Drug reference

Warfarin

Anticoagulant

Also known as Warfarin Sodium, Coumadin, Jantoven

START

5 mg PO once daily × 2 days, then adjust to INR

TYPICAL MAX

individualized — no fixed daily ceiling

STOP IF

Active bleeding · INR >5 · pregnancy (teratogen)

WATCH

INR (target 2-3) · bleeding · drug/diet interactions

CDSCO approvedSchedule HJan AushadhiATC B01AA03

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1d · factor depletion begins
PEAK: 4h · Cmax (PK, not clinical)
t½: 1.7d · plasma t½ (long)
DURATION: 4d · anticoagulant duration after dose change (3-5 days)

EXCRETION

CYP2C9 + CYP3A4 hepatic · renal metabolites

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Category X (1st trimester) → D — LMWH preferred

FDA category + note

Top interactionssee all 12 →

RivaroxabanContraindicatedDatabaseKimi deep-research + Cla
AllopurinolSevereTextbook-citedKDT 7e · p948
AmoxicillinSevereTextbook-citedKDT 7e · p948
AmpicillinSevereTextbook-citedKDT 7e · p948

Available in India

17 branded formulations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Warfarin inhibits the enzyme Vitamin K epoxide reductase complex subunit 1 (VKORC1) in the liver. This prevents the regeneration of reduced vitamin K, a crucial cofactor for the gamma-carboxylation of clotting factors II (prothrombin), VII, IX, and X, as well as anticoagulant proteins C and S. Consequently, functionally inactive forms of these factors are produced, leading to a dose-dependent anticoagulant effect and prolonged clotting times.

Indications

Treatment and prophylaxis of venous thrombosis and its extension (e.g., deep vein thrombosis, pulmonary embolism)Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacementReduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction (off-label, historically common)Prevention of recurrent transient ischemic attacks and stroke (off-label)patients at high risk for thrombotic disease (in supportive care for PAH)Prevent the progression of acute deep vein thrombosisPrevent the recurrence of acute deep vein thrombosisPrevent the progression of pulmonary embolismPrevent the recurrence of pulmonary embolismPrevent stroke in patients with atrial fibrillationPrevent systemic embolization in patients with atrial fibrillationPrevent stroke in patients with mechanical heart valvesPrevent systemic embolization in patients with mechanical heart valvesPrevent stroke in patients with ventricular assist devicesPrevent systemic embolization in patients with ventricular assist devicestreatment of venous thromboembolism (in tandem with parenteral anticoagulation)secondary prevention of venous thromboembolismprevention of stroke in atrial fibrillationprevention of stroke in patient with mechanical heart valves or ventricular assist devicesProphylaxis of deep vein thrombosisTreatment of deep vein thrombosisPulmonary embolism (treatment and prophylaxis)Transient ischaemic attacks (TIAs)Prevention of stroke in patients with atrial fibrillationRecurrent thromboembolismArterial disease (MI)Prosthetic heart valvesMaintenance therapy after initial heparinTreatment for deep venous thrombosis or pulmonary embolism in cancer patients (after initial heparinization)Mitral stenosis with atrial fibrillationMitral stenosis with a history of thromboembolismMitral stenosis with demonstrated left atrial thrombusReduction of risk for stroke or systemic embolism in at-risk patients with rheumatic mitral stenosisVTEstandard treatment for Antiphospholipid syndrome (APS)prophylaxis for VTE

Dosing

Adult: Initial dose typically 2-5 mg orally once daily. Titrate dose based on daily or alternate-day INR monitoring until stable therapeutic INR (usually 2.0-3.0 for most indications, 2.5-3.5 for mechanical mitral valves). Maintenance dose usually 2-10 mg orally once daily. Administration at the same time each day is recommended.
Pediatric: Not routinely recommended and should only be initiated under specialist supervision. Initial dose typically 0.1-0.2 mg/kg/day orally, with a maximum initial dose of 10 mg. Doses are adjusted based on INR.
Renal adjustment: No specific dose adjustment for mild to moderate renal impairment. Use with caution in severe renal impairment (CrCl <30 mL/min) due to increased bleeding risk; monitor INR more frequently.
Hepatic adjustment: Dose reduction is often necessary in hepatic impairment due to decreased synthesis of clotting factors and impaired metabolism of warfarin. Monitor INR closely. Avoid in severe hepatic disease.
Geriatric: Lower initial doses (e.g., 2 mg/day) are often appropriate due to increased sensitivity, higher risk of bleeding, and potential for more drug interactions. Close INR monitoring is crucial.
Max dose: Daily doses typically rarely exceed 10-15 mg, but the maximum dose is individualized based on INR response and patient factors.

Pharmacokinetics

Onset

Anticoagulant effect (reduction in procoagulant factors) within 24-72 hours. Full therapeutic effect (INR stabilization) takes 5-7 days.

Peak effect

INR response starts to be noticeable within 36-72 hours after initial dose, but stabilization to therapeutic range takes several days.

Duration

2-5 days after discontinuation.

Half-life

20-60 hours (average 40 hours) for the racemic mixture.

Bioavailability

Nearly 100% after oral administration.

Protein binding

Approximately 99% bound to plasma proteins, primarily albumin.

Metabolism

Hepatic metabolism via cytochrome P450 enzymes, primarily CYP2C9 (S-warfarin), CYP1A2, and CYP3A4 (R-warfarin).

Excretion

Metabolites excreted mainly in urine (92%) and feces (6%).

Contraindications

Pregnancy (causes fetal warfarin syndrome and fetal hemorrhage)
Active hemorrhage or increased tendency to bleed (e.g., hemophilia, severe thrombocytopenia)
Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces
Intracranial hemorrhage
Severe uncontrolled hypertension
Aneurysms (cerebral, aortic)
Bacterial endocarditis
Pericarditis or pericardial effusion
Lumbar puncture or other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
Severe hepatic disease (coagulopathy)
Unsupervised patients with senility, alcoholism, or psychosis where compliance is doubtful
Pregnancy
pregnancy (fetal risk)
Bleeding disorders
Severe hypertension (risk of cerebral haemorrhage)
G.I. ulcers (risk of aggravated bleeding)
Subacute bacterial endocarditis (risk of embolism)
Large malignancies (risk of bleeding in the central necrosed area of the tumour)
Ocular and neurosurgery
Lumbar puncture
Chronic alcoholics
Cirrhosis
Renal failure
Pregnancy (early pregnancy due to birth defects, later due to CNS defects, fetal haemorrhage, fetal death, neonatal hypoprothrombinemia)

Side effects

Common

Bleeding (minor, e.g., epistaxis, gum bleeding, bruising)NauseaVomitingDiarrheaAbdominal painBloatingFlatulenceBleeding (most common side effect; major bleeding generally less than 3% per year with INR 2-3)AlopeciaUrticariaDermatitisFeverAbdominal crampsAnorexiaBleeding (ecchymosis, epistaxis, hematuria, g.i.t. bleeding)DiarrhoeaBleeding (epistaxis, hematuria, gastrointestinal bleeding)arterial vascular calcification

Serious

Major hemorrhage (e.g., intracranial, retroperitoneal, gastrointestinal, genitourinary)
Warfarin-induced skin necrosis (rare, often due to rapid drop in Protein C)
Purple toe syndrome (rare, cholesterol microembolization)
Hepatotoxicity (elevated liver enzymes, jaundice)
Hypersensitivity reactions (rash, urticaria, anaphylaxis)
Alopecia
Priapism
bleeding (increased risk in CYP2C9 poor/intermediate metabolizers and with certain VKORC1 variants)
Intracranial hemorrhage (risk increases dramatically with INR greater than 4, but up to two-thirds occur with therapeutic INR)
Birth defects (fetal warfarin syndrome)
Abortion
Fetal or neonatal hemorrhage
Intrauterine death
Skin necrosis
Purple toe syndrome
Fatal calciphylaxis
Calcium uremic arteriolopathy
higher risk of bleeding (with low activity CYP2C9 variants)
depressed nose (teratogenic)
eye and hand defects (teratogenic)
growth retardation (teratogenic)
Intracranial or other internal haemorrhages (potentially fatal)
Cutaneous necrosis
Fetal warfarin syndrome (hypoplasia of nose, eye socket, hand bones, growth retardation, CNS defects, fetal haemorrhage, fetal death)
Life-threatening intracranial bleeding
Skin necrosis (rare)
Fetal abnormalities (nasal hypoplasia, stippled epiphyses, CNS abnormalities)
Fetal bleeding
major hemorrhage, including intracranial hemorrhage

Pregnancy & lactation

Pregnancy

Category X (1st trimester) → D — LMWH preferred

Lactation

Warfarin is considered compatible with breastfeeding. Studies indicate minimal transfer of active warfarin into breast milk, making it safe for nursing infants. Monitor infant for signs of bleeding.