Is long-term use of Tessalon (benzonatate) harmful?

Long-term Use of Benzonatate (Tessalon) Safety Concerns

Long-term use of benzonatate (Tessalon) is not recommended due to significant safety concerns including risk of severe adverse events, lack of long-term safety data, and potential for life-threatening complications with overdose.

Safety Profile and Risks

• Benzonatate is chemically related to local anesthetic agents of the para-amino-benzoic acid class (like procaine and tetracaine) and has been associated with adverse CNS effects 1
• The FDA drug label does not support long-term use, with the maximum recommended dosage being 600 mg per day (200 mg three times daily) 1
• Benzonatate has been associated with life-threatening adverse events including cardiac arrest, even at therapeutic doses 2
• Overdose can lead to rapid onset of serious symptoms (within 15-20 minutes) and death (within one hour of ingestion) 1

Mechanism of Action and Concerns

• Benzonatate works by inhibiting voltage-gated sodium channels, similar to local anesthetics, which affects sensory nerve fibers that mediate cough 3
• This mechanism affects Nav1.7 channels which are important for normal neurological function, raising concerns about long-term inhibition 3
• Detectable effects of benzonatate occur at concentrations as low as 0.3 μM, which has been reported in humans, suggesting potential for cumulative effects 3

Risk of Dependence

• While benzonatate itself has not been specifically identified in guidelines on medication dependence, other medications that affect neural pathways can lead to dependence with prolonged use 4
• The Lancet Psychiatry review notes that sudden cessation of medications affecting neural pathways can lead to physical and psychological withdrawal symptoms, suggesting caution with long-term use of agents affecting neural function 4

Documented Cases of Severe Toxicity

• Multiple case reports document fatal outcomes from benzonatate overdose in both adults and children 2, 5, 6
• A case report described a 37-year-old female who suffered cardiac arrest after ingesting less than 30 pills of benzonatate 200 mg with alcohol 2
• Another case documented torsades de pointes and cardiac arrest in a pediatric patient following benzonatate overdose 5

Carcinogenicity Data

• While recent animal studies suggest benzonatate is not carcinogenic in rodent models 7, the FDA label notes that comprehensive carcinogenicity, mutagenicity, and reproduction studies have not been conducted 1
• This represents a gap in knowledge regarding very long-term safety 1

Alternatives for Chronic Cough Management

• For patients requiring long-term cough suppression, particularly those with cancer-related cough, centrally acting cough suppressants such as dihydrocodeine and hydrocodone may be more appropriate options with established safety profiles for longer use 4
• For chronic cough management, addressing the underlying cause rather than prolonged symptomatic treatment is generally preferred 4

Recommendations for Use

• Benzonatate should be used for short-term cough suppression only, not as a long-term treatment 1
• Patients should be instructed to swallow benzonatate capsules whole and never break, chew, dissolve, cut, or crush them 1
• If numbness or tingling of the tongue, mouth, throat, or face occurs, patients should refrain from oral ingestion until the numbness resolves 1
• Benzonatate should be kept out of reach of children due to risk of accidental ingestion and death 1

In conclusion, while benzonatate may be effective for short-term cough suppression, its long-term use is not supported by current evidence and carries significant safety concerns. Patients requiring extended cough management should be evaluated for alternative therapies with better established long-term safety profiles.