The Effect of Flucloxacillin on Warfarin Anticoagulation: A Swedish Register-Based Nationwide Cohort Study

Buster Mannheimer*, Tore B Stage, Anton Pottegård, Jonatan D Lindh

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Resumé

Background Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. Objectives This article investigates the effect of flucloxacillin on warfarin anticoagulation. Patients and Methods In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. Results Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95% confidence interval [CI] 2.34; 2.37) to 2.20 (95% CI 2.19; 2.21) and from 2.24 (95% CI 2.16; 2.32) to 1.96 (95% CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22% in the week preceding flucloxacillin initiation to 35% in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63% by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. Conclusion One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.

OriginalsprogEngelsk
TidsskriftThrombosis and Haemostasis
Vol/bind19
Udgave nummer10
Sider (fra-til)1617-1623
ISSN0340-6245
DOI
StatusUdgivet - okt. 2019

Fingeraftryk

Floxacillin
Warfarin
International Normalized Ratio
Cohort Studies
Confidence Intervals
Penicillin V
Retrospective Studies

Citer dette

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title = "The Effect of Flucloxacillin on Warfarin Anticoagulation: A Swedish Register-Based Nationwide Cohort Study",
abstract = "Background Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. Objectives This article investigates the effect of flucloxacillin on warfarin anticoagulation. Patients and Methods In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. Results Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95{\%} confidence interval [CI] 2.34; 2.37) to 2.20 (95{\%} CI 2.19; 2.21) and from 2.24 (95{\%} CI 2.16; 2.32) to 1.96 (95{\%} CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22{\%} in the week preceding flucloxacillin initiation to 35{\%} in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63{\%} by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. Conclusion One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.",
keywords = "cytochrome P-450 CYP2C9, drug interactions, flucloxacillin, international normalized ratio, warfarin",
author = "Buster Mannheimer and Stage, {Tore B} and Anton Potteg{\aa}rd and Lindh, {Jonatan D}",
year = "2019",
month = "10",
doi = "10.1055/s-0039-1693462",
language = "English",
volume = "19",
pages = "1617--1623",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
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}

The Effect of Flucloxacillin on Warfarin Anticoagulation : A Swedish Register-Based Nationwide Cohort Study. / Mannheimer, Buster; Stage, Tore B; Pottegård, Anton; Lindh, Jonatan D.

I: Thrombosis and Haemostasis, Bind 19, Nr. 10, 10.2019, s. 1617-1623.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The Effect of Flucloxacillin on Warfarin Anticoagulation

T2 - A Swedish Register-Based Nationwide Cohort Study

AU - Mannheimer, Buster

AU - Stage, Tore B

AU - Pottegård, Anton

AU - Lindh, Jonatan D

PY - 2019/10

Y1 - 2019/10

N2 - Background Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. Objectives This article investigates the effect of flucloxacillin on warfarin anticoagulation. Patients and Methods In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. Results Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95% confidence interval [CI] 2.34; 2.37) to 2.20 (95% CI 2.19; 2.21) and from 2.24 (95% CI 2.16; 2.32) to 1.96 (95% CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22% in the week preceding flucloxacillin initiation to 35% in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63% by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. Conclusion One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.

AB - Background Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. Objectives This article investigates the effect of flucloxacillin on warfarin anticoagulation. Patients and Methods In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. Results Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95% confidence interval [CI] 2.34; 2.37) to 2.20 (95% CI 2.19; 2.21) and from 2.24 (95% CI 2.16; 2.32) to 1.96 (95% CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22% in the week preceding flucloxacillin initiation to 35% in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63% by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. Conclusion One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.

KW - cytochrome P-450 CYP2C9

KW - drug interactions

KW - flucloxacillin

KW - international normalized ratio

KW - warfarin

U2 - 10.1055/s-0039-1693462

DO - 10.1055/s-0039-1693462

M3 - Journal article

C2 - 31352678

VL - 19

SP - 1617

EP - 1623

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 10

ER -