Drug Interaction Report

Coadministration with aluminum- or magnesium-containing antacids may decrease the serum concentrations of orally administered phenothiazines. The proposed mechanism is antacid adsorption resulting in reduced phenothiazine bioavailability. The interaction has been reported for chlorpromazine but may occur with other phenothiazines. In a study of ten patients treated with chlorpromazine, 30 mL of an antacid containing aluminum and magnesium hydroxide reduced the urinary excretion of chlorpromazine by 10% to 45%. In another study with six psychiatric patients, coadministration of chlorpromazine oral suspension with 30 mL of an antacid containing aluminum hydroxide and magnesium trisilicate resulted in a 20% reduction in serum chlorpromazine level two hours later. The clinical significance is unknown. Psychiatric relapse occurred in a chlorpromazine-treated patient following the addition of antacid therapy according to a single case report. Separating the times of administration by 2 to 3 hours may help if an interaction is suspected.

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.