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MyDeficiencies

Apixaban

Anticoagulant (DOAC)

Also sold as Eliquis.

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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.

Apixaban's own prescribing information confirms the mechanistic claim this dossier was built to check: apixaban is a selective, direct inhibitor of factor Xa that "does not require antithrombin III for antithrombotic activity." It does not touch the vitamin K cycle at any point. This is the opposite pharmacology from warfarin, which works by blocking vitamin K epoxide reductase (VKORC1) and thereby starving the liver of the reduced vitamin K it needs to carboxylate clotting factors II, VII, IX, and X. Apixaban's factor Xa is already fully carboxylated and functional; the drug simply blocks the enzyme's active site downstream of that entire pathway. The label states plainly that routine coagulation-test monitoring is "not useful in monitoring the anticoagulation effect of apixaban," and it imposes no dietary vitamin K guidance anywhere in its text. This is not a hedge: it is a structural fact of the drug's mechanism, and it is the reason apixaban does not require the food-consistency counseling that has defined warfarin management for seventy years.

direct oral anticoagulant (factor Xa inhibitor) · ATC B01AF02 · also sold as Eliquis · reviewed 2026-09-06, expanded 2026-09-10. 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 Apixaban in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
severe: 2 or more Tier A sources, this drug in the cohort, directly measured, consistent direction, clinically meaningful, named mechanism, no substantial contradiction.
Orange — Moderate
moderate: at least 1 Tier A source with this drug in the cohort, a real but bounded deficit (exposure window, subgroup, or functional marker only).
Yellow — Low
low/theoretical: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) where at least one class member has real data but this drug does not; also context flags and reverse-direction interactions.
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

Apixaban's own blood level, not a nutrient

Yellow — Low

See study details

Grapefruit and other strong combined P-glycoprotein/CYP3A4 inhibitors raise apixaban's own blood level; this is a drug-affected-by-substance interaction, not a nutrient depleted by the drug.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) where at least one class member has real data but this drug does not; also context flags and reverse-direction interactions. Yellow · candidate only

Limits on what this shows

  • Key negative/null findings: No nutrient-status endpoint is measured or claimed in this interaction; it is a PK safety interaction only.
  • At-risk subgroups: Patients on the 2.5 mg twice-daily reduced dose, and anyone prescribed a strong CYP3A4/P-gp inhibitor or inducer concurrently.

Regulatory status

Label-mandated 50% dose reduction with strong combined P-gp/CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) at standard doses, and avoidance at the 2.5 mg twice-daily dose; avoidance also directed with strong combined P-gp/CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort).

Population evidence

Tier A for apixaban's own pharmacokinetics (label-cited interaction studies); not applicable as a nutrient-status claim since the direction runs food/drug-to-drug, not drug-to-nutrient.

Mechanism

Reverse direction of this protocol's mechanism classes: the substance (grapefruit-family citrus, or a strong CYP3A4/P-gp inhibitor or inducer drug) changes apixaban's own exposure. No mechanism by which apixaban changes a nutrient's level.

Counter-evidence held on record

None needed; this entry exists to document the interaction correctly rather than to advance a nutrient claim. This must never be presented as a nutrient depletion. It is a drug-level safety interaction: grapefruit-family citrus and certain other substances can raise apixaban exposure and bleeding risk, and separation or avoidance guidance belongs with a prescriber or pharmacist, not on a nutrient-status page.

Confounding by indication

Yellow — Low

See study details

Patients prescribed apixaban are disproportionately older, have atrial fibrillation, DVT, or PE, and often carry polypharmacy and renal-function decline that independently affect nutrient status, apart from anything apixaban itself does.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) where at least one class member has real data but this drug does not; also context flags and reverse-direction interactions. Yellow · context flag

Limits on what this shows

  • Key negative/null findings: No trial reviewed here found nutrient-status differences attributable to apixaban itself once the underlying population's age and comorbidity burden is accounted for.
  • At-risk subgroups: Elderly patients, renal impairment (apixaban 2.5 mg dose-reduction criteria: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL, any two of three, for the AFib indication), and patients on multiple concurrent medications.

Regulatory status

Not a labeled interaction; a population-characteristic flag.

Population evidence

ARISTOTLE (apixaban vs warfarin, atrial fibrillation, n=18,201) and AMPLIFY (apixaban vs enoxaparin/warfarin, VTE, n=5,395) enrolled predominantly older adults, many with renal impairment and multiple comorbidities; the trials measured stroke, systemic embolism, VTE recurrence, and major bleeding as primary endpoints, not baseline-to-follow-up nutrient status.

Mechanism

Present at the population level (indication I): age, renal impairment, and polypharmacy are established independent drivers of micronutrient deficiency (notably B12, vitamin D, iron) regardless of anticoagulant choice.

Counter-evidence held on record

The ARISTOTLE anemia substudy (Hijazi et al.) explicitly analyzed baseline anemia as a pre-existing risk factor, present before apixaban exposure, that predicted bleeding and mortality but not stroke; this supports confounding by indication rather than a drug effect and argues against attributing any deficiency finding in this population to apixaban. Never state or imply that apixaban causes age-related or polypharmacy-related nutrient decline; the population that takes it is simply at general risk for reasons unrelated to the drug's own pharmacology.

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 mechanism, no drug-specific evidence at any tier, and no circulating consumer claim were found connecting apixaban to mitochondrial function. This is recorded as an open gap, not as reassurance that no effect exists.

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: Both conditions for Ungraded are met on the evidence actually reached: no Tier B or Tier C evidence was found, and no circulating consumer claim exists to rebut. Because part of the search was blocked before completion, this gap should be treated as unresolved rather than as a clean negative result.

Mechanism screen

None of the nine mechanism classes in this protocol's screen (absorption interference, hepatic enzyme induction, renal wasting, cofactor antagonism, mitochondrial interference, dilutional/hormonal disturbance, microbiome disruption, changed intake, increased utilization) point to a mitochondrial pathway for apixaban. The label describes no mitochondrial DNA polymerase inhibition, no oxidative phosphorylation uncoupling, and no class-level mitochondrial toxicity signal of the kind documented for other drug classes (for example nucleoside reverse transcriptase inhibitors or valproate).

Evidence search performed

PubMed search-listing queries for "apixaban mitochondrial" and "apixaban mitochondria" returned no apixaban-specific result. Attempts to broaden the search (factor Xa inhibitor and mitochondrial toxicity) were blocked by repeated gateway-level rate limiting on Crossref, Semantic Scholar, and Europe PMC, and intermittently on PubMed itself, after which this review stopped retrying per this protocol's tooling guidance rather than continuing to burn time on backoff. The search is therefore incomplete, not exhaustive.

Circulating claim check

No consumer drug-nutrient-depletion source was located pairing apixaban with mitochondrial support or CoQ10, the kind of claim that circulates for statins; none was found to rebut.

Counter-evidence held on record

None found in either direction. This absence of evidence must never be shown as "apixaban is safe for mitochondrial function" or as any form of reassurance. It means the question has not been adequately studied for this drug, not that the answer is known to be no.

Oxidative Stress

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

Oxidative stress markers

Yellow — Low

See study details

No evidence was found that apixaban imposes an oxidative stress burden; the limited apixaban-specific evidence that exists points the other way, toward a mild, preliminary anti-oxidative signal in cell and animal models, not a deficiency or depletion pattern.

Full detail, limits and 1 references

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) where at least one class member has real data but this drug does not; also context flags and reverse-direction interactions. Yellow · candidate only

Limits on what this shows

  • Key negative/null findings: No Tier A or Tier B source located during this review measured an apixaban-attributable increase in any oxidative stress marker. No study was found comparing apixaban to no anticoagulation on any oxidative-stress endpoint; the in vitro and animal-model sources above used apixaban as the sole treated condition against an untreated or disease-model comparator, not against another anticoagulant, which bounds how far the reverse-direction signal can be generalized.
  • At-risk subgroups: Not applicable; there is no demonstrated burden to bound to a subgroup.

Regulatory status

Not a labeled effect. The FDA label does not describe apixaban as affecting reactive oxygen species, antioxidant capacity, or any oxidative-stress biomarker in either direction.

Population evidence

Tier A context, not a demonstrated treatment effect: Wallentin and Hijazi et al. (Circulation, 2014) measured growth differentiation factor 15 (GDF-15), described in the study's own title as "a marker of oxidative stress and inflammation," within the ARISTOTLE trial population (apixaban vs warfarin, n=18,201). This confirms apixaban was in the studied cohort and that a validated oxidative-stress-associated biomarker was measured in that cohort. It does not confirm that apixaban changed GDF-15 relative to warfarin; full text could not be opened during this review (repeated gateway rate-limiting), so this is cited as cohort-level context only, on the same evidentiary footing as the existing ARISTOTLE anemia substudy (Hijazi et al., 2016) already in this dossier's Yellow tier, not as evidence of a drug effect.

Mechanism

Tier B, reverse direction. Torramade-Moix et al. (Cardiovascular Drugs and Therapy, 2021) treated endothelial cells directly with apixaban in an in vitro model of endothelial dysfunction in uremia, and measured reactive oxygen species (ROS) alongside VCAM-1, ICAM-1, eNOS, and von Willebrand factor; the study's own title states that apixaban "downregulates" the inflammatory and prothrombotic phenotype, indicating a reduction, not an increase, in these markers including ROS. A second, title-only source, Matsui and Sotokawauchi et al. (International Journal of Molecular Sciences, 2025), "Apixaban Inhibits Progression of Experimental Diabetic Nephropathy," points in the same protective direction, in what its title indicates is an experimental (non-human) model. Its abstract and full text could not be opened during this review despite repeated attempts, and this citation is not treated as load-bearing, only as a title-level pointer in the same direction as the Torramade-Moix finding.

Counter-evidence held on record

Every apixaban-specific source located on this question, thin as the evidence base is, runs toward a protective or neutral signal rather than a harm signal. This entry exists to document that absence of a burden finding accurately, not to imply a benefit. This must never be presented as "apixaban reduces oxidative stress" or as any kind of antioxidant benefit. The supporting evidence is preliminary, mostly in vitro or animal, apixaban-specific but far short of a demonstrated human clinical effect, and must not be used to suggest apixaban has therapeutic antioxidant properties or to discourage ordinary attention to antioxidant-relevant nutrient intake.

Copper and Iron Balance

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

Iron status via bleeding-related blood loss

Yellow — Low

See study details

Any anticoagulant that increases GI bleeding risk can, in principle, contribute to iron loss in a patient who bleeds; this is a class-level mechanistic plausibility, not an apixaban-specific measured finding.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) where at least one class member has real data but this drug does not; also context flags and reverse-direction interactions. Yellow · candidate only

Limits on what this shows

  • Key negative/null findings: ARISTOTLE substudy (Hijazi et al., 2016) analyzed baseline anemia's association with subsequent bleeding and mortality in apixaban- and warfarin-treated atrial fibrillation patients; it studied anemia present before anticoagulation as a risk predictor, and did not find or claim that apixaban caused new anemia. This is a confounding-by-indication finding, not evidence that apixaban depletes iron.
  • At-risk subgroups: Patients with pre-existing anemia, elderly patients, and anyone with an unrecognized GI lesion, per general anticoagulant precaution; not apixaban-specific.

Regulatory status

FDA label lists gastrointestinal hemorrhage (hematemesis, melena) and hematochezia as labeled adverse reactions for apixaban, and anemia as a recorded adverse event in surgical trials (2.6%).

Population evidence

Tier C / mechanistic. A network meta-analysis of DOAC-class trials (37 RCTs) found standard-dose apixaban (10 mg/day) had significantly lower major GI bleeding risk than dabigatran 300 mg/day (OR 0.58, 95% CrI 0.34-0.97), edoxaban 60 mg/day (OR 0.53, 95% CrI 0.28-0.86), and rivaroxaban ≥15 mg/day (OR 0.55, 95% CrI 0.31-0.93), with apixaban the lowest-GI-risk DOAC at standard dose. This is a bleeding-outcome comparison across DOACs, apixaban distinguishable, not a measured iron-status outcome for apixaban, so it supports plausibility, not a graded iron-deficiency claim.

Mechanism

Present at the class level (A: mucosal injury/bleeding as a route to iron loss), absent as an apixaban-specific measured pathway. No apixaban-specific chelation, absorption, or transporter mechanism affecting iron was found.

Counter-evidence held on record

The label itself does not list iron deficiency or anemia as an expected on-treatment complication outside the surgical adverse-event tables, and apixaban's comparative GI-bleeding profile is favorable versus other DOACs, working against (not for) an apixaban-specific depletion narrative. Any GI bleeding on apixaban is a safety event requiring prompt medical evaluation, not a nutrition problem to self-treat with iron supplements. This entry must never be shown as "apixaban depletes iron"; the honest statement is that any anticoagulant can unmask bleeding, and blood loss from any cause can cause iron deficiency, which is worth a clinician's attention if it occurs.

Copper status

Not graded — disclosed evidence gap

See study details

No mechanism, no drug-specific evidence, and no circulating consumer claim were found connecting apixaban to copper status, assessed here independently of iron.

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: No Tier B or Tier C evidence and no circulating claim were found on the portion of the search that was reachable. Given how little of the search was completed before tooling was blocked, this should be read as an open gap rather than a settled negative.

Mechanism screen

The label describes no cuproenzyme interaction, no effect on ceruloplasmin, and no chelation mechanism involving copper. Apixaban's absorption is not pH-dependent (food does not affect its bioavailability), which rules out the gastric-acid-suppression route by which some other drug classes are linked to reduced copper absorption.

Evidence search performed

A PubMed search-listing query for "apixaban copper" returned no result before this review's search tools were blocked by repeated gateway-level rate limiting; the query could not be repeated or broadened within this review's session.

Circulating claim check

No consumer source was located claiming apixaban affects copper status; none was found to rebut.

Counter-evidence held on record

None found in either direction. Do not present this as evidence apixaban is neutral for copper status. It means no adequate drug-specific study was found, in a search that was itself cut short by source access problems.

Iron absorption and regulation

Not graded — disclosed evidence gap

See study details

Separately from bleeding-related iron loss, already covered elsewhere in this dossier, no evidence or mechanism was found linking apixaban to iron absorption, hepcidin regulation, or transporter-level iron handling.

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: No Tier B or Tier C evidence and no distinct circulating claim were found for this non-bleeding mechanism. This is a genuine gap: the absorption question has essentially not been studied for apixaban, as distinct from the bleeding-loss question, which has at least a case report.

Overlap note

Bleeding-related iron loss is already graded in the Yellow-tier entry "Iron status via bleeding-related blood loss" and discussed under the Orange-tier reasoning (the Choo et al. case report) elsewhere in this dossier. This entry does not re-argue that pathway; it addresses only whether apixaban affects iron by a separate, non-bleeding route.

Mechanism screen

The label states food does not affect apixaban's bioavailability, ruling out a shared gastric-pH mechanism with iron absorption. No transporter competition (DMT1, ferroportin) or hepcidin-pathway interaction is described for apixaban anywhere in the label or in the sources reviewed for this dossier.

Evidence search performed

No apixaban-specific study on iron absorption, hepcidin, or iron transporter activity was located. Searches on this specific question were limited by the same repeated gateway rate-limiting affecting other entries in this section; this review stopped retrying per this protocol's tooling guidance.

Circulating claim check

The only circulating iron-related claim found for apixaban ("apixaban causes iron deficiency / calls for iron supplementation") is already listed and rebutted in the Claims that fail verification section of this dossier, on bleeding-loss grounds; no separate absorption-based claim was found.

Counter-evidence held on record

The label's food-effect statement (bioavailability unaffected by food) works against, not for, a gastric-pH-mediated iron-absorption mechanism, though it does not address transporter- or hepcidin-level pathways directly. Do not merge this entry with the bleeding-related iron entry elsewhere in this dossier; they address different mechanisms and neither should be used to inflate the apparent evidence base for the other.

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 apixaban- or DOAC-class study measuring gut microbiome composition or function was located. A structural feature of apixaban's own pharmacokinetics, its unusually large non-renal excretion fraction, is flagged here as a reason this question deserves study, not as a finding.

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

  • Confounding by indication, considered first: Per this protocol's rule that confounding by indication is presumed until actively considered, especially for this category: patients prescribed apixaban for atrial fibrillation or VTE are frequently co-prescribed antibiotics (for intercurrent infection or periprocedural prophylaxis), proton pump inhibitors, and antiarrhythmic drugs, all of which have documented, better-established effects on gut microbial composition than anything described for apixaban itself. Any microbiome finding in this population would need to rule out these co-exposures before being attributed to apixaban.
  • Why no grade: No Tier B or Tier C evidence was reached and no circulating claim was found, so this meets the formal definition of Ungraded. Given the search was cut short by tooling access problems and given the flagged intestinal drug-exposure fact above, this gap is recorded with more emphasis than the others in this section: it is a real open question, not a reassurance.

Mechanism screen

Mechanism class G (microbiome disruption affecting endogenous synthesis) has no supporting or refuting evidence for apixaban. The one PK fact worth flagging as context, already stated in this dossier's pharmacokinetic basis, is that renal excretion accounts for only about 27% of apixaban clearance, with biliary and direct intestinal excretion of unchanged drug accounting for most of the remainder, an unusually large non-renal fraction for an anticoagulant. This means unchanged apixaban is present in the gut lumen to a degree most renally-cleared drugs are not. No study has measured whether this has any microbiome effect; it is listed here as a plausible question, not as evidence of harm.

Evidence search performed

PubMed and Europe PMC queries for "apixaban gut microbiome," "apixaban gut microbiota," and "direct oral anticoagulant gut microbiome" were attempted; results could not be retrieved because of repeated gateway-level rate limiting across every search tool available in this review, and this review stopped retrying per its tooling guidance rather than continuing to burn time on backoff. This is a materially incomplete search and should be revisited when these sources are reachable.

Circulating claim check

No consumer source was located claiming apixaban disrupts the gut microbiome; none was found to rebut.

Counter-evidence held on record

None found in either direction; this section is a gap flag, not a null result. Never state or imply that apixaban is confirmed safe for gut microbiome health. It has simply not been adequately studied, and the population that takes it carries other, better-documented microbiome-disrupting exposures that any future study would need to separate out.

Oxygen and ATP Output

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

Oxygen delivery and utilization

Not graded — disclosed evidence gap

See study details

No mechanism or evidence was found for a direct apixaban effect on oxygen delivery or tissue oxygen utilization, independent of the already-covered question of bleeding-related 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: No Tier B or Tier C evidence and no circulating claim were found for a direct mechanism. Ungraded, with the anemia-mediated pathway already accounted for elsewhere in this dossier.

Overlap note

Any oxygen-delivery deficit arising from bleeding-induced anemia is a downstream restatement of the bleeding-related iron-loss pathway already covered in this dossier's Yellow tier and Orange-tier reasoning. It is not re-counted here. This entry addresses only a direct, non-anemia mechanism: hemoglobin oxygen affinity, arterial oxygen saturation, pulmonary gas exchange, or tissue oxygen extraction.

Mechanism screen

The label describes no methemoglobinemia signal, no pulmonary toxicity, and no effect on the oxygen-hemoglobin dissociation curve (P50) for apixaban. No mechanism connects a direct factor Xa inhibitor to oxygen transport physiology outside of its bleeding risk.

Evidence search performed

No apixaban-specific study on oxygen delivery, oxygen saturation, or tissue oxygen utilization was located; broader searches on this question were constrained by the same repeated gateway rate-limiting described elsewhere in this section.

Circulating claim check

No consumer source was located making an oxygen-delivery claim about apixaban specifically; none was found to rebut.

Counter-evidence held on record

None found in either direction. Do not conflate this entry with the bleeding/anemia pathway covered elsewhere; if a consumer surface ever needs to explain oxygen delivery risk on apixaban, it should point to the bleeding-related entry, not to this one, which found no separate direct mechanism.

ATP production

Not graded — disclosed evidence gap

See study details

No mechanism or evidence was found linking apixaban to cellular ATP synthesis or energy metabolism, assessed here independently of the broader mitochondrial-burden question above.

Full detail and limits

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

Limits on what this shows

  • Why no grade: No Tier B or Tier C evidence and no circulating claim were found. Ungraded, and, as with Mitochondrial burden above, this should be read as an incompletely searched gap rather than a confirmed negative.

Overlap note

This entry is graded separately from Mitochondrial burden above, per this dossier's protocol: that entry addresses general mitochondrial structural and toxicity questions, while this one addresses functional cellular energy output specifically (oxidative phosphorylation, ATP synthase activity, glycolytic contribution). Neither entry's absence of evidence is used to support the other; each was searched and evaluated on its own terms.

Mechanism screen

Apixaban is not described anywhere in its label or in the sources reviewed for this dossier as an oxidative-phosphorylation uncoupler, an ATP synthase inhibitor, or a modulator of glycolysis. No mechanism class in this protocol's screen implicates cellular energy metabolism for this drug.

Evidence search performed

No apixaban-specific study on ATP production, oxidative phosphorylation, or cellular energy metabolism was located; this question could not be searched as thoroughly as intended because of the repeated gateway rate-limiting described elsewhere in this section.

Circulating claim check

No consumer source was located claiming apixaban affects ATP production or cellular energy; none was found to rebut.

Counter-evidence held on record

None found in either direction. Do not present this as reassurance about energy or fatigue symptoms in patients on apixaban. Fatigue has many causes in an anticoagulated, typically older population, most unrelated to apixaban itself and most falling under the confounding-by-indication flag already documented in this dossier; this entry only says that a direct ATP-production mechanism was not found in the literature reached during this review.

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.

  • "Apixaban patients must limit vitamin K foods like warfarin patients do."

    Where it comes from: A plausible class-confusion error given how strongly vitamin K counseling is associated with anticoagulation generally; searched for directly in consumer sources (drugs.com interaction checker, singlecare.com, medxdrg.com) and not found stated in the sources checked for this dossier as of the access date below.

    Why it fails: Apixaban's own label and every consumer source checked confirm no vitamin K interaction exists; the mechanism (direct factor Xa inhibition, no VKORC1 involvement) makes this claim factually reversed for apixaban even though it is true and important for warfarin. Included here as a rebuttal in case this error surfaces elsewhere, since the underlying confusion is a real and foreseeable risk in a consumer-facing anticoagulant database.

  • "Grapefruit depletes a nutrient when taken with Eliquis."

    Where it comes from: Consumer food-interaction pages (e.g. medxdrg.com) correctly flag grapefruit/citrus as raising apixaban blood levels via CYP3A4 inhibition, but a nutrient-depletion framing is not supported.

    Why it fails: The documented interaction runs citrus-to-drug (raising apixaban exposure and bleeding risk), not drug-to-nutrient. No nutrient is depleted; this is a PK safety interaction, correctly described by the sources checked as a bleeding-risk caution, not a nutrient claim.

  • "Apixaban causes iron deficiency / calls for iron supplementation."

    Where it comes from: Generic drug-nutrient depletion handbooks and AI-generated summary sites sometimes extend a "blood thinners cause bleeding, bleeding causes iron loss" syllogism to any anticoagulant by class.

    Why it fails: No apixaban-specific study measuring ferritin or transferrin saturation before/after apixaban exposure was found. The label's own anemia adverse-event data are surgical-trial counts, not a nutrient-status study, and cannot be read as a depletion claim per this protocol's rule against filing a clinical outcome as a deficiency finding.

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.

  • Hemoglobin / hematocrit

    Worth periodic clinical attention in any anticoagulated patient, especially after a documented bleeding event, to detect blood loss early. This is bleeding surveillance, not a nutrient-status test, and should follow a clinician's judgment rather than a fixed schedule set here.

  • Ferritin / iron studies, if anemia is found

    If anemia is identified in a patient on apixaban, standard iron-status workup (ferritin, transferrin saturation) is reasonable to distinguish iron deficiency from other causes, and to look for an occult GI source, exactly as it would be for anemia found in any patient, apixaban or not.

  • No dietary vitamin K timing needed

    Unlike warfarin, apixaban requires no consistent vitamin K intake and no separation from vitamin K-containing foods or supplements. This absence of a restriction is itself the clinically useful fact for a consumer reading this page.

  • Grapefruit-family citrus

    Discuss with a prescriber or pharmacist before regularly consuming grapefruit, Seville oranges, or pomelo alongside apixaban, since these can raise apixaban's own blood level. This is a bleeding-risk safety question, not a nutrient-timing question.

  • Renal function

    Renal function should be monitored per standard anticoagulation care, since it determines apixaban dosing (the 2.5 mg reduced dose criteria) even though the label states no dose adjustment is needed for renal impairment outside those specific criteria, including patients on dialysis.

  • Age-related nutrient screening

    Patients on apixaban are often older adults for whom B12, vitamin D, and general micronutrient screening is reasonable on general geriatric-care grounds, independent of and not caused by apixaban itself.

All references used above
  1. ELIQUIS (apixaban) full prescribing information — FDA label, revision reflected in accessdata.fda.gov docket 202155s039s040. Clinical Pharmacology (12.2, 12.3), Dosage and Administration (2.5-2.6), Warnings and Precautions (5.5), Adverse Reactions (6.1), Use in Specific Populations (8.1, 8.2, 8.6). Source for metabolism, absorption, elimination, protein binding, CYP3A4/P-gp interaction dosing guidance, absence of vitamin K/monitoring requirement, and surgical-trial anemia adverse-event rate (2.6%).
  2. Granger CB et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE). — New England Journal of Medicine, 2011. Randomized, double-blind, n=18,201. Primary trial establishing apixaban's comparative efficacy and safety (major bleeding 2.13 vs 3.09 per 100 patient-years) versus warfarin, cited here for cohort characteristics and the FDA label's summary of trial bleeding rates; abstract-level detail used, full text not independently reloaded for this review.
  3. Hijazi Z et al. Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: insights from the ARISTOTLE trial. — American Heart Journal, 2016. Post-hoc analysis of baseline anemia (n=18,201) within the ARISTOTLE cohort. Studied whether anemia present before anticoagulation predicted subsequent bleeding, mortality, and stroke; did not test or claim apixaban-caused new anemia.Full text access blocked (429/robots restrictions on PubMed and ScienceDirect during this review); title, abstract framing, and study design confirmed via search-result metadata and cross-referencing secondary discussion, not by opening the full article. No specific hazard ratios from this paper are cited above as a result.
  4. Frontiers in Pharmacology network meta-analysis of major GI bleeding risk among DOACs. — Traditional and Bayesian network meta-analysis, 37 randomized controlled trials, apixaban distinguishable as a study arm at 5 mg and 10 mg doses. Found standard-dose apixaban (10 mg/day) had lower major GI bleeding odds than dabigatran 300 mg/day (OR 0.58, 95% CrI 0.34-0.97), edoxaban 60 mg/day (OR 0.53, 95% CrI 0.28-0.86), and rivaroxaban ≥15 mg/day (OR 0.55, 95% CrI 0.31-0.93); apixaban had the lowest major GI bleeding risk among standard-dose DOACs.
  5. Comparative risk of osteoporotic fractures with direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients: a systematic review. — PMC systematic review synthesizing multiple retrospective cohort studies with apixaban distinguishable from other DOACs, including Huang et al. 2020 (n=19,414: apixaban significantly associated with lower hip fracture risk, P=0.029), Bezabhe et al. 2022 (n=18,454: each DOAC, apixaban P<0.001, associated with lower osteoporosis risk than warfarin), and Lau et al. 2020 (n=23,515: lower fracture risk with apixaban vs warfarin over 24 months). Proposes that warfarin's vitamin K antagonism reduces osteocalcin carboxylation, a mechanism apixaban does not share. Cited here as corroborating context for the drug's absence of vitamin K interference, not as a graded nutrient-status entry, since fracture and osteoporosis diagnosis are clinical outcomes rather than directly measured nutrient levels. Figures for the underlying Huang, Bezabhe, and Lau studies are reported as summarized in this review; those three primary papers were not separately opened for this dossier.
  6. Choo MH et al. Sustained resolution of anticoagulation related iron deficiency anemia with the use of apixaban. — Clinical Case Reports, 2020. Single case report proposing that switching to apixaban from a prior anticoagulant resolved a patient's iron deficiency anemia, attributed to lower GI blood loss on apixaban. Case-report level (Tier B), cannot support a graded population claim.Full text access blocked (403/429 on Wiley Online Library and ResearchGate during this review); title and abstract-level framing only, no statistics cited above beyond the case narrative itself.
  7. WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index. — Confirms apixaban's ATC classification B01AF02, direct factor Xa inhibitors.
  8. drugs.com interaction checker: Eliquis with Vitamin K; medxdrg.com food/supplement interaction page. — Tier D consumer sources, cited only to document what circulates and confirm neither source found stated an apixaban-vitamin K dietary restriction claim as of the access date below. Both correctly identify grapefruit-family citrus as a CYP3A4-mediated exposure interaction and correctly state vitamin K is not restricted on apixaban.
  9. Wallentin L, Hijazi Z, Andersson U, et al. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE trial. — Circulation, 2014. Randomized cohort, apixaban vs warfarin, n=18,201 (ARISTOTLE). Confirms apixaban was in the studied cohort and that GDF-15, a validated oxidative-stress and inflammation biomarker, was measured in that cohort. Cited for the oxidative stress entry in this dossier's Yellow tier.Full text access blocked (repeated gateway rate-limiting on PubMed, Crossref, Semantic Scholar, and Europe PMC during this review); title and search-result metadata confirmed only. Whether GDF-15 differed between the apixaban and warfarin arms, as opposed to serving only as a baseline risk predictor, could not be verified and is not claimed above.
  10. Torramade-Moix S, Palomo M, Vera M, et al. Apixaban Downregulates Endothelial Inflammatory and Prothrombotic Phenotype in an In Vitro Model of Endothelial Dysfunction in Uremia. — Cardiovascular Drugs and Therapy, 2021. In vitro study, apixaban applied directly to endothelial cells in a uremic-serum dysfunction model. Measured surface VCAM-1 and ICAM-1, intracellular eNOS, reactive oxygen species (ROS), and von Willebrand factor production; title indicates apixaban reduced (downregulated) these markers. Cited for the oxidative stress entry in this dossier's Yellow tier.Confirmed at search-result abstract-snippet and title level; full article not opened during this review because of repeated gateway rate-limiting. No specific effect-size figures are cited above beyond the direction stated in the title and snippet.
  11. Matsui T, Sotokawauchi A, Nishino Y, et al. Apixaban Inhibits Progression of Experimental Diabetic Nephropathy. — International Journal of Molecular Sciences, 2025. Title indicates an experimental (non-human) model. Cited only as a title-level pointer alongside the Torramade-Moix finding in this dossier's oxidative stress entry, not as load-bearing evidence.Abstract and full text access blocked (repeated gateway rate-limiting on PubMed, Crossref, and Semantic Scholar during this review); title, authors, and journal confirmed only via search-result metadata. Not treated as load-bearing evidence anywhere in this dossier.
  12. Wolowiec L, Wesolowska W, Skibicka K, et al. Pleiotropic effects of direct oral anticoagulants. — Biomedicine & Pharmacotherapy, 2026. Narrative review of the direct oral anticoagulant class, apixaban included. Cited only as a pointer to the wider pleiotropic-effects literature referenced in this dossier's oxidative stress entry, not as a source of any specific graded figure.Full text and abstract access blocked (repeated gateway rate-limiting during this review); title and journal confirmed only via search-result metadata. Not treated as load-bearing evidence anywhere in this dossier.