Warfarin

Mechanism :

Warfarin acts by inhibiting the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S.

Indication :

Thromboembolic disease prophylaxis (Anticoagulant)

Contraindications :

Contraindicated in bleeding tendencies associated with active ulceration or overt bleeding of: Gastrointestinal, genitourinary or respiratory tracts; Cerebrovascular hemorrhage;

Aneurysms-cerebral, dissecting aorta; Pericarditis and pericardial effusions;

Bacterial endocarditis, threatened abortion, eclampsia and preeclampsia and severe hypertension.

It is avoided in pregnant mothers, as it is teratogenic in nature.

Dosing :

Birth to 1 month:

There is very little experience of the use of warfarin in the neonatal period.

Children: 0.1 mg/kg PO 24 hourly for 2 days (Maximum dose: 10 mg). Maintenance Dose: 0.05-0.35 mg/kg/day in 4 divided doses. Its action starts after a few days. Target INR is usually 2-3.5. Dosage should be titrated according to the INR. If INR = 1.1-1.4, increase dose by 20% of previous dose, If INR = 1.5-1.9, increase dose by 10% of previous dose, If INR = 2-3 then do not change the dose. If INR = 3.1-3.5 then decrease dose by 10% of initial dose; If INR is >3.5 then hold the drug until INR <3.5 then restart at 20% less than the previous dose.

Adverse Effect :

Commonly reported adverse effects are hemorrhage, hypersensitivity, rash, alopecia, diarrhea, skin necrosis, jaundice and hepatic dysfunction.

Interaction :

Warfarin: Monitor INR whenever a drug is added to or withdrawn from a patient therapeutic regimen.
Aspirin, NSAIDS, Dipyridamole, Clopidogrel, Anti-Arrhythmics (Amiodarone, Propafenone, Quinidine). Antibiotics (Chloramphenicol, Ciprofloxacin, Cotrimoxazole, Erythromycin, Metronidazole, Ofloxacin and Sulphonamides), possible other Antibiotics (Aztreonam, Clarithromycin and some other Macrolides, Nalidixic Acid, Neomycin, Norfloxacin, Tetracyclines, Trimethoprim), SSRIs, Antifungals (Fluconazole, Itraconazole, Ketoconazole, Miconazole), Proguanil, Sodium Valproate, Ifosfamide, Clofibrates, Simvastatin, Levothyroxine (Thyroxine), Cimetidine, Omeprazole, Paracetamol, Dextropropoxyphene: Enhanced effect.
Rifampicin, Griseofulvin, Barbiturates, Primidone and Carbamazepine: Reduce effect.
Phenytoin and Cholestyramine: Enhanced or reduced effect.

Renal Dose :

Dose in Renal Impairment GFR (mL/min)

20-50	Dose as in normal renal function
10-20	Dose as in normal renal function
<10	Dose as in normal renal function

Dose in Patients undergoing Renal Replacement Therapies

CAPD	Not dialysed. Dose as in normal renal function
HD	Not dialysed. Dose as in normal renal function
HDF/High flux	Unknown dialysability. Dose as in normal renal function
CAV/VVHD	Not dialysed. Dose as in normal renal function

Hepatic Dose :

Use cautiously. Dose reduction may be needed as response to anticoagulants will be enhanced in hepatic impairment. Monitor INR frequently.