Warfarin

Category: pharmacological

Aliases: Coumadin, Jantoven

Pharmacological Mechanism

Inhibits vitamin K epoxide reductase (VKOR) → depletes reduced vitamin K → prevents γ-carboxylation of factors II, VII, IX, X + proteins C/S. Narrow therapeutic index + massive interaction list + dietary K variability → DOACs (apixaban, rivaroxaban) now preferred for non-valvular indications.

Half-Life (t½)

PO: 40h

Dosing Guidelines

• PO: Typical 4.67 mg (Range: 2–10 mg)

Target Organ Systems

• immune-hematologic

Interactions

• Vitamin K1 (major): Direct antagonism — consistent dietary K is the principle. [Holbrook 2005]
• Vitamin K2 MK-7 (major): Extrahepatic K2 still reaches VKOR — stabilise intake. [Holbrook 2005]
• Vitamin E (caution): Additive antiplatelet at ≥200 IU/d. [Holbrook 2005]
• St. John's Wort (major): CYP2C9 + CYP3A4 induction reduces warfarin exposure and INR. [Holbrook 2005]
• Cholestyramine (caution): Binds warfarin — separate dosing by ≥4 h. [Holbrook 2005]
• Acetaminophen (caution): Chronic APAP ≥2 g/d raises INR modestly (mechanism unclear — possibly CYP2C9 substrate competition). Dose-related; intermittent low-dose use is generally safe. [Holbrook 2005]
• Apixaban (caution): Do not combine; overlapping anticoagulation. Transition protocols exist.
• Dabigatran (caution): Do not co-administer; transition per protocol only.
• Edoxaban (caution): Do not co-administer; transition per protocol.
• Rivaroxaban (caution): Do not combine; overlapping anticoagulation.
• Tamoxifen (major): CYP2C9 inhibition + estrogenic hepatic effects raise INR — monitor closely. [Holbrook 2005]
• CoQ10 (caution): Structural similarity to vitamin K — may modestly reduce warfarin effect; monitor INR if initiating high-dose CoQ10. [Holbrook 2005]
• Menaquinone-4 (MK-4) (major): Antagonises warfarin. Avoid or monitor INR closely. [Holbrook 2005]

Pathways It Modulates

• Coagulation cascade (inhibitor) — vitamin-K-dependent factors II/VII/IX/X (upstream γ-carboxylation)
• Vitamin K cycle (γ-carboxylation) (inhibitor) — VKORC1

Chemical Identifiers

• PubChem CID: 54678486
• Formula: C19H16O4
• Molecular weight: 308.33 g/mol
• InChIKey: PJVWKTKQMONHTI-UHFFFAOYSA-N
• SMILES: CC(=O)CC(C1=CC=CC=C1)C2=C(C3=CC=CC=C3OC2=O)O

References

• PMID 3542339
• PMID 15911722