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Clin Pharma and Therapeutics - 2023 - Salem - Warfarin‐Rifampin‐Gene WARIF‐G Interaction A Retrospective Genetic Case.pdf (599.55 kB)
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Warfarin‐Rifampin‐Gene (WARIF‐G) Interaction: A Retrospective, Genetic, Case–Control Study

journal contribution
submitted on 2024-01-09, 07:20 and posted on 2024-01-14, 07:42 authored by Muhammad Salem, Ahmed El‐Bardissy, Mohamed Nabil Elshafei, Ahmed Khalil, Hesham Mahmoud, Amr Mohamed Fahmi, Mohamed Kasem, Loulia Bader, Mohamed Sherbash, Mostafa Ibrahim Elawady, Walaa Abdalazim, Faraj Howady, Hazem Elewa

Warfarin is extensively metabolized by cytochrome P450 2C9 (CYP2C9). Concomitant use with the potent CYP2C9 inducer, rifampin, requires close monitoring and dosage adjustments. Although, in theory, warfarin dose increase should overcome this interaction, most reported cases over the last 50 years have not responded even to high warfarin doses, but some have responded to modest doses. To investigate the genetic polymorphisms' impact on this unexplained interpatient variability, we performed genotyping of CYP2C9, VKORC1, and CYP4F2 for warfarin and rifampin concomitant receivers from 2016 to 2022 at Hamad Medical Corporation, Doha, Qatar. We identified and included 36 patients: 22 responders and 14 nonresponders. Warfarin‐responders were significantly more likely to have one or more warfarin‐sensitizing CYP2C9/VKORC1 alleles than nonresponders (odds ratio = 23.2, 95% confidence interval = 3.2–195.6; P = 0.0001). The mean genetic‐based pre‐interaction calculated dose was significantly lower for responders than for nonresponders (P < 0.001); and was negatively correlated with warfarin sensitivity index (WSI) (r = −0.58; P = 0.0002). The median percentage time in therapeutic range and mean WSI were significantly higher in the warfarin‐sensitizing CYP2C9/VKORC1 alleles carriers than noncarriers (P = 0.017 and 0.0004, respectively). Whereas the warfarin‐sensitizing CYP2C9/VKORC1 genotypes were associated with modest on‐rifampin warfarin dose requirements, the noncarriers would have required more than double these doses to respond. Warfarin‐sensitizing CYP2C9/VKORC1 genotypes and low genetic‐based warfarin calculated doses were associated with higher warfarin sensitivity and better anticoagulation quality in patients receiving rifampin concomitantly.

Other Information

Published in: Clinical Pharmacology & Therapeutics
License: http://creativecommons.org/licenses/by-nc/4.0/
See article on publisher's website: https://dx.doi.org/10.1002/cpt.2871

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Qatar University
  • Qatar University Health - QU
  • College of Pharmacy - QU HEALTH
  • Biomedical and Pharmaceutical Research Unit - QU HEALTH

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    Hamad Medical Corporation

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