The observation that dependent oedema in a group of epileptics was higher than expected, and that response to diuretic treatment seemed to be reduced, prompted further study. In 30 patients taking phenytoin 200 to 400mg daily with phenobarbital 60 to 180mg daily maximal diuresis in response to furosemide 20 or 40mg occurred after 3 to 4 hrs instead of usual 2 hours, and total diuresis was reduced by 32 % for 20mg dose and 49 % for 40mg dose. When intravenous furosemide 20mg was given, total diuresis was reduced by 50%. Some of patients were also taking carbamazepine, pheneturide, ethosuximide, diazepam or chlordiazepoxide (See reference number 1).
Another study in 5 healthy subjects given phenytoin 100mg three times daily for 10 days found that maximum serum levels of furosemide 20 mg, given orally or intravenously, were reduced by 50 % (See reference number 2).
Not fully understood. One suggestion is that phenytoin causes changes in jejunal sodium pump activity, which reduces absorption of furosemide,(See reference number 2)but this is not whole story because an interaction also occurs when furosemide is given intravenously (See reference number 1). Another suggestion, based on in vitro evidence, is that phenytoin generates a liquid membrane, which blocks transport of furosemide to its active site (See reference number 3).
Information is limited but interaction is established. A reduced diuretic response should be expected in presence of phenytoin
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