Warfarin dosage

Unknown Not specified Warfarin, dosage regimen not specified None None provided Inhibition of platelet aggregation... 

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased INR without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient s goal INR (91). 

Treatment with warfarin should be initiated with standard doses of 5-10 mg rather than the large loading doses formerly used. The initial adjustment of the prothrombin time takes about 1 week, which usually results in a maintenance dose of 5-7 mg/d. The prothrombin time should be increased to a level representing a reduction of prothrombin activity to 25% of normal and maintained there for long-term therapy. When the activity is less than 20%, the warfarin dosage should be reduced or omitted until the activity rises above 20%. 

Advise Mrs RP of the interaction and the need to more carefully monitor her clotting and adjust her warfarin dosage. Mrs RP should be advised of the signs of enhanced warfarin effect (e.g. bleeding from gums, cuts, unexplained bruising etc.). 

Azathioprine or mercaptopurine have been sometimes involved in reduced warfarin and acenocoumarol activity, and increased warfarin dosages may be necessary (103). Similar findings were found in a patient taking maintenance phenprocoumon (SEDA-21, 382). 

Weiner B, Faraci PA, Fayad R, Swanson L. Warfarin dosage following prosthetic valve replacement effect of smoking history. Drug Intell Clin Pharm 1984 18(ll) 904-6. 

D. Hold patient s warfarin dosage and recheck INR tomorrow. 

Engelsen J, Nielsen JD, Winthere K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomized, double-blind, placebo-crossover trial. Thromb Haemost 2002 87 1075-1076. 

Wen MS, Lee M, Chen JJ, et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORCl genotypes. Clin Pharmacol Ther 2008 84(l) 83-9. 

It has been demonstrated that 25% of dose variability could be explained by the patient s VKORCl SNP haplotype, which shows a strong correlation with their warfarin dosage requirement (low-, intermediate-, and high-dose)... 

In a double-blind, placebo-controlled study in 28 healthy subjects who were stabilised on warfarin, repaglinide did not alter the anticoagulant effects of warfarin or the steady-state warfarin pharmacokinetics. Therefore, no warfarin dosage adjustment would be anticipated on concurrent use. 

Davis DA, Fugate SE, Increasing warfarin dosage reductions associated widi concurrent warfarin and repeated cycles of 5-fluorouracil therapy. Pharmaco erapy (2005) 25, 442-7. 

Information appears to be limited to the reports cited here but the interaction would seem to be established and clinically important. Monitor the INR closely. A reduced warfarin dosage (the study cited above suggests a 30 to 60% reduction) is likely to be needed if both drugs are used concurrently to avoid excessive anticoagulation and possible bleeding. Note that bucolome is sometimes used with warfarin to enhance its therapeutic effect. Based on the mechanism of action, acenocoumarol and phenpro-coumon would be anticipated to be similarly affected. 

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