Dataset Information

Carbamazepine, phenytoin, and oral anticoagulants: Drug-drug interaction and clinical events in a retrospective cohort.

ABSTRACT:

Background

Carbamazepine and phenytoin are potent inducers of enzymes that metabolize oral anticoagulants.

Objectives

To determine the clinical impact of drug-drug interactions between these anticonvulsants and oral anticoagulants, and whether they affect the treatment with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).

Material and methods

Data on patients cotreated with carbamazepine or phenytoin and an oral anticoagulant were retrospectively retrieved from medical records from 2011 to 2020. Outcomes were time in therapeutic range (TTR), DOAC levels, thromboembolic events, major bleeding, and all-cause mortality.

Results

Among 85 patients (37% female, median age 68 years) treated with carbamazepine (n = 43 [51%]) or phenytoin (n = 42 [49%]), 53 (62%) were initially treated with VKAs and 32 (38%) with DOACs. TTR in VKA patients was 63%, which improved in year 2. Four of seven trough and five of 12 peak DOAC plasma levels were lower than expected. The incidence rate (95% confidence interval) per 100 person-years for thromboembolism was 3.6 (3.1-4.2) for VKA patients and 4.4 (3.5-5.6) for DOAC patients; for major bleeding 1.8 (1.5-2.1) and 1.5 (1.2-1.9), and for all-cause mortality 3.6 (3.1-4.2) and 1.5 (1.2-1.9), respectively. Incidence rates between VKAs and DOACs and between carbamazepine and phenytoin were similar.

Conclusion

There was a high incidence of thromboembolism in patients cotreated with anticoagulants and carbamazepine or phenytoin. The incidence rates of thrombotic and bleeding events were similar between VKA and DOAC patients. DOAC levels were lower than expected in 47% of cases tested, without correlation with clinical outcomes.

SUBMITTER: Candeloro M

PROVIDER: S-EPMC8851583 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Carbamazepine, phenytoin, and oral anticoagulants: Drug-drug interaction and clinical events in a retrospective cohort.

Candeloro Matteo M Eikelboom John W JW Chan Noel N Bhagirath Vinai V Douketis James D JD Schulman Sam S

Research and practice in thrombosis and haemostasis 20220217 2

<h4>Background</h4>Carbamazepine and phenytoin are potent inducers of enzymes that metabolize oral anticoagulants.<h4>Objectives</h4>To determine the clinical impact of drug-drug interactions between these anticonvulsants and oral anticoagulants, and whether they affect the treatment with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).<h4>Material and methods</h4>Data on patients cotreated with carbamazepine or phenytoin and an oral anticoagulant were retrospectively retrieve ...[more]

PMID: 35224414

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Project description:ObjectivesTo determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding.DesignRetrospective cohort study.SettingLarge administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012.ParticipantsEnrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46,163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39,607 using warfarin.Main outcome measureTime to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors.ResultsDabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69).ConclusionsAlthough rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.

Dataset Information

Carbamazepine, phenytoin, and oral anticoagulants: Drug-drug interaction and clinical events in a retrospective cohort.

Background

Objectives

Material and methods

Results

Conclusion

Publications

Carbamazepine, phenytoin, and oral anticoagulants: Drug-drug interaction and clinical events in a retrospective cohort.

Similar Datasets

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