Drug Interactions between Actonel with Calcium and tacrolimus

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.

In vitro data suggest that the presence of antacids may reduce the bioavailability of tacrolimus. An in vitro study showed that tacrolimus incubated in 100 mL simulated gastric fluid with the equivalent of 500 mg of various antacids resulted in loss of tacrolimus, due presumably to a pH-mediated degradation of tacrolimus. Specifically, aluminum-magnesium hydroxide caused a 14% loss of tacrolimus in 24 hours, magnesium oxide caused a 98% loss in 12 hours, and calcium carbonate caused a 30% loss in 24 hours. In contrast, aluminum hydroxide gel caused an immediate 35% loss of tacrolimus (within 2 minutes) and no further loss for 24 hours, suggesting adsorption of tacrolimus. Whether these effects occur in vivo, and to what extent, are unknown. Sodium bicarbonate has been reported to cause widely variable trough plasma levels and reduced blood concentrations of tacrolimus when given close to the time of administration of tacrolimus. No other details were available in the report. However, in a single-dose study, administration of tacrolimus with aluminum-magnesium hydroxide in healthy volunteers resulted in a 10% and 21% increase (not decrease) in tacrolimus peak concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration without aluminum-magnesium hydroxide.