Drug Interactions between Actonel with Calcium and vadadustat

ADJUST DOSING INTERVAL: Coadministration of vadadustat with oral products containing multivalent cations such as calcium, magnesium, or aluminum may significantly decrease the bioavailability of vadadustat. The mechanism of this interaction has not been fully described but may involve the formation of an insoluble complex or chelate with multivalent cations that is poorly absorbed from the gastrointestinal tract. According to product labeling, when non-iron-containing phosphate binders were coadministered-administered with vadadustat, the systemic exposure (AUC) and peak plasma concentration (Cmax) decreased by 55% and 52%, respectively.

MANAGEMENT: Vadadustat should be administered at least one hour before, or two hours after the administration of oral non-iron-containing phosphate binders or other medicinal products whose primary component consists of multivalent cations such as calcium, magnesium, or aluminum.

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.

MONITOR: Coadministration of hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitors, such as vadadustat or daprodustat, with drugs that are known to increase the risk of gastrointestinal erosion may increase the risk of gastric or esophageal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, were reported during vadadustat and daprodustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat or daprodustat are coadministered with drugs that have a known risk of gastrointestinal erosion, including but not limited to NSAIDs, corticosteroids, oral bisphosphonates, oral potassium formulations, anticoagulants as well as certain chemotherapeutic agents (e.g., kinase inhibitors) and antibiotics. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.