See Available Brands of Warfarin in India

P - Contraindicated in pregnancy
L - Caution when used during lactation
FI - Food *
LI - Lab *

Warfarin (also known under the brand names Coumadin, Jantoven, Marevan, Lawarin, and Waran) is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed. Despite its effectiveness, treatment with warfarin has several shortcomings. Many commonly used medications interact with warfarin, as do some foods, and its activity has to be monitored by frequent blood testing for the international normalized ratio (INR) to ensure an adequate yet safe dose is taken.

Warfarin is a synthetic derivative of coumarin, a chemical found naturally in many plants, notably woodruff (Galium odoratum, Rubiaceae), and at lower levels in licorice, lavender, and various other species. Warfarin and related coumarins decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme that recycles oxidized vitamin K to its reduced form after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII. For this reason, drugs in this class are also referred to as vitamin K antagonists.

Pharmacodynamics

Pharmacokinetics

Warfarin inhibits synthesis of vit K-dependent coagulation factors VII, IX, X and II and anticoagulant protein C and its cofactor protein S. No effects on established thrombus but further extension of the clot can be prevented. Secondary embolic phenomena are avoided.

Onset
24 hours.

Duration
2-5 days.

Absorption
Absorbed readily from the GI tract (oral); used as racemic isomers, S-isomers more potent. Peak plasma concentration: within first 4 hours.

Distribution
Protein binding: Extensive (99%) to albumin. Crosses placenta.

Metabolism
Hepatic; mainly by the cytochrome P450 isoenzyme CYP2C9, which shows genetic polymorphism. Other enzymes involved include CYP2C19, CYP2C8, CYP2C18, CYP1A2, and CYP3A4. S-isomer is metabolised more rapidly than R-isomer.

Excretion
Via urine (as metabolites after reabsorption from the bile); 37 hr (elimination half-life).

Warfarin Indications / Warfarin Uses

Information Not Available

Warfarin Adverse Reactions / Warfarin Side Effects

Hypersensitivity, rash, alopecia, diarrhoea, drop in haematocrit, purple toes syndrome, skin necrosis, jaundice, nausea, vomiting, hepatic dysfunction, pancreatitis, increased LFT.

Potentially Fatal: Haemorrhage (narrow therapeutic index).

Precautions

Overdosage

Symptoms: Haemorrhage. Management: Approach depends on severity of haemorrhage, the urgency to restore normal haemostasis, and whether the anticoagulant is to be maintained. Minor haemorrhage or INR < 5 will usually respond to dose reduction or withholding of one or more doses of the drug. In patients with INR < 9 with no appreciable bleeding, phytonadione (1-2.5 mg) may be admin after omitting the next dose of warfarin. For fast reversal of anticoagulation, phytonadione (not exceeding 5 mg orally) can be admin and a reduction in the INR should occur in 24 hr. If the INR remains high after 24 hr, additional phytonadione (1-2 mg orally) may be admin. In patients with INR >9 with no appreciable bleeding, withhold warfarin and admin a higher dose of phytonadione (5-10 mg orally), INR should be reduced in 24-48 hr. In patients with severe bleeding, withhold warfarin and admin phytonadione (10 mg by slow IV infusion every 12 hr as needed). As the effects of phytonadione may take several hr, fresh plasma or prothrombin complex concentrate may be admin concomitantly with phytonadione if the need arises. Phytonadione if given excessively, may make the patient unresponsive to warfarin therapy for several days or wk. It should therefore be avoided in patients with minor bleeding in whom the warfarin must be continued.

Special Precautions

Heparin induced thrombocytopenia, DVT, infectious disease, disturbances of intestinal flora, surgery or trauma, indwelling catheters, hypertension, Vit C, Vit K, protein C or S deficiency. Elderly, lactation, alcoholics. Purple toes syndrome (due to cholesterol microembolisation) may occur between 3-10 wk after start of therapy. Discontinue therapy if necrosis develops. Periodic determination of PT/INR. Patient to report any signs of bleeding, symptoms of blood clot and avoid activities or sports that can cause injuries. An INR <2 generally represents insufficient anticoagulation while INR>4 represents higher risk of bleeding.

Other Drug Interactions

Information Not Available

Other Interactions

Food Interaction

Avoid major changes in dietary intake of Vit K (green vegetables eg broccoli, spinach). Increased anticoagulant effects with chamomile, cranberry, gingko biloba, alfalfa, dong quai, black cohosh, celery, capsicum, clove, omega 3 triglycerides, fenugreek, ginger. Reduced anticoagulant effect with St John's wort, Panax ginseng, coenzyme Q10, mistletoe.

Dosage

Oral
Treatment and prevention of venous thromboembolism
Adult: Initially, 5 mg daily. Rapid anti-coagulation: Initially, 10 mg daily for 2 days. Adjust subsequent doses based on PT/INR. Usual maintenance dose: 2-10 mg daily.
Elderly: Lower initial dose.
Renal impairment: Severe: Avoid.
Hepatic impairment: Severe: Avoid.

Intravenous
Treatment and prevention of venous thromboembolism
Adult: Given as slow bolus Inj over 1-2 min into peripheral vein. Initially, 5 mg daily. Rapid anti-coagulation: Initially, 10 mg daily for 2 days. Adjust subsequent doses based on PT/INR. Usual maintenance dose: 2-10 mg daily.
Elderly: Lower initial dose.
Renal impairment: Severe: Avoid.
Hepatic impairment: Severe: Avoid.

Food(before/after)

May be taken with or without food

List of Contraindications

Warfarin and Pregnancy

Contraindicated in pregnancy.

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Warfarin and Lactation

Caution when used during lactation

Warfarin and Children

Information Not available

Warfarin and Geriatic

Information Not available

Warfarin and Other Contraindications

Hypersensitivity; haemorrhagic tendencies or blood dyscrasia; recent surgery; peptic ulcer; severe hypertension; bacterial endocarditis; cerebrovascular disorders; psychosis; senility; aneurysms; pericarditis; pericardial effusion; eclampsia; pre-eclampsia; threatened abortion; alcoholism; severe renal and hepatic impairment; pregnancy.

Storage

Intravenous
Store at 15-30°C (59-80°F). Protect from light.

Oral
Store at 15-30°C (59-80°F). Protect from light.

Lab interference

May cause false decrease in serum theophylline concentrations with the Schack and Waxler ultraviolet method.