Drug Interaction Report

MONITOR: Coadministration of remdesivir with nephrotoxic agents may increase the plasma concentrations of its metabolites, GS-704277 and GS-441524, as well as the excipient, sulfobutylether-beta-cyclodextrin sodium (SBECD). Both GS-441524 and SBECD are primarily eliminated by the kidneys, thus renal impairment secondary to the use of nephrotoxic agents may reduce their clearance and increase the risk of accumulation. Exposures of GS-441524, GS-704277, and SBECD were up to 7.9-, 2.8-, and 21-fold higher, respectively, in adults with renal impairment compared to adults with normal renal function. However, these changes are not generally considered to be clinically significant. Safety data in pediatric patients with renal impairment is limited. Clinical data evaluating the use of remdesivir concurrently with another agent that causes nephrotoxicity are not available.

MANAGEMENT: Caution and additional monitoring may be advisable if remdesivir is used in patients who have recently received or are currently using potentially nephrotoxic agents. Some authorities recommend avoiding the concomitant use of remdesivir with drugs that can reduce renal function; as well as monitoring renal function prior to starting remdesivir and as clinically appropriate during treatment.

Concurrent ingestion of calcium-fortified foods (i.e., cereal, orange juice) may alter the bioavailability of gatifloxacin. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. Data have been conflicting: One study has reported no effect with milk coadministration. Another study reported a modest decrease in gatifloxacin bioavailability (13.5% decrease in Cmax,12% decrease in AUC, 15% increase in total clearance) when taken with 12 ounces of calcium-fortified orange juice instead of water, which could be clinically significant if the infecting organisms have borderline susceptibilities. The manufacturer states that gatifloxacin may be taken without regard to food, milk, or calcium. Clinicians should be aware of the possibility of an interaction if subtherapeutic effects are observed.