Drug Interactions between moxifloxacin / triamcinolone and vadadustat

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4, CYP450 2C8 and CYP450 2C9 isoenzymes as well as substrates of the organic anion transporter 3 (OAT3). Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro and an inhibitor of CYP450 2C9 and OAT3 in vivo. A drug interaction study evaluating the effect of vadadustat (600 mg) on the pharmacokinetics of celecoxib, a CYP450 2C9 substrate, showed an increase in peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 11%, respectively. In another drug interaction study evaluating the effect of repeat doses of vadadustat (600 mg once daily) on the pharmacokinetics of furosemide, an OAT1/OAT3 substrate, a 2-fold increase in furosemide systemic exposure (AUC) was observed. However, clinical data are not available for vadadustat with CYP450 3A4 or CYP450 2C8 substrates.

MONITOR: Coadministration of vadadustat 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 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 coadministered with drugs that are substrates of CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 and that also carry a known risk of gastrointestinal erosion including certain NSAIDs (e.g., naproxen, ibuprofen, diclofenac), corticosteroids (e.g., methylprednisolone, prednisolone, prednisone), and certain chemotherapeutic agents (e.g., kinase inhibitors, paclitaxel, docetaxel). 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. Monitoring for other signs and symptoms of increased exposure to the affected 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 a CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 inhibitor.