Drug Interactions between etranacogene dezaparvovec and moxifloxacin / triamcinolone

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 other hepatotoxic agents may increase the risk of liver injury and decrease the therapeutic efficacy of fidanacogene elaparvovec and etranacogene dezaparvovec, liver-directed adeno-associated virus (AAV) vectors designed to help replace missing coagulation factor IX. Increased transaminase levels, particularly those observed in the first 3 to 4 months after administration of these agents, have been attributed to immune-mediated injury of transduced hepatocytes, which may decrease its therapeutic efficacy. In a prospective, open-label, single-arm, multinational clinical study of adult male patients with moderately severe to severe hemophilia B (n=45) receiving a single dose of fidanacogene elaparvovec (5 x 10[11] vector genomes [vg]/kg), 29 patients experienced increased transaminase levels greater than or equal to 1.5 times baseline. Of these patients, 28 received treatment with corticosteroids due to increased transaminases and/or a decline in factor IX activity, with a mean initiation time to corticosteroid therapy reported at 45 days. However, no serious adverse reactions were reported. Likewise, clinical studies with etranacogene dezaparvovec have also reported asymptomatic and mostly mild elevations in transaminases. The majority of elevated ALT levels returned to baseline; however, there were cases where they remained between 48 IU/L to 193 IU/L at two years post-administration of etranacogene dezaparvovec.

MANAGEMENT: As part of monitoring post-administration of fidanacogene elaparvovec, the manufacturer generally recommends monitoring of ALT and factor IX activity levels (e.g., one to two times a week for at least 4 months). The manufacturer of etranacogene dezaparvovec advises weekly transaminase level monitoring at weekly intervals for 3 months after its administration and, in patients with elevated levels, until those enzymes return to baseline. Initiation of corticosteroid therapy and monitoring of Factor IX activity should be considered in cases where ALT levels rise above the upper limit of normal or double baseline levels. The risk of additive hepatotoxicity and decreased therapeutic efficacy of fidanacogene elaparvovec should be considered after coadministration with other hepatotoxic agents. Alternative treatment may be required if an interaction is suspected. The manufacturer of etranacogene dezaparvovec does not provide specific recommendations concerning coadministration with other hepatotoxic agents. Local protocols and/or the product labeling of the concomitant drug(s) should be consulted for additional guidance.