Warfarin

Indications
 Oral
Treatment and prophylaxis 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 prophylaxis 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.
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.
Warnings / 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.
Adverse Reactions
 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).
Overdose Reactions
 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.
Drug Interactions
 Potentially Fatal: Acute alcoholism, allopurinol, NSAIDs, anabolic steroids, amiodarone, propafenone, quinidine, chloramphenicol, ciprofloxacin, co-trimoxazole, erythromycin, metronidazole, ofloxacin, sulfonamides, azithromycin, clarithromycin, norfloxacin, tetracyclines, SSRI, fluconazole, itraconazole, miconazole, ketoconazole, proguanil, cisapride, ifosfamide, disulfiram, piracetam, zafirlukast, interferon-α, isoniazid, tramadol, glucagon, doxycycline, propylthiouracil, danazol, flutamide, tamoxifen, clofibrate, simvastatin, cimetidine, sulfinpyrazone enhance anticoagulant effect of warfarin. Drugs eg, rifampicin, carbamazepine, phenobarbital, barbiturates, bosentan, nafcillin, azathioprine, menthol, primidone, griseofulvin and aminoglutethimide, oral contraceptives containing oestrogens, corticosteroids, sucralfate, vit K as well as chronic alcoholism reduce anticoagulant effect. Cholestyramine may reduce anticoagulant effect, avoid admin of warfarin 1 hr before or 4-6 hr after cholestyramine.
See Below for More warfarin Drug Interactions
Lab Interactions
 May cause false decrease in serum theophylline concentrations with the Schack and Waxler ultraviolet method.
Food Interactions
 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.
Mechanism of Actions
 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 hr
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 hr.
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).
Administration
 May be taken with or without food.
Storage Conditions
 Intravenous: Store at 15-30°C (59-80°F). Protect from light. Oral: Store at 15-30°C (59-80°F). Protect from light.
ATC Classification
 B01AA03 - warfarin ; Belongs to the class of vitamin K antagonists. Used in the treatment of thrombosis.
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.
Available As
  • Warfarin 1 mg
  • Warfarin 10 iu
  • Warfarin 2 mg
  • Warfarin 3 mg
  • Warfarin 5 mg

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