Drug Interactions between Cuprimine and PCE Dispertab

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: Food may interfere with the gastrointestinal absorption of penicillamine. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a standard breakfast reduced the mean peak plasma concentrations of penicillamine by 48% compared to administration in the fasting state.

MANAGEMENT: Penicillamine should be administered on an empty stomach, at least one hour before or two hours after meals, and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation by metal binding in the gastrointestinal tract.

ADJUST DOSING INTERVAL: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

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.