BLACK BOX WARNING
- fetal hemorrhage and teratogenicity
warfarin
Brand: Coumadin, Jantoven
⚠ BBW ISMP High Alert TDM Required Prototype Drug
Drug Class: anticoagulant
Drug Family: anticoagulant
Subclass: vitamin K antagonist (VKA)
Organ Systems: cardiovascularhematology-oncology
Mechanism of Action
Inhibits VKORC1 preventing regeneration of vitamin K, blocking hepatic synthesis of factors II, VII, IX, X and proteins C and S.
vitamin K epoxide reductase complex 1 (VKORC1)
Indications
- atrial fibrillation stroke prevention
- DVT/PE treatment
- mechanical heart valve
- post-MI LV thrombus
Contraindications
- active bleeding
- severe hepatic impairment
- pregnancy
- hemorrhagic stroke within 3 months
Adverse Effects
Common
- bleeding
- bruising
- alopecia
Serious
- life-threatening hemorrhage
- warfarin skin necrosis
- fetal warfarin syndrome
Pharmacokinetics (ADME)
| Absorption | ~100% oral |
| Distribution | highly protein-bound |
| Metabolism | hepatic CYP2C9 (S-warfarin, major) and CYP3A4 (R-warfarin) |
| Excretion | renal as inactive metabolites |
| Half-life | 36-42 hours |
| Onset | days |
| Peak | days |
| Duration | days |
| Protein Binding | ~99% albumin |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| amiodarone | CYP2C9 inhibition increases INR; reduce warfarin 30-50% | major |
| fluconazole | CYP2C9 inhibition increases INR | major |
| rifampin | CYP2C9/3A4 induction decreases INR | major |
| NSAIDs | increase bleeding risk and reduce platelet function | major |
| vitamin K (dietary) | decreases INR | major |
Nursing Considerations
- INR target: AF/DVT/PE 2.0-3.0; mechanical valve 2.5-3.5
- Check INR q4-8 weeks when stable; more frequently with dose changes
- Reversal: vitamin K IV 5-10 mg plus 4-factor PCC or FFP for major bleeding
- Vitamin K dietary consistency (not avoidance) prevents INR fluctuations
- Genetic polymorphisms: CYP2C9*2/*3 and VKORC1 affect warfarin dose requirements
Clinical Pearls
- S-warfarin 3-5x more potent than R-enantiomer; metabolized by CYP2C9
- Warfarin skin necrosis: protein C depletion before thrombin inhibition at initiation requires heparin overlap
- INR therapeutic range: anticoagulation without excessive bleeding
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.