Vilanterol

Vilanterol is a substrate of cytochrome P450 3A4 (CYP3A4). Concomitant administration of strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin) may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Co-administration with ketoconazole (400 mg) in healthy volunteers increased mean vilanterol AUC_(0-t) and C_max, 65% and 22% respectively. The increase in vilanterol exposure was not associated with an increase in beta-adrenergic agonist related systemic effects on heart rate, blood potassium or QT interval (corrected using the Fridericia method). Care is advised when co-administering umeclidinium/vilanterol with ketoconazole and other known strong CYP3A4 inhibitors as there is potential for an increased systemic exposure to vilanterol, which could lead to an increase in the potential for adverse reactions. Verapamil, a moderate CYP3A4 inhibitor, did not significantly affect the pharmacokinetics of vilanterol.

Medicinal products containing beta-adrenergic blockers may weaken or antagonise the effect of beta₂-adrenergic agonists, such as vilanterol. Concurrent use of either non-selective or selective beta-adrenergic blockers should be avoided unless there are compelling reasons for their use.

Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta₂-adrenergic agonists, therefore use with caution.

Studies in animals have shown reproductive toxicity at exposures which are not clinically relevant after administration of vilanterol.

It is unknown if vilanterol is excreted in human milk. However, other beta₂-adrenergic agonists are detected in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility