What are the recommended dosing, administration, contraindications, precautions, and adverse effects of Tessalon (benzonatate) for adults and children ≥ 10 years, including considerations for frail patients, hepatic impairment, concurrent CNS depressants, pregnancy, and severe liver disease?

Tessalon (Benzonatate) Prescribing Information

Dosing and Administration

Adults and children ≥10 years should take 100-200 mg orally three times daily as needed for cough, with a maximum daily dose of 600 mg in three divided doses. 1

• Capsules must be swallowed whole—never broken, chewed, dissolved, cut, or crushed 1
• Release of benzonatate in the mouth produces temporary local anesthesia of oral mucosa and can cause choking 1
• If numbness or tingling of the tongue, mouth, throat, or face occurs, patients must refrain from oral ingestion until numbness resolves 1
• If a dose is missed, skip it and take the next scheduled dose—never double dose 1

Absolute Contraindications

Benzonatate is contraindicated in children under 10 years of age due to risk of fatal overdose. 1

• Accidental ingestion has resulted in death in children, with signs of overdose appearing within 15-20 minutes and death reported within one hour 1
• Keep out of reach of children at all times 1

Critical Safety Warnings

Benzonatate overdose can cause cardiac arrest and death in adults, with life-threatening symptoms developing rapidly within 1-2 hours of ingestion. 2, 3

• Overdose manifestations include restlessness, tremors, convulsions, coma, cardiac arrest, and potentially permanent blindness 1, 2, 3
• A 37-year-old woman experienced cardiac arrest after ingesting less than 30 capsules (200 mg each), requiring 30 minutes of resuscitation 2
• A 17-year-old developed cardiac arrest and permanent blindness after ingesting at least 10 capsules (200 mg each) 3
• Never exceed a single dose of 200 mg or total daily dose of 600 mg 1

Special Populations and Precautions

CNS Depressant Interactions

Benzonatate is chemically related to para-aminobenzoic acid anesthetics (procaine, tetracaine) and has been associated with adverse CNS effects, particularly with concomitant CNS medications or prior sensitivity to related agents. 1

Pregnancy and Lactation

• Pregnancy Category C: Animal reproduction studies have not been conducted; use only if clearly needed 1
• Nursing mothers: Unknown if excreted in human milk; exercise caution when administering to nursing women 1

Hepatic Impairment

• No specific dosing adjustments are provided in the FDA label for hepatic impairment 1
• Given the drug's structural similarity to local anesthetics and potential for hepatotoxicity in overdose (one case showed elevated liver enzymes with pH 6.87), use with caution in severe liver disease 2

Frail or Elderly Patients

• No specific dosing adjustments are provided, but the standard adult dosing applies 1
• Exercise heightened vigilance given the narrow therapeutic window and rapid onset of toxicity 2, 3

Common Adverse Effects

The most concerning adverse effect is local anesthesia of the oral cavity if capsules are chewed or dissolved, leading to choking risk. 1

• Numbness or tingling of tongue, mouth, throat, or face requires immediate cessation of oral intake until resolved 1
• Serious adverse effects from therapeutic dosing are rare in surveillance data 4

Emerging Safety Concerns

Pediatric benzonatate exposures are increasing, particularly unintentional ingestions in children 0-5 years and intentional ingestions in adolescents 10-16 years. 4

• Among 4,689 pediatric exposure cases (2010-2018), 80% were single-substance exposures and 77% were unintentional 4
• Cases involving misuse or abuse were predominantly in children 10-16 years (61%) 4
• Rational prescribing and improved caregiver awareness are essential to reduce exposure risks 4

Mechanism of Action

Benzonatate inhibits voltage-gated sodium channels (including Nav1.7) in vagal sensory nerve fibers, producing local anesthetic-like effects that suppress the cough reflex. 5

• Effects are detectable at concentrations as low as 0.3 μM, which have been reported in humans 5
• The drug causes both tonic and phasic inhibition with greater effects on channel inactivation than activation 5
• The 9-ethoxy component of benzonatate is the most potent inhibitor of sodium currents 5

Genotoxicity Profile

Benzonatate and its major metabolite 4-(butylamino)benzoic acid (BBA) are not mutagenic and do not cause chromosomal aberrations. 6

• Testing showed no significant mutagenicity in bacterial strains with or without metabolic activation 6
• No biologically relevant structural or numerical aberrations occurred in human chromosomes 6
• Oral rodent carcinogenicity assays showed no increase in malignancies 6

Clinical Pitfalls to Avoid

• Never prescribe for children under 10 years 1
• Never instruct patients to chew or open capsules 1
• Never prescribe more than 600 mg daily or 200 mg per dose 1
• Always counsel patients on keeping medication away from children 1, 4
• Always warn about rapid onset of life-threatening toxicity in overdose 2, 3
• Always screen for prior sensitivity to local anesthetics (procaine, tetracaine) 1