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.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.