Indacaterol and Mometasone

Like other medicinal products containing a beta₂-adrenergic agonist, this medicinal product should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants or medicinal products known to prolong the QT interval, as any effect of these on the QT interval may be potentiated. Medicinal products known to prolong the QT interval may increase the risk of ventricular arrhythmia.

Inhibition of CYP3A4 and P-glycoprotein (P-gp) has no impact on the safety of therapeutic doses of indacaterol/mometasone.

Inhibition of the key contributors of indacaterol clearance (CYP3A4 and P-gp) or mometasone furoate clearance (CYP3A4) raises the systemic exposure of indacaterol or mometasone furoate up to two-fold.

Due to the very low plasma concentration achieved after inhaled dosing, clinically significant interactions with mometasone furoate are unlikely. However, there may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

No data are available for the use of the medicinal product in patients with severe hepatic impairment, therefore it should be used in these patients only if the expected benefit outweighs the potential risk.

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

There are insufficient data from the use of indacaterol/mometasone or its individual components (indacaterol and mometasone furoate) in pregnant women to determine whether there is a risk.

Indacaterol was not teratogenic in rats and rabbits following subcutaneous administration. In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate caused increased foetal malformations and decreased foetal survival and growth.

Like other medicinal products containing beta~2~-adrenergic agonists, indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle.

Indacaterol/mometasone should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus.

There is no information available on the presence of indacaterol or mometasone furoate in human milk, on the effects on a breast-fed infant, or on the effects on milk production. Other inhaled corticosteroids similar to mometasone furoate are transferred into human milk. Indacaterol (including its metabolites) and mometasone furoate have been detected in the milk of lactating rats.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Reproduction studies and other data in animals did not indicate a concern regarding fertility in either males or females.

Indacaterol/mometasone has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most common adverse reactions over 52 weeks were asthma (exacerbation) (26.9%), nasopharyngitis (12.9%), upper respiratory tract infection (5.9%) and headache (5.8%).

Tabulated list of adverse reactions

Adverse drug reactions (ADRs) are listed by MedDRA system organ class (Table). The frequency of the ADRs is based on the PALLADIUM study. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Adverse reactions:

^* Indicates grouping of preferred terms (PTs):
¹ Oral candidiasis, oropharyngeal candidiasis.
² Drug eruption, drug hypersensitivity, hypersensitivity, rash, rash erythematous, rash pruritic, urticaria.
³ Allergic oedema, angioedema, periorbital swelling, swelling of eyelid.
⁴ Blood glucose increased, hyperglycaemia.
⁵ Headache, tension headache.
⁶ Cataract, cataract cortical.
⁷ Heart rate increased, tachycardia, sinus tachycardia, supraventricular tachycardia.
⁸ Oral pain, oropharyngeal discomfort, oropharyngeal pain, throat irritation, odynophagia.
⁹ Drug eruption, rash, rash erythematous, rash pruritic.
¹⁰ Anal pruritus, eye pruritus, nasal pruritus, pruritus, pruritus genital.
¹¹ Back pain, musculoskeletal pain, myalgia, neck pain, musculoskeletal chest pain.