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J Am Soc Nephrol. 2017 Jul;28(7):2241-2248. doi: 10.1681/ASN.2016090980. Epub 2017 Mar 16.

Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients.

Author information

1
Division of Nephrology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; and thomas.mavrakanas@mail.mcgill.ca.
2
Division of General Internal Medicine and.
3
Department of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
4
Division of Nephrology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; and.

Abstract

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.

KEYWORDS:

apixaban; atrial fibrillation; hemodialysis; pharmacokinetics

PMID:
28302754
PMCID:
PMC5491286
DOI:
10.1681/ASN.2016090980
[Indexed for MEDLINE]
Free PMC Article

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