Methylnaltrexone
peripherally acting mu-opioid receptor antagonist (quaternary ammonium)
Also sold as Relistor.
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.
Methylnaltrexone has almost no classical depletion machinery. It is a quaternary ammonium molecule whose passage across the blood-brain barrier is restricted, it neither inhibits nor induces CYP1A2, 2A6, 2B6, 2C9, 2C19 or 3A4, it is only a minor substrate for sulfation and carbonyl reduction, and it is cleared by a mix of renal (with active tubular secretion) and fecal routes [1][3]. The label sections retrieved list no nutrient, vitamin, mineral, electrolyte, hematologic, iron, copper, mitochondrial, oxidative-stress or microbiome statements; the only gastrointestinal warnings are perforation, severe or persistent diarrhea, and opioid withdrawal [1]. Methylnaltrexone is a different molecule from naltrexone; nothing from naltrexone data is carried over here.
peripherally acting mu-opioid receptor antagonist (quaternary ammonium) · ATC A06AH01 (WHO ATC/DDD Index [2]) · also sold as Relistor injection and Relistor tablets · reviewed 2026-10-04. 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 Methylnaltrexone 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
Food and meal timing: high-fat meal lowers tablet exposure (food affects drug)
Yellow — LowSee study details
Taking methylnaltrexone tablets with a high-fat breakfast lowered Cmax by 60% and AUC by 43% and delayed Tmax by 2 hours, so the label directs tablets on an empty stomach at least 30 minutes before the first meal of the day.
Full detail and limits
Food and meal timing: high-fat meal lowers tablet exposure (food affects drug)
Yellow — LowWhat 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: None located.
- At-risk subgroups: Tablet users who take the dose with meals; no nutrient-status subgroup is implicated.
Direction
Food affects the drug (Hard Rule 4). This is a timing interaction, not a depletion of any nutrient by the drug, and it carries no implication for nutrient intake.
Regulatory status
Stated in the label dosing and pharmacokinetic sections [1]. Read through a summarizing fetch tool, not verbatim in full.
Population evidence
Label food-effect study: percent changes as above; the number of participants was not reported in the text retrieved [1].
Mechanism
Not described in the sections retrieved; oral bioavailability is itself undetermined [1].
Separation interval
Tablets: empty stomach, at least 30 minutes before the first meal of the day (label). No separation interval for any mineral, vitamin or antacid was found in the sections retrieved. A food effect for the injection was not stated in the sections retrieved.
Counter-evidence held on record
Counter-evidence and confounding Not applicable to a nutrient claim; the finding concerns drug exposure only. Framing caution This is a dosing-timing instruction, not a nutrient deficiency. It is not a reason to change diet or add a supplement.
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
Not graded — disclosed evidence gapSee study details
No study located measured mitochondrial structure, membrane potential, respiration or biogenesis after methylnaltrexone exposure.
Full detail and limits
Mitochondrial burden
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence was found, and no circulating consumer claim was located to rebut. This is a disclosed gap, not a finding of safety.
- Confounding: Opioids themselves are studied for mitochondrial effects; any future methylnaltrexone finding needs an opioid-matched comparator.
Channels tried
PubMed listings: "methylnaltrexone mitochondria" (HTTP 429, not retried), "methylnaltrexone mitochondrial" (HTTP 404 page), "methylnaltrexone bioenergetics" (3 results, none a mitochondrial endpoint: two body-weight papers in ob/ob mice and neonatal rats and the metabolism paper [3]), "methylnaltrexone oxygen consumption" (HTTP 429, not retried). Label read for mitochondrial text: none [1]. Crossref title searches returned only title matches without a mitochondrial paper. Europe PMC (429) and OpenAlex list endpoint (429) were blocked. Repair pass 2026-10-04: PubMed listings "methylnaltrexone mitochondria" and "methylnaltrexone mitochondrial" both returned HTTP 404 again; a Crossref bibliographic query ("methylnaltrexone oxidative stress mitochondria") returned only generic mitochondria book chapters and no methylnaltrexone record; the OpenAlex search endpoint returned 429 again; web search (which worked again for part of this pass) for "methylnaltrexone mitochondrial function cells respiration membrane potential" and "methylnaltrexone oxidative stress ischemia reperfusion mitochondria" returned only generic mitochondrial-method and ischemia-reperfusion reviews with no methylnaltrexone study; the FDA label PDF [16] and the Drugs.com professional monograph [17] contain no mitochondrial text; the full text of the Coluzzi review [6] (MDPI) names methylnaltrexone only as a PAMORA and reports no mitochondrial data.
Related studies set aside
Methylnaltrexone cancer-angiogenesis and endothelial-barrier papers [9][13] report receptor transactivation (Src, S1P3, RhoA/ROCK per [9]); they did not report mitochondrial endpoints in the text read.
Gap type
Probable genuine gap, with verification partly tooling-limited (429s and 404s on direct PubMed, Crossref and OpenAlex queries, and the web-search budget is again exhausted at 200 of 200). The repair pass found no study to grade. A later revision should re-run these queries.
Oxidative Stress
Each finding below is counted once, in this area only.
Oxidative stress
Not graded — disclosed evidence gapSee study details
No study located measured a redox or antioxidant-capacity marker (MDA, glutathione, SOD, total antioxidant capacity) in methylnaltrexone-exposed animals, cells or people.
Full detail and limits
Oxidative stress
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence for a redox or antioxidant-capacity endpoint, and no circulating claim located. This is a disclosed gap, not a finding of safety.
- Confounding: Sepsis, surgery and cancer, the settings in which methylnaltrexone has been studied, independently change redox markers.
Channels tried
PubMed listings: "methylnaltrexone oxidative stress" (HTTP 429, not retried); "methylnaltrexone oxidative" and an OR query with antioxidant, reactive oxygen and malondialdehyde (8 results each time, none a redox marker in methylnaltrexone-exposed subjects; two were rat nitric oxide synthase papers); "methylnaltrexone reactive oxygen species" (HTTP 429, not retried). Label: no oxidative-stress text [1]. Crossref title queries: no relevant record. Repair pass 2026-10-04: PubMed listing "methylnaltrexone oxidative" re-read in full (8 records: an opioid-induced constipation systematic review in cancer patients, a kaolin-intake rat paper, the metabolism paper [3], two splenocyte nitric oxide papers including Lysle and How [12], and three nitric oxide pathway pharmacology papers in which methylnaltrexone or naltrexone was a control compound; none measured MDA, glutathione, SOD, reactive oxygen species or antioxidant capacity). PubMed listings "methylnaltrexone ischemia" (5 records: the MOVEMENT trial of platelet reactivity in myocardial infarction, a Lancet review of opioid antagonists, a wound-repair review, a case report, and a 1999 rat arrhythmia paper), "methylnaltrexone reperfusion" (1 record, the same 1999 arrhythmia paper) and "methylnaltrexone sepsis" (3 records: a trauma cholestasis cohort, Singleton 2007 [9], Babrowski 2012 [4]) contained no redox endpoint; these records were read as listing text only and were not opened individually. Web searches for methylnaltrexone with ischemia-reperfusion, sepsis and oxidative stress returned only generic ischemia-reperfusion and sepsis-redox literature with no methylnaltrexone study. FDA label PDF [16] and Drugs.com monograph [17]: no oxidative-stress text.
Related studies set aside
Lysle and How 1999 [12] (rat LPS model): intracerebroventricular but not peripheral N-methylnaltrexone reduced splenic inducible nitric oxide synthase expression. That is an immune-signalling readout through central receptors, not a redox or antioxidant-capacity marker, so it was not used to grade. Neefjes 2014 [14] (195 patients) collected immunomodulatory and anti-angiogenic laboratory markers; only the first lines of the abstract were read and no redox marker was identified.
Gap type
Probable genuine gap, partly tooling-limited (429s on the oxidative stress and reactive oxygen species PubMed queries, search budget exhausted). The one redox-adjacent signal in the methylnaltrexone literature is the nitric oxide and iNOS splenocyte work in rats, which is immune signalling through central receptors and was not graded. Re-check with Europe PMC or PubMed once access recovers.
Copper and Iron Balance
Copper and iron are assessed separately. Nothing here is counted twice.
Copper
Not graded — disclosed evidence gapSee study details
No study located measured copper status, ceruloplasmin or copper handling in methylnaltrexone-exposed subjects.
Full detail and limits
Copper
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence and no circulating claim located. Copper is kept as its own entry and not merged with iron. This is a disclosed gap, not a finding of safety.
- Confounding: Any copper change in treated patients would be confounded by opioid use, malabsorption, nutrition status and underlying disease.
Channels tried
PubMed listing "methylnaltrexone copper" (HTTP 404 page; the HTML variant returned HTTP 429 and was not retried). Label: no copper text [1]. Crossref title queries: none relevant. Repair pass 2026-10-04: FDA label PDF [16] and Drugs.com monograph [17] contain no copper, mineral or laboratory-abnormality text (summarizing tool report). A second PubMed copper query was not attempted because the PubMed proxy had returned a do-not-retry 429; a Crossref iron/hemoglobin/anemia title query was likewise refused with 429.
Gap type
Probable genuine gap. The 404 is read as a probable zero-hit result but is not proven, because a control query with a nonsense token returned generic results, so zero-hit behavior could not be told apart from an error. Tooling-limited verification.
Iron
Not graded — disclosed evidence gapSee study details
No study located measured ferritin, transferrin saturation, iron absorption or hemoglobin as an iron outcome in methylnaltrexone-exposed subjects.
Full detail and limits
Iron
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence and no circulating claim located. Iron is kept as its own entry and not merged with copper. This is a disclosed gap, not a finding of safety.
- Confounding: Anemia and iron deficiency are common in advanced illness, cancer and after surgery regardless of drug, and anemia would not be an iron-deficiency finding without iron measured (Hard Rule 2).
Channels tried
PubMed listings "methylnaltrexone iron" (HTTP 404 page), "methylnaltrexone hemoglobin" (404), "methylnaltrexone anemia" (404), "methylnaltrexone hemoglobin OR anemia OR iron" (HTTP 429, not retried), "methylnaltrexone hematologic" (8 results, none reporting a hematologic outcome for the drug; the first was a pediatric intravenous-use report whose abstract was not opened). Label adverse-reaction tables list no hematologic abnormality [1]. Repair pass 2026-10-04: PubMed listing "methylnaltrexone hemoglobin" returned 404 again and "methylnaltrexone ferritin" returned a do-not-retry 429. The FDA 2018 label PDF [16] was reported by the summarizing tool to contain no hemoglobin, anemia, iron, electrolyte or laboratory-abnormality text, and its adverse-reaction tables (4, 5, 6) list clinical symptoms only; the Drugs.com monograph [17] likewise. A web search for methylnaltrexone with hemoglobin decrease, anemia and laboratory adverse events surfaced the NEJM advanced-illness trial (Thomas 2008) and a 1997 healthy-volunteer intravenous safety study (PMID 9048269); the NEJM page returned HTTP 403 and the 1997 study was seen only as a search title, so neither was opened and neither is cited as evidence. The FDA medical review documents (not located; only label PDFs surfaced) are the one remaining untried regulatory channel for laboratory data.
Gap type
Probable genuine gap; verification partly tooling-limited (404 behavior unproven, 429s, NEJM full text blocked, FDA review documents not reached).
Gut Microbiome Risk
Each finding below is counted once, in this area only.
Gut microbiome risk: reverse direction relative to opioid; one in vitro arm and narrative reviews
Yellow — LowSee study details
In one bacterial assay methylnaltrexone partly blocked morphine-induced virulence expression in gut Pseudomonas aeruginosa, and narrative reviews describe peripheral mu-opioid antagonists as improving opioid-disrupted intestinal permeability; no study located measured gut microbiome composition, diversity or function in methylnaltrexone-treated animals or people.
Full detail and limits
Gut microbiome risk: reverse direction relative to opioid; one in vitro arm and narrative reviews
Yellow — LowWhat 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
- Opioid confounding: Morphine alone altered the mouse gut microbiome and metabolome within one day (more pathogenic-function communities, Enterococcus faecalis expansion); that study used no peripheral antagonist [8]. Methylnaltrexone-treated people are on opioids, often with advanced illness, surgery or critical care, so opioid dose, constipation, laxatives, antibiotics and diet are not separable from the drug.
- Null findings: None for microbiome composition; no such measurement was located. PubMed listing queries for "methylnaltrexone microbiome" returned a single 2022 review of postoperative constipation (listing text only, not opened).
- At-risk subgroups: The populations that receive the drug: critically ill, post-surgical, advanced illness and cancer pain patients on chronic opioids.
Direction
Reverse or neutral relative to the opioid effect (a possible mitigating action). This is not a depletion and not an excess or retention finding.
Regulatory status
Label warnings are gastrointestinal perforation, severe or persistent diarrhea (stop therapy and consult) and opioid withdrawal. Clostridioides difficile and microbiome are not mentioned in the sections retrieved [1].
Population evidence
No human microbiome-composition study with a methylnaltrexone arm was located. In the MOTION randomized trial (84 critically ill ventilated adults, 41 methylnaltrexone and 43 placebo) no C. difficile case was reported among serious adverse events and the primary laxation outcome did not differ (69.2% vs 65.1%, HR 1.42, 95% CI 0.82 to 2.46) [7]. That is an infection-event observation, not a microbiome measurement.
Mechanism (Tier B)
Babrowski 2012 [4]: mice with a morphine pellet plus cecal P. aeruginosa showed suppressed intestinal mucus, disrupted epithelium and higher mortality. Methylnaltrexone was tested only in the in vitro step: morphine-induced expression of the barrier-disrupting PA-I lectin was "attenuated in part by methylnaltrexone". There was no methylnaltrexone arm in the mice, and microbiome composition was not the endpoint.
Class extrapolation
CLASS EXTRAPOLATION and narrative review, capped at yellow. Lacy and Cangemi 2024 [5] is a narrative review that names methylnaltrexone among peripherally active mu-opioid antagonists said to ameliorate opioid-disrupted intestinal permeability; it is not a cohort. Coluzzi 2024 [6] reviews opioid use and dysbiosis in cancer pain and refers to PAMORAs only as a class without naming methylnaltrexone, so for this drug it is Tier C context. Methylnaltrexone was not in any microbiome-measuring cohort among these sources.
Counter-evidence held on record
Counter-evidence and confounding The only methylnaltrexone-specific datum is an in vitro bacterial assay run against morphine, so it speaks to blocking an opioid effect, not to any effect of methylnaltrexone alone. Opioid exposure, not the antagonist, is the presumed driver of any microbiome shift in treated patients. Framing caution This is not a claim that methylnaltrexone damages or restores the gut microbiome. It is not a prompt for probiotics or other supplements. Do not publish as a deficiency claim.
Oxygen and ATP Output
Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.
Oxygen delivery/utilization
Not graded — disclosed evidence gapSee study details
No study located measured hemoglobin, hematocrit, red-cell mass, arterial oxygenation or tissue oxygen delivery as an outcome of methylnaltrexone.
Full detail and limits
Oxygen delivery/utilization
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence for an oxygen delivery or utilization endpoint, and no circulating claim located. This is a disclosed gap, not a finding of safety.
- Confounding: Opioid-induced respiratory depression, critical illness and anemia of chronic disease all alter oxygen delivery independent of methylnaltrexone.
Channels tried
PubMed listings: "methylnaltrexone hypoxia" (1 result, Amin 1994 [10]), the hemoglobin, anemia and hematologic queries listed under Iron, and "methylnaltrexone oxygen consumption" (HTTP 429, not retried). Label adverse reactions list no hematologic abnormality [1]. Repair pass 2026-10-04: PubMed listings "methylnaltrexone ischemia" and "methylnaltrexone reperfusion" returned the MOVEMENT trial (PMID 30636504, platelet reactivity and ticagrelor exposure in ST-elevation myocardial infarction, listing text only, no oxygen delivery endpoint) and a 1999 rat paper on ischemia-induced ventricular arrhythmias (PMID 9890406, listing text only, arrhythmia endpoint). Neither measured hemoglobin, oxygenation or tissue oxygen delivery, and neither was opened individually, so neither is graded or listed in Sources.
Related studies set aside
Amin 1994 [10] (10 healthy volunteers, double-blind crossover per the reconstructed abstract): naloxone reversed morphine's depression of the hypoxic ventilatory response while methylnaltrexone did not clearly do so, consistent with the restricted blood-brain barrier passage. This is a respiratory-drive outcome and a mechanism clarification, not hemoglobin or tissue oxygen delivery, so it is not graded as a finding (Hard Rule 2). Singleton 2007 [9] shows methylnaltrexone reduced LPS-induced vascular hyperpermeability in murine lung and human pulmonary endothelial cells; permeability is not an oxygen delivery measure.
Gap type
Probable genuine gap; verification partly tooling-limited (hemoglobin PubMed query 404, ferritin and oxygen consumption queries 429, NEJM trial full text 403).
ATP production
Not graded — disclosed evidence gapSee study details
No study located measured mitochondrial ATP synthesis or cellular ATP content after methylnaltrexone exposure.
Full detail and limits
ATP production
Not graded — disclosed evidence gapWhat 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: Both conditions of the Step 7 test are met: no Tier B or C evidence for an ATP endpoint, and no circulating "low energy" claim located. ATP is kept separate from mitochondrial burden and from oxygen delivery. This is a disclosed gap, not a finding of safety.
- Confounding: Opioids, illness and reduced intake alter whole-body energy status independent of the drug.
Channels tried
PubMed listings: "methylnaltrexone ATP" (2 results, both pain-pharmacology papers referencing the KATP channel pathway, not ATP synthesis), "methylnaltrexone bioenergetics" (3 results; see below), "methylnaltrexone oxygen consumption" (HTTP 429, not retried). Label: no ATP or energy-metabolism text [1]. Repair pass 2026-10-04: the ischemia, reperfusion, sepsis and oxidative PubMed listings read in this pass (see Oxidative stress) returned no ATP, adenine nucleotide, energy charge or oxygen consumption endpoint for methylnaltrexone; FDA label PDF [16] and Drugs.com monograph [17] have no ATP or energy-metabolism text.
Related studies set aside
Yuan 2009 [11]: in neonatal rats, methylnaltrexone 3.0 mg/kg potentiated leptin's reduction of body weight and retroperitoneal fat-pad weight (p < 0.01). Energy expenditure is mentioned as background, but oxygen consumption, UCP1 and mitochondrial function were not measured. Body weight is an outcome, not ATP, so it is not graded as an ATP finding.
Gap type
Probable genuine gap; verification partly tooling-limited (oxygen consumption query 429, search budget exhausted).
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.
Any nutrient or category claim attributed to naltrexone, applied to methylnaltrexone
Where it comes from: Not observed for this drug. Recorded as a guard against pooling the two names.
Why it fails: Methylnaltrexone is the N-methyl quaternary derivative of naltrexone, a different molecule with restricted blood-brain barrier passage and its own metabolism [1][3][10]. No naltrexone finding is carried onto it. Where an old study used N-methylnaltrexone as a tool compound [12], it is read as methylnaltrexone data only for the endpoint it reported.
How the body handles this medication
- Metabolism and enzymes
- Minor metabolism by sulfation (SULT1E1, SULT2A1) to methylnaltrexone sulfate and carbonyl reduction (aldo-keto reductase 1C enzymes) to methyl-6-alpha-naltrexol and methyl-6-beta-naltrexol. Methylnaltrexone did not significantly inhibit or induce CYP1A2, 2A6, 2B6, 2C9, 2C19 or 3A4.[1] DailyMed Relistor label sec 7, 12.3; [3] Tong 2010 abstract (listing text)
- Elimination
- After an intravenous radiolabeled dose about 54% was recovered in urine and 17% in feces (71% recovered by 7 days); after oral dosing about 1% of parent drug appeared in urine. Renal clearance is about 4 to 5 times creatinine clearance, suggesting active tubular secretion. Oral terminal half-life is about 15 hours.[1] label sec 12.3 (via summarizing fetch tool)
- Absorption and transporters
- Oral absolute bioavailability has not been determined; Tmax is about 1.5 hours oral and 0.5 hours after injection. Methylnaltrexone is a substrate of OCT1, OCT2, MATE1 and MATE2-K, and not of P-gp, BCRP, MRP2 or OATP isoforms. Protein binding 11 to 15%; volume of distribution about 1.1 L/kg.[1] label sec 12.3
- Blood-brain barrier
- Label wording: as a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is restricted, allowing peripheral-only antagonism.[1] label sec 12
- Renal and hepatic impairment
- Exposure rises 1.3 to 1.9 fold with declining renal function; dose reduction is directed when creatinine clearance is below 60 mL/min. For tablets, moderate or severe hepatic impairment (Child-Pugh B or C) raises Cmax 2.1 to 4.8 fold and a reduced dose is directed.[1] label sec 2.4, 2.5, 8.6, 8.7
- Food and drug interactions
- A high-fat breakfast lowered tablet Cmax by 60% and AUC by 43% and delayed Tmax by 2 hours; tablets are taken with water on an empty stomach at least 30 minutes before the first meal of the day. Cimetidine raised AUC about 10% and cut renal clearance about 40%, judged not clinically meaningful. No mineral or antacid interaction appeared in the sections retrieved.[1] label sec 2, 7, 12.3
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.
Adverse effect, not a nutrient
Severe or persistent diarrhea
The label directs stopping therapy and consulting a prescriber if diarrhea is severe or persistent [1]. If prolonged diarrhea occurs, hydration and electrolyte status (sodium, potassium, magnesium) are a clinical judgement; this is the drug's own adverse effect and is not filed as a nutrient deficiency.
Timing
Tablets on an empty stomach
Take tablets with water at least 30 minutes before the first meal of the day; a high-fat meal lowers exposure [1]. No supplement or mineral separation interval was found in the label sections retrieved.
Renal and hepatic function
Exposure rises with impairment
Creatinine clearance below 60 mL/min and, for tablets, Child-Pugh B or C hepatic impairment call for label dose reductions [1]. Check renal function as the label directs.
GI wall integrity
Perforation risk groups
Gastrointestinal perforation is reported in patients with conditions that reduce structural integrity of the gut wall [1]. Not a nutrient item; listed because it governs who should not be treated.
Underlying illness
Baseline hemoglobin and iron indices
Anemia and iron deficiency are common in advanced illness and cancer independent of this drug. Check as part of care for the underlying condition, not as a methylnaltrexone finding.
Pregnancy, lactation, children
Special populations
Label: use in pregnancy may precipitate opioid withdrawal in a fetus; breastfeeding is not recommended during treatment; safety and effectiveness in pediatric patients are not established [1]. Renal impairment: see above.
Overlap map, to prevent double counting
Mitochondrial burden; ATP production; Oxidative stress
Shares evidence with: Each other
Note: All three rest on the same null search set (PubMed methylnaltrexone queries on mitochondria, bioenergetics, oxygen consumption and oxidative terms) and the same label silence [1]. Their ungraded status is one gap seen three ways, not three independent confirmations; the repair-pass listings (ischemia, reperfusion, sepsis, oxidative) are the same shared null set. The same set-aside studies [11][12] touch more than one.
Copper; Iron
Shares evidence with: Each other; Oxygen delivery/utilization
Note: Copper and iron are separate entries. Their ungraded status shares the same label silence on hematology and the same PubMed 404 pages for the copper, iron, hemoglobin and anemia queries. Oxygen delivery/utilization shares the hematology null set with Iron but is a separate entry.
Gut microbiome risk
Shares evidence with: Food and meal timing: none. Oxidative stress and Oxygen delivery: Singleton 2007 [9] (set aside)
Note: The microbiome entry rests on Babrowski [4], the narrative reviews [5][6], MOTION [7] and the morphine confound study [8]. The reviews cite primary work that was not independently opened, so [4] and [5] must not be counted as two independent confirmations.
Food and meal timing
Shares evidence with: Pharmacokinetic basis section
Note: Both draw on the same label food-effect statement [1]; one source, not two.
All eight entries
Shares evidence with: Opioid co-exposure
Note: Confounding by opioid use is a shared limitation of every entry, not separate evidence for any of them.
All references used above
- RELISTOR (methylnaltrexone bromide) tablets and injection, prescribing information, DailyMed, last updated May 1, 2024 (per page). — Tier A, regulatory label. Sections 2, 5, 6, 7, 8, 12, 13 read through a summarizing fetch tool in several fetches; wording was not seen verbatim in full, and some quotes are as returned by the tool.
- WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index, A06AH01 methylnaltrexone bromide (A06AH Peripheral opioid receptor antagonists). — Reference; opened.
- Tong Z, Chandrasekaran A, Li H, et al. In vitro metabolism and identification of human enzymes involved in the metabolism of methylnaltrexone. Drug Metab Dispos 2010. PMID 20173089; DOI 10.1124/dmd.110.032169. — Tier B, in vitro human enzyme study of this drug. Only the first two sentences of the abstract were seen (via a PubMed listing read by a summarizing tool); OpenAlex returned metadata only. Full text not opened.
- Babrowski T, Holbrook C, Moss J, et al. Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration. Ann Surg 2012. PMID 21989372; DOI 10.1097/SLA.0b013e3182331870. — Tier B. Mouse morphine-pellet model plus in vitro bacterial assay; methylnaltrexone used only in the in vitro assay. Full abstract read via a summarizing tool on a PubMed record; full text not opened.
- Lacy BE, Cangemi DJ. Opioids and the gastrointestinal tract: the role of peripherally active mu-opioid receptor antagonists in modulating intestinal permeability. Am J Gastroenterol 2024. PMID 38870087; DOI 10.14309/ajg.0000000000002887. — Tier C, narrative review (not a cohort). Abstract only, reconstructed from OpenAlex by a summarizing tool; full text not opened.Narrative review: names methylnaltrexone but contributes no cohort data.
- Coluzzi F, Scerpa MS, Loffredo C, et al. Opioid use and gut dysbiosis in cancer pain patients. Int J Mol Sci 2024. PMID 39063241; DOI 10.3390/ijms25147999. — Tier C, narrative review. Abstract only, read via a summarizing tool; full text not opened.Excluded cohort: refers to PAMORAs as a class only; methylnaltrexone not named in the abstract. Class extrapolation, context only.
- Patel P, Brett SJ, O'Callaghan D, et al. Methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients. Results from the MOTION trial. Intensive Care Med 2020;46:747-755. PMID 32016532; DOI 10.1007/s00134-019-05913-6. — Tier A for safety observations; multicenter double-blind randomized trial, 84 randomized (41 methylnaltrexone, 43 placebo). Read via the Springer page through a summarizing tool. Reported no C. difficile cases among serious adverse events. A mortality imbalance (10 vs 2 deaths) was also reported; it is not a nutrient finding and is not interpreted here. No nutrient or microbiome endpoint was identified.
- Wang F, Meng J, Zhang L, Johnson T, Chen C, Roy S. Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model. Sci Rep 2018. PMID 29483538. — Mouse morphine model. Abstract read via a summarizing tool. Used only to document opioid confounding.Excluded cohort: no methylnaltrexone or other peripheral antagonist arm.
- Singleton PA, Moreno-Vinasco L, Sammani S, et al. Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation. Am J Respir Cell Mol Biol 2007. PMID 17395891. — Tier B, in vitro human pulmonary endothelial cells and murine lung with methylnaltrexone. Full abstract read via a summarizing tool. Endothelial permeability, not an entry in this dossier; set aside under Oxygen delivery/utilization. Abstract mentions no reactive oxygen species or mitochondria.
- Amin HM, Sopchak AM, Foss JF, Esposito BF, Roizen MF, Camporesi EM. Efficacy of methylnaltrexone versus naloxone for reversal of morphine-induced depression of hypoxic ventilatory response. Anesth Analg 1994. PMID 8135389; DOI 10.1213/00000539-199404000-00015. — Human volunteer study with methylnaltrexone. Abstract reconstructed from OpenAlex by a summarizing tool; the numerical results in that reconstruction were not relied upon. Respiratory-drive outcome, not an oxygen delivery measure.
- Yuan CS, Sun S, Attele A, Wang CZ, Tong R, Israel RJ. Methylnaltrexone potentiates body weight and fat reduction with leptin. J Opioid Manag 2009. PMID 20073411. — Tier B, neonatal rat study with methylnaltrexone. Abstract read via a summarizing tool. Body weight outcome; set aside under ATP production.
- Lysle DT, How T. Endogenous opioids regulate the expression of inducible nitric oxide synthase by splenocytes. J Pharmacol Exp Ther 1999;288:502-508. PMID 9918551. — Tier B, rat LPS model using N-methylnaltrexone as a tool compound. Abstract read via a summarizing tool. Immune-signalling readout, not a redox marker; set aside under Oxidative stress.
- Singleton PA, Lingen MW, Fekete MJ, Garcia JGN, Moss J. Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res 2006;72:3-11. PMID 16820176; DOI 10.1016/j.mvr.2006.04.004. — Tier B, in vitro angiogenesis work with methylnaltrexone.Only the first two sentences of the abstract were seen (PubMed listing via summarizing tool); OpenAlex and Crossref returned no abstract. Cited only as an example of the cancer-angiogenesis literature; nothing is graded from it.
- Neefjes ECW, van der Vorst MJDL, Boddaert MSA, et al. Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone. BMC Palliat Care 2014. PMID 25165428. — Tier A design for constipation efficacy (195 patients). Only a short abstract was read via a summarizing tool; no redox, hematologic or nutrient endpoint identified.
- Drugs.com, Relistor consumer page. — Tier D, consumer content. Opened to audit circulating claims; no nutrient, mitochondrial, oxidative-stress or microbiome statements found. Never used to support a claim.
- RELISTOR (methylnaltrexone bromide) prescribing information, FDA label PDF, 2018 revision (NDA 021964 / 208271). — Tier A, regulatory label. Opened through a summarizing fetch tool during the repair pass and searched for hemoglobin, anemia, iron, copper, oxidative, mitochondrial, microbiome, C. difficile, electrolyte and laboratory-abnormality text: reported absent; adverse-reaction tables list clinical symptoms only. Not read verbatim in full.
- Drugs.com, Methylnaltrexone Monograph for Professionals. — Tier D, secondary compilation. Opened through a summarizing fetch tool and searched for the same terms: reported absent. Used only to document a null; never used to support a claim.
- Coluzzi F, et al. Opioid use and gut dysbiosis in cancer pain patients. Int J Mol Sci 2024 (full text, MDPI) [same paper as 6]. — Tier C, narrative review. Full text opened through a summarizing fetch tool in the repair pass: it names methylnaltrexone, naloxegol and naldemedine as PAMORAs, discusses "the possible role of PAMORAs in reversing opioid-induced dysbiosis", and calls for further research on PAMORAs versus laxatives for the gut microbiota. No primary microbiome study with a methylnaltrexone arm is cited. Documents the gap; nothing is graded from it.
- Opioid agonist and antagonist use and the gut microbiota: associations among people in addiction treatment. Sci Rep 2020. — Cohort of 46 participants (opioid agonists, buprenorphine-naloxone, naltrexone, neither). Opened through a summarizing fetch tool.Excluded cohort: methylnaltrexone was not in the cohort (naltrexone and buprenorphine-naloxone were); naltrexone data are not carried onto methylnaltrexone.
- Banerjee S, et al. Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation. Mucosal Immunol 2016. — Mouse morphine model. Opened through a summarizing fetch tool: the antagonist arm was naltrexone, which prevented the morphine-induced microbiome and bile-acid changes.Excluded cohort: methylnaltrexone was not an arm; naltrexone is a different molecule and its findings are not carried over.
- PubMed search-listing pages queried for this review (format=pubmed), methylnaltrexone with: microbiome, microbiota or dysbiosis, gut bacteria, intestinal barrier, permeability, sepsis, postoperative ileus, angiogenesis cancer, oxidative, ATP, bioenergetics, hypoxia, hematologic, Clostridium difficile; plus a morphine dysbiosis query and an opioid antagonist microbiome query. Repair pass additions: ischemia, reperfusion, "gut microbiome", ferritin, hemoglobin, mitochondria, mitochondrial, microbiota, dysbiosis, oxidative, sepsis. — Search listings, not studies. Results were read through a summarizing fetch tool and individual studies were cited only after their records were opened.Blocked or empty (repair pass: 404 for mitochondria, mitochondrial, microbiota, hemoglobin; do-not-retry 429 for dysbiosis and ferritin): HTTP 429 (not retried) for oxidative stress, mitochondria, reactive oxygen species, oxygen consumption, hemoglobin OR anemia OR iron, and the HTML copper query; HTTP 404 pages for mitochondrial, hemoglobin, anemia, iron, copper and morphine dysbiosis methylnaltrexone.