title: The effect of carbamazepine on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population.
abstract: 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.
  
  
  OBJECTIVE
  To investigate the effect of carbamazepine on warfarin anticoagulation and warfarin maintenance doses by the use of data from three nationwide registries.
  
  
  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.
authors.affiliation: Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Mannheimer
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M L
authors.initials: ML
authors.lastname: Andersson
authors.affiliation: Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Järnbert-Pettersson
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: J D
authors.initials: JD
authors.lastname: Lindh
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy; D002220:Carbamazepine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012737:Sex Factors; D020521:Stroke / Q000188:drug therapy; D013548:Sweden; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D002220:Carbamazepine; D014859:Warfarin
keywords: International Normalized Ratio; carbamazepine; cytochrome P450 (CYP2C9); drug interactions; warfarin