What is benzonatate?

What is Benzonatate?

Benzonatate is a peripherally-acting, non-narcotic oral antitussive (cough suppressant) that works by anesthetizing stretch receptors in the lungs and airways, thereby reducing the cough reflex. 1

Mechanism of Action

• Benzonatate is structurally related to local anesthetics like tetracaine and procaine, and functions by inhibiting voltage-gated sodium channels, particularly Nav1.7, which are highly expressed in vagal sensory nerve fibers that mediate the cough reflex 2
• The drug anesthetizes pulmonary stretch receptors located in the respiratory passages, lungs, and pleura, dampening their activity and suppressing the cough reflex 1, 2
• Unlike opioid cough suppressants, benzonatate acts peripherally rather than centrally, making it a non-narcotic alternative 3, 1

Formulation and Dosing

• Each soft gelatin capsule contains 200 mg of benzonatate USP, along with inactive ingredients including gelatin, glycerin, and purified water 1
• The recommended dosage is 100-200 mg three to four times daily for cough suppression 4
• The medication undergoes rapid ester hydrolysis in plasma, producing 4-(butylamino) benzoic acid (BBA) and methylated polyethylene glycol polymer as metabolites 5

Clinical Applications

• Lung cancer-associated cough: The American College of Chest Physicians guidelines recommend benzonatate as a treatment option for opioid-resistant cough in patients with lung cancer, particularly when peripheral antitussives are needed 3
• Acute viral cough: Benzonatate has demonstrated efficacy in reducing cough-reflex sensitivity in patients with acute upper respiratory tract infections, especially when combined with guaifenesin 6
• Porphyria: Benzonatate is considered safe in patients with porphyria, as there is no evidence suggesting it triggers acute porphyria attacks 4

Safety Profile and Important Warnings

• Overdose risk: Benzonatate can cause life-threatening adverse events including seizures, cardiac dysrhythmias, central nervous system depression, and death in overdose settings 7, 8
• Intentional exposures: Serious adverse effects occur in approximately 22% of intentional overdoses, with a 38% hospitalization rate 8
• Unintentional exposures: Rarely cause serious toxicity, particularly in pediatric populations, where no serious adverse effects were observed in a 20-year review 8
• The drug's structural similarity to local anesthetics means it can cause sodium channel blockade effects similar to these agents 7, 2

Duration of Use

• For acute cough due to upper respiratory infections, treatment should be limited to 7-10 days 4
• For chronic bronchitis, benzonatate is recommended only for short-term symptomatic relief 4
• The medication should be discontinued if symptoms persist beyond 1 week, as prolonged cough may indicate a more serious underlying condition requiring diagnostic evaluation 4

Position in Treatment Algorithms

• The CHEST guidelines suggest a pyramidal approach to cough management in lung cancer patients, with benzonatate positioned as a treatment option when demulcents and opioids are ineffective or contraindicated 3
• It serves as an alternative to opioid-based cough suppressants, particularly valuable when opioid side effects are problematic or in patients where opioids are contraindicated 3, 4