, CYP2D6, CYP2E1 and CYP3A4 and to a lesser extent CYP2C8, CYP2C9 and CYP2C19, and excreted in the urine as unidentified metabolites; the label states that it neither inhibits the nine CYP enzymes tested nor induces CYP1A2, CYP2B6 or CYP3A4 [1][2][3]. The label texts read mention no vitamin, mineral or antacid interaction, and the only food statement concerns drug exposure: a high-fat meal raises metaxalone peak and total exposure, a food-to-drug timing interaction and not a depletion [1][3]. Of the nine mechanism classes screened, none is documented as changing a nutrient in people. Red and orange tiers are empty. Seven entries are yellow and four are ungraded, and no yellow entry is a nutrient deficiency.

centrally acting skeletal muscle relaxant (oxazolidinone) [5] · ATC: none listed for metaxalone in the WHO ATC/DDD group M03BX listing [4] · also sold as Skelaxin; many generics · reviewed 2026-10-07. 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 Metaxalone 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

Leukopenia: labeled adverse reaction only, no study and no nutrient measured (context flag)

Yellow — Low

See study details

Metaxalone labeling lists leukopenia among adverse reactions; no case report, cohort or frequency was retrieved and no nutrient was measured, so the entry records the label statement and nothing more.

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

Key null findings: No white-cell count, differential or nutrient measurement in metaxalone users was found. LiverTox does not address leukopenia [16].
At-risk subgroups: None identified in retrieved data.

Direction

Drug adverse reaction (toxicity). Not a depletion and not a nutrient effect; low white-cell count is an outcome (Hard Rule 2). No link to copper, vitamin B12 or folate is asserted by any source read, and none is made here.

Regulatory status

Skelaxin label as read lists "leukopenia; hemolytic anemia" among adverse reactions [3]; the generic label texts read list the same hemic reactions [1][2]. Frequency and the label subsection were not seen in the summaries.

Population evidence

None retrieved. A Crossref title search for metaxalone with hemolytic anemia and leukopenia returned no leukopenia item with metaxalone in the title [25]. The web search "metaxalone leukopenia agranulocytosis case report OR pharmacovigilance" returned pages by title on metamizole and agranulocytosis, none opened and none naming metaxalone. The PubMed listing for metaxalone AND leukopenia was refused (HTTP 429) and not retried.

Mechanism

Not stated in any source read.

Counter-evidence held on record

Counter-evidence and limits The only support is a regulatory adverse-reaction list, which establishes that the event is reported, not its frequency or cause. Confounding by co-medication and indication is not excludable from the sources read. The linezolid label lists myelosuppression [19]; this was considered and not extrapolated because metaxalone was not in the cohorts and no mechanism link was retrieved. Framing caution Do not present leukopenia as a vitamin or mineral problem or as a sign that any supplement is needed. It is a labeled drug adverse reaction for a prescriber to evaluate.

Serotonergic toxicity: labeled serotonin syndrome warning with MAO-A inhibition in vitro (interaction, excess direction)

Yellow — Low

See study details

Metaxalone labeling warns of serotonin syndrome with serotonergic drugs at recommended doses and alone above recommended doses, an in vitro assay shows dose-related MAO-A inhibition at concentrations seen in overdose cases, and case reports document the syndrome; no nutrient or supplement interaction was tested in any source retrieved.

Full detail and limits

Limits on what this shows

Key null findings: No incidence rate at recommended doses was retrieved; most reported cases are overdoses, one case with a co-ingested serotonergic drug (tramadol) and one with metaxalone alone [11]. The assay [10] is cell-free and was done at concentrations well above the therapeutic peak (0.87 µg/mL as quoted in [11]).
At-risk subgroups: People taking serotonergic drugs [1][3]; people with cirrhosis per the title of [14]; overdose.

Direction

Excess and interaction (pharmacodynamic). It is the combination with another serotonergic agent, or an overdose, that carries the risk. This is not a depletion and not a nutrient finding (Hard Rules 2 and 4); it is recorded because the request named it as an angle.

Regulatory status

Label text read: "Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of serotonergic drugs with SKELAXIN used within the recommended dosage range ... and with SKELAXIN as a single agent taken at doses higher than the recommended dose"; serotonergic drugs named include SSRIs, SNRIs, TCAs, MAO inhibitors, tramadol and triptans; CNS depressant effects are additive [1][3]. Overdosage section: serotonin syndrome reported above the recommended dose [1].

Population evidence

Case reports and one in vitro assay, all Tier B. Bosak and Skolnik 2014, two overdoses: 12 g metaxalone with tramadol 1.5 g (metaxalone 34 µg/mL; hyperthermia to 39.8 C, clonus, status epilepticus) and 32 to 40 g alone (61 µg/mL; rigidity, clonus, hyperthermia, rhabdomyolysis, acute kidney injury); both recovered in intensive care [11]. Martini et al. 2015, two overdoses on paroxetine (metaxalone 31 µg/mL) and escitalopram (58 µg/mL) [12]. Rivera-Maldonado et al. 2025, a case at therapeutic dosing with duloxetine, bupropion and phentermine [13]. Surmaitis et al. (AJEM; 2015 per OpenAlex, 2016 per PubMed), therapeutic metaxalone in a patient with cirrhosis: title and metadata only, abstract not available, not used for any fact beyond its title [14]. Cherrington et al. (Clin Toxicol; 2019 per OpenAlex, 2020 per PubMed listing): recombinant human MAO-A with metaxalone 1.56 to 400 µM showed significant dose-related inhibition; reported case concentrations of 31 to 61 µg/mL correspond to 140 to 276 µM; an IC50 was not in the abstract [10].

Mechanism

Named, proposed: reversible MAO-A inhibition at supratherapeutic concentrations, which Bosak and Skolnik compare with oxazolidinones such as linezolid and toloxatone (hypothesis in a summarized case report) [11]. A practitioner commentary (Tier D, not used for grading) cites about 75% MAO-A inhibition at overdose concentrations [15].

Counter-evidence held on record

Counter-evidence and limits A regulatory warning plus case reports establish that the event occurs; they do not give a rate at therapeutic doses, and the in vitro inhibition is at overdose-range concentrations. No retrieved source examines serotonergic supplements (for example tryptophan, 5-HTP, SAMe or St John's wort) with metaxalone; extending to them would be CLASS EXTRAPOLATION from drug interactions to supplements, and no cohort supports it, so it is not made here. Framing caution This is a drug-interaction safety signal, not a nutrient deficiency or a reason to add a supplement. Any new serotonergic drug or supplement should be reviewed with a prescriber or pharmacist.

Hepatic function: labeled jaundice and impairment caution against a LiverTox score of E (context flag)

Yellow — Low

See study details

Metaxalone labeling lists jaundice, contraindicates severe hepatic impairment and asks for serial liver function studies in pre-existing liver damage, while LiverTox finds no associated aminotransferase elevations or clinically apparent injury; no nutrient was measured.

Full detail and limits

Limits on what this shows

Key null findings: No clinical hepatotoxicity series or case with a nutrient measurement was found. The cirrhosis serotonin-syndrome case [14] was not opened beyond its title.
At-risk subgroups: Patients with severe hepatic or renal impairment (contraindicated) and pre-existing liver damage (caution) per the label [1][3].

Direction

Two directions, neither nutritional. Drug adverse reaction (jaundice, label) and effect of hepatic impairment on the drug (exposure not characterized). Liver injury is an outcome, not a nutrient deficiency (Hard Rule 2).

Regulatory status

Label text read: contraindicated in "Severe renal or hepatic impairment"; "should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients"; the pharmacokinetic effect of hepatic and renal disease "has not been determined"; "jaundice" listed as an adverse reaction [1][2][3].

Population evidence

LiverTox monograph (likelihood score E, unlikely cause of clinically apparent liver injury): "has not been associated with serum aminotransferase elevations during therapy or with clinically apparent hepatic injury" and "there are no specific case reports of hepatotoxicity from metaxalone in the literature" (read through a third-party mirror of the Bookshelf page; the NCBI page itself returned a reCAPTCHA; abstract confirmed in a PubMed record) [16]. In vitro, Liu et al. 2023 found oxidative and glutathione-conjugated metabolites in liver preparations and rat hepatocytes with cytotoxicity that fell when CYP2A6 or sulfotransferase was inhibited [9].

Mechanism

Hypothesized reactive-metabolite formation in vitro [9]; no clinical injury pattern is described to match it [16].

Counter-evidence held on record

Counter-evidence and limits The label and the monograph point in different directions on liver risk, and the monograph date was not seen (PubMed lists the book as 2012). The in vitro metabolism paper does not show injury in people. This entry exists because the request named liver as an angle; it does not support any nutrient claim. Framing caution Do not read this as metaxalone causing liver damage or as a vitamin or mineral signal. Liver tests are a prescriber decision for people with existing liver disease.

Dietary intake: labeled nausea, vomiting and gastrointestinal upset; no nutrient or intake measured (context flag)

Yellow — Low

See study details

Regulatory labeling lists nausea, vomiting and gastrointestinal upset among the most frequent reactions, so a changed-intake mechanism is documented as present, but no study measured food or nutrient intake in metaxalone users and no nutrient is implicated.

Full detail and limits

Limits on what this shows

Key null findings: No intake, weight, BMI or nutrient measurement in metaxalone users was found. LiverTox lists nausea among common side effects and describes no nutritional effect [16].
At-risk subgroups: Older adults for the food-related CNS depression statement [1]; females showed higher exposure than males and older adults higher fasted peaks per the label text read [2].

Direction

Context flag, neutral. An adverse reaction is not a nutrient deficiency (Hard Rule 2). Separately, the food interaction runs from food to drug (Hard Rule 4): a high-fat meal raised metaxalone exposure, which is a timing interaction and not a depletion.

Regulatory status

Label text read: "The most frequent reactions to metaxalone were: CNS: drowsiness, dizziness, headache, and nervousness or irritability. Digestive: nausea, vomiting, gastrointestinal upset" [2][3]. Food effect: a high-fat meal increased Cmax and AUC (generic label text: Cmax +177.5%, AUC +123.5%, at a 400 mg dose; Skelaxin label as summarized: Cmax +94% and AUC +46% for 800 mg); "Taking SKELAXIN with food may enhance general CNS depression; elderly patients may be especially susceptible" [1][3]. Both label versions were read through a summarizing fetch tool and the dose attached to each food-effect figure was not independently verified.

Population evidence

None on intake. A PubMed listing of 10 metaxalone records showed no record on appetite, weight or nutrition [24]. Tier D pages (drugs.com food-interaction page: alcohol only; Columbia Doctors drug information: generic advice to tell the doctor about vitamins) do not describe a nutrient effect [20][21].

Mechanism

Not stated for the gastrointestinal reactions. Sedation and nausea are plausible routes to reduced eating (mechanism class H) but this is not demonstrated.

Counter-evidence held on record

Counter-evidence and limits Graded yellow only as a context flag: the evidence is a labeled adverse reaction, not a study of intake or of any nutrient. Confounding by indication (acute painful musculoskeletal condition, other drugs) is not excluded and there is no comparison with non-users. Framing caution Do not present metaxalone as causing malnutrition or any specific deficiency. Do not change how the drug is taken relative to meals without a prescriber or pharmacist. No supplement is implied.

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: reverse direction, PGC-1α expression in stimulated microglia only

Yellow — Low

See study details

In IL-1β-stimulated human microglial cells, metaxalone restored expression of PGC-1α that the stimulus had lowered; no study measured mitochondrial structure, respiration, membrane potential or biogenesis, and no human data exist.

Full detail and limits

Limits on what this shows

Key null findings: A PubMed listing for metaxalone AND mitochondria returned a 404 page (the no-match response); metaxalone AND ATP did the same [24]. The metabolic activation study [9] reports cytotoxicity but its abstract does not name mitochondria. The macrophage study [8] reports apoptosis and caspase-3 without a mitochondrial assay.
At-risk subgroups: None identified.

Direction

Reverse (protective-looking in vitro). Not a burden finding.

Regulatory status

No mitochondrial content in the label texts read [1][2][3].

Population evidence

None in humans. Pallio et al. 2021: IL-1β raised NF-κB and lowered PPAR-γ and PGC-1α in HMC3 cells; metaxalone 10 to 40 µM for 6 hours reversed these [7]. PGC-1α is commonly read as a marker of mitochondrial biogenesis signaling; that characterization is background knowledge and was not stated in the abstract read.

Mechanism

Named only as MAO-A inhibition with reduced inflammatory signaling in the authors' framing [7]. No direct mitochondrial target was reported.

Counter-evidence held on record

Counter-evidence and limits Tier B, single study, expression of one gene in an immortalized cell line at concentrations above therapeutic plasma levels (see Oxidative stress entry). CLASS EXTRAPOLATION considered and not made: linezolid, a structurally different oxazolidinone antibacterial, carries labeled lactic acidosis and myelosuppression [19], but the label text read gives no mitochondrial mechanism, metaxalone was not in any linezolid cohort, and no source retrieved links metaxalone to those effects. Nothing is graded on it. Framing caution Do not present metaxalone as protecting mitochondria or as damaging them. There is one test-tube expression finding and nothing in people.

Oxidative Stress

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

Oxidative stress: opposing in vitro signals, reactive metabolite with glutathione conjugation versus reduced malondialdehyde in stimulated microglia

Yellow — Low

See study details

In cell and microsome systems metaxalone forms oxidative and glutathione-conjugated metabolites linked to cytotoxicity, while in IL-1β-stimulated human microglial cells it lowered malondialdehyde and raised Nrf2 expression; no study measured oxidative stress, glutathione or antioxidant capacity in metaxalone users.

Full detail and limits

Limits on what this shows

Key null findings: No malondialdehyde, glutathione, superoxide dismutase, total antioxidant capacity or reactive oxygen species measurement in metaxalone-treated humans or animals was found. A PubMed listing for metaxalone AND oxidative returned 6 records; apart from [9] they were stability-indicating HPLC and degradation-kinetics methods (oxidative stress conditions applied to the tablet substance, not biology) and a zopiclone bioanalytical paper [24]. A PubMed listing for metaxalone AND glutathione was refused (HTTP 429) and not retried.
At-risk subgroups: None identified.

Direction

Mixed and unresolved. Burden-direction signal: metabolic activation to species that are trapped by glutathione in liver preparations [9]. Reverse-direction signal: lower malondialdehyde and higher Nrf2 in a stimulated microglial cell line [7]. Neither is a depletion finding and neither was measured in a person.

Regulatory status

No oxidative or antioxidant content in the label texts read [1][2][3].

Population evidence

None in humans. Liu et al. 2023 (Chem Biol Interact 382:110628): oxidative and glutathione-conjugated metabolites identified in liver preparations and rat hepatocyte cultures; CYP2A6 dominated oxidation; inhibiting CYP2A6 or sulfotransferase significantly reduced metabolite formation and cellular damage (abstract as shown in a PubMed record via a summarizing fetch tool; OpenAlex had no abstract) [9]. Pallio et al. 2021 (Int J Mol Sci): human microglial HMC3 cells stimulated with IL-1β, metaxalone 10 to 40 µM for 6 hours reduced NF-κB, TNF-α, IL-6 and MAO-A activity and malondialdehyde, and increased IL-13, PPAR-γ, PGC-1α and Nrf2 expression (OpenAlex abstract) [7].

Mechanism

Named, in vitro: metabolic activation with glutathione trapping [9]; MAO-A inhibition with an anti-inflammatory and antioxidant phenotype in stimulated cells [7]. Whether glutathione stores fall in a cell or a person was not stated in the abstracts read.

Counter-evidence held on record

Counter-evidence and limits Tier B only (mechanistic in vitro studies using this drug). The 10 to 40 µM exposure in [7] is roughly 2.5 to 10 times the therapeutic peak concentration quoted in a case report (0.87 µg/mL, about 3.9 µM by this dossier's own conversion) [11], the protective effect was measured against an IL-1β insult rather than baseline, and a third in vitro study found metaxalone (1 to 100 µM) decreased mouse macrophage cell number and raised caspase-3, which points toward cytotoxicity (Yamaguchi and Levy 2020; one author lists Primus Pharmaceuticals as affiliation; OpenAlex abstract) [8]. The two directions come from different cell types and conditions and are not reconciled. Framing caution Do not describe metaxalone as an antioxidant, and do not describe it as causing oxidative stress or glutathione depletion. These are test-tube findings. No antioxidant supplement is implied.

Copper and Iron Balance

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

Copper

Not graded — disclosed evidence gap

See study details

No evidence was retrieved that metaxalone alters copper status, absorption, excretion or ceruloplasmin.

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 evidence on copper status was found, and no circulating copper claim for metaxalone was found. Leukopenia and hemolytic anemia are labeled adverse reactions; copper deficiency can also lower blood counts in general, but no source read connects metaxalone to copper, so no link is made. Not a finding of safety.

What was searched

PubMed: metaxalone AND copper was refused (HTTP 429, not retried); metaxalone AND ceruloplasmin was refused (429, not retried); the multi-term query metaxalone AND (iron OR ferritin OR copper OR ceruloplasmin OR vitamin OR magnesium OR folate OR zinc) returned only the generic trending page, discarded as invalid [24]. Crossref title search "metaxalone gut microbiota iron copper vitamin" returned 20 items, of which only three USP monograph entries had metaxalone in the title and none concerned copper [25]. Web search "metaxalone copper OR ceruloplasmin OR serum iron OR ferritin" returned unrelated pages by title (none opened, none naming metaxalone in the title seen). Label texts read contain no copper or mineral interaction [1][2][3]; drugs.com food-interaction page lists alcohol only [20]. Hepatic metabolism with unidentified urinary metabolites gives no copper-handling mechanism [2]. Repair pass (same date): PubMed metaxalone AND copper opened and returned 2 records, both organic-chemistry methods papers in which metaxalone is one demonstration substrate for copper catalysis (PMID 38649350, copper metallaphotoredox N-glycosylation; PMID 42146798, copper-mediated (18)F-radiofluorination); neither measures copper in a biological system, listing summaries only, papers not opened, no evidence used. PubMed metaxalone AND ceruloplasmin returned a 404 no-match page [24]. Two Crossref title searches (metaxalone with mitochondrial; metaxalone with iron, ferritin, copper, anemia) were refused (HTTP 429, not retried).

Channel outcomes

PubMed HTML listings (format=pubmed) opened intermittently on 2026-10-07: several requests were refused with HTTP 429 and were not retried on the same page, some topic queries returned a 404 page (the PubMed no-match response, interpreted as zero results but not independently confirmed), and one multi-term query returned PubMed's generic trending-articles page, which was discarded as invalid. DailyMed label pages for two set IDs were refused with HTTP 429 (not retried); label text was instead read from a label mirror, DrugCentral and drugs.com pages. OpenAlex single-record lookups and Crossref title searches opened; one OpenAlex search endpoint call was refused (429). The web search budget worked for a run of queries and was then exhausted. Europe PMC and Semantic Scholar were not used (blocked hosts). PubMed Central and NCBI Bookshelf pages returned reCAPTCHA pages.

Gap type

Genuine gap on the channels that opened, and the repair pass reopened the PubMed copper listing (2 chemistry-only records) and the ceruloplasmin listing (no match), so the PubMed channel is no longer the limiting factor for this entry: genuine gap on PubMed, label, Crossref (earlier pass) and web search (earlier pass). Residual limits: Europe PMC and Semantic Scholar not usable, the 404 reading is not independently confirmed, and the repair-pass Crossref queries and web search were blocked. Kept independent of Iron (Hard Rule 7).

Iron

Not graded — disclosed evidence gap

See study details

No evidence was retrieved that metaxalone alters iron absorption, stores, ferritin or iron-deficiency anemia.

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 evidence on iron was found (the organic chemistry record is not a biological system), and no circulating iron claim for metaxalone was found. Not a finding of safety.

What was searched

PubMed: metaxalone AND iron returned 1 record, a 2023 J Org Chem paper on iron(III) chloride catalysed thiocyanation in which metaxalone is one substrate (chemistry, no biological iron measurement; read as a summarized listing entry) [24]. metaxalone AND hemolysis returned 2 records: the immune hemolysis case report [6] and an LC-MS/MS method paper [24]; the case report abstract names no iron index. Label texts read list no iron interaction [1][2][3]. The label contraindication for "other anemias" runs from patient state to drug use and does not say that metaxalone causes iron deficiency [3]. Crossref and web search as for Copper. Repair pass (same date): PubMed metaxalone AND ferritin returned a 404 no-match page; metaxalone AND "iron deficiency" was refused (HTTP 429, not retried); the copper listing's two records are copper-catalysis chemistry and carry no iron data [24].

Channel outcomes

Gap type

Genuine gap on the channels that opened; tooling-limited for the combined multi-term PubMed query. Hemolysis would be a theoretical source of iron turnover, but no iron index was measured in the case report, and no inference is made. Anemia is an outcome, not iron deficiency (Hard Rule 2). The repair pass added a ferritin no-match listing and did not change the result; hemoglobin, serum iron and transferrin-specific listings were not obtained.

Gut Microbiome Risk

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

Gut microbiome risk

Not graded — disclosed evidence gap

See study details

No evidence was retrieved on metaxalone and gut microbiome composition, diversity or function.

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 evidence, and no circulating microbiome claim for metaxalone was found. Absence of a documented mechanism is not evidence of absence. Not a finding of safety.

What was searched

PubMed: metaxalone AND microbiome and metaxalone AND microbiota were refused (HTTP 429, not retried); metaxalone AND gut returned a 404 page (no match) [24]. Web search "metaxalone gut microbiota OR gut microbiome OR fecal muscle relaxant drug effect on bacteria" returned generic drug-microbiome reviews and database pages. Opened: Maier et al. 2018, Nature, in vitro screen of more than 1,000 marketed drugs against gut bacteria, main text as rendered does not mention metaxalone or skeletal muscle relaxants, and supplementary drug tables were not accessible [22]; Vich Vila et al. 2020, Nat Commun, population cohort, abstract page only, which names proton-pump inhibitors, metformin, antibiotics and laxatives as the strongest associations and does not discuss muscle relaxants [23]; the review "Interplays between drugs and the gut microbiome" (PMC8991093), which does not mention metaxalone or skeletal muscle relaxants per the fetch tool (summarized). Crossref title search with gut microbiota terms returned no metaxalone microbiome item [25]. Label texts read contain no microbiome content [1][2][3]. Hepatic metabolism with urinary excretion of metabolites gives no documented gut-exposure mechanism [2]. Repair pass (same date): PubMed metaxalone AND microbiota returned a 404 no-match page; metaxalone AND bacteria returned 1 record, "Biocatalytic Synthesis of Metaxalone and Its Analogues" (PMID 37405417), an enzyme-engineering chemistry paper using a bacterial enzyme as a synthetic catalyst, with no gut microbiome content (listing summary only, not opened, no evidence used); metaxalone AND microbiome was refused twice (HTTP 429, not retried again) and metaxalone AND (gut microbiome OR dysbiosis) was refused (429) [24].

Channel outcomes

Gap type

Genuine gap on the channels that opened, including two large drug-microbiome resources that do not list this drug. Residual limits: the PubMed microbiome listings were refused, the 404 reading for the gut query is not independently confirmed, Maier supplementary tables were not accessible, and the Vich Vila full text was not opened. The repair pass obtained two new PubMed no-evidence results (microbiota, bacteria) but the exact microbiome and dysbiosis listings stayed rate-limited, so this entry remains partly tooling-limited.

Oxygen and ATP Output

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

Oxygen delivery/utilization: labeled hemolytic anemia and one case report of immune hemolysis (drug toxicity direction)

Yellow — Low

See study details

Metaxalone labeling lists hemolytic anemia as an adverse reaction and contraindicates use in patients with a known tendency to drug-induced, hemolytic or other anemias, and one 2023 case report describes warm-type hemolytic anemia after starting metaxalone; no study measured hemoglobin, hematocrit, red-cell mass or tissue oxygen delivery in metaxalone users against non-users.

Full detail and limits

Limits on what this shows

Key null findings: A PubMed listing for metaxalone AND hemolysis returned 2 records: this case report and a bioanalytical LC-MS/MS method paper [24]. A Crossref title search for metaxalone with hemolytic anemia and leukopenia returned this case report and two USP monograph entries as the only items with metaxalone in the title [25]. No cohort, pharmacovigilance disproportionality study, hemoglobin outcome or incidence figure was retrieved. Hemoglobin, hematocrit and oxygen saturation were not reported in any metaxalone source opened.
At-risk subgroups: Patients with a known tendency to hemolytic or other anemias (label contraindication) [3]. No other subgroup is supported by retrieved data.

Direction

Drug toxicity (idiosyncratic, immune-mediated per the case title and abstract). Not a depletion, not a retention effect and not an oxygen-delivery deficiency in the nutrient sense. The label direction runs two ways: hemolytic anemia is a listed adverse reaction (drug to patient), and a pre-existing tendency to anemia is a contraindication (patient state to drug use, Hard Rule 4). Anemia is an outcome, not a nutrient (Hard Rule 2).

Regulatory status

Skelaxin label as read (revision 6/2024 as reported by the fetch tool): contraindicated in patients with "Known tendency to drug induced, hemolytic, or other anemias"; adverse reactions listed include "leukopenia; hemolytic anemia" and "jaundice" [3]. The generic label texts read carry the same contraindication and adverse reaction wording [1][2]. Incidence is not stated in any label summary read, and the label does not define "other anemias" or say whether nutrient-deficiency anemias are meant. The exact label subsection that holds the adverse reaction list was not seen.

Population evidence

Onyechi et al. 2023 (J Community Hosp Intern Med Perspect), case report, n=1. A patient presented with yellow skin and orange-colored urine after starting metaxalone for lumbosacral sprain; laboratory studies were consistent with warm hemolytic anemia; symptoms improved remarkably after metaxalone was stopped and glucocorticoids and rituximab were started [6]. Age, sex, dose, time to onset, hemoglobin, antiglobulin test result and other drugs were not in the abstract read (OpenAlex record and the journal landing page); the PubMed Central full text returned a reCAPTCHA page and was not opened.

Mechanism

Immune-mediated hemolysis is stated in the case title and abstract [6]; the antibody type, drug-dependence testing and any dose relationship were not seen. No in vitro or animal hemolysis study of metaxalone was found in the channels tried.

Counter-evidence held on record

Counter-evidence and limits Single case report with no rechallenge reported in the abstract. Because glucocorticoids and rituximab were started when metaxalone was stopped, improvement cannot be attributed to withdrawal alone. The case does not establish frequency, dose dependence or causality beyond the authors' assessment. The sibling muscle relaxant dossiers were opened for structure only; their hemolysis findings concern a different drug, a different vehicle and a different route and are not carried to metaxalone (metaxalone was not in those cohorts, so no class extrapolation is made). Framing caution Do not present this as metaxalone lowering iron, hemoglobin or oxygen delivery through a nutrient mechanism. It is a rare, labeled immune adverse reaction documented in one reported patient. No supplement is implied.

ATP production

Not graded — disclosed evidence gap

See study details

No evidence was retrieved on metaxalone and cellular ATP synthesis, oxidative phosphorylation or energy output.

Full detail, limits and 1 references

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 evidence exists to support even a yellow grade (the PGC-1α expression finding sits in the Mitochondrial burden entry and is not an ATP measurement), and no circulating consumer claim of metaxalone "low energy" or ATP effects was found to rebut. This is a disclosed gap, not a finding of safety. The repair pass did not change this result. Re-check when access is restored, particularly with a Europe PMC or Tox21 mitochondrial membrane potential query.

What was searched

PubMed listings: metaxalone AND ATP returned a 404 page; metaxalone AND mitochondria returned a 404 page [24]. Web search "metaxalone mitochondria OR oxidative stress OR ATP OR membrane potential toxicity in vitro" returned generic mitochondrial-toxicity reviews, a renal mitochondria review, a vendor product-data sheet and drug-label pages; none had metaxalone and ATP in the title seen and none was opened. The label texts read contain no energy-metabolism content [1][2][3]. The only metaxalone mechanistic papers found [7][8][9] measured cytokines, MAO-A, malondialdehyde, Nrf2, PGC-1α, apoptosis or metabolites, not ATP, respiration or membrane potential. Fatigue and drowsiness are not labeled as ATP findings. Repair pass (same date, after waiting out rate limits): PubMed metaxalone AND respiration returned 1 record, the serotonin syndrome case report by Martini et al. (PMID 25671244, already cited as [12]), which matched on overdose respiratory text and has no energy-metabolism content; the multi-term query metaxalone AND (energy OR respiration OR phosphorylation) was refused (HTTP 429, not retried); the web search tool refused further queries (shared budget used up) so no new web search could be run [24].

Channel outcomes

Gap type

Genuine gap on every channel that opened (two PubMed no-match pages, one web search, three label texts, three mechanistic papers). Residual tooling limits: Europe PMC, Semantic Scholar and Tox21 per-compound data were not used, and the 404 reading is not independently confirmed. Kept independent of Mitochondrial burden (yellow) and Oxygen delivery/utilization (Hard Rule 7); the shared empty search is disclosed in the Overlap map.

Martini DI, et al. Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor. Clin Toxicol 2015. — Case reports, 2 patients (Tier B; this drug). DOI 10.3109/15563650.2015.1009993; PMID 25671244.Abstract via a reconstructed OpenAlex record through a summarizing fetch tool.

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.

No circulating metaxalone nutrient-depletion claim located
Where it comes from: Pages opened: the drugs.com metaxalone food-interaction page (alcohol only; no food, vitamin or supplement interaction) [20] and the Columbia Doctors drug information page (generic advice to tell the doctor about vitamins; no depletion, hemolytic anemia, leukopenia or serotonin mention in the tool's reading) [21]. A web search for metaxalone with depletion, vitamins, minerals, magnesium, B vitamins and CoQ10 returned patient-information pages by title (none opened beyond the two above) and a second, more specific depletion search was blocked when the shared search budget ran out. No depletion-handbook page naming metaxalone was found. Retailer and handbook sites were not enumerated.
Why it fails: There is nothing to rebut from the sources reached. This is not a finding that no such claim exists elsewhere. If a claim (for example magnesium, B vitamins, iron or "hemolytic anemia means iron loss") is found later, it should be graded against the evidence recorded here, which currently supports no depletion. The labeled hemolytic anemia and leukopenia are adverse reactions, not nutrient claims [1][3][6].

How the body handles this medication

Metabolism and enzymes: "Metaxalone is primarily metabolized by CYP1A2, CYP2D6, CYP2E1, and CYP3A4 and, to lesser extent, CYP2C8, CYP2C9, and CYP2C19." In vitro the label states it "does not inhibit" CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 and "does not induce" CYP1A2, 2B6 or 3A4. A 2023 liver-preparation study found CYP2A6 dominated oxidation and produced glutathione-conjugated metabolites, a CYP not named in the label list.[1][2][3][9] label texts via summarizing fetch tool; [9] abstract only
Elimination and exposure: "Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites." Peak plasma concentration about 3 hours after a fasted dose; terminal half-life 9.0 ± 4.8 hours (400 mg fasted) and 8.0 hours (800 mg fasted) in the generic label text; apparent volume of distribution about 800 L; plasma protein binding "unknown".[1][2][3] sec Clinical Pharmacology
Food effect (direction: food to drug): A high-fat meal raised Cmax and AUC (generic label text: +177.5% and +123.5%; Skelaxin label as summarized: +94% and +46% for 800 mg). Food may enhance CNS depression, especially in older adults. This is a timing interaction on drug exposure, not a nutrient depletion (Hard Rule 4).[1][3]; the two versions differ and the dose attached to each figure was not independently verified
Hepatic and renal impairment, special populations: Contraindicated in severe renal or hepatic impairment; caution in milder impairment; the pharmacokinetic effect of hepatic and renal disease "has not been determined". Serial liver function studies advised in pre-existing liver damage. Older adults showed higher fasted peaks and females higher exposure than males. Not recommended in pregnancy unless benefit outweighs hazard; safety in pregnancy "has not been established". The Skelaxin label as summarized covers patients 13 years and older.[1][2][3]
Interactions: Serotonergic drugs (SSRIs, SNRIs, TCAs, MAO inhibitors, tramadol, triptans) carry a serotonin syndrome warning; CNS depressants (alcohol, benzodiazepines, opioids, TCAs) are additive. Serotonin syndrome was also reported with metaxalone as a single agent above the recommended dose. No mineral, vitamin or antacid interaction appears in the label texts read; the drugs.com food page lists alcohol only.[1][3][20]
Absorption site and transporter: Not stated in the label sections retrieved. No chelation, gastric pH or transporter effect is documented in any source read.[1][2][3]
Mechanism screen, classes A to I: A absorption interference: absent for nutrients. B enzyme induction: absent (no induction of the three CYPs tested). C renal wasting: none documented. D cofactor antagonism: none documented (MAO-A inhibition in vitro is enzyme inhibition, not a cofactor depletion). E mitochondrial or conjugation-driven loss: glutathione conjugation shown in vitro only [9]. F dilutional or hormonal: none documented. G microbiome: none documented. H changed intake: labeled nausea, vomiting and GI upset. I increased demand: hemolysis would raise red-cell turnover but nothing was measured.[1][2][3][6][9]

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.

Hematologic / only if prompted
Jaundice, dark or orange urine, pallor, unusual fatigue
These were the presenting features in the one reported hemolysis case [6]. The label contraindicates use with a known tendency to hemolytic or other anemias [3]. A blood count and a prescriber's evaluation are the response; no label-mandated hematologic monitoring schedule was found in the sections read. This is a drug-safety matter, not a nutrient finding.
Hematologic / leukopenia
Infection signs or a low white-cell count
Leukopenia is a labeled adverse reaction with no frequency or monitoring schedule in the sections read [1][3]. A white-cell count is a prescriber decision if signs of infection or a low count appear. A low count is not evidence of a vitamin or mineral problem.
Interaction / CNS
Serotonergic drugs and doses above the recommended amount
Features in the case reports were rigidity, clonus, hyperthermia and tachycardia [11][12]; LiverTox also lists agitation, confusion and hallucinations [16]. The label lists SSRIs, SNRIs, TCAs, MAO inhibitors, tramadol and triptans [1]. Recent case reports add duloxetine, bupropion and phentermine [13]. No retrieved source examined serotonergic supplements with metaxalone; ask a prescriber or pharmacist before combining. Alcohol and other CNS depressants add to sedation [1][20].
Hepatic / renal
Pre-existing liver or kidney disease
Contraindicated in severe renal or hepatic impairment; serial liver function studies are advised by the label in pre-existing liver damage [1][3]. In people without liver disease LiverTox found no associated injury (score E) [16].
Timing
Meals and drug exposure
A high-fat meal raised metaxalone exposure and the label says food may enhance CNS depression, especially in older adults [1][3]. Keep the way the drug is taken consistent and discuss any change with a prescriber or pharmacist. No separation interval from a vitamin or mineral applies because no such interaction was found.
Pregnancy / pediatric / nutrient labs
Pregnancy, adolescents and routine nutrient testing
Safe use in pregnancy has not been established per the label [1]. The Skelaxin label as summarized lists patients 13 years and older [3]. No nutrient lab is indicated by metaxalone itself on current evidence; baseline testing depends on the person's other drugs and conditions.

Overlap map, to prevent double counting

Entries resting on the same underlying source, mechanism or empty search.

Oxidative stress
Shares evidence with: Mitochondrial burden
Note: Both yellow entries draw on the same Pallio 2021 microglia paper [7] (malondialdehyde and Nrf2 for oxidative stress; PGC-1α for mitochondria). One cell-line study, not two lines of evidence.
Oxidative stress
Shares evidence with: Hepatic function
Note: Both cite the Liu 2023 metabolic activation paper [9] (glutathione-conjugated metabolites and cytotoxicity). One source.
Oxygen delivery/utilization
Shares evidence with: Leukopenia; Iron
Note: Hemolytic anemia and leukopenia are listed together in the same label adverse-reaction sentence [1][3], so the label statement is one source. The only case report [6] concerns hemolysis, not leukopenia. No iron index was measured, so Iron is not supported by the hemolysis report.
Serotonergic toxicity
Shares evidence with: Hepatic function
Note: The cirrhosis serotonin-syndrome case [14] is title-only and supports neither entry beyond its title. The label hepatic statements and the label serotonin warning are separate sections of the same documents [1][3].
Mitochondrial burden
Shares evidence with: ATP production
Note: The ungraded ATP entry rests on the same empty PubMed listings (mitochondria and ATP, both 404) as the mitochondrial search, so their shared absence of evidence is one gap, not two. Mitochondrial burden is yellow on a separate source [7].
Copper
Shares evidence with: Iron
Note: Both were searched with overlapping PubMed, Crossref and web queries that returned no biological record. Kept as two independent entries (Hard Rule 7).
Dietary intake
Shares evidence with: None
Note: Rests on the label adverse-reaction list and food-effect statements [1][2][3] and an empty PubMed listing only.

All references used above

Skelaxin (metaxalone) prescribing information, drugs.com professional label text. — Regulatory label text (Tier A). Source of contraindications, serotonin syndrome warning, adverse reactions, food effect (+177.5% Cmax, +123.5% AUC), metabolism, half-life, hepatic and renal statements, pregnancy and overdosage.Read through a summarizing fetch tool; quotations are the tool's rendering of the label. Label version and date not seen.
Metaxalone tablets USP 800 mg, label as shown on DrugCentral (Actavis Pharma; DailyMed set ID b3a4f6bc-abd4-4b8e-970f-59b3aa6f17a0). — Regulatory label mirror (Tier A). Source of CYP metabolism list, "does not inhibit" and "does not induce" statements, urinary excretion of unidentified metabolites, volume of distribution about 800 L, protein binding unknown, special populations, adverse reaction list.Read through a summarizing fetch tool. The DailyMed page for the same set ID and a second DailyMed label (Amneal, set ID 3aa9dba9-29b0-4520-a0f7-66d19d52c6bc) were refused with HTTP 429 and not retried.
SKELAXIN (metaxalone) tablet label, Pfizer labeling site. — Regulatory label (Tier A). Source of the contraindication wording (hypersensitivity; known tendency to drug induced, hemolytic or other anemias; severe renal or hepatic impairment), the adverse reaction list including "leukopenia; hemolytic anemia" and "jaundice", the 13-years-and-older indication, Tmax 3.3 hours and the Cmax +94% and AUC +46% food-effect figures.Read through a summarizing fetch tool; the revision date 6/2024 and the exact label subsection of the adverse reaction list are the tool's rendering and were not verified.
WHO Collaborating Centre, ATC/DDD Index, group M03BX (other centrally acting agents). — Reference index. Listing returned M03BX01 baclofen to M03BX09 eperisone, M03BX30, M03BX53 and M03BX55; metaxalone was not listed. Pages M03BX06 (mephenesin) and M03BX07 (tetrazepam) were also opened and are not metaxalone. Other M03 subgroups were not searched, so "none listed" refers to M03BX only.Read through a summarizing fetch tool.
Wikipedia: Metaxalone. — Reference summary (not a primary source). Used for the chemical class (oxazolidinone), brand name and the statement that no ATC code is listed. Its pharmacokinetic figures differ from the labels and were not used.Read through a summarizing fetch tool. Not used to support any grade.
Onyechi A, et al. Metaxalone-induced immune hemolytic anemia. J Community Hosp Intern Med Perspect 2023;13(5). — Case report, n=1 (Tier B; this drug in cohort). DOI 10.55729/2000-9666.1236. Abstract only.Abstract via a reconstructed OpenAlex record and the journal landing page (https://scholarlycommons.gbmc.org/jchimp/vol13/iss5/18), both through a summarizing fetch tool. The PubMed Central full text (PMC10589045) returned a reCAPTCHA page and was not opened. Patient age, laboratory values and timing were not seen.
Pallio G, et al. MAO-A inhibition by metaxalone reverts IL-1β-induced inflammatory phenotype in microglial cells. Int J Mol Sci 2021. — In vitro, human microglial HMC3 cells (Tier B; this drug). DOI 10.3390/ijms22168425; PMID 34445126.Abstract via a reconstructed OpenAlex record through a summarizing fetch tool; full text not opened.
Yamaguchi M, Levy RM. Metaxalone suppresses production of inflammatory cytokines associated with painful conditions in mouse macrophages RAW264.7 cells in vitro: synergistic effect with β-caryophyllene. Curr Mol Med 2020. — In vitro, mouse macrophage cell line (Tier B; this drug). DOI 10.2174/1566524020666200217102508; PMID 32065089. One author is listed with Primus Pharmaceuticals, Inc. in the record.Abstract via OpenAlex through a summarizing fetch tool; full text not opened.
Liu H, et al. Metabolic activation and cytotoxicity of metaxalone mediated by cytochrome P450 enzymes and sulfotransferases. Chem Biol Interact 2023;382:110628. — In vitro, liver preparations and rat hepatocytes (Tier B; this drug). DOI 10.1016/j.cbi.2023.110628; PMID 37442290.Abstract as shown in a PubMed search-listing record through a summarizing fetch tool; the OpenAlex record had no abstract (a first fetch-tool summary of it speculated about content and was discarded). Full text not opened.
Cherrington B, et al. Monoamine oxidase A inhibition by toxic concentrations of metaxalone. Clin Toxicol (Phila) 2019 (OpenAlex; PubMed listing shows 2020). — In vitro enzyme assay, recombinant human MAO-A (Tier B; this drug). DOI 10.1080/15563650.2019.1648815; PMID 31373522.Abstract via a reconstructed OpenAlex record through a summarizing fetch tool; full text not opened.
Bosak AR, Skolnik AB. Serotonin syndrome associated with metaxalone overdose. J Med Toxicol 2014. — Case report, 2 overdoses (Tier B; this drug). DOI 10.1007/s13181-014-0404-5; PMID 24805103.Read through a summarizing fetch tool; the case figures and the oxazolidinone analogy are the tool's rendering.
Martini DI, et al. Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor. Clin Toxicol 2015. — Case reports, 2 patients (Tier B; this drug). DOI 10.3109/15563650.2015.1009993; PMID 25671244.Abstract via a reconstructed OpenAlex record through a summarizing fetch tool.
Rivera-Maldonado, Song, Noel, Fusick. Serotonin syndrome induced by the combined use of metaxalone, phentermine, and duloxetine: a case report. J Clin Basic Psychosom 2025;3(1). DOI 10.36922/jcbp.4490. — Case report (Tier B; this drug).Read through a summarizing fetch tool (landing page content).
Surmaitis RM, Nappe TM, Cook MD. Serotonin syndrome associated with therapeutic metaxalone in a patient with cirrhosis. Am J Emerg Med (2015 per OpenAlex, 2016 per PubMed listing). DOI 10.1016/j.ajem.2015.06.043; PMID 26159819. — Case report.Not opened: no abstract was available; title and metadata only. No fact beyond the title was used.
Gillman K. Metaxalone (Skelaxin) potential serotonin toxicity. psychotropical.com commentary. — Tier D practitioner commentary (cites about 75% MAO-A inhibition at overdose concentrations).Read through a summarizing fetch tool. Not used to support any grade.
Metaxalone. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (NBK548838; PMID 31644145). — Established pharmacology reference (Tier B). Likelihood score E; no aminotransferase elevations or case reports of hepatotoxicity.The NCBI page returned a reCAPTCHA page. Text read from a third-party mirror of the Bookshelf page (https://git.lsit.ucsb.edu/publicdata/nih-gov/raw/commit/a3492137cada35c1427e5783c176e4344e6cbb56/www.ncbi.nlm.nih.gov/books/NBK548838/index.html%3Freport=reader) through a summarizing fetch tool, and the abstract confirmed in a PubMed record. Monograph date not seen.
Bruce RB, et al. Metabolism of metaxalone. J Med Chem 1966. DOI 10.1021/jm00321a004; PMID 5960889. — Metabolism paper.Not opened: no abstract in the record; title and metadata only. No fact used.
Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage 2004. DOI 10.1016/j.jpainsymman.2004.05.002; PMID 15276195. — Systematic review listing metaxalone as a keyword.Not opened: no abstract in the record. No fact used. A Drug Class Review on NCBI Bookshelf (NBK10697) returned a reCAPTCHA page.
ZYVOX (linezolid) prescribing information, drugs.com. — Regulatory label for a different oxazolidinone antibacterial (context only; linezolid was not tied to metaxalone). Lactic acidosis, myelosuppression, serotonin syndrome and MAO-inhibition statements.Read through a summarizing fetch tool; only the first 100000 of 115515 characters were read. Metaxalone not in the cohort; no class extrapolation made.
Drugs.com. Metaxalone food and alcohol interactions. — Tier D consumer page. Alcohol only; no food, vitamin or supplement interaction listed.Read through a summarizing fetch tool. Not used to support any grade.
Columbia Doctors. Metaxalone drug information. — Tier D consumer page. Generic advice to tell the doctor about vitamins and supplements; no depletion content.Read through a summarizing fetch tool. Not used to support any grade.
Maier L, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018. DOI 10.1038/nature25979. — In vitro screen of marketed drugs against gut bacteria.Read through a summarizing fetch tool: metaxalone and muscle relaxants not mentioned in the text as rendered; supplementary drug tables not accessible, so absence from the screen is not confirmed. Not used as evidence.
Vich Vila A, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun 2020. DOI 10.1038/s41467-019-14177-z. — Population cohort analysis (abstract page only).Abstract page only through a summarizing fetch tool; names PPIs, metformin, antibiotics and laxatives; muscle relaxants not discussed in the abstract. Metaxalone not shown to be in the cohort. Not used as evidence. A drug-microbiome review (PMC8991093, https://pmc.ncbi.nlm.nih.gov/articles/PMC8991093) was also opened and does not mention metaxalone or skeletal muscle relaxants per the fetch tool.
PubMed search listings (format=pubmed), 2026-10-07: metaxalone (10 records on the first page); metaxalone AND oxidative (6); AND serotonin (7); AND hemolysis (2); AND iron (1); AND mitochondria, AND ATP, AND gut (each a 404 no-match page); and several refused or invalid requests. Repair pass 2026-10-07: AND copper (2 records, copper-catalysis chemistry papers), AND ceruloplasmin, AND ferritin, AND microbiota (each a 404 no-match page), AND bacteria (1 record, biocatalytic synthesis chemistry), AND respiration (1 record, the Martini serotonin syndrome case report already cited as [12]). — Search listings, not studies. The first-page metaxalone listing included the LiverTox monograph, the immune hemolysis case report, a biocatalytic synthesis paper, a 2004 forensic death report, an American Family Physician article, the 1966 metabolism paper, the MAO-A microglia paper, the macrophage paper, the 2004 systematic review and a 1964 JAMA evaluation (titles only, apart from those opened above). A 2004 J Anal Toxicol death report (Poklis et al., hydrocodone intoxication with metaxalone 19 mg/L in aortic blood; DOI 10.1093/jat/28.6.537) was opened as an OpenAlex abstract and contains no nutrient content.Refused with HTTP 429 and not retried: metaxalone AND copper, AND ceruloplasmin, AND microbiome, AND microbiota, AND glutathione, AND leukopenia, and two multi-term queries (serotonin, monoamine, hemolytic, anemia, leukopenia, hepatic; and hemolysis, methemoglobin, anemia, leukopenia, neutropenia). A multi-term vitamin and mineral query returned PubMed's generic trending page, discarded. Repair pass refused (429) and not retried: AND microbiome (twice), AND (gut microbiome OR dysbiosis), AND (energy OR respiration OR phosphorylation), AND "iron deficiency". 404 pages are read as no match but are not independently confirmed.
Crossref title/bibliographic searches (2026-10-07): "metaxalone" (50 items); "metaxalone hemolytic anemia leukopenia" (20); "metaxalone gut microbiota iron copper vitamin" (20). — Search listings, not studies. Titles with metaxalone included USP monographs, textbook chapters (including a drug eruption manual and a xenobiotic metabolism handbook, titles only, not opened), forensic and poison-center series, formulation papers and the cases above. A query with oxidative stress and mitochondria terms was refused (HTTP 429, not retried).Titles only; none of the unopened items was used.
DailyMed search listing for metaxalone (92 results). — Search listing: manufacturers and set IDs for generic tablets (Actavis, Amneal, BluePoint, Dr. Reddy's, Highmark, Lannett, ScieGen).Read through a summarizing fetch tool. The individual DailyMed label pages tried were refused with HTTP 429.

Metaxalone

Findings for this medication

What the research found

Leukopenia: labeled adverse reaction only, no study and no nutrient measured (context flag)

Serotonergic toxicity: labeled serotonin syndrome warning with MAO-A inhibition in vitro (interaction, excess direction)

Hepatic function: labeled jaundice and impairment caution against a LiverTox score of E (context flag)

Dietary intake: labeled nausea, vomiting and gastrointestinal upset; no nutrient or intake measured (context flag)

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: reverse direction, PGC-1α expression in stimulated microglia only

💥Oxidative Stress

Oxidative stress: opposing in vitro signals, reactive metabolite with glutathione conjugation versus reduced malondialdehyde in stimulated microglia

⚖️Copper and Iron Balance

Copper

Iron

🌿Gut Microbiome Risk

Gut microbiome risk

💨Oxygen and ATP Output

Oxygen delivery/utilization: labeled hemolytic anemia and one case report of immune hemolysis (drug toxicity direction)

ATP production

Claims checked and not supported

No circulating metaxalone nutrient-depletion claim located

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