Drug Interaction Report

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 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.

MONITOR: The risk of seizures induced by the use of bowel cleansing preparations may be increased in patients on concomitant medications that can lower the seizure threshold such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), systemic steroids, carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. Rare cases of generalized tonic-clonic seizures and/or loss of consciousness in association with low serum osmolality and electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia) have been reported with the use of bowel cleansing products in patients with no prior history of seizures. The condition resolved with correction of fluid and electrolyte abnormalities.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with agents that can lower the seizure threshold. Bowel cleansing preparations should not be used if these patients have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. Baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be considered, particularly in the elderly. Patients should be advised not to exceed the recommended dosage of their bowel cleansing preparation and to drink sufficient quantities of clear fluids before, during, and after the bowel preparation process. Administration of an electrolyte rehydration solution may help attenuate the electrolyte abnormalities and hypovolemia.

ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

MONITOR: Smoking and alcohol consumption during therapy with vadadustat may increase the risk of gastrointestinal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during vadadustat 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 is prescribed to current tobacco smokers or alcohol drinkers. 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.