Rapid development of numbness of the tongue and choking can occur. In severe cases, excessive absorption can lead to laryngospasm, bronchospasm, seizures, and circulatory collapse. This may be due to a hypersensitivity reaction to benzonatate or a systemic local anesthetic toxicity, both of which have similar symptoms. There is a potential for these adverse effects to occur at a therapeutic dose, that is, a single capsule, if chewed or sucked on in the mouth. Psychiatric effects
Isolated cases of bizarre behavior, mental confusion, and visual hallucinations have been reported during concurrent use with other prescribed medications. Central nervous system effects associated with other para-aminobenozic acid (PABA) derivative local anesthetics, for example procaine or tetracaine, could occur with benzonatate and should be considered. Children
Safety and efficacy in children below the age of 10 have not been established. Accidental ingestion resulting in death has been reported in children below the age of 10. Benzonatate may be attractive to children due to its appearance, a round-shaped liquid-filled gelatin capsule, which looks like candy. Chewing or sucking of a single capsule can cause death of a small child. Signs and symptoms can occur rapidly after ingestion (within 15–20 minutes) and include restlessness, tremors, convulsions, coma, and cardiac arrest. Death has been reported within one hour of ingestion. Pregnancy and breast feeding
In the U.S., benzonatate is classified by the U.S. Food and Drug Administration (FDA) as pregnancy category C. It is not known if benzonatate can cause fetal harm to a pregnant woman or if it can affect reproduction capacity.
After absorption and circulation to the respiratory tract, benzonatate acts as a local anesthetic, decreasing the sensitivity of vagal afferent fibers and stretch receptors in the bronchi, alveoli, and pleura in the lower airway and lung. This dampens their activity and reduces the cough reflex. Benzonatate also has central antitussive activity on the cough center in central nervous system at the level of the medulla. However, there is minimal inhibition of the respiratory center at a therapeutic dosage. Pharmacokinetics
The antitussive effect of benzonatate begins within 15 to 20 minutes after oral administration and typically lasts between 3 and 8 hours.Benzonatate is hydrolyzed by plasma butyrylcholinesterase (BChE) to the metabolite 4-(butylamino)benzoic acid (BABA) as well as polyethylene glycol monomethyl esters. Like many other local anesthetic esters, the hydrolysis of the parent compound is rapid. There are concerns that those with pseudocholinesterase deficiencies may have an increased sensitivity to benzonatate as this hydrolysis is impaired, leading to increased levels of circulating medication. Chemical structure
Benzonatate is a butylamine, structurally related to other polyglycol ester local anesthetics such as procaine and tetracaine. The molecular weight of benzonatate is 603.7 g/mol. However, the reference standard for benzonatate is a mixture of n-ethoxy compounds, differing in the abundance of 7-9 repeating units, with an average molecular weight of 612.23 g/mol. There is also evidence that the compound is not uniform between manufacturers. Society and culture
Benzonatate was first made available in the U.S. in 1958 as a prescription medication for the treatment of cough in individuals over the age of 10.