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The effect of carbamazepine on warfarin anticoagulation: a register‐based nationwide cohort study involving the Swedish population
Author(s) -
Mannheimer B.,
Andersson M. L.,
Järnbertpettersson H.,
Lindh J. D.
Publication year - 2016
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13268
Subject(s) - warfarin , carbamazepine , medicine , cohort , confidence interval , stroke (engine) , anesthesia , retrospective cohort study , population , atrial fibrillation , epilepsy , mechanical engineering , environmental health , psychiatry , engineering
Essentials The clinical impact of the carbamazepine‐warfarin drug interaction is largely unknown. We studied the interaction in 166 patients, using data from three nationwide registries. Co‐treatment with carbamazepine increased warfarin dose requirements by 49%. International normalized ratio remained reduced for months, indicating poor control.Summary Background There are data indicating that the interaction between warfarin and carbamazepine results in decreased warfarin efficacy. However, the evidence on the magnitude of and interindividual differences in susceptibility to this interaction has remained scarce. Objectives To investigate the effect of carbamazepine on warfarin anticoagulation and warfarin maintenance doses by the use of data from three nationwide registries. Patients/Methods In a retrospective cohort study including 166 patients, warfarin doses were compared 2–4 weeks before and 10–13 weeks after initiation of cotreatment with carbamazepine. In addition, warfarin doses and International Normalized Ratio (INR) values were calculated week‐by‐week during cotreatment. Data on prescribed warfarin doses and INR measurements were obtained from two large Swedish warfarin registers. Data on carbamazepine use were retrieved from the Swedish Prescribed Drug Register. Results The average warfarin doses were 49% (95% confidence interval 43–56) higher during carbamazepine treatment. The INR decreased upon carbamazepine initiation, and subtherapeutic INR levels were observed in 79% of all patients during the fifth week of cotreatment. Warfarin maintenance dose increases exceeding 50% and 100% were observed in 59% and 17% of patients, respectively. Conclusions Four of five warfarin‐treated patients in whom cotreatment with carbamazepine was initiated experienced subtherapeutic anticoagulative effect within 3–5 weeks. The warfarin dose was subsequently increased by 49%, a change that differed widely between patients. In order to avoid thrombosis and ischemic stroke, carbamazepine initiation should be accompanied by close INR monitoring to better meet the anticipated increase in dose demand.