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A marked increase in the effects of warfarin with bleeding has been seen in a small number of patients when concurrently treated with erythromycin, but most patients are unlikely to develop a clinically important interaction. This interaction has also been seen in a patient on nicoumalone (acenocoumarol).
A case report describes an elderly woman on warfarin, digoxin, hydrochlorothiazide and qumidine who developed haematuna and bruising within a week of starting to take 2 g erythromycin stearate daily.
Seven other cases of bleeding and/or hypoprothrombinaerrua have been described2 8in patients on warfarin when given erythromycin (as ethylsuccinate, stearate, estolate, lacto-bionate or base). A study in 12 normal subjects showed that the clearance of a single dose of warfarin was reduced by an average of 14% (range zero to almost one third) after taking 1 g erythromycin daily for eight days. In another study on eight patients erythromycin caused only a small increase in the effects of warfarin.
Haemorrhage occurred in a patient on nicoumalone when treated with erythromycin.
It is believed that erythromycin can stimulate the liver enzymes to produce metabolites which bind to cytochrome P450 to form inactive complexes, the result being that the metabolism of warfarin is reduced and its effects are thereby increased. But why it only happens in a few individuals is not clear.
An established interaction, but unpredictable. The incidence is uncertain but the paucity of reports suggests that it is low. The effect in a few patients is evidently considerable but in most it is likely to be small and unimportant. Concurrent use need not be avoided but it would be prudent to monitor the effects, especially m those who clear warfarin slowly and who therefore only need low doses. The elderly in particular would seem to fall into this higher risk category Information about anticoagulants other than warfarin and nicoumalone seems not to be available but the same precautions would be advisable.
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