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MOTS-c and Apixaban Interaction: What Patients and Clinicians Need to Know

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Key numbers

  • 27%Share of apixaban clearance that goes through the kidneysSource: accessdata.fda.gov, as cited 2026-11-07
  • 99%Rise in apixaban AUC (total exposure) when ketoconazole is taken with itSource: pubmed.ncbi.nlm.nih.gov, as cited 2026-11-07
  • 54%Drop in oral apixaban AUC (total exposure) when rifampin is taken with itSource: pubmed.ncbi.nlm.nih.gov, as cited 2026-11-07
  • 1.8% to 3.4% per yearYearly bleeding rate on Eliquis with and without aspirin, in the ARISTOTLE trialSource: accessdata.fda.gov, as cited 2026-11-07
  • 50%Apixaban dose cut the label requires with combined P-gp and strong CYP3A4 inhibitorsSource: accessdata.fda.gov, as cited 2026-11-07

At a glance

  • MOTS-c in the lab / breaks down rapidly in human blood in vitro [1]
  • Apixaban class / direct factor Xa inhibitor (DOAC) [2]
  • Label bleeding interactions / aspirin, antiplatelets, heparin, NSAIDs, SSRIs, SNRIs [2]
  • Strong P-gp/CYP3A4 inhibitors / label: 50% apixaban dose cut at 5 or 10 mg twice daily; avoid at 2.5 mg twice daily [2]
  • Status / not FDA-approved; advisory committee vote non-binding [1][3]

What MOTS-c is

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, first reported in 2015 [4]. In mice, it prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity, with skeletal muscle as the main target and AMPK activation as the route [4]. A later mouse study found late-life intermittent treatment increased physical capacity and healthspan [5]. Those mouse studies examined metabolic outcomes, physical capacity and healthspan, not an interaction with apixaban [4][5]. No dose is approved, and the products nominated to FDA were 5 mg and 10 mg subcutaneous injections; rodent doses cannot be converted to a human dose [1].

What the apixaban label documents

Apixaban is a direct factor Xa inhibitor, approved in 2012 as Eliquis [2]. It is cleared mainly by CYP3A4 with P-gp and BCRP transport; about 27% of clearance is renal [2]. Ketoconazole raised apixaban AUC by 99% and Cmax by 62% in 18 healthy subjects; diltiazem raised AUC by 40% and Cmax by 31% [6]. Rifampin cut oral apixaban AUC by 54% in 20 healthy participants [7]. For known combined P-gp and strong CYP3A4 inhibitors, the label calls for a 50% apixaban dose reduction at 5 or 10 mg twice daily and avoiding the combination at 2.5 mg twice daily; for inducers, the label says avoid [2]. The label says apixaban can cause serious, potentially fatal bleeding, and aspirin, other antiplatelets, other anticoagulants, heparin, thrombolytics, SSRIs, SNRIs and NSAIDs add to that risk [2]. In ARISTOTLE, aspirin use raised bleeding on Eliquis from 1.8% to 3.4% per year [2].

Call on the Chemist on apixaban bleeding risk and interactions with other medicines

The presenter explains that apixaban, also called Eliquis, is an anticoagulant that helps blood flow more easily, and says its main downside is bleeding that can be heavier or last longer than usual. On other medicines, the speaker stresses that patients should tell their doctor before starting apixaban if they take other anticoagulants, antifungal or antibiotic treatments, medicines for an abnormal heartbeat, transplant anti-rejection drugs, epilepsy medicines, or anti-inflammatory painkillers such as ibuprofen or aspirin, because these can raise the chance of bleeding. In this view, older people, those with low body weight, and those with kidney impairment are at higher bleeding risk and may need a reduced dose. The presenter also notes that a reversal agent exists for serious bleeding, and wants viewers to understand the medicine well enough to make an informed decision.

Who is speaking?

Call on the Chemist. Presenter of the Call on the Chemist channel, as named on the channel; no role is stated in the description Background

Episode notes and full video

Can a test detect an interaction?

In spiked plasma samples, anti-Xa assays calibrated with apixaban could reliably measure apixaban concentrations [8]. That shows apixaban levels can be measured. It does not show whether MOTS-c changes them, because no human data on MOTS-c exist [1][8].

Bottom line

The documented risks are on the apixaban side: serious bleeding, additive drugs, and the label's dose rules for strong CYP3A4 and P-gp inhibitors and inducers [2].

Questions worth asking

Choose the questions you want to keep

Frequently asked questions

What does the Eliquis label say about bleeding risk?
It says apixaban can cause serious, potentially fatal bleeding, and that aspirin, other antiplatelets, other anticoagulants, heparin, thrombolytics, SSRIs, SNRIs and NSAIDs add to that risk [2].
Does MOTS-c affect CYP3A4 or P-gp?
FDA found no pharmacokinetic data for MOTS-c in humans or live animals [1]. Apixaban is cleared mainly by CYP3A4 with P-gp and BCRP transport, and the label gives dose rules for combined P-gp and strong CYP3A4 inhibitors and says to avoid inducers [2].
Is MOTS-c FDA-approved?
No. It is not an FDA-approved drug or a component of one [1]. In July 2026 an FDA advisory committee voted in favor of adding it to a compounding list, but the vote is non-binding and MOTS-c is not on that list [3][9].

What people actually ask

What are the potential drug-drug interactions with apixaban?

The Eliquis label lists aspirin, other antiplatelets, other anticoagulants, heparin, thrombolytics, SSRIs, SNRIs and NSAIDs as drugs that add to apixaban's bleeding risk. Ketoconazole and diltiazem raised apixaban levels in studies, and rifampin cut them. For known combined P-gp and strong CYP3A4 inhibitors the label calls for a 50% dose reduction at 5 or 10 mg twice daily, and for inducers it says to avoid the drug.

Is MOTS-C snake oil?

MOTS-c is not FDA-approved, and no dose is approved for it. Its supporting evidence comes from mouse studies on metabolic outcomes, physical capacity and healthspan. No human data on MOTS-c interactions exist, and whether it interacts with apixaban is unknown.

References

  1. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  2. Drugs@FDA: FDA-Approved Drugs. Drugs@FDA: FDA-Approved Drugs
  3. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  4. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-54. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
  5. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
  6. Frost CE, Byon W, Song Y, Wang J, Schuster AE, Boyd RA, et al. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol. 2015;79(5):838-46. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor
  7. Vakkalagadda B, Frost C, Byon W, Boyd RA, Wang J, Zhang D, et al. Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa. Am J Cardiovasc Drugs. 2016;16(2):119-27. Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa
  8. Gouin-Thibault I, Flaujac C, Delavenne X, Quenet S, Horellou MH, Laporte S, et al. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study. Thromb Haemost. 2014;111(2):240-8. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study
  9. Official web page. Official web page
  10. Call on the Chemist. THE TRUTH ABOUT ELIQUIS SIDE-EFFECTS, SECRETS AND MORE!. Accessed 2026-11-11.
Evidence overview for MOTS-c and Apixaban Interaction: What Patients and Clinicians Need to Know