Warfarin
Warfarin
Coumadin (discontinued in US but name in common use), Jantoven
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Summary
Classes
Common uses
Mechanical heart valves0, Antiphospholipid syndrome thromboprophylaxis0, Atrial fibrillation with mitral stenosis or mechanical valves0, VTE treatment and secondary prevention0, VTE in advanced CKD (DOACs less established)0
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