Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions
Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulphate is not recommended.

Pharmacokinetic interactions

Effects of other medicinal products on remdesivir
In vitro, remdesivir is a substrate for esterases in plasma and tissue, drug metabolizing enzyme CYP3A4 and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OATP1B1) and P-glycoprotein (P-gp) transporters. GS-704277 (a metabolite of remdesivir) is a substrate for OATP1B1 and OATP1B3.

A drug-drug interaction study was conducted with remdesivir. Table 5 summarises the pharmacokinetic effects of studied drugs on remdesivir and metabolites GS-704277 and GS-441524.


Table 5:       Effect of other drugs on remdesivir and metabolites GS-704277 and GS-441524 Co-administered Drug                               Interaction                            Recommendation Dose (mg)                              Geometric mean change (%)                      concerning co- administration remdesivir:   Cmax         ↑49%
Cyclosporin                          AUCinf       ↑89%                          No dose adjustment of 400 single dose         GS-704277: maxC            ↑151%                         remdesivir is required
AUCinf       ↑197%                         when it is co-administered GS-441524: Cmax            ↑17%                          with inhibitors of AUCinf                                     OATP1B1 and OATP1B3.
No interactions are expected when co-administering remdesivir with inhibitors of OATP1B1/1B3 and/or P-gp.
 remdesivir:   Cmax          13%
Carbamazepine                         AUCinf        8%                           No dose adjustment of 300 twice daily         GS-704277: Cmax                                          remdesivir is required AUCinf                                     when it is co-administered GS-441524: Cmax                                          with strong CYP3A4 AUCinf        17%                          and/or P-gp inducers.
No interactions are expected when co-administering remdesivir with strong CYP3A4 inducers or CYP3A4 inhibitors.

NOTE: Interaction study conducted in healthy volunteers.

Effects of remdesivir on other medicinal products
In vitro, remdesivir is an inhibitor of CYP3A4, UGT1A1, MATE1, OAT3, OCT1, OATP1B1 and OATP1B3.
Until respective clinical data become available, the coadministration of sensitive substrates of these enzymes and/or transporters should be considered with caution. Remdesivir induced CYP1A2 and potentially CYP3A in vitro. Co-administration of remdesivir with CYP1A2 or CYP3A4 substrates with narrow therapeutic index may lead to loss of their efficacy.

Dexamethasone is a substrate of CYP3A4 and although remdesivir inhibits CYP3A4, due to remdesivir's rapid clearance after IV administration, remdesivir is unlikely to have a significant effect on dexamethasone exposure.