Acute alcohol intake may possibly increase serum phenytoin levels,but moderate social drinking appears to have little clinical effect. However,chronic heavy drinking reduces serum phenytoinlevels so that above-average doses of phenytoin may be needed tomaintain adequate levels.
In a study designed to test effects of acute alcohol intoxication in epileptics, 25 patients were given a 12 oz (about 340 mL) drink of alcohol 25%. Blood-alcohol levels ranged from 39 to 284 mg%. All patients had signs of alcohol intoxication without any effect on seizure frequency (See reference number 1). The metabolism of a single dose of phenytoin was not affected in one study in healthy subjects by acute ingestion of alcohol (See reference number 2). However, manufacturers say that acute alcoholic intake may increase phenytoin serum levels (See reference number 3,4).
In a group of 15 drinkers (consuming a minimum of 200 g of ethanol daily for at least 3 months) phenytoin levels measured 24 hrs after last dose of phenytoin were approximately half those of 76 non-drinkers
Another study confirmed that alcoholics without liver disease have lower than usual plasma levels of phenytoin after taking standard doses while drinking (See reference number 6). Two reports describes a chronic alcoholic who was resistant to large doses of phenytoin,(See reference number 7) and seizures,which developed in a man when an increase in his alcohol consumption appeared to cause a reduction in his serum phenytoin levels (See reference number 8).
A study in non-drinking epileptics (17 in experimental group, 14 in control group) found that serum levels of phenytoin were unchanged by moderate drinking, and there was no influence on tonic-clonic convulsions or partial complex seizures. The experimental group drank 1 to 3 glasses of an alcoholic beverage (equivalent to a glass of beer containing
9.85 g of ethanol) over a 2-hour period,twice a week, for 16 weeks, and their maximum blood alcohol levels ranged from 5 to 33 mg% (See reference number 9).
Supported by animal data,(See reference number 10) evidence suggests that repeated exposure to large amounts of alcohol induces liver microsomal enzymes so that rate of metabolism and clearance of phenytoin is increased. Conversely,acute alcohol intake may decrease hepatic metabolism (See reference number 11).
An established and clinically important interaction, although documentation is limited. Heavy drinkers may need above-average doses of phenytoin to maintain adequate serum levels. However, be aware that patients with liver impairment usually need lower doses of phenytoin, so picture may be more complicated. Moderate drinking appears to be safe in those taking phenytoin (See reference number 1,9). Consider also Alcohol + Antiepileptics interaction.
Rodin EA,Frohman CE, Gottlieb JS. Effect of acute alcohol intoxication on epileptic patients. Arch Neurol (1961) 4, 115–18.
Schmidt D. Effect of ethanol intake on phenytoin metabolism in volunteers. Experientia (1975) 31,1313–14.
Epanutin Capsules (Phenytoin sodium). Pfizer Ltd. UK Summary of product characteristics,February 2007.
Dilantin Kapseals (Phenytoin sodium). Pfizer Inc. US Prescribing information,September2006.
Kater RMH,Roggin G, Tobon F, Zieve P, Iber FL. Increased rate of clearance of drugs fromthe circulation of alcoholics. Am J Med Sci (1969) 258, 35–9.
Sandor P,Sellers EM, Dumbrell M, Khouw V. Effect of short- and long-term alcohol use onphenytoin kinetics in chronic alcoholics. Clin Pharmacol Ther (1981) 30, 390–7.
Birkett DJ,Graham GG, Chinwah PM, Wade DN, Hickie JB. Multiple drug interactions withphenytoin. Med J Aust (1977) 2, 467–8.
Bellibas SE,Tuglular I. A case of phenytoin-alcohol interaction. Therapie (1995) 50, 487–8.
Höppener RJ,Kuyer A, van der Lugt PJM. Epilepsy and alcohol: the influence of social alcohol intake on seizures and treatment in epilepsy. Epilepsia (1983) 24, 459–71.
Rubin E,Lieber CS. Hepatic microsomal enzymes in man and rat: induction and inhibitionby ethanol. Science (1968) 162, 690–1.
Tanaka E. Toxicological interactions involving psychiatric drugs and alcohol: an update. J Clin Pharm Ther (2003) 28,81–95.