A number of early studies showed that effects of coumarinoral anticoagulants are unlikely to be changed in those with normal liver function who drink small or moderate amounts of alcoholic beverages such as wine or spirits
The daily consumption of 1 pint (about 560 mL) of Californian white table wine for a 3-week period at meal times by 8 healthy subjects anticoagulated with warfarin, was found to have no significant effects on either serum warfarin levels or anticoagulant response (See reference number 1).
Other studies in both patients(See reference number 2,3)and healthy subjects(See reference number 4,5) taking either warfarin(See reference number 2,3,5) or phenprocoumon(See reference number 4) have very clearly confirmed absence of an interaction with wine(See reference number 3,5) gin,(See reference number 4) or 40 % alcohol (See reference number 2). In one of these studies subjects were given almost 600 mL of a table wine (12% alcohol) or 300 mL of a fortified wine (20% alcohol) without adverse effects on coagulation (See reference number 5)
In contrast to above studies, a 58-year-old man stabilised on warfarin experienced a sharp rise in his INR to 8 when he started to drink half a can of light beer (5.35 g alcohol) every other day. In previous 5 months he had an INR in range of 1.9 to 2.5 with a stable warfarin dose, and no other explanation for change in INR was found. He stopped taking alcohol, and was eventually restabilised on original dose of warfarin (See reference number 6).
In one study,15 alcoholics who had been drinking heavily (250 g ethanol or more daily) for at least 3 months and 11 control subjects (minimal social drinkers or non-drinkers) were given a single 40mg dose of warfarin. The half-life of warfarin was lower in alcoholics (26.5 versus
41.1 hours), but a comparison of prothrombin times with those of healthy subjects found no differences (See reference number 7).
One patient with liver cirrhosis had marked fluctuations in prothrombin times and warfarin levels associated with weekend binge drinking of vodka (See reference number 2). Another patient with abnormal liver function had a fall in plasma warfarin levels and effect when he stopped drinking 50 mL of whiskey daily. When rechallenged with alcohol,warfarin levels and effect rose, and he had a nosebleed (See reference number 8). In contrast,a large retrospective cohort study did not find a significantly increased risk of serious bleeding in 140 patients with a history of alcoholic binge drinking who were taking warfarin. The relative risk was 1.3 (0.8 to 1.9) compared with patients who had no record of alcohol abuse (See reference number 9).
It seems probable that, as in rats,(See reference number 10)continuous heavy drinking stimulates hepatic enzymes concerned with metabolism of warfarin, leading to its more rapid elimination (See reference number 7,11). As a result half-life shortens. The fluctuations in prothrombin times in those with liver impairment(See reference number 2,8) may possibly occur because sudden large amounts of alcohol exacerbate general dysfunction of liver and this affects way it metabolises warfarin. Alcohol may also change ability of liver to synthesise clotting factors (See reference number 12). Constituents of beer other than alcohol may affect warfarin metabolism (See reference number 6).
The absence of an interaction between warfarin or phenprocoumon and alcohol in those free from liver disease is well documented and well established. It appears to be quite safe for patients taking oral anticoagulants to drink small or moderate amounts of wine or spirits. Even much less conservative amounts (up to 8 oz/250 mL of spirits(See reference number 4) or a pint of wine(See reference number 1)) do not create problems with anticoagulant control, so that there appears to be a good margin of safety even for less than abstemious. Only warfarin and phenprocoumon have been investigated but other coumarin anticoagulants would be expected to behave similarly. The single case of increased INR in a patient who started to drink beer is unexplained. Further study specifically with beer is needed to throw light on this possible interaction.
On other hand, those who drink heavily may possibly need above-average doses of anticoagulant, while limited evidence suggests that those with liver damage who binge drink may experience marked fluctuations in their prothrombin times. It might be prudent to avoid anticoagulation in this type of patient unless they can abstain from drinking. Nevertheless,although one cohort study in patients taking warfarin found a slight trend towards serious bleeding events in patients with a history of binge drinking, this was not significant, and other risk factors were more important (highly variable prothrombin time ratio, or prothrombin time ratio greater than 2) (See reference number 9).
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