Drug Interactions between Actonel with Calcium and elvitegravir

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.

ADJUST DOSING INTERVAL: The concomitant use of antacids or oral products containing polyvalent cations (e.g., Mg, Al, Ca, Fe, Zn) may significantly decrease the plasma concentrations of elvitegravir. According to the elvitegravir manufacturer, the mechanism of the interaction may be related to local complexation in the gastrointestinal tract and not to changes in gastric pH. When 20 mL of an antacid containing magnesium and aluminum was given 2 hours before a 50 mg dose of elvitegravir with ritonavir (100 mg pharmacokinetic booster dose) to 11 study subjects, mean elvitegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were reduced by 18%, 15%, and 10%, respectively. When the antacid was given 2 hours after elvitegravir to 10 study subjects, the mean elvitegravir Cmax, AUC, and Cmin decreased by approximately 20% each. When the antacid was given simultaneously with elvitegravir to 13 study subjects, the mean elvitegravir Cmax, AUC, and Cmin decreased by approximately 47%, 45%, and 41%, respectively. In contrast, when the antacid was given 4 hours before or 4 hours after elvitegravir, no significant differences were observed in elvitegravir pharmacokinetics compared to the administration of elvitegravir alone. The interaction has not been studied with other polyvalent cation-containing products, but they are expected to decrease elvitegravir plasma concentrations as well.

MANAGEMENT: Antacid and oral products containing polyvalent cations should be administered at least 2 hours before or 2 hours after the elvitegravir dose. Some experts recommend an interval of at least 4 hours. Alternatively, H2-receptor antagonists or proton pump inhibitors may be considered instead of antacids, with no dosage adjustment needed.