Warfarin: Difference between revisions
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| halflife = 36-42 hours (R/S enantiomers differ; S-warfarin is 2-5× more potent and cleared by CYP2C9)<ref name="coumadin-label">FDA Prescribing Information, Coumadin (warfarin sodium), Bristol-Myers Squibb, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009218s108lbl.pdf</ref> | | halflife = 36-42 hours (R/S enantiomers differ; S-warfarin is 2-5× more potent and cleared by CYP2C9)<ref name="coumadin-label">FDA Prescribing Information, Coumadin (warfarin sodium), Bristol-Myers Squibb, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009218s108lbl.pdf</ref> | ||
| bioavailability = ~100% (oral)<ref name="coumadin-label" /> | | bioavailability = ~100% (oral)<ref name="coumadin-label" /> | ||
| pregnancy = '''Contraindicated in pregnancy''' (warfarin embryopathy, fetal hemorrhage) except in mechanical mitral valves where the maternal mortality of alternative agents may exceed fetal risk. | | pregnancy = '''Contraindicated in pregnancy''' (warfarin embryopathy, fetal hemorrhage) except in mechanical mitral valves where the maternal mortality of alternative agents may exceed fetal risk.<ref name="coumadin-label" /> | ||
| legal = [[USLegal:Prescription only|Rx-only]] in US | | legal = [[USLegal:Prescription only|Rx-only]] in US | ||
| mechanism = <vote slug="warfarin-mech-claim">Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), preventing regeneration of reduced vitamin K and γ-carboxylation of glutamate residues on factors II, VII, IX, X, and proteins C and S; the result is hypofunctional clotting factors, the most clinically important being factor II (prothrombin, half-life ~60 hours) whose depletion drives the steady-state anticoagulant effect.</vote> CYP2C9 (S-warfarin clearance) and VKORC1 (drug target) polymorphisms together explain 30-50% of inter-individual dosing variance and are the prototype pharmacogenomic target in clinical use<ref name="cpic-warfarin">CPIC Guideline for CYP2C9, VKORC1, CYP4F2, and Warfarin, 2017. https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/</ref>. Reversal: vitamin K, 4F-PCC for life-threatening bleeding (FFP if PCC unavailable). | | mechanism = <vote slug="warfarin-mech-claim">Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), preventing regeneration of reduced vitamin K and γ-carboxylation of glutamate residues on factors II, VII, IX, X, and proteins C and S; the result is hypofunctional clotting factors, the most clinically important being factor II (prothrombin, half-life ~60 hours) whose depletion drives the steady-state anticoagulant effect.</vote> CYP2C9 (S-warfarin clearance) and VKORC1 (drug target) polymorphisms together explain 30-50% of inter-individual dosing variance and are the prototype pharmacogenomic target in clinical use<ref name="cpic-warfarin">CPIC Guideline for CYP2C9, VKORC1, CYP4F2, and Warfarin, 2017. https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/</ref>. Reversal: vitamin K, 4F-PCC for life-threatening bleeding (FFP if PCC unavailable). | ||