LYFNUA Film-coated tablet Ref.[51267] Active ingredients: Gefapixant

Obstructive sleep apnoea

In patients with moderate to severe obstructive sleep apnoea (OSA, n=19) who were not using positive airway pressure (PAP), gefapixant 180 mg daily at bedtime was associated with a lower mean SaO₂ and a higher mean proportion of time with SaO₂ <90% across all sleep stages compared to placebo. The clinical relevance of these findings for the use of 45 mg gefapixant twice daily in patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) with comorbid OSA is not known. For patients with OSA, appropriate treatment for OSA should be considered prior to initiating treatment with gefapixant.

Hypersensitivity

Gefapixant contains a sulphonamide moiety but is considered to be a non-sulphonylarylamine. Gefapixant has not been studied in patients with a history of hypersensitivity to sulphonamide, therefore, cross-hypersensitivity with sulphonamide hypersensitivity cannot be excluded. Gefapixant should be used with caution in patients with known hypersensitivity to sulphonamides.

Acute lower respiratory tract infection

Treatment with gefapixant should be evaluated and individualised in patients who develop an acute lower respiratory tract infection (see section 5.1).

Taste-related adverse reactions

Taste-related adverse reactions were very commonly reported in the clinical studies. In most patients, these adverse reactions resolved soon after discontinuation of gefapixant (median time 5 days). In a few patients, these reactions persisted for more than a year after discontinuation (see section 4.8).

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

Based on in vitro studies (see section 5.2), relevant clinical interaction studies were performed and no clinically meaningful interactions have been identified.

Paediatric population

Interaction studies have only been performed in adults.

Pregnancy

There are no data from the use of gefapixant in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Lyfnua during pregnancy and in women of childbearing potential not using contraception.

Lactation

Available pharmacodynamic/toxicological data in animals have shown excretion of gefapixant in milk (see section 5.3).

A risk to newborns/infants cannot be excluded.

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

Fertility

No human data on the effect of gefapixant on fertility are available. In rats, there was no effect on mating or fertility with gefapixant treatment (see section 5.3).

Gefapixant has no or negligible influence on the ability to drive and use machines. In individual cases, dizziness may occur following administration of gefapixant that may influence the ability to drive and use machines.

Summary of the safety profile

The most frequently reported adverse reactions were dysgeusia (41%), ageusia (15%), and hypogeusia (11%).

Tabulated list of adverse reactions

The safety of gefapixant was evaluated in two phase III clinical studies (COUGH-1 and COUGH-2) which included a total of 1,369 patients treated with gefapixant (15 mg or 45 mg twice daily) (see section 5.1). The duration of exposure with gefapixant was 52 weeks.

The adverse reactions reported with gefapixant obtained from clinical studies are listed in the table below by MedDRA system organ class and by frequency. Frequencies are defined as 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), and very rare (<1/10,000).

Table 1. Adverse reactions:

^* Dysgeusia was commonly reported as taste bitter, taste metallic or taste salty.
^** Cough includes reports of ‘worsening’, ‘exacerbation’, ‘increase’, or ‘increased’ cough.

Description of selected adverse reactions

Taste-related adverse reactions

The majority of patients with taste-related adverse reactions (dysgeusia, ageusia, hypogeusia and taste disorder) experienced the onset of the adverse reactions within 9 days of starting gefapixant; the majority were mild (65%) to moderate (32%) in intensity. Resolution of the taste-related adverse reactions occurred in 96% of patients with 25% reporting resolution on or before the last dose of gefapixant. Taste-related adverse reactions persisted for more than a year after discontinuation in 1.6% (7/447) of patients in the gefapixant group and 12.8% (6/47) of patients in the placebo group. Adverse reactions resulting in discontinuation occurred in 22% of patients receiving gefapixant. The most frequently reported adverse reactions leading to discontinuation of treatment were dysgeusia (9%) and ageusia (4%).

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 national reporting system listed in Appendix V.

Not applicable.