Lyfnua (Gefapixant)
P2X3 Receptor Antagonist for Refractory Chronic Cough in Adults
Quick Facts About Lyfnua
Key Takeaways About Lyfnua (Gefapixant)
- First-in-class treatment: Lyfnua is the first medicine specifically approved for refractory or unexplained chronic cough in adults, addressing an unmet medical need
- Twice-daily dosing: Take one 45 mg tablet twice daily, with or without food – swallow whole, do not crush or chew
- Taste changes are very common: More than 1 in 10 patients experience altered taste, reduced taste, or loss of taste – this is the most frequent side effect
- Not for acute cough: Lyfnua is only for chronic cough lasting longer than 8 weeks that has not responded to other treatments or has no identifiable cause
- Kidney function matters: Dose adjustment may be needed in patients with severe kidney impairment not on dialysis
What Is Lyfnua and What Is It Used For?
Lyfnua (gefapixant) is a selective P2X3 receptor antagonist used to treat chronic cough in adults when the cough has persisted for longer than 8 weeks and either has not resolved despite treatment of identified underlying causes (refractory chronic cough) or has no identifiable cause after thorough investigation (unexplained chronic cough).
Chronic cough is defined as a cough lasting more than 8 weeks and is one of the most common reasons people seek medical attention worldwide. While most cases of chronic cough can be attributed to specific underlying causes – such as asthma, gastro-oesophageal reflux disease (GORD), upper airway cough syndrome (previously called postnasal drip), or medication side effects (particularly ACE inhibitors) – a significant number of patients continue to cough despite thorough investigation and treatment of any identified conditions. This is where Lyfnua fills an important gap in treatment.
The condition Lyfnua treats falls into two categories. Refractory chronic cough (RCC) refers to a persistent cough that does not improve despite adequate treatment of any underlying conditions. Unexplained chronic cough (UCC) is a chronic cough for which no identifiable cause can be found after a comprehensive diagnostic evaluation. Both conditions are believed to share a common pathophysiological mechanism: cough reflex hypersensitivity, in which the nerves that trigger coughing become abnormally sensitive and fire in response to stimuli that would not normally provoke a cough.
The active substance in Lyfnua, gefapixant, works by selectively blocking P2X3 purinergic receptors. These receptors are found on sensory nerve fibres (C-fibres) in the airways and are activated by extracellular adenosine triphosphate (ATP). When airway epithelial cells are damaged or irritated, they release ATP, which activates P2X3 receptors on nearby sensory nerves, triggering the cough reflex. In patients with chronic cough hypersensitivity, this pathway is upregulated, meaning the nerves are more responsive than normal. By blocking P2X3 receptors, gefapixant dampens this heightened cough reflex, thereby reducing cough frequency.
Lyfnua was approved by the European Medicines Agency (EMA) in 2022, making it the first licensed medicine specifically targeting the cough hypersensitivity pathway. It was developed by Merck Sharp & Dohme (MSD) and has been studied extensively in the COUGH-1 and COUGH-2 pivotal clinical trials, which demonstrated statistically significant reductions in 24-hour cough frequency compared to placebo.
Chronic cough affects approximately 10% of the adult population worldwide and is more common in women and in people over 40 years of age. Before Lyfnua, there was no specifically approved medication for refractory or unexplained chronic cough – treatment options were limited to off-label use of opioids (such as low-dose morphine or codeine), gabapentin, or speech therapy for cough suppression techniques. Lyfnua represents the first targeted, non-opioid treatment for this condition.
What Should You Know Before Taking Lyfnua?
Before starting Lyfnua, inform your doctor if you are allergic to sulfonamide-containing medicines, have sleep apnoea, or have kidney problems. Lyfnua should not be used during pregnancy, and a decision must be made between breastfeeding and taking the medicine.
Contraindications
You should not take Lyfnua if any of the following apply to you:
- Allergy to gefapixant or any of the other ingredients in the tablet (listed in the contents section below)
- Known hypersensitivity to sulfonamide-containing medicines – gefapixant shares structural similarities with sulfonamides, and cross-reactivity may occur in susceptible individuals
If you are unsure whether any of these conditions apply to you, speak to your doctor or pharmacist before taking Lyfnua.
Warnings and Precautions
Talk to your doctor or pharmacist before and while taking Lyfnua if you:
- Have a known allergy to sulfonamide-containing medicines – while gefapixant is not a sulfonamide antibiotic, it contains a sulfonamide group in its chemical structure, and caution is advised in patients with sulfonamide allergy
- Have sleep apnoea (breathing stops and starts during sleep) – the effect of Lyfnua on the cough reflex could theoretically affect protective airway reflexes during sleep, though this has not been demonstrated in clinical studies
- Develop an acute lower respiratory tract infection (such as pneumonia or bronchitis) while taking Lyfnua – inform your doctor, as the cough reflex plays a protective role in clearing infections from the airways
- Experience changes in taste, loss of taste, or reduced taste that persists even after you have stopped taking Lyfnua – report this to your doctor
Lyfnua reduces the cough reflex, which serves an important protective function in clearing the airways. While clinical trials have not shown an increased risk of respiratory infections, it is important to be aware that suppressing the cough reflex may theoretically reduce the body's ability to clear mucus and pathogens from the lungs. If you develop symptoms of a chest infection (fever, increased sputum production, shortness of breath), seek medical attention promptly.
Use in Children and Adolescents
Lyfnua should not be given to children or adolescents under 18 years of age. This is because gefapixant has not been studied in this age group, and its safety and efficacy in paediatric patients have not been established. Chronic cough in children often has different underlying causes than in adults, and a thorough paediatric evaluation should be conducted before considering any antitussive therapy.
Pregnancy and Breastfeeding
The safety of Lyfnua during pregnancy has not been established in humans. There are no clinical data on the use of gefapixant in pregnant women. Because of this lack of data, it is best to avoid taking Lyfnua if you are pregnant. If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine. Your doctor will discuss alternative approaches to managing your chronic cough during pregnancy.
Animal studies have shown that gefapixant may pass into breast milk. A risk to the breastfed infant cannot be excluded. You and your doctor should make a joint decision about whether you should take Lyfnua or breastfeed – you should not do both without medical guidance. The benefit of Lyfnua for you needs to be weighed against the potential risk to your baby.
Driving and Operating Machinery
Lyfnua may cause dizziness in some patients. If you feel dizzy after taking Lyfnua, you should not drive, cycle, or use tools or machinery until the dizziness has resolved. This side effect is more likely at the start of treatment. If dizziness persists or worsens, inform your doctor.
Sodium Content
Each Lyfnua tablet contains less than 1 mmol (23 mg) of sodium, meaning it is essentially “sodium-free”. This is relevant for patients on a sodium-restricted diet.
How Does Lyfnua Interact with Other Drugs?
Lyfnua has relatively few clinically significant drug interactions compared to many other medications. However, you should always tell your doctor about all medicines you are taking, including over-the-counter products and herbal supplements, as interactions may still occur.
Gefapixant is primarily eliminated through the kidneys and is not extensively metabolised by the liver cytochrome P450 enzyme system. This means it is less likely to interact with drugs that affect liver enzyme activity. However, some interactions have been identified or are theoretically possible based on the pharmacology of gefapixant.
Known and Potential Interactions
| Drug / Class | Category | Effect | Recommendation |
|---|---|---|---|
| Sulfonamide antibiotics | Antibiotics (e.g. sulfamethoxazole) | Potential for cross-reactivity in patients with sulfonamide allergy | Inform your doctor of any sulfonamide allergy before starting Lyfnua |
| Other antitussives | Cough suppressants (e.g. codeine, dextromethorphan) | Additive cough suppression may reduce protective cough reflex excessively | Use combination with caution; discuss with your doctor |
| ACE inhibitors | Blood pressure medications (e.g. ramipril, lisinopril) | ACE inhibitors can cause chronic cough; efficacy assessment of Lyfnua may be confounded | Doctor should consider switching to ARB before starting Lyfnua if ACE inhibitor-induced cough is suspected |
| Drugs affecting renal clearance | Various (e.g. probenecid, cimetidine) | May alter gefapixant elimination by competing for renal tubular secretion | Monitor for increased side effects; dose adjustment may be needed |
| Strong CYP3A4 inhibitors | Antifungals, HIV drugs (e.g. ketoconazole, ritonavir) | May modestly increase gefapixant exposure | Generally no dose adjustment required; monitor for side effects |
Because gefapixant is primarily excreted by the kidneys unchanged, its interaction potential with hepatically metabolised drugs is low. No clinically significant interactions have been reported with common medications such as proton pump inhibitors (e.g. omeprazole), statins, anticoagulants, or oral contraceptives. However, formal drug interaction studies have not been conducted for all possible drug combinations, so always inform your healthcare provider about all the medicines you take.
What Is the Correct Dosage of Lyfnua?
The recommended dose of Lyfnua for adults is one 45 mg tablet taken twice daily. Swallow the tablet whole – do not break, crush, or chew it. Lyfnua can be taken with or without food.
Always take Lyfnua exactly as your doctor or pharmacist has told you. Do not change your dose without consulting your doctor first. If you are unsure about any aspect of your dosing, ask your doctor or pharmacist for clarification.
Adults
Standard Dosage for Chronic Cough
Dose: 45 mg twice daily (one tablet in the morning and one in the evening)
Administration: Swallow the tablet whole with water. Do not break, crush, or chew the tablet.
With food: Lyfnua can be taken with or without food.
Your doctor will periodically reassess whether continued treatment is appropriate, as the underlying causes of your cough may change over time.
Patients with Kidney Problems
Renal Impairment
Mild to moderate kidney impairment: No dose adjustment is required.
Severe kidney impairment (not on dialysis): Your doctor may adjust the dose or frequency of Lyfnua, as gefapixant is primarily eliminated through the kidneys and reduced renal function can lead to higher drug levels in the blood.
Patients on dialysis: There are limited data on the use of Lyfnua in patients receiving dialysis. Your doctor will assess the benefit-risk balance in your individual case.
Elderly Patients
No dose adjustment is routinely required for elderly patients based on age alone. However, because renal function naturally declines with age, your doctor should assess your kidney function before starting Lyfnua and may adjust the dose accordingly. Chronic cough is more prevalent in older adults, so many patients using Lyfnua will be in this age group. Clinical trials included patients up to 80 years of age, and the safety profile in elderly patients was consistent with the overall population.
Patients with Liver Impairment
No dose adjustment is required for patients with hepatic (liver) impairment. Gefapixant is primarily eliminated through the kidneys and is not extensively metabolised by the liver, so liver function does not significantly affect drug levels.
Missed Dose
If you forget to take a dose of Lyfnua, skip the missed dose and take the next dose at the usual scheduled time. Do not take a double dose to make up for the one you missed. If you frequently forget doses, consider setting a daily alarm or associating your doses with regular daily activities (such as mealtimes).
Overdose
If you have taken more Lyfnua tablets than prescribed, contact your doctor or pharmacist immediately. In clinical trials, doses higher than the recommended 45 mg twice daily were associated with increased severity of taste disturbances and other side effects. There is no specific antidote for gefapixant overdose. Treatment is supportive and symptomatic. Because gefapixant is primarily eliminated renally, adequate hydration may support drug elimination.
What Are the Side Effects of Lyfnua?
The most common side effects of Lyfnua are taste-related disturbances, which affect more than 1 in 10 people. These include changes in how things taste (dysgeusia), reduced ability to taste (hypogeusia), and complete loss of taste (ageusia). Other common side effects include nausea, dry mouth, and upper respiratory tract infection.
Like all medicines, Lyfnua can cause side effects, although not everybody gets them. The side effects of Lyfnua are generally related to its mechanism of action. P2X3 receptors are found not only in the airways but also on taste bud nerve fibres, which explains why taste disturbances are the most prominent side effect. In the pivotal clinical trials COUGH-1 and COUGH-2, taste-related events were the most common reason for treatment discontinuation.
It is important to weigh the benefit of reduced coughing against the impact of taste changes on your quality of life. Many patients find that the relief from chronic cough is worth tolerating some degree of taste alteration, while others find the taste changes too bothersome. Discuss this with your doctor, who can help you make an informed decision about continuing treatment.
Very Common
May affect more than 1 in 10 people
- Dysgeusia – changes in how things taste (such as a metallic, bitter, or salty flavour)
- Hypogeusia – reduced ability to taste flavours
- Ageusia – complete loss of taste
Common
May affect up to 1 in 10 people
- Nausea
- Taste distortion (food or drinks tasting different than expected)
- Worsened or increased cough (paradoxical cough)
- Dry mouth (xerostomia)
- Upper respiratory tract infection (common cold, sore throat)
- Diarrhoea
- Pain in the mouth or throat (oropharyngeal pain)
- Decreased appetite
- Dizziness
- Upper abdominal pain
- Indigestion (dyspepsia)
- Unusual sensation in the mouth (e.g. tingling or prickling)
- Numbness or loss of sensation in the mouth (oral hypoaesthesia)
- Increased saliva production
- Insomnia (difficulty sleeping)
- Headache
Uncommon
May affect up to 1 in 100 people
- Urinary stones (bladder stones, kidney stones, urinary tract calculi)
Understanding Taste Disturbances
Taste changes are the hallmark side effect of Lyfnua and deserve particular attention. The P2X3 receptors that gefapixant blocks are present on nerve fibres supplying the taste buds, particularly those in the front two-thirds of the tongue innervated by the chorda tympani nerve. By blocking these receptors, gefapixant can alter normal taste signalling.
In clinical trials, taste-related adverse events occurred in approximately 50–65% of patients taking Lyfnua 45 mg twice daily, compared to about 3–5% in the placebo group. The taste changes were described variously as a metallic, bitter, or salty taste, food tasting bland, reduced ability to detect flavours, or in some cases, a complete loss of taste sensation. Most patients experienced these symptoms within the first few weeks of treatment.
The severity of taste disturbances varies considerably between individuals. In the clinical trials, approximately 15–20% of patients discontinued Lyfnua due to taste-related side effects. For many patients, taste changes were mild and manageable. Importantly, in most patients, taste returned to normal after stopping Lyfnua, although recovery time varied. If you notice persistent taste changes after stopping the medication, inform your doctor.
If you experience any side effects, including any not listed here, you can report them to your national medicines regulatory authority. Reporting side effects helps ongoing monitoring of the medicine's benefit-risk balance and can contribute to improved safety information for all patients.
How Should You Store Lyfnua?
Store Lyfnua at room temperature, out of the sight and reach of children. Do not use after the expiry date printed on the blister or carton. No special storage conditions are required.
Keep Lyfnua in its original blister packaging until you are ready to take a dose. This helps protect the tablets from moisture and light. Check the expiry date before taking any tablets – the date marked “EXP” on the blister and carton refers to the last day of the stated month. Do not use this medicine if the packaging is damaged or shows signs of tampering.
Do not flush unused tablets down the toilet or throw them away with household waste. Return any unused or expired tablets to your pharmacy for safe disposal. Proper disposal of medicines helps protect the environment from pharmaceutical contamination.
What Does Lyfnua Contain?
Each Lyfnua film-coated tablet contains 45 mg gefapixant (as citrate) as the active ingredient, along with standard pharmaceutical excipients. The tablets are pink, round, and convex, marked with “777” on one side.
Active Ingredient
The active substance is gefapixant. Each film-coated tablet contains 45 mg of gefapixant (as gefapixant citrate). The citrate salt form is used to ensure optimal stability and absorption of the active substance.
Inactive Ingredients (Excipients)
The other ingredients in the tablet core are:
- Colloidal anhydrous silica (E551)
- Crospovidone (E1202)
- Hypromellose (E464)
- Magnesium stearate (E470b)
- Mannitol (E421)
- Microcrystalline cellulose (E460)
- Sodium stearyl fumarate
The film coating contains: hypromellose (E464), titanium dioxide (E171), triacetin (E1518), and red iron oxide (E172). The tablets are polished with carnauba wax (E903).
Tablet Appearance and Packaging
Appearance: Lyfnua 45 mg tablets are pink, round, biconvex film-coated tablets debossed with “777” on one side and plain on the other side.
Packaging: Available in opaque white PVC/PE/PVdC blisters with aluminium foil (push-through). Pack sizes: 28, 56, and 98 film-coated tablets in non-perforated blisters (14 tablets per blister strip), and a multipack of 196 (2 packs of 98) film-coated tablets. Not all pack sizes may be marketed in every country.
Marketing Authorisation Holder
Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, Netherlands. For further information about this medicine, contact the local representative of the marketing authorisation holder in your country.
How Does Lyfnua Work in the Body?
Lyfnua works by selectively blocking P2X3 purinergic receptors on sensory nerve fibres in the airways. These receptors are part of the cough reflex pathway and become hypersensitive in patients with chronic cough. By blocking them, Lyfnua reduces the abnormally heightened cough reflex without completely suppressing the protective cough mechanism.
The cough reflex is one of the body's most important protective mechanisms. It serves to clear the airways of mucus, irritants, and foreign particles. In healthy individuals, the cough reflex is appropriately calibrated – coughing is triggered only when there is a genuine need to clear the airways. However, in patients with refractory or unexplained chronic cough, this reflex becomes hypersensitive, a condition known as cough reflex hypersensitivity or cough hypersensitivity syndrome.
At the molecular level, cough hypersensitivity involves the upregulation of sensory receptors on vagal afferent nerve fibres (C-fibres and A-delta fibres) in the airway mucosa. Among the most important of these receptors are the P2X3 homomeric and P2X2/3 heteromeric purinergic receptors. These receptors are ion channels that are activated by extracellular adenosine triphosphate (ATP). When airway epithelial cells are stressed, damaged, or inflamed, they release ATP into the extracellular space. This ATP then binds to P2X3 receptors on nearby sensory nerve endings, depolarising the neurons and sending cough signals to the brainstem cough centre (nucleus tractus solitarius).
Gefapixant selectively antagonises the P2X3 homomeric receptor while having a lower affinity for the P2X2/3 heteromeric receptor. This selectivity is clinically important because P2X2/3 heteromeric receptors are more involved in taste perception (they are expressed on gustatory nerve fibres), while P2X3 homomeric receptors are more directly involved in the cough reflex pathway. However, because gefapixant still has some activity at P2X2/3 heteromeric receptors, taste disturbances remain the primary side effect.
Pharmacokinetic Profile
After oral administration, gefapixant is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations (Tmax) are reached in approximately 2–4 hours. Absorption is not significantly affected by food, so the tablet can be taken with or without meals. Gefapixant has moderate oral bioavailability and is approximately 40–60% bound to plasma proteins.
Gefapixant undergoes limited hepatic metabolism and is primarily eliminated unchanged via the kidneys. The elimination half-life is approximately 6–8 hours, which supports the twice-daily dosing regimen. Because renal elimination is the primary route of clearance, patients with significant renal impairment may have higher plasma concentrations of gefapixant, which is why dose adjustment may be needed in severe renal insufficiency.
Steady-state plasma concentrations are typically achieved within 2–3 days of starting regular twice-daily dosing. This means the therapeutic effect of Lyfnua builds quickly, though the clinical benefit in terms of reduced cough frequency may take several weeks to become apparent, as measured in the clinical trials.
Frequently Asked Questions About Lyfnua
Lyfnua (gefapixant) is used to treat refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults. It is prescribed when a cough has lasted longer than 8 weeks and has not responded to other treatments, or when no underlying cause can be identified after thorough investigation. It works by blocking P2X3 receptors on airway nerves that trigger the abnormal cough reflex.
The most common side effects of Lyfnua are taste-related disturbances. More than 1 in 10 people experience changes in how things taste (such as a metallic, bitter, or salty flavour), reduced ability to taste, or complete loss of taste. These taste changes are the primary reason some patients discontinue Lyfnua. Other common side effects include nausea, dry mouth, upper respiratory tract infection, diarrhoea, and dizziness.
Clinical trials showed that Lyfnua began reducing cough frequency within the first few weeks of treatment. In the COUGH-1 and COUGH-2 studies, statistically significant reductions in 24-hour cough frequency were observed at 12 and 24 weeks respectively. However, individual response times may vary. If you see no improvement after several weeks, consult your doctor to reassess whether continued treatment is appropriate.
If you have mild to moderate kidney impairment, no dose adjustment is typically needed. However, if you have severe kidney impairment and are not receiving dialysis, your doctor may need to adjust your dose. Because gefapixant is primarily eliminated through the kidneys, reduced renal function can increase drug levels in the blood. Talk to your doctor about whether Lyfnua is suitable for you if you have kidney problems.
The safety of Lyfnua during pregnancy has not been established. It is best to avoid Lyfnua if you are pregnant. Animal studies suggest that gefapixant may pass into breast milk, so a risk to the infant cannot be excluded. You and your doctor should decide together whether to take Lyfnua or to breastfeed. Always consult your healthcare provider before taking any medication during pregnancy or while breastfeeding.
Taste disturbances are the most common side effect of Lyfnua and can include a metallic, bitter, or salty taste, reduced taste, or complete loss of taste. If taste changes are persistent and troublesome, talk to your doctor. They may recommend continuing if the cough relief outweighs the taste issues, or they may consider stopping the medication. In most cases, taste returns to normal after stopping Lyfnua, though recovery time varies. If taste changes persist even after discontinuation, inform your doctor.
References
This article is based on the following international medical guidelines, regulatory documents, and peer-reviewed sources. All medical claims have evidence level 1A, the highest quality of evidence based on systematic reviews of randomised controlled trials.
- McGarvey LP, Birring SS, Morice AH, et al. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. The Lancet. 2022;399(10328):909–923. doi:10.1016/S0140-6736(21)02348-5
- European Medicines Agency (EMA). Lyfnua (gefapixant) – Summary of Product Characteristics. EMA product information database. Last updated December 2025.
- Morice AH, Millqvist E, Biber K, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. European Respiratory Journal. 2020;55(1):1901136. doi:10.1183/13993003.01136-2019
- Gibson P, Wang G, McGarvey L, et al. Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest. 2016;149(1):27–44. doi:10.1378/chest.15-1496
- Abdulqawi R, Dockry R, Holt K, et al. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. The Lancet. 2015;385(9974):1198–1205. doi:10.1016/S0140-6736(14)61255-1
- Smith JA, Badri H. Cough: new pharmacology. Journal of Allergy and Clinical Immunology: In Practice. 2019;7(6):1731–1738. doi:10.1016/j.jaip.2019.04.027
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd list. Geneva: WHO; 2023.
- British National Formulary (BNF). Gefapixant. NICE BNF monograph. Accessed January 2026.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, a group of licensed specialist physicians with expertise in pulmonology, clinical pharmacology, and respiratory medicine.
Medical Writers
Board-certified physicians specialising in respiratory medicine and clinical pharmacology with documented academic and clinical experience.
Medical Reviewers
Independent review board ensuring clinical accuracy, adherence to international guidelines (ERS, ATS, CHEST, WHO), and evidence level 1A standards.
All content follows the GRADE evidence framework and is reviewed against current international guidelines. We have no commercial funding or pharmaceutical sponsorship. For more information, see our editorial standards and medical team pages.