Drug Interactions between Actonel with Calcium and divalproex sodium

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 30 minutes after the bisphosphonate dose.

Limited data suggest that concurrent administration of antacids may increase the bioavailability of valproic acid. The mechanism of interaction is unknown. In seven healthy volunteers, coadministration of a single 500 mg dose of valproic acid one hour after breakfast and an antacid containing aluminum-magnesium hydroxide (dose equal to 160 mEq of neutralizing capacity) one and three hours after meals and at bedtime on the same day resulted in a mean 12% increase (range 3% to 28%) in the total area under the concentration-time curve (AUC) of valproic acid compared to administration alone. These changes are unlikely to be of clinical importance, and no special precautions appear to be necessary. Equivalent doses of antacids containing either aluminum hydroxide-magnesium trisilicate or calcium carbonate also increased the AUC of valproic acid, but the differences were not statistically significant.