Brinsupri · 4.4 Special warnings and precautions for use · 1

HOS-288627 · has-adverse-reaction-information · PDF-Seite 4

Summary of the safety profile The most frequently reported adverse reactions are headache (9.2%), hyperkeratosis (5.9%), dermatitis (4.2%), rash (4.1%), upper respiratory tract infections (3.9%), and dry skin (3.0%). Tabulated list of adverse reactions The safety of brensocatib was evaluated on the pooled safety population from two placebo-controlled clinical trials, ASPEN and WILLOW, which consisted of 1 326 adult and 41 adolescent patients 12 years of age and older with NCFB who received at least one dose of brensocatib for up to 52 weeks. The frequency of adverse reactions is defined using the following convention: 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1: Adverse reactions System organ class Frequency Adverse reaction Upper respiratory tract infection Infections and infestations Common Gastroenteritis Nervous system disorders Common Headache Gingival disorder Gastrointestinal disorders Common Periodontal disease Hyperkeratosis* Rash Skin and subcutaneous tissue Dry skin Common disorders Dermatitis Skin exfoliation Alopecia * See ‘Description of selected adverse reactions’ below. 4 Description of selected adverse reactions Hyperkeratosis In the pooled safety population, hyperkeratosis (including skin lesion, keratosis pilaris, exfoliative rash and seborrheic keratosis) was reported more frequently with brensocatib 25 mg than placebo (5.9% vs 3.1%). All events were of mild or moderate severity. Paediatric

Auszug; vollständigen Abschnitt im Original lesen.

HOS-288623 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-288622 · has-indication-information · PDF-Seite 2

Brinsupri is indicated for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in patients 12 years of age and older with two or more exacerbations in the prior 12 months.

HOS-288625 · has-interaction-information · PDF-Seite 3

In vitro studies are inconclusive regarding the potential of brensocatib to induce CYP2B6 and CYP3A4 (see section 5.2). In vivo induction cannot be excluded. Co-administration with CYP3A4 substrates used in bronchiectasis (e.g. inhaled corticosteroids, macrolide antibiotics or inhaled bronchodilators such as salmeterol or vilanterol) may result in decreased plasma concentrations and reduced therapeutic effect. Adjustment of the concomitant treatment may be considered if efficacy is reduced. Paediatric population Interaction studies have only been performed in adults.

HOS-288626 · has-pregnancy-information · PDF-Seite 3

Pregnancy There are no data on the use of brensocatib in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Brinsupri is not recommended during pregnancy and in women of childbearing potential not using contraception. 3 Breast-feeding It is unknown whether brensocatib or its metabolites are excreted in human milk. Available data in animals have suggested excretion of brensocatib in milk (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from brensocatib therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no fertility data in humans. Animal studies indicate no impact on male or female fertility (see section 5.3).

HOS-288624 · has-warning-information · PDF-Seite 3

Fungal infections In clinical studies, fungal infections, mainly candida-related, indicative of immunosuppression (i.e., oral candidiasis, oesophageal candidiasis, oropharyngeal candidiasis, fungal bronchitis) and isolated cases of Aspergillus infections, were more frequent with brensocatib 25 mg (1.5%) compared to placebo (1.1%). Immunocompromised patients The safety of brensocatib has not been established in immunocompromised patients. Caution is advised when using brensocatib in patients with moderate to severe neutropenia (absolute neutrophil count [ANC] < 1,000/mm³). Vaccinations The concomitant use of brensocatib and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving brensocatib. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.