title: Warfarin therapy is feasible in CYP2C9*3 homozygous patients.
abstract: Background: Patients carrying variant CYP2C9 alleles are prone to bleeding complications under standard warfarin treatment. Our aim was to test the feasibility of warfarin therapy in patients with severe, inherited CYP2C9 deficiency. Methods: CYP2C9 genotypes and clinical characteristics were compared retrospectively in patients who maintain stable anticoagulation on low or regular doses of warfarin. Results: In the low-dose (10.5+/-2.9 mg/week) group (N=16), we identified six (37.6%) patients with severe CYP2C9 deficiency and three each with *2/*3 and *3/*3 genotypes as compared to none in the standard dose (39.2+/-17.9 mg/week) group (N=17). Warfarin dose (mg/week) was correlated with genotype in all patients as follows: *1/*1 (N=14) dose=33.6+/-19.4; *1/*2 (N=9) dose=30.4+/-21.6; *1/*3 (N=4) dose=15.3+/-10.7; *2/*3 (N=3) dose=10.6+/-3.6; *3/*3 (N=3) dose=7.3+/-3.1. Age and frequency of concurrent warfarin potentiating medication administration were higher in the low-dose group than in the standard dose group of patients. Conclusions: Warfarin treatment is feasible in individuals with severe, inherited CYP2C9 deficiency. Dose requirement was correlated with CYP2C9 genotype and possibly affected by age and concurrent intake of interfering drugs. Prospective studies are needed to test the feasibility and cost effectiveness of using algorithms based on these parameters for adjusting initial warfarin dose to meet individual needs.
authors.affiliation: Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Ablin
authors.forename: Shaltiel
authors.initials: S
authors.lastname: Cabili
authors.forename: Amiram
authors.initials: A
authors.lastname: Eldor
authors.forename: Ayala
authors.initials: A
authors.lastname: Lagziel
authors.forename: Hava
authors.initials: H
authors.lastname: Peretz