What is the mechanism of action and use of benzonate (cough suppressant)?

Benzonatate: Mechanism and Clinical Use

Benzonatate is a peripherally-acting cough suppressant that works by anesthetizing stretch receptors in the respiratory passages, lungs, and pleura, thereby reducing the cough reflex at its source without affecting the respiratory center. 1

Mechanism of Action

Benzonatate functions as a local anesthetic on pulmonary sensory receptors:

• Acts peripherally by dampening stretch receptor activity in the respiratory tract, which reduces afferent signaling that triggers the cough reflex 1
• Onset of action occurs within 15-20 minutes with effects lasting 3-8 hours 1
• Does not inhibit the respiratory center at recommended doses, distinguishing it from centrally-acting opioid antitussives 1
• Structurally similar to local anesthetics like tetracaine and procaine 2

Clinical Indications

• Indicated for symptomatic relief of cough across various etiologies 1
• Studied specifically in advanced cancer patients with cough, demonstrating efficacy and safety at recommended doses 3
• May be effective for acute viral upper respiratory tract infection (URI) cough, particularly when combined with guaifenesin 4

Efficacy Considerations

The evidence for benzonatate's effectiveness is limited compared to other antitussives:

• While extensively studied in acute and chronic cough settings with relatively high efficacy and safety profiles 3, the ACCP guidelines from 2006 do not specifically highlight benzonatate among the most effective agents
• In contrast, centrally-acting agents like codeine and dextromethorphan suppress cough by 40-60% in chronic bronchitis/COPD 5
• Peripherally-acting levodropropizine (not available in the US) achieves approximately 75% cough suppression in bronchitis 5, 6

Critical Safety Warnings

Benzonatate carries significant overdose risk with rapid progression to life-threatening complications:

• Overdose can cause cardiac arrest, arrhythmias (including torsades de pointes), seizures, and death within 2 hours of ingestion 2, 7
• As few as 14 capsules (200 mg each) have caused cardiac arrest in adolescents 7
• Rational prescribing and thorough patient education about overdose risks are essential 2
• Side effects in therapeutic dosing are rare (0.5-1% of patients) and may include skin rash, nausea, diarrhea, and dizziness 8

Practical Application

Benzonatate is most appropriate when:

• Short-term symptomatic relief is needed while awaiting specific therapy or when etiology is unknown 5
• Non-opioid antitussive is preferred to avoid sedation and respiratory depression 3
• Patient can reliably follow dosing instructions to prevent accidental overdose 2