Question explored with the scientific record
What specific drug or food interactions with letrozole could affect apixaban?
The short version: no evidence exists that any food or supplement meaningfully changes apixaban levels through the letrozole pathway.
The evidence shows apixaban is cleared mainly by CYP3A4 and by the efflux transporters P-glycoprotein and BCRP [7, 9]. Letrozole is a CYP19 (aromatase) inhibitor, not a CYP3A4 inhibitor or inducer [3]. The two drugs do not compete for the same metabolic enzyme. The case report of a woman on letrozole, apixaban, and niraparib who developed DRESS syndrome does not show a pharmacokinetic interaction between letrozole and apixaban [1]. She later tolerated letrozole alone.
No study in the evidence tests whether a food or supplement that inhibits or induces CYP3A4 (grapefruit, St. John's wort, certain herbs) changes apixaban levels differently when letrozole is present. The apixaban metabolism studies were done in healthy volunteers not on letrozole [4, 5, 6]. The sulfation of apixaban's metabolite is carried out by SULT1A1, not by a pathway letrozole affects [6].
My call: there is no known interaction. Confidence: moderate. The gap is that no study has measured apixaban levels in patients on letrozole, so a subtle interaction cannot be ruled out, but the mechanism makes one unlikely.
Sources examined 12
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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) caused by niraparib: a novel antineoplastic agent
This case report documents the first known instance of niraparib-induced DRESS syndrome in a 73-year-old woman with high-grade serous ovarian cancer, confirmed by positive patch testing and successfully managed with corticosteroids after Niraparib discontinuation, highlighting t…
DOI: 10.1186/s13223-025-00959-2 -
Persistent endocrine disruption effects in medaka fish with early life-stage exposure to a triazole-containing aromatase inhibitor (letrozole)
This study investigates the persistent endocrine disruption effects of the triazole-containing aromatase inhibitor letrozole on medaka fish, revealing significant reproductive toxicity and alterations in gene expression following early life-stage exposure.
DOI: 10.1016/j.jhazmat.2014.02.013 -
A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17,20-lyase (CYP17)
A comprehensive review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17,20-lyase (CYP17), detailing how two distinct P450-catalyzed reactions occur at the same active site, the regulatory role of cytochrome b5 in CYP17, structural insights from X-ray studies, i…
DOI: 10.1016/j.jsbmb.2010.11.003 -
Comparative Metabolism of 14C-Labeled Apixaban in Mice, Rats, Rabbits, Dogs, and Humans
This study investigates the metabolism and disposition of 14C-labeled apixaban in various species, including mice, rats, rabbits, dogs, and humans, revealing significant differences in metabolic profiles and elimination pathways across species.
DOI: 10.1124/dmd.108.025981 -
Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans
This study characterizes the metabolism, mass balance, and pharmacokinetics of oral apixaban in 10 healthy male humans using [14C] labeling, showing predominant fecal excretion with significant renal clearance, a major circulating metabolite (O-demethyl apixaban sulfate), and a …
DOI: 10.1124/dmd.108.023143 -
Sulfation of O-Demethyl Apixaban: Enzyme Identification and Species Comparison
This study identifies the sulfotransferases responsible for the sulfation of O-demethyl apixaban, a major metabolite of the anticoagulant apixaban, and compares the enzyme activities across different species, revealing significant differences in metabolic pathways.
DOI: 10.1124/dmd.108.025593 -
Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review
A comprehensive pharmacokinetic and pharmacodynamic review of apixaban detailing its absorption, distribution, metabolism, excretion, drug interactions, safety in special populations, pediatric considerations, and reversal options, demonstrating its predictable PK/PD, fixed-dose…
DOI: 10.1007/s40262-019-00775-z -
Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor
This study investigates the pharmacokinetics and pharmacodynamics of apixaban, a selective factor Xa inhibitor, demonstrating its favorable absorption, distribution, and anticoagulant effects in preclinical models.
DOI: 10.1007/s13318-011-0037-x -
Characterization of Efflux Transporters Involved in Distribution and Disposition of Apixaban
This study investigates the transport characteristics of apixaban, revealing that it is a substrate for the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which significantly influence its distribution and disposition in the body.
DOI: 10.1124/dmd.112.050260 -
Formulation and Evaluation of Buccal Mucoadhesive Bilayer Tablets of Apixaban
Design and evaluation of buccal mucoadhesive bilayer tablets of Apixaban identify an optimized F7 formulation with strong mucoadhesion, near-neutral surface pH, and diffusion-controlled release achieving 88.84% drug release in 180 minutes while remaining stable under accelerated…
DOI: 10.22270/jddt.v15i12.7466 -
Su1497 - Different Types of Dietary Fat-Fructose Interactions Contribute to the Development of Distinct Patterns of Hepatic Steatosis in Male Mice
This study investigates the pharmacokinetics of apixaban and rosuvastatin in patients with non-alcoholic fatty liver disease (NAFLD) and finds no significant differences compared to healthy controls, suggesting that NAFLD does not affect the pharmacokinetics of these drugs.
DOI: 10.1016/S0016-5085(18)33838-1 -
Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development
A concise review of the pharmacokinetic/pharmacodynamic properties, clinical efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban, and apixaban across preclinical and phase III trials, highlighting their potential to improve on warfarin and enoxaparin in …
DOI: 10.1160/TH09-09-0659