Oral anticoagulation with warfarin is significantly influenced by steroids and CYP2C9 polymorphisms in children with cancer.
Clinical management of warfarin therapy is complex, and dosing algorithms do not include genetic factors or interactions with other drugs for warfarin dose determinations. We evaluated the interaction of warfarin and CYP2C9 polymorphisms and concomitant corticosteroids in 29 children with cancer. Children with heterozygous polymorphisms of CYP2C9 achieved target INR sooner and more frequently had INR above the target level, compared to children without mutations. Children on concomitant steroids had significantly lower warfarin requirements. Thus, awareness of CYP2C9 genotype and steroid-induced responsiveness to warfarin may be important when administrating oral anticoagulation in children.
Ruud
Ellen
E
Department of Paediatrics, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway. ellen.ruud@rikshospitalet.no
Holmstrøm
Henrik
H
Bergan
Stein
S
Wesenberg
Finn
F
D000293:Adolescent; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D019934:International Normalized Ratio; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D013927:Thrombosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin; D003907:Dexamethasone; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D011241:Prednisone