Warfarin

ATC code

B01AA03

Therapeutic class

Vitamin K antagonist · Antithrombotic agent

Forms

oral tablet

Brand names

Coumadin (US) · Aldocumar (ES) · Marevan (GB)

Overall confidence

medium

Regulatory sources consulted

AEMPS CIMA FT 63062 (https://cima.aemps.es/cima/dochtml/ft/63062/FT_63062.html)
PubMed PMID:37951634 ↗
PubMed PMID:34347858 ↗
PubMed PMID:39076339 ↗
Standard Clinical Pharmacology Knowledge (Flockhart Table for CYP profile)
AEMPS CIMA · nº registro 63062 ↗

Approved indications

Prophylaxis and/or treatment of venous thrombosis and pulmonary embolism.
Prophylaxis and/or treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement.
Reduction of the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Contraindications

Absolute

Pregnancy.
Hemorrhagic tendencies or blood dyscrasias; active bleeding.
Recent or planned major surgery (neurosurgery, ophthalmic).

Relative

Malignant hypertension.

Clinical warnings

Boxed warning · Bleeding Risk: Can cause major or fatal bleeding. Perform regular monitoring of INR on all treated patients. — FDA
Major warning · Tissue Necrosis: Necrosis and/or gangrene of the skin and other tissues has been reported, which can be severe. Discontinue treatment if suspected. — AEMPS CIMA FT
Major warning · Calciphylaxis: Cases of calciphylaxis (calcific uremic arteriolopathy) have been reported in patients with or without end-stage renal disease. If diagnosed, discontinue warfarin. — AEMPS CIMA FT

Drug interactions

HighAmiodaroneC01BD01
Mechanism: Inhibition of S-warfarin (CYP2C9) and R-warfarin (CYP3A4, CYP1A2) metabolism, significantly increasing INR.
Recommendation: Reduce warfarin dose by 30-50% when starting amiodarone. Monitor INR frequently.
AEMPS CIMA FT
HighRifampicinJ04AB02
Mechanism: Potent induction of CYP2C9 and CYP3A4, accelerating warfarin metabolism and significantly decreasing INR.
Recommendation: Increase warfarin dose (may require doubling or tripling the dose). Monitor INR closely when starting and stopping rifampicin.
AEMPS CIMA FT

Adverse events

Common (≥1%)

hemorrhage · nausea · vomiting · diarrhea

Rare but serious

skin necrosis · purple toe syndrome · calciphylaxis · liver injury

Pregnancy and lactation

FDA category: X

Contraindicated during pregnancy due to its teratogenic potential (warfarin embryopathy) and risk of fetal hemorrhage. It can be administered during lactation as it is not excreted in breast milk in significant amounts.

Recent literature (PubMed)

Controversies in Stoppage of Antiplatelet and Anticoagulant Medications Prior to Oral Surgery.
Chan MH, et al. · Dent Clin North Am · 2024 · Relevance 4/5
Revisa la controversia sobre la suspensión de antitrombóticos como la warfarina antes de la cirugía oral. Examina la evidencia y las guías para manejar el riesgo de sangrado frente al riesgo de eventos tromboembólicos, destacando la falta de consenso y la necesidad de una evaluación individualizada.
Narrow Therapeutic Index drugs: clinical pharmacology perspective.
Habet S · J Pharm Pharmacol · 2021 · Relevance 3/5
Artículo de perspectiva que discute la definición y características de los fármacos de Índice Terapéutico Estrecho (NTI), como la warfarina. Señala que las listas de fármacos NTI son a menudo arbitrarias y que la variabilidad farmacocinética es un factor clave para la seguridad y eficacia.
Multimodality Imaging of Cardiac Myxomas.
Hrabak-Paar M, et al. · Rev Cardiovasc Med · 2024 · Relevance 1/5
Revisión sobre el diagnóstico por imagen de mixomas cardíacos. Menciona la 'cresta de Coumadin' (Coumadin ridge), una estructura anatómica normal en la aurícula izquierda, como un diagnóstico diferencial de masas cardíacas, ilustrando un uso incidental del nombre del fármaco en la terminología anatómica.