Naloxegol

peripherally acting mu-opioid receptor antagonist (PAMORA); PEGylated naloxol

Also sold as Movantik, Moventig.

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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.

Naloxegol has no classical nutrient-depletion machinery in the sources retrieved. It is a CYP3A4 and P-glycoprotein substrate, not described as an enzyme inducer or inhibitor in the label summaries read, with plasma protein binding of about 4.2% and elimination mainly in feces (68%) and urine (16%) [1][2][5]. The retrieved label sections list no vitamin, mineral, iron, copper, hemoglobin or electrolyte statement and report no laboratory abnormalities in the adverse reaction section [1][2][16]. Its documented risks are the drug's own effects (abdominal pain, diarrhea, opioid-withdrawal-like symptoms, GI perforation), which are never filed here as nutrient deficiencies (Hard Rule 2).

peripherally acting mu-opioid receptor antagonist (PAMORA); PEGylated naloxol · ATC A06AH03 (WHO ATC/DDD Index [3]) · also sold as Movantik (US) and Moventig (EU) · 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 Naloxegol 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

Grapefruit, high-fat meals and CYP3A4-active herbs: nutrient affects drug (interaction, not depletion)

Yellow — Low

See study details

Direction: food or herb changes naloxegol exposure. Grapefruit and a high-fat meal raise naloxegol levels, St. John's Wort lowers them. Naloxegol does not deplete any of these.

Full detail and limits

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

Limits on what this shows

Null findings: No mineral, vitamin or antacid interaction is listed in the label sections retrieved [1][2]. A weak CYP3A4 inhibitor needs no dose change [1].
At-risk subgroups: People on diltiazem, verapamil, erythromycin or clarithromycin; people with moderate or severe renal impairment, who already have higher exposure [2][6]; people taking a St. John's Wort product.

Regulatory status

Both label versions read list grapefruit and grapefruit juice as "avoid"; strong CYP3A4 inducers including St. John's Wort are "not recommended"; strong CYP3A4 inhibitors are contraindicated [1][2]. The label summaries state a high-fat meal increased Cmax by about 30% and AUC by about 45% [1][2]. A review reads that dosing is advised on an empty stomach, 1 hour before meals [12].

Population evidence

Bui 2015 [4]: open-label fixed-sequence crossover studies in healthy volunteers (naloxegol 25 mg). Exposure rose 12.9-fold with ketoconazole 400 mg and 3.4-fold with diltiazem 240 mg, and fell 89% with rifampin 600 mg. One subject stopped for liver enzyme elevation attributed to rifampin co-administration. The grapefruit-specific change in exposure was not found in any source opened; the grapefruit instruction rests on the label and review statements [1][2][12].

Mechanism

Present. Naloxegol is a sensitive CYP3A4 substrate [4] and a P-gp substrate [2][16]. The label lists grapefruit among the CYP3A4-related interactions [1][2]; the specific grapefruit mechanism and its measured effect on naloxegol exposure were not retrieved.

Counter-evidence held on record

Counter-evidence and confounding This is not a nutrient status finding. It is filed as an interaction because the relationship is a food or herb altering drug exposure (Hard Rule 4). Higher exposure is the hazard (a daily dose of twice the recommended amount increased GI adverse reactions in the label overdosage section [2]); the label gives avoidance, not a separation interval, as the instruction [1][2]. Framing caution Do not present this as a deficiency or as a reason to add or remove a supplement. Any change to grapefruit, herbal products or meal timing should be discussed with the prescriber or pharmacist.

Fluid and electrolytes: diarrhea is a drug effect (outcome entry, nutrient not measured)

Yellow — Low

See study details

Direction: possible loss through GI adverse effects. Diarrhea and vomiting are more frequent on naloxegol, but no electrolyte, magnesium or potassium value was reported in any source retrieved.

Full detail and limits

Limits on what this shows

Null findings: No electrolyte disturbance was reported in the abstracts or label summaries read. Absence of a report is not a measurement: none of the sources states that electrolytes were tested.
At-risk subgroups: Methadone users had higher GI adverse reaction frequencies than other opioid users [2]; people with higher exposure (renal impairment, CYP3A4 inhibitor co-use); people also taking laxatives.

Regulatory status

Adverse reactions in the pooled phase 3 studies (25 mg, 12.5 mg, placebo): abdominal pain 21%, 12%, 7%; diarrhea 9%, 6%, 5%; nausea 8%, 7%, 5%; vomiting 5%, 3%, 4% [1]. No laboratory abnormality, hemoglobin, electrolyte or creatine kinase data are reported in the label summaries [1][2][16]. Overdose (50 mg daily for 4 weeks) increased abdominal pain, diarrhea and nausea [2].

Population evidence

Chey 2014 [7]: two identical phase 3 double-blind trials, noncancer pain with opioid-induced constipation; adverse events were most frequent in naloxegol groups (abstract as reconstructed from OpenAlex; numbers per arm not available to me). Webster 2014 [8]: 52-week open-label randomized trial, 804 patients (534 naloxegol 25 mg, 270 usual-care laxatives); adverse events 81.8% versus 72.2%, with diarrhea and abdominal pain more frequent on naloxegol and most resolving early. Webster 2013 phase 2 [9]: 207 patients, most common events abdominal pain, diarrhea, nausea, mostly mild and transient at lower doses.

Mechanism

Present as pharmacology: antagonism of GI mu-opioid receptors reverses opioid-induced delay in transit [1]. Faster transit and a withdrawal-like GI cluster (the label lists diarrhea and abdominal pain among the opioid-withdrawal-like symptoms) are the drug's intended or direct effects, not a nutrient mechanism.

Counter-evidence held on record

Counter-evidence and confounding Diarrhea is an outcome and a drug effect (Hard Rule 2), not an electrolyte or mineral deficiency. The usual-care arm in [8] was on laxatives, which also cause diarrhea, so the comparison there is not a placebo comparison. Patients are all on chronic opioids with baseline constipation; the placebo-controlled trials [7] control for this, the open-label trial does not. Framing caution Persistent diarrhea or vomiting is a reason to contact the prescriber, not a reason to start potassium, magnesium or other supplements. Severe or worsening abdominal pain can signal GI perforation, which the label reports including fatal postmarketing cases [1].

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 gap

See study details

No naloxegol-specific data on mitochondrial structure, electron transport or biogenesis were found.

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 after the repair searches: no Tier B or C source on naloxegol and mitochondria exists in what was reached, and no circulating claim of naloxegol mitochondrial toxicity was found to rebut (consumer-page checks are listed under Fails verification). This is a disclosed gap, not a finding of safety. Opioid confounding: opioids themselves are studied in mitochondrial toxicity, but no such source was opened and none is borrowed.

What was searched

Crossref bibliographic query "naloxegol oxidative stress mitochondria" (20 results, none about naloxegol; Crossref ranking dropped the rare term). Crossref title listing "naloxegol" (100 titles read): none on mitochondria, respiration or toxicity; the one preclinical title, "Pharmacological characterization of naloxegol: in vitro and in vivo studies" [Costanzini 2021, Eur J Pharmacol], has no abstract in OpenAlex and appears to concern receptor pharmacology, so it was not used. Label summaries [1][2][16]: no mitochondrial statement. Nonclinical toxicology in the label summary: not genotoxic, not tumorigenic in mice, interstitial cell adenomas in male rats at 400 mg/kg/day (not a mitochondrial finding) [2]. Repair pass: PubMed listing "naloxegol mitochondria" returned zero results [27]; the FDA nonclinical (pharmacology/toxicology) review [25], read through a fetch tool, covers receptor binding, safety pharmacology, metabolism and standard toxicity, reports negative Ames, mouse lymphoma and mouse micronucleus genotoxicity results, and states nothing on mitochondrial toxicity or reactive oxygen species.

Channel outcomes

Original pass: PubMed listing for "naloxegol oxidative stress" returned 429. Repair pass: the same listing returned a genuine zero-hit page after a wait (a control query "naloxegol safety" returned 57 results, so the zero pages are real) [27]; "naloxegol mitochondria" also zero. Europe PMC and Crossref listing fetches were rate-limited (429). A WebSearch for naloxegol, intestinal barrier and oxidative stress returned only morphine barrier papers and naloxegol pharmacology papers, none opened for this entry. Result: a genuine gap on PubMed, with Europe PMC and OpenAlex search still untested.

Oxidative Stress

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

Oxidative stress

Not graded — disclosed evidence gap

See study details

No naloxegol-specific data on redox or antioxidant-capacity markers were found.

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 claim found. Not a finding of safety. The Overlap map notes that this entry shares no evidence with mitochondrial burden or ATP production.

What was searched

The same Crossref query as above (oxidative stress, mitochondria), the Crossref title listing of 100 naloxegol items, label summaries [1][2][16], the Dovepress clinical-utility review [12] (no laboratory findings reported) and the Wikipedia entry [11] (no such statement). No MDA, glutathione, ROS or antioxidant-enzyme study of naloxegol surfaced. Repair pass: PubMed "naloxegol oxidative stress" zero results [27]; the review of opioid-induced constipation mechanisms [21], read through a fetch tool, mentions oxidative stress only as nitric oxide-induced damage to interstitial cells of Cajal in animal work, with no naloxegol content.

Channel outcomes

PubMed, Europe PMC, OpenAlex search: 429. WebSearch: exhausted. Publisher pages for the NEJM paper and the Wiley 52-week paper: 403. Repair pass: PubMed zero-hit page (above) and the FDA nonclinical review [25] with no oxidative-stress statement. Likely a genuine gap, with Europe PMC untested.

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 on naloxegol and copper absorption, status or ceruloplasmin was found.

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, no circulating copper claim found. Kept independent of Iron per Hard Rule 7. Not a finding of safety.

What was searched

Label summaries [1][2][16]: no copper, chelation or mineral statement. Mechanism screen: no chelating group or gastric-pH effect is described for naloxegol in the sections retrieved. Crossref title listing of naloxegol items: none on copper. The PubMed listing for hemoglobin or anemia (below) returned no naloxegol records. Repair pass: PubMed listing "naloxegol AND (ferritin OR copper OR ceruloplasmin OR serum iron)" returned zero results [27], which covers copper directly.

Channel outcomes

Genuine zero on the label, the title listing and the repair-pass PubMed listing; Europe PMC and OpenAlex search were not obtained. Probably a true gap.

Iron

Not graded — disclosed evidence gap

See study details

No evidence on naloxegol and iron absorption, ferritin or iron status was found.

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, no circulating iron claim found. Opioid and constipation confounding would apply to any observational iron signal (GI blood loss, diet). Not a finding of safety.

What was searched

Label summaries [1][2][16]: no iron statement and no laboratory abnormality reported. PubMed listing "naloxegol hemoglobin OR anemia": returned only general anemia reviews, none involving naloxegol (the results were unrelated titles such as "Anaemia: A disease or symptom"). Crossref bibliographic query "naloxegol hemoglobin anemia laboratory": 16 results, none about naloxegol. Naloxegol does not change gastric pH in any source read, so the acid-dependent absorption pathway used for acid suppressants does not apply here; no class borrowing was done. Repair pass: PubMed "naloxegol AND (ferritin OR copper OR ceruloplasmin OR serum iron)" zero results [27]; the FDA medical review [24], read through a fetch tool, lists hemoglobin below 9 g/dL only as a trial exclusion criterion and says clinical laboratory evaluations (hematology, clinical chemistry, urinalysis) were collected, but its laboratory findings section (7.4.2) came back empty in the excerpt, so no arm-level hemoglobin data were read; the reimbursement document [26] has no hematologic or nutrient statement; the FDA summary review [23] has no laboratory statement.

Channel outcomes

Several channels answered with clean zeros, including repair-pass PubMed listings; Europe PMC and OpenAlex search listings were rate-limited, and the arm-level laboratory tables in the FDA medical review could not be read. Tooling-limited for those tables, with a probable true gap otherwise.

Gut Microbiome Risk

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

Gut microbiome risk: class extrapolation from a non-peripheral mu-opioid antagonist (naloxegol not in cohort)

Yellow — Low

See study details

CLASS EXTRAPOLATION. In mice, the mu-opioid antagonist naltrexone antagonized morphine-induced gut microbiome and bile-acid changes and, given alone, shifted the microbiome from placebo. Naloxegol was not tested. Direction is possible reversal of opioid-associated change, not depletion.

Full detail and limits

Limits on what this shows

Null findings: Human observational study [19]: 6 participants on naltrexone only versus 31 on neither agonist nor antagonist showed no significant differences in alpha diversity, enterotype or taxa abundance; no PAMORA was in that cohort. PubMed listing queries "naloxegol microbiome" and "naloxegol intestinal permeability" each returned zero results [27], so no naloxegol-specific microbiome or barrier study is indexed under those terms.
At-risk subgroups: None can be defined for naloxegol from these sources. The population of interest is chronic opioid users with opioid-induced constipation, in whom the opioid itself is the main modifier.

Regulatory status

No microbiome statement in the label summaries read [1][2][16], and none in the FDA summary, medical and nonclinical review documents as returned by the fetch tool [23][24][25] or the CADTH-type reimbursement document [26].

Population evidence

Cohort test: antagonist studied in [17] was naltrexone (one passage returned by the fetch tool used the word naloxone for the metabolome sentence, so the identity of the antagonist should be re-checked in the full text); naloxegol and every other PAMORA were NOT in the cohort, so this is Tier C, capped at yellow. Wang 2018 [17]: C57BL/6J female mice, 8 to 10 weeks old, n=4 per group in key experiments, subcutaneous pellets (morphine 25 mg, naltrexone 30 mg, or both) over days 0 to 6; the authors report that naltrexone "antagonized morphine-induced alterations of the gut microbiome" on principal coordinate plots at days 3 and 6, including the Enterococcus faecalis signal, and reversed morphine effects on bile acid metabolism; naltrexone alone clustered apart from placebo at day 3, which the authors read as endogenous opioids setting a basal tone on the microbial profile. Narrative review [20] (as returned by the fetch tool): only naltrexone has dysbiosis data, from animal studies; human and in vitro microbiota studies of PAMORAs remain unpublished. Review [21]: opioid exposure is associated with dysbiosis and barrier impairment mainly in animal models, and OIC-specific clinical microbiota evidence is sparse. AJG review [22] (abstract only): PAMORAs are said to ameliorate disrupted intestinal permeability, but the abstract names methylnaltrexone and not naloxegol.

Mechanism

Plausible but untested for naloxegol. Morphine-induced bacterial translocation and barrier compromise were absent in mu-opioid receptor knockout mice [18], so the opioid effect on the gut is receptor dependent in that model. Naloxegol blocks gut mu receptors and about a quarter of fecal radioactivity is unchanged drug [5], so luminal exposure exists. Whether peripheral blockade alone reproduces the naltrexone result is unknown; the antagonist in [17] was given as a systemic pellet, and the CNS penetration of naltrexone was not documented in any source opened.

Counter-evidence held on record

Counter-evidence and confounding Small mouse experiment (n=4 per group) with a different drug given as a systemic pellet; naloxegol is a P-gp substrate with limited CNS entry [2][5], so peripheral-only blockade may not reproduce the result. The only human naltrexone data [19] showed no microbiome difference. Chronic opioid use and constipation are themselves associated with microbiome differences, so any human difference in naloxegol users could not be assigned to naloxegol without a placebo-on-opioid comparator. Under Hard Rule 2 this is a physiological-category context flag, not a nutrient finding. Framing caution Do not present this as a microbiome harm or benefit of naloxegol, and do not use it to suggest probiotics or other supplements. The direction in the cited mouse work is reversal of an opioid effect, and it has not been shown for naloxegol.

Oxygen and ATP Output

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

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

No evidence that naloxegol alters hemoglobin, red-cell mass or tissue oxygen delivery was found.

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 oxygen delivery and no circulating claim found. Any anemia effect would run through the Iron entry and is not double-counted. Anemia is an outcome, not a nutrient (Hard Rule 2). Kept independent of ATP production (Hard Rule 7).

What was searched

PubMed listing "naloxegol hemoglobin OR anemia" (no naloxegol records); Crossref bibliographic query on hemoglobin, anemia and laboratory terms (no naloxegol records); label summaries [1][2][16] (no hemoglobin or hematologic abnormality reported). The radiolabel study reports minimal distribution of naloxegol-derived radioactivity into red blood cells [5], which is a pharmacokinetic fact and not an oxygen-delivery finding. No methemoglobin or hemolysis report was found. Repair pass: PubMed "naloxegol AND (hemoglobin OR haemoglobin OR methemoglobin OR hemolysis OR erythrocyte)" returned zero results [27]. The FDA nonclinical review [25] returned no statement on hematology in animal toxicity studies, as read through a fetch tool.

Channel outcomes

Several channels answered with clean zeros, including a repair-pass PubMed listing; label sections and FDA reviews were read only through a summarizing tool, and the FDA medical review laboratory section (7.4.2) was not readable. Tooling-limited for arm-level laboratory data, plus a likely thin literature.

ATP production

Not graded — disclosed evidence gap

See study details

No evidence on naloxegol and cellular ATP synthesis, oxidative phosphorylation or membrane potential was found.

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 "low energy" claim specific to naloxegol found. Not a finding of safety. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7).

What was searched

The Crossref mitochondria and oxidative stress query and the 100-title naloxegol listing contained no respiration, oxidative phosphorylation or ATP title. Label summaries [1][2][16] and the reviews [11][12] have no energy-metabolism statement. The QTc study [10] found no cardiac repolarization effect, which is not an energy-production measure. Repair pass: PubMed "naloxegol AND (ATP OR oxidative phosphorylation OR energy metabolism OR respiration)" returned 5 records, all pharmacokinetic or P-gp papers (quinidine interaction studies and two drug-interaction or P-gp reviews, from their titles as listed); none concerns cellular energy production and none was used [27].

Channel outcomes

Same as Mitochondrial burden: clean zeros on the channels that answered, the one PubMed repair-pass listing returned only pharmacokinetic records (read from titles only), and Europe PMC listings were rate-limited.

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 nutrient-depletion claim located (provisional, audit limited)
Where it comes from: Consumer-page checks: the Antidote Research naloxegol nutrient-depletion URL returned 404 (no page); the Drugs.com Movantik page [14] mentions only the grapefruit interaction and no nutrient depletion; the Mayo Clinic and Drugs.com food-interaction URLs tried returned 404; Google and DuckDuckGo are blocked to the fetch tool by robots rules; WebSearch budget exhausted.
Why it fails: Nothing was found to rebut, so no white entry is printed and none is counted in the Entries chip. Because search coverage was thin, a claim could still circulate on pages not reached; re-check when search is available. This row is a disclosure, not a graded claim.
Opioid-withdrawal-like symptoms and GI perforation as "deficiency" or "depletion" problems
Where it comes from: Guard row, not a located claim. Both are in the label warnings [1][2].
Why it fails: They are drug effects (label: possible opioid withdrawal in under 1% on placebo, 1% at 12.5 mg and 3% at 25 mg; GI perforation reported postmarketing including fatal cases). Under Hard Rule 2 they are never filed as a nutrient deficiency, and no nutrient is implicated by either.

How the body handles this medication

Metabolism and enzymes: Metabolized primarily by the CYP3A system into six metabolites (N-dealkylation, O-demethylation, oxidation, PEG chain shortening); no major metabolite. Naloxegol is a sensitive CYP3A4 substrate: with ketoconazole 400 mg exposure rose 12.9-fold, with diltiazem 240 mg extended release 3.4-fold, and with rifampin 600 mg it fell by 89%. No CYP induction or inhibition by naloxegol is stated in the label summaries retrieved, and a thorough QT study found placebo-corrected QTcF increases under 5 ms at 25 mg and 150 mg.[1][2][4][10] label sec 7, 12.3; Bui 2015; Gottfridsson 2013
Transport and absorption: P-glycoprotein substrate; quinidine raised Cmax 2.5-fold and AUC 1.4-fold (no dose change advised). Peak concentration within 2 hours, with a secondary peak thought to reflect enterohepatic recycling. A high-fat meal raised Cmax about 30% and AUC about 45%. Absolute bioavailability is not stated in the sections retrieved.[2][5][16] label sec 12.3; ADME study
Distribution: Plasma protein binding about 4.2%; apparent volume of distribution 968 to 2140 L; the radiolabel study reports minimal distribution to red blood cells. P-gp efflux limits CNS entry, which is the basis of its peripheral action.[2][5]
Elimination: [14C] study in 6 fasted healthy men: 84.2% of dose recovered in 96 hours, 67.7% in feces and 16.0% in urine; unchanged naloxegol was about one quarter of fecal radioactivity and under 6% of the dose appeared unchanged in urine. Half-life 6 to 11 hours; minimal accumulation on repeat dosing.[2][5]
Renal and hepatic impairment: In moderate and severe renal impairment (8 per group) exposure rose 1.7-fold and 2.2-fold; some subjects with CrCl under 60 mL/min had up to 10-fold higher exposure, so the label starts 12.5 mg. Hemodialysis does not remove the drug. Mild to moderate hepatic impairment lowered AUC slightly; the label advises avoiding use in severe hepatic impairment.[2][6]
Food, herb and mineral interactions: Label: avoid grapefruit and grapefruit juice; strong CYP3A4 inhibitors contraindicated; moderate inhibitors (diltiazem, erythromycin, verapamil) require 12.5 mg; strong inducers (rifampin, carbamazepine, St. John's Wort) not recommended; avoid other opioid antagonists. No mineral, antacid or chelation interaction is listed in the sections retrieved.[1][2][12][13]

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.

Interactions
CYP3A4 and P-gp co-medications
Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) are contraindicated; moderate inhibitors (diltiazem, erythromycin, verapamil) call for 12.5 mg; strong inducers (rifampin, carbamazepine, St. John's Wort) are not recommended [1][2]. Pharmacist review of every new prescription or herbal product is the relevant check.
Timing and food
Grapefruit and meal timing
Avoid grapefruit and grapefruit juice [1][2]. High-fat meals raise exposure; the review advises dosing on an empty stomach [12]. The label gives avoidance and timing, not a supplement separation interval. No supplement dose appears in this dossier, so no upper-limit comparison was needed.
Symptoms
GI effects and perforation warning
Abdominal pain, diarrhea, nausea and vomiting are the common reactions [1]. Severe, persistent or worsening abdominal pain should be reported promptly because GI perforation, including fatal cases, is in the label [1][2]. Persistent diarrhea or vomiting is a prescriber question; routine electrolyte testing is not supported by any naloxegol source retrieved.
Symptoms
Opioid-withdrawal-like symptoms
Sweating, chills, diarrhea, abdominal pain, anxiety, irritability and yawning have occurred [1]. These are drug effects, not nutrient signs. They were more frequent with 25 mg (3%) than 12.5 mg (1%) or placebo (under 1%) [1].
Renal / hepatic
Kidney and liver function
Starting dose 12.5 mg is the label approach when CrCl is under 60 mL/min, because some patients reach up to 10-fold higher exposure; avoid in severe hepatic impairment [2][6].
Nutrient status
No naloxegol-driven lab to track
No source retrieved links naloxegol to a nutrient or hematologic change, so no nutrient lab is specifically indicated by this drug. Nutrient status questions in this population usually arise from the underlying pain condition, long-term opioid use, constipation, diet or other medicines, and should be judged on those grounds.
Special populations
Pregnancy, lactation, pediatrics, older adults
The label states it may precipitate opioid withdrawal in pregnant women and the fetus, breastfeeding is not recommended, and pediatric safety and effectiveness are not established (current label summary read) [1]. Geriatric: no overall differences in safety or effectiveness, though a Japanese elderly subgroup had about 45% higher Cmax and 54% higher AUC than younger subjects [2].

Overlap map, to prevent double counting

Grapefruit, high-fat meals and CYP3A4-active herbs
Shares evidence with: Pharmacokinetic basis
Note: The same label statements [1][2] and Bui 2015 [4] underlie the interaction entry and the Pharmacokinetic basis section. One evidence base, not two confirmations. It is unrelated to any depletion entry.
Fluid and electrolytes
Shares evidence with: Fails verification: opioid-withdrawal-like symptoms
Note: The label lists diarrhea among the withdrawal-like symptoms [1] and also among the common adverse reactions, so one set of label rates [1] supports both. The two are one drug effect viewed twice.
Iron
Shares evidence with: Oxygen delivery/utilization (ungraded)
Note: Any hemoglobin effect would be mediated through iron. Both entries rest on the same null search (PubMed hemoglobin or anemia listing, Crossref hemoglobin query, label summaries). One gap, not independent gaps.
Mitochondrial burden
Shares evidence with: Oxidative stress; ATP production
Note: The three ungraded entries share the same Crossref query, the same 100-title listing, the same FDA nonclinical review [25] and the PubMed zero-hit pages [27]. No source supports any of them. They are one search outcome viewed three times.
Copper
Shares evidence with: Iron
Note: No shared evidence beyond the shared label summaries. The pair is graded separately per Hard Rule 7.
Gut microbiome risk
Shares evidence with: Pharmacokinetic basis (exposure only); no graded entry
Note: The class-extrapolation sources [17][19][20][21] are used only in this entry. The radiolabel fecal data [5] are cited for luminal exposure only, shared with the Pharmacokinetic basis. A microbiome or transit change is a hypothetical modifier of absorption (Iron, Fluid and electrolytes) and is not claimed or counted there.

All references used above

Naloxegol

Findings for this medication

What the research found

Grapefruit, high-fat meals and CYP3A4-active herbs: nutrient affects drug (interaction, not depletion)

Fluid and electrolytes: diarrhea is a drug effect (outcome entry, nutrient not measured)

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden

💥Oxidative Stress

Oxidative stress

⚖️Copper and Iron Balance

Copper

Iron

🌿Gut Microbiome Risk

Gut microbiome risk: class extrapolation from a non-peripheral mu-opioid antagonist (naloxegol not in cohort)

💨Oxygen and ATP Output

Oxygen delivery/utilization

ATP production

Claims checked and not supported

No circulating nutrient-depletion claim located (provisional, audit limited)

Opioid-withdrawal-like symptoms and GI perforation as "deficiency" or "depletion" problems

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