Potential for Other Medicinal Products to Affect Lemborexant
Weak, Moderate and Strong CYP3A Inhibitors
Metabolism by CYP3A is the major elimination pathway of lemborexant. Co-administration of lemborexant with moderate CYP3A inhibitors (e.g., fluconazole) or strong CYP3A inhibitors (e.g., itraconazole) increased the exposure (AUC) of lemborexant by approximately 4-fold and Cmax by 1.6-fold. Other moderate and strong inhibitors of CYP3A would be expected to have similar effects on plasma levels of lemborexant. Using a physiologically based pharmacokinetic (PBPK) model, a weak effect is predicted when weak CYP3A inhibitors (e.g., fluoxetine) are co-administered with lemborexant. Avoid concomitant use of lemborexant 5 or 10 mg with moderate or strong CYP3A inhibitors. The maximum recommended dose of lemborexant is 5 mg when co-administered with weak CYP3A inhibitors.
Moderate and Strong CYP3A Inducers
Avoid co-administration of lemborexant with moderate or strong CYP3A inducers. Co-administration with a strong CYP3A inducer resulted in a 97% reduction in lemborexant systemic exposure. This may result in a decrease in efficacy.
In Vitro Studies with Transporters
Lemborexant is a poor substrate of P-gp, but its major metabolite (M10) is a substrate of P gp.
Lemborexant and M10 are not substrates of BCRP, OATP1B1, or OATP1B3.
Lemborexant Cmax and AUC increased by 35% and 70%, respectively, when co-administered with
alcohol. Lemborexant did not affect alcohol concentrations. Alcohol should not be consumed with lemborexant.
Potential for Lemborexant to Affect Other Medicinal Products
Clinical Studies with Substrates of CYP3A or CYP2B6
Lemborexant does not induce or inhibit CYP3A as shown by the absence of a drug-drug interaction with midazolam (a CYP3A substrate). Lemborexant weakly induces CYP2B6 based on study with bupropion as a CYP2B6 substrate. Substrates of CYP3A and CYP2B6 can be co-administered with lemborexant.
In Vitro Studies with Substrates of CYP
In vitro, lemborexant has a potential to induce CYP3A and a weak potential to inhibit CYP3A and induce CYP2B6. Lemborexant and M10 do not have the potential to inhibit other CYP isoforms. Lemborexant and M10 do not induce CYP2C8, CYP2C9, and CYP2C19 at clinically relevant concentrations.
In Vitro Studies with Substrates of Transporters
Lemborexant and M10 do not have the potential to inhibit P-gp, BCRP, BSEP, OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT 2, MATE1, and MATE2-K.