Drug Interactions between E.E.S. Granules and fidanacogene elaparvovec

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

GENERALLY AVOID: Coadministration with other hepatotoxic agents such as alcohol may increase the risk of liver injury and decrease the therapeutic efficacy of liver-directed adeno-associated virus (AAV) vector fidanacogene elaparvovec, designed to help replace missing and coagulation factor IX. Increased transaminase levels from AAV therapy have been attributed to immune-mediated injury of transduced hepatocytes, which may decrease their therapeutic efficacy. In addition, alcohol may impact liver enzyme elevation as well as reduce the activity of coagulation factor IX. 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), increased transaminase levels greater than or equal to 1.5 times baseline were reported in 29 patients. 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.

MANAGEMENT: According to the manufacturer, for the first year after administration of fidanacogene elaparvovec, alcohol consumption should be limited.

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.