TY  - CHAP
M1  - Book, Section
TI  - Pharmacogenetics of Warfarin
A1  - Scott, Stuart A.
A1  - Desnick, Robert J.
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
PY  - 2014
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Drug  summary:Warfarin  (Coumadin)  is  a  commonly  prescribed  vitamin  K  antagonist  for  the  prevention  of  thromboembolism.  However,  the  drug  has  a  very  narrow  therapeutic  index  and  a  large  interindividual  variability  in  response,  in  part  due  to  inherited  genetic  variability  within  genes  involved  in  warfarin  pharmacokinetics  and  pharmacodynamics.Clinical  indications  for  anticoagulation  therapy  include  atrial  fibrillation,  mechanical  heart  valves,  deep  venous  thrombosis,  and  dilated  cardiomyopathies.Interindividual  and  interethnic  variability  in  therapeutic  warfarin  dose  requirements  is  responsible  for  frequent  adverse  drug  reactions  and  underutilization  due  to  its  toxicity.Several  factors  affect  warfarin  dosage,  including  age,  body  weight,  concomitant  medications,  and  DNA  sequence  variants  in  cytochrome  P450  2C9  (CYP2C9)  and  vitamin  K  epoxide  reductase  subunit  1  (VKORC1).Common  variant  CYP2C9  and  VKORC1  alleles  are  associated  with  impaired  warfarin  metabolism  and  sensitivity  to  warfarin,  respectively,  both  resulting  in  lower  therapeutic  dose  requirements.Individuals  with  impaired  warfarin  metabolism  and/or  increased  sensitivity  require  decreased  dosage  to  avoid  their  international  normalized  ratio  (INR)  increasing  beyond  the  target  range  (typically  2-3).  Increased  INR  values  can  be  associated  with  morbidity  and  mortality  due  to  major  bleeding  episodes.Although  many  variant  CYP2C9  and  VKORC1  alleles  are  found  in  several  major  racial  and  ethnic  groups,  some  are  specific  to  various  subpopulations.Pharmacogenetic  dosing  algorithms  including  both  clinical  and  genetic  variables  have  been  developed  that  predict  the  therapeutic  warfarin  dose.Clinical  testing  for  variant  CYP2C9  and  VKORC1  alleles  is  available  and  generalized  FDA-approved  dosing  recommendations  are  now  noted  on  the  warfarin  package  insert.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1102698531
ER  -