Warfarin
Warfarin
Coumadin (discontinued in US but name in common use), Jantoven
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Summary
Classes
Pharmacy
Starting dose
Typical 5 mg PO daily; 2.5 mg in elderly, low body weight, malnutrition, hepatic dysfunction. Genotype-guided initial dosing per CPIC/IWPC algorithms (CYP2C9, VKORC1, CYP4F2) is one of the most-established PGx applications in current practice
Preparations
1, 2, 2.5, 3, 4, 5, 6, 7.5, 10 mg tablets (color-coded by strength)
US FDA Max
No fixed maximum; titrated to INR target
Pharmacology
Routes
Oral, IV (rarely used; same dose)
Onset
Anticoagulant effect at 24-72 hours; full INR effect 5-7 days
Duration
2-5 days after stopping (factor II resynthesis-limited)
Half-life
36-42 hours (R/S enantiomers differ; S-warfarin is 2-5× more potent and cleared by CYP2C9)[2]
Bioavailability
~100% (oral)[2]
Pregnancy
Contraindicated in pregnancy (warfarin embryopathy, fetal hemorrhage) except in mechanical mitral valves where the maternal mortality of alternative agents may exceed fetal risk.[citation needed]
Legal status
Rx-only in US
Purported mechanism
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.0 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[1]. Reversal: vitamin K, 4F-PCC for life-threatening bleeding (FFP if PCC unavailable).
References
- ↑ CPIC Guideline for CYP2C9, VKORC1, CYP4F2, and Warfarin, 2017. https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/
- ↑ 2.0 2.1 FDA Prescribing Information, Coumadin (warfarin sodium), Bristol-Myers Squibb, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009218s108lbl.pdf