Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Data from in vitro studies have demonstrated that idebenone and its metabolite QS10 do not exert systemic inhibition of cytochrome P450 isoforms CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 at clinically relevant concentrations of idebenone or QS10. In addition, no induction of CYP1A2, CYP2B6 or CYP3A4 was observed.
In vivo idebenone is a mild inhibitor of CYP3A4. Data from a drug-drug interaction study in 32 healthy volunteers indicate that on the first day of oral administration of 300 mg idebenone t.i.d., the metabolism of midazolam, a CYP3A4 substrate, was not modified when both medicinal products were administered together. After repeated administration Cmax and AUC of midazolam were increased by 28% and 34%, respectively, when midazolam was administered in combination with 300 mg idebenone t.i.d. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving idebenone.

Idebenone may inhibit P-glycoprotein (P-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. These medicines should be administered with caution in patients receiving idebenone. Idebenone is not a substrate for P-gp in vitro.