What Is Gefapixant?
Gefapixant, marketed under the brand name Lyfnua, is a first-in-class, non-narcotic oral medication developed to treat adults with refractory chronic cough (RCC) or unexplained chronic cough (UCC) [1.5.1, 1.5.2]. RCC is a cough that persists despite treatment for any underlying conditions, while UCC is a cough where no specific cause can be identified after a thorough evaluation [1.6.6]. For millions suffering from the disruptive effects of constant coughing, gefapixant represents a novel therapeutic approach.
How Gefapixant Works
The mechanism of action for gefapixant is targeted and unique. It is a selective P2X3 receptor antagonist [1.6.4]. These P2X3 receptors are located on sensory nerve fibers within the airway lining [1.5.2]. When chemical stimuli like adenosine triphosphate (ATP) are released during inflammation or irritation, they bind to these receptors, which the body interprets as a signal of potential damage. This process creates an action potential that travels to the brain and initiates the cough reflex [1.6.3, 1.6.4]. By blocking ATP from binding to these receptors, gefapixant is thought to reduce the activation of these sensory nerves, thereby calming the urge to cough [1.5.2].
Global Prescription Status: Is Gefapixant Available on Prescription?
The answer to whether gefapixant is available on prescription is highly dependent on your location. The regulatory journey for this drug has been mixed, with different health authorities reaching different conclusions about its risk-benefit profile.
United States (FDA)
In the United States, gefapixant is not available on prescription. The U.S. Food and Drug Administration (FDA) has declined to approve the New Drug Application for gefapixant on two separate occasions, most recently in December 2023 [1.2.6, 1.3.4]. The agency's primary concern was not safety, but a lack of substantial evidence of effectiveness [1.3.1, 1.3.4]. An FDA advisory committee voted 12-to-1 against approval, citing the small clinical benefit observed in trials, where gefapixant reduced cough frequency by only one to two coughs per hour compared to placebo [1.2.4, 1.3.2].
European Union (EMA)
In contrast, gefapixant is available on prescription in the European Union. The European Medicines Agency (EMA) authorized Lyfnua for medical use on September 15, 2023 [1.5.3]. The EMA acknowledged that the medication had a 'modest effect' on reducing cough frequency but concluded that its benefits were greater than its risks, especially given the lack of other approved treatments for the condition [1.5.3].
United Kingdom (MHRA & NICE)
In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) approved gefapixant in December 2023 [1.2.3]. However, its widespread availability on the National Health Service (NHS) is uncertain. In May 2024, the National Institute for Health and Care Excellence (NICE), which provides guidance on the use of medicines within the NHS, terminated its appraisal of gefapixant because the manufacturer did not provide a required evidence submission [1.2.3].
Other Regions
Gefapixant has been approved and is available on prescription in other parts of the world, including:
- Japan: Approved in 2022 [1.5.2, 1.5.4].
- Switzerland: Approved in 2022 [1.5.2, 1.5.6].
Efficacy vs. Side Effects
The debate surrounding gefapixant centers on the trade-off between its effectiveness and its side effects.
Clinical Trial Results
Phase 3 clinical trials (COUGH-1 and COUGH-2) did show a statistically significant reduction in 24-hour cough frequency for patients taking a 45 mg twice-daily dose compared to placebo [1.7.1, 1.7.2]. However, the magnitude of this reduction was small, which led to differing interpretations by regulatory bodies [1.7.3]. While the EMA found this modest benefit acceptable, the FDA did not deem it clinically meaningful enough to warrant approval [1.3.2, 1.5.3].
Common Side Effects
The most significant and frequent adverse reaction associated with gefapixant is taste disturbance. This is believed to occur because the drug may also block P2X2/3 receptors located on taste buds [1.2.3].
- Very Common (may affect more than 1 in 10 people): Changes in taste (dysgeusia), loss of taste (ageusia), or reduced sense of taste (hypogeusia) [1.8.2, 1.8.4].
- In clinical trials, taste-related adverse events were reported in over 65% of patients taking the 45 mg dose, leading to about 14% of participants discontinuing the treatment [1.3.2].
- Other, less common side effects include nausea, headache, and dizziness [1.8.1].
Comparison of Chronic Cough Treatments
| Feature | Gefapixant (Lyfnua) | Camlipixant (Investigational) | Conventional Therapies (e.g., Benzonatate) |
|---|---|---|---|
| Mechanism | Selective P2X3 receptor antagonist; blocks nerve signals in airways [1.6.4] | Selective P2X3 receptor antagonist [1.3.1] | Anesthetic; numbs stretch receptors in the lungs [1.9.3] |
| Availability | Prescription-only in EU, Japan, UK, Switzerland. Not approved in the US [1.3.3, 1.4.3]. | Not yet approved; GSK targeting a 2026 launch [1.3.1]. | Widely available by prescription globally [1.9.3]. |
| Efficacy | Modest reduction in cough frequency shown in trials [1.7.3]. | Efficacy data is still emerging from Phase 3 trials [1.3.1]. | Varies by patient; often used for symptomatic relief [1.9.3]. |
| Key Side Effect | High incidence of taste disturbance (>60%) [1.3.2]. | Expected to have a lower incidence of taste disturbance [1.9.1]. | Drowsiness, dizziness, headache [1.9.3]. |
Alternatives to Gefapixant
With gefapixant's limited availability, patients and doctors continue to rely on other strategies.
Investigational Drugs
- Camlipixant: Another P2X3 antagonist from GSK, which may offer a better balance of efficacy and tolerability with fewer taste-related side effects [1.9.1].
- Haduvio (nalbuphine): An investigational drug with a different mechanism of action that targets the central and peripheral nervous systems [1.9.2].
Conventional Therapies
Treatment often focuses on addressing underlying causes:
- Antihistamines and nasal corticosteroids for postnasal drip and allergies [1.9.4].
- Inhaled corticosteroids and bronchodilators for asthma-related cough [1.9.4].
- Acid blockers for cough caused by gastroesophageal reflux disease (GERD) [1.9.4].
- Benzonatate as a non-narcotic prescription cough suppressant [1.9.3].
Conclusion
The question 'Is gefapixant available on prescription?' has a complex, region-specific answer. As of late 2025, it is a treatment option for patients in the European Union, UK, Japan, and Switzerland, but not in the United States. Its approval hinges on a delicate balance: it offers a novel mechanism for a condition with no approved therapies, but its clinical benefit is modest and comes with a high probability of taste-related side effects. As competitors like camlipixant move through the pipeline, the treatment landscape for refractory chronic cough will continue to evolve.
