Drug Interactions between Acid Controller Complete Dual Action 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: 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.

MONITOR: Coadministration with vadadustat, an organic anion transporter 3 (OAT3) inhibitor, may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of OAT3. A drug interaction study evaluating the effect of repeat doses of vadadustat (600 mg once daily) on the pharmacokinetics of furosemide, an OAT1/OAT3 substrate, showed a 2-fold increase in furosemide systemic exposure (AUC).

MANAGEMENT: Caution is advised if vadadustat is used in combination with organic anion transporter 3 (OAT3) substrates. Monitoring for signs and symptoms of increased exposure to the OAT3 substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of an OAT3 inhibitor.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.