Is Tessalon (benzonatate) effective for Upper Respiratory Infection (URI) associated cough?

Tessalon (Benzonatate) for URI-Associated Cough

Benzonatate is not recommended as first-line therapy for URI-associated cough due to limited and inconsistent evidence of efficacy, though it may be considered as a second-line option for short-term symptomatic relief when first-line treatments fail. 1, 2

First-Line Treatment Recommendation

Inhaled ipratropium bromide is the only recommended first-line treatment for URI-associated cough, with substantial benefit and Grade A evidence from the American College of Chest Physicians (ACCP). 1, 3

• Ipratropium works through anticholinergic activity in the airways, with only 7% systemic absorption, minimizing side effects. 3
• This is the sole inhaled anticholinergic agent recommended for cough suppression in URI. 1

Benzonatate's Role and Evidence

Mechanism and FDA Indication

• Benzonatate acts peripherally by anesthetizing stretch receptors in the respiratory passages, lungs, and pleura, reducing the cough reflex at its source. 4
• It begins working within 15-20 minutes with effects lasting 3-8 hours. 4
• FDA-approved for symptomatic relief of cough. 4

Clinical Evidence Quality

The evidence for benzonatate in URI-associated cough is inconsistent and of fair quality at best:

• Mixed trial results: One study of 52 patients showed benzonatate 333 mg three times daily significantly improved cough symptoms on days 3,5, and 6 (p<0.05). 2
• Negative studies: Two other studies found no significant difference between benzonatate and placebo for cough frequency or symptoms. 2
• Additional negative trial: A 1996 trial of 91 patients using 250 mg four times daily showed no significant reduction in cough frequency. 2

Guideline Classification

• The ACCP classifies benzonatate as a peripheral cough suppressant that has limited efficacy for URI-related cough (Grade D recommendation - good evidence, no benefit). 1
• However, the ACCP suggests benzonatate can be offered for short-term symptomatic relief in acute bronchitis with Grade C recommendation (fair quality evidence, small/weak benefit). 2

What NOT to Use for URI Cough

Central cough suppressants are not recommended for URI-associated cough:

• Codeine and dextromethorphan have limited efficacy (Grade D recommendation). 1, 3
• Over-the-counter combination cold medications are not recommended until proven effective in randomized trials. 1

Clinical Algorithm for URI-Associated Cough

Step 1: First-Line Treatment

• Inhaled ipratropium bromide as initial therapy. 3, 2

Step 2: Second-Line Options (if ipratropium fails)

• Benzonatate 100-200 mg three times daily for short-term relief, particularly for dry, bothersome cough disrupting sleep. 1, 2
• Consider combination with guaifenesin, as one study showed benzonatate plus guaifenesin suppressed capsaicin-induced cough more than either agent alone (p<0.001 vs benzonatate alone). 5

Step 3: Important Exclusions

• Do NOT suppress productive cough with sputum, as cough serves a physiological function to clear mucus. 2
• Rule out pneumonia, asthma, or COPD exacerbation before treating as simple URI. 3, 2

Critical Caveats

• Short-term use only: Benzonatate should only be used for symptomatic relief, not as definitive treatment. 2, 6
• Self-limiting condition: Most URI episodes resolve in 1-3 weeks without treatment. 2
• Inconsistent evidence: The fair quality evidence and small/weak benefit must be weighed against potential side effects. 2
• Peripheral suppressants generally ineffective: The ACCP states peripheral cough suppressants (including benzonatate) have limited efficacy for URI cough. 1

Special Context: Cancer-Related Cough

In advanced cancer patients with cough, benzonatate has been specifically studied and shown to be effective and safe at recommended doses, representing a different clinical context where evidence is stronger. 6 The lung cancer guidelines suggest benzonatate as a trial option for opioid-resistant cough. 1