Drug Interactions between Colestid and E.E.S. Granules

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K. By binding bile acids, these agents may interfere with normal fat digestion and absorption, thereby preventing the absorption of fat-soluble vitamins. When 8 grams of cholestyramine was administered simultaneously with a normal meal containing 250,000 units of vitamin A acetate in four healthy young adult subjects, plasma vitamin A levels were significantly reduced during a 9-hour postprandial period compared to the values obtained with the control meal. Coadministration with 4 grams of cholestyramine had no significant effect. In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h/mL vs 318 pg*h/mL and Cmax 40.1 pg/mL vs 49.7 pg/mL, respectively). Chronic use of bile acid sequestrants has been rarely associated with an increased bleeding tendency due to hypoprothrombinemia resulting from vitamin K deficiency. Isolated cases of Vitamin A (including one case of night blindness) and D deficiencies have also been reported with chronic cholestyramine therapy.

MANAGEMENT: When bile acid sequestrants are given for prolonged periods, some manufacturers recommend that concomitant supplementation with water-miscible or parenteral forms of fat-soluble vitamins be considered. If oral vitamin supplements are used with cholestyramine or colestipol, advise patients to take them at least 1 hour before or 4 to 6 hours after the bile acid sequestrant to minimize the potential impact on their absorption. No recommendations are available for sevelamer, but it may be advisable to follow the same precautions.

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.