Drug Interactions between amoxicillin / clarithromycin / omeprazole and remdesivir

MONITOR: Concomitant use of remdesivir with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Data from investigational use and clinical studies suggest that remdesivir may be associated with transaminase elevations. Transient treatment-emergent Grade 1 or Grade 2 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed during multiple-dose Phase 1 studies in healthy volunteers. The mechanism of potential hepatotoxicity is unknown and the contribution of remdesivir is difficult to determine, as transaminase elevations have also been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir.

MANAGEMENT: Caution and increased monitoring may be required if remdesivir is given concurrently with other agents associated with liver injury. Hepatic function should be evaluated prior to starting remdesivir and during treatment as clinically appropriate. The manufacturer of remdesivir recommends considering discontinuation of remdesivir if ALT levels increase to greater than 10 times the upper limit of normal. Additionally, the manufacturer recommends discontinuing remdesivir if ALT elevation is accompanied by signs or symptoms of liver inflammation. The labeling of the other agent(s) involved should also be consulted as they may contain dose adjustment or discontinuation recommendations for those agent(s) in the event of hepatotoxicity.

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.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.