Apixaban trough concentrations in atrial fibrillation patients with reduced renal function

• Published in: Biomedicine & pharmacotherapy 2024-11, Vol.180, p.117613, Article 117613
• Main Authors: Al-Aieshy, Fadiea, Skeppholm, Mika, Fyrestam, Jonas, Johansson, Fredrik, Pohanka, Anton, Malmström, Rickard E.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Apixaban; Atrial Fibrillation - drug therapy; Drug Monitoring - methods; Factor Xa Inhibitors - administration & dosage; Factor Xa Inhibitors - blood; Factor Xa Inhibitors - pharmacokinetics; Female; Glomerular Filtration Rate - drug effects; Humans; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Male; Middle Aged; Plasma concentration; Pyrazoles - administration & dosage; Pyrazoles - blood; Pyrazoles - pharmacokinetics; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - blood; Pyridones - pharmacokinetics; Renal function; Renal impairment; Renal insufficiency; Renal Insufficiency - blood; Renal Insufficiency - physiopathology; Tandem Mass Spectrometry; Therapeutic drug monitoring
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117613

The direct factor Xa inhibitor apixaban is partially eliminated by the kidneys but is still prescribed at fixed doses without therapeutic drug monitoring across varying levels of renal function. If apixaban accumulates due to renal impairment, this may translate into safety concerns, e.g. the risk for bleeding. The purpose of this study was to measure apixaban trough concentrations in patients with different stages of renal function/renal impairment. Apixaban trough concentrations were measured using LC-MS/MS in patients with atrial fibrillation, having normal renal function (apixaban 5 mg BID, n=39), moderate renal impairment (apixaban 5 mg BID, n=40) and severe renal impairment (apixaban 2.5 mg BID, n=6). The median (min-max) relative eGFR values were 84.8 (71.7–111.4), 51.4 (31.3–67.2) and 23.0 (21.9–28.4) mL/min/1.73 m², in the three groups, respectively. Patients with moderate renal impairment had significantly higher apixaban trough concentrations than patients with normal renal function. The median (min-max) trough concentrations were 59.8 ng/mL (15.5–170.9) for normal renal function, 128.9 ng/mL (41.4–295.4) for moderate renal impairment and 81.7 ng/mL (61.8–109.0) for severe renal impairment. The trough concentrations correlated significantly with renal function measured as relative/absolute eGFR creatinine/cystatin C. The standard dosing regimen of 5 mg apixaban BID renders exposure that is roughly twice as high in patients with moderately reduced renal function compared to patients with normal renal function. We suggest that patients with moderately reduced renal function ought to be monitored. Possibly, a dose reduction may be considered to achieve similar exposure as in patients with normal renal function. [Display omitted] •Apixaban trough concentrations were measured in patients with varying renal function.•Normal and moderately reduced renal function were compared at apixaban 5 mg BID.•Concentrations were twice as high in patients with moderately reduced renal function.