Drug Interaction Report

MONITOR: Coadministration of bisphosphonates and loop diuretics may potentiate the risk of hypocalcemia. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium. These effects may be additive with those of loop diuretics, which tend to increase the urinary excretion of calcium.

MANAGEMENT: Caution is advised if bisphosphonates are coadministered with loop diuretics. Renal function as well as serum calcium levels should be monitored during and after treatment, since the effects of bisphosphonates can continue for many weeks after discontinuation. Patients and clinicians should be alert to signs and symptoms of clinical hypocalcemia such as muscle spasm, carpopedal spasm, laryngeal spasm, tetany, convulsions, mental changes (irritability, depression, psychosis), increased intracranial pressure, papilledema, QT interval prolongation, and cardiac arrhythmias.

ADJUST DOSING INTERVAL: Food, especially calcium-containing food such as dairy products, significantly decreases the bioavailability of oral etidronate.

MANAGEMENT: Oral etidronate should be administered on an empty stomach and no other food or drink should be taken within least 2 hours of administration.

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 2 hours before or 2 hours after the bisphosphonate dose.