Resumé
The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug–drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7–28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51–2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56–3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97–4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical Pharmacology & Therapeutics |
| ISSN | 0009-9236 |
| DOI | |
| Status | Udgivet - 28. sep. 2019 |
Fingeraftryk
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Ischemic stroke and systemic embolism in warfarin users with atrial fibrillation or heart valve replacement exposed to dicloxacillin or flucloxacillin. / Kristensen, Kasper Bruun.
I: Clinical Pharmacology & Therapeutics, 28.09.2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
TY - JOUR
T1 - Ischemic stroke and systemic embolism in warfarin users with atrial fibrillation or heart valve replacement exposed to dicloxacillin or flucloxacillin
AU - Kristensen, Kasper Bruun
PY - 2019/9/28
Y1 - 2019/9/28
N2 - The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug–drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7–28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51–2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56–3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97–4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.
AB - The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug–drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7–28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51–2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56–3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97–4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.
UR - http://dx.doi.org/10.1002/cpt.1662
U2 - 10.1002/cpt.1662
DO - 10.1002/cpt.1662
M3 - Journal article
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
ER -