Smoking and warfarin disposition

Abstract

Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.

A review of smoking cessation: potentially risky effects on prescribed medications

“…An early prospective study and case reports documented the effects of smoking cessation on warfarin requirements. Although Bachmann et al (1979) reported that smoking cessation did not affect prothrombin time in healthy smokers given a subtherapeutic dose of warfarin, this study did report a 13% increase in average study-state warfarin level and a 13% decrease in warfarin clearance rate when smokers stopped smoking. However, Colucci and Knapp (2001) and Evans and Lewis (2005) reported INR prolongation and need to reduce warfarin dose 14-23% in individuals who stopped smoking after previously achieving a stable warfarin dose.…”

Increase in International Normalized Ratio After Smoking Cessation in a Patient Receiving Warfarin

“…A prospective study, however, involving nine cigarette smokers who took warfarin at an average daily dose of 0.032 mg/kg for 2 weeks while smoking and then for an additional 2 weeks after a month of abstaining from smoking noted some effect on metabolism. 6 Prothrombin time was not affected, but warfarin concentration increased 13%, clearance decreased by 13%, halflife went up 23%, and volume of distribution increased by 11%. Because these studies remain some of the only investigations of cigarette smoking and warfarin, drawing definite conclusions about interaction or effects is difficult.…”

Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism

“…Polycyclic aromatic hydrocarbons produced by the incomplete combustion of cigarette smoke may induce the activities of hepatic microsomal enzymes, including cytochrome 1A1 (CYP1A1), cytochrome 1A2 (CYP1A2) and cytochrome 2E1 (CYP2E1), which increases the clearance rate of warfarin and mitigates its anticoagulant effects (35,36). To date, the effect of smoking on the first TTA time remains uncertain.…”