Frågedatum: 1993-05-11
RELIS database 1993; id.nr. 9500, DRUGLINE
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A 21-year-old male patient who needs life-long anticoagulant treatment had been treated with warfar



Fråga: A 21-year-old male patient who needs life-long anticoagulant treatment had been treated with warfarin (Waran) starting with seven tablets (17.5 mg) per day, with decreasing doses over a seven day period, during which the PK value remained at about 20. Then without any reason the PK value increased to 47 overnight. The patient was not taking any other drugs except Nicorette (nicotine chewing gum) (amount unknown).

Is there any information concerning an interaction between warfarin and Nicorette?

Sammanfattning: No information has been found concerning an interaction between nicotine and warfarin. The liver enzyme induction effect of cigarette smoking is not believed to be due to nicotine but to other components of smoke, such as polycyclic hydrocarbons. A retrospective study has shown that smoking history did not affect warfarin dose requirement.

Svar: A thorough literature search has found one study which aimed at testing the relationship between smoking history and warfarin daily maintenance dose (DMD) in patients undergoing cardiac valve replacement. This retrospective study included 117 nonsmokers, 23 light smokers and 34 heavy smokers. As a whole, 33 per cent of patients required a low DMD of warfarin (less than or equal to 2.5 mg), 43 per cent required a moderate DMD (2.5-7.5 mg), and 24 per cent required a high DMD (more than 7.5 mg). Each of the subgroups followed a similar pattern. There was no statistically significant difference between smokers and nonsmokers in regard to warfarin DMD (1).

There is no documentation on the interaction between warfarin and nicotine. Due to induction of liver enzymes cigarette smoking reduces the bioavailability and increases clearance rates of many drugs. However, this effect is not thought to be due to nicotine but to other components of tobacco smoke, particularly polycyclic hydrocarbons (2).

Warfarin is metabolized by CYPIIC9, a cytochrome P450 enzyme. Nicotine is also metabolized partly through P450 enzymes (3). However, there is no documentation of any metabolic interaction between the two drugs. Contact with the drug manufacturer did not add any more information (4).

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