Veoza Drug Interactions

Effect of other medicinal products on fezolinetant: CYP1A2 inhibitors: Fezolinetant is primarily metabolised by CYP1A2 and to a lesser extent by CYP2C9 and CYP2C19. Concomitant use of fezolinetant with medicinal products that are moderate or strong inhibitors of CYP1A2 (e.g., ethinyl oestradiol containing contraceptives, mexiletine, enoxacin, fluvoxamine) increase the plasma C_max and AUC of fezolinetant.
Concomitant use of moderate or strong CYP1A2 inhibitors with Veoza is contraindicated (see Contraindications).
Co-administration with fluvoxamine, a strong CYP1A2 inhibitor, resulted in an overall 1.8-fold increase in fezolinetant C_max and 9.4-fold increase in AUC; no change in t_max was observed. Given the large effect of a strong CYP1A2 inhibitor and supportive modelling, the increase in fezolinetant concentrations is expected to be of clinical concern also following concomitant use with moderate CYP1A2 inhibitors (see Contraindications). The increase in fezolinetant exposure was however not predicted to be clinically relevant following concomitant use with weak CYP1A2 inhibitors.
CYP1A2 inducers: In vivo data: Smoking (moderate inducer of CYP1A2) decreased fezolinetant C_max to a geometric LS mean ratio of 71.74%, while AUC decreased to a geometric LS mean ratio of 48.29%. No significant difference in efficacy was observed between smokers and non-smokers. No dose modification is recommended for smokers.
Transporters: In vitro data: Fezolinetant is not a substrate of P-glycoprotein (P-gp). Major metabolite ES259564 is a substrate of P-gp.
Effect of fezolinetant on other medicinal products: Cytochrome P450 (CYP) enzymes: In vitro data: Fezolinetant and ES259564 are not inhibitors of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Fezolinetant and ES259564 are not inducers of CYP1A2, CYP2B6, and CYP3A4.
Transporters: In vitro data: Fezolinetant and ES259564 are not inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OCT2, MATE1, and MATE2-K (IC₅₀ > 70 μmol/l). Fezolinetant inhibited OAT1 and OAT3 with IC₅₀ values of 18.9 μmol/l (30 x C_max,u) and 27.5 μmol/l (44 x C_max,u), respectively. ES259564 does not inhibit OAT1 and OAT3 (IC₅₀ > 70 μmol/l).