4.1. Therapeutic indications

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.

4.2. Posology and method of administration

Posology

The recommended dose is 25 mg orally once daily with or without food.

Missed dose

Patients who miss a dose should take the next dose at their regular time the next day. Patients should not double the dose to make up for the missed dose.

Special populations

Elderly

No dose adjustment is required for elderly patients (see section 5.2).

Renal and hepatic impairment

No dose adjustment is required for patients with renal or hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Brinsupri in children younger than 12 years of age have not yet been established. No data are available.

Method of administration

For oral use.

This medicinal product should be taken once daily with or without food.

4.3. Contraindications

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

4.4. Special warnings and precautions for use

Immunocompromised patients

Safety data in patients with known or suspected immunodeficiencies, immunocompromised conditions, or receiving any immunomodulatory therapy are limited or not established. Administration of brensocatib in these patients should be considered with caution. 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'.

4.5. Interaction with other medicinal products and other forms of interaction

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.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no data on the use of brensocatib in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3).

Benefits and potential risks of use of brensocatib during pregnancy have not been established. Brensocatib may be used during pregnancy where the expected benefit to the mother justifies the unknown risk to the fetus.

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).

The potential treatment benefit or risk to the newborn or infants via breastfeeding is not known.

Decisions on whether to breastfeed during treatment or to abstain from brensocatib therapy should take 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 at the clinically relevant exposure in patients treated with brensocatib (see section 5.3).

4.7. Effects on ability to drive and use machines

Brinsupri has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

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

Infections and infestations

Common

Upper respiratory tract infection

Gastroenteritis

Nervous system disorders

Common

Headache

Gastrointestinal disorders

Common

Gingival disorder

Periodontal disease

Skin and subcutaneous tissue disorders

Common

Hyperkeratosis*

Rash

Dry skin

Dermatitis

Skin exfoliation

Alopecia

* See 'Description of selected adverse reactions' below.

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. Most resolved with no action taken with study treatment. Most cases were manageable or improved/resolved with emollients or topical steroids.

Paediatric population

The safety assessment in adolescents aged 12 to 17 with NCFB is based on 41 subjects exposed to brensocatib in the 52-week Phase 3 ASPEN trial (see section 5.1). The safety profile in these adolescents was similar to that observed in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Doses of up to 120 mg, given as a single dose, did not have evidence of dose-related toxicities.

There is no specific treatment for an overdose with brensocatib. If an overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.