Gefapixant Citrate

• Approved Indication:
• Treatment of Chronic Cough associated with refractory or unexplained chronic cough (RCC or UCC) in adults.
  This includes persistent cough lasting longer than 8 weeks, where other causes have been excluded or treated without relief.
• Off-label/Clinically Accepted Uses:
• Investigational use for cough related to other respiratory conditions such as interstitial lung disease or chronic obstructive pulmonary disease (COPD), but not yet approved.

• Adults:
• Typical recommended oral dose is 45 mg twice daily (BID).
• Initial dose may start at 15 mg BID or 30 mg BID in some clinical settings, titrated up to 45 mg BID based on efficacy and tolerability.
• Pediatrics:
• Safety and efficacy not established; not recommended for use in patients under 18 years.
• Elderly:
• No specific dose adjustment required; monitor for tolerability.
• Renal/Hepatic Impairment:
• No formal dose adjustment established; caution advised due to limited data.
• Administration Route:
• Oral tablets, swallowed whole with or without food.

Gefapixant is a selective antagonist of the P2X3 receptor, a ligand-gated ion channel activated by extracellular ATP on sensory neurons. P2X3 receptors are predominantly expressed on afferent neurons involved in cough reflex pathways. By blocking P2X3 receptors, Gefapixant reduces the hypersensitivity of airway sensory nerves, thereby decreasing the frequency and intensity of chronic cough. This receptor-level blockade disrupts the abnormal sensory nerve signaling responsible for persistent coughing, providing symptomatic relief.

• Absorption: Rapidly absorbed after oral administration; peak plasma concentration (Tmax) approximately 1–3 hours.
• Bioavailability: Moderate oral bioavailability; food has minimal effect on absorption.
• Distribution: Widely distributed; volume of distribution is moderate, suggesting tissue penetration.
• Metabolism: Metabolized primarily by hepatic enzymes, mainly CYP3A4 and CYP2D6 pathways.
• Active Metabolites: Minimal; parent compound responsible for pharmacologic activity.
• Elimination: Primarily excreted via feces and urine; elimination half-life approximately 8–15 hours, supporting twice-daily dosing.

• Pregnancy:
• No adequate, well-controlled studies in pregnant women. Animal studies are limited. Use only if potential benefit justifies potential risk.
• Lactation:
• Unknown if excreted in human milk; caution advised during breastfeeding due to potential adverse effects on the infant.

• Primary Therapeutic Class: Antitussive agent
• Subclass: P2X3 receptor antagonist

• Known hypersensitivity to Gefapixant or any of its components.
• Severe hepatic impairment (due to lack of data).
• Concurrent use with other P2X3 antagonists (if any available).

• Taste Disturbances: Dysgeusia, ageusia, or hypogeusia are common and may affect adherence.
• Hypersensitivity Reactions: Rare but may occur; discontinue if severe allergic symptoms develop.
• Renal and Hepatic Monitoring: Use caution in patients with renal or hepatic impairment.
• Potential Drug Interactions: Caution when coadministered with CYP3A4 or CYP2D6 substrates/inhibitors.
• Pregnancy and Lactation: Use only when clearly needed; avoid unless benefits outweigh risks.

Common Adverse Effects:

• Taste disturbances (dysgeusia, ageusia, hypogeusia) – frequently reported and dose-dependent
• Headache
• Nausea

Less Common/Rare Side Effects:

• Fatigue
• Oral hypoesthesia
• Dizziness

Severity and Onset:

• Taste alterations typically occur within days to weeks of treatment initiation and may improve over time or after discontinuation.
• Most side effects are mild to moderate.

• Potential interaction with CYP3A4 inhibitors or inducers, which may alter Gefapixant metabolism and plasma levels.
• Caution with CYP2D6 substrates due to shared metabolism pathways.
• No significant interactions with food or alcohol reported.
• No known direct interactions with other cough suppressants.

• FDA Approval: Gefapixant received FDA approval for treatment of refractory or unexplained chronic cough in adults.
• Label Updates: Emphasis on monitoring for taste-related adverse effects and patient counseling regarding this common side effect.
• Guidelines: Increasing recognition of P2X3 antagonists as a novel therapeutic class for chronic cough management in patients refractory to traditional treatments.
• Ongoing clinical trials are evaluating long-term safety and broader indications.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Protect from moisture and light; keep in original container tightly closed.
• Avoid freezing.
• Keep out of reach of children.