Benzonatate

603.74

603.74

203-194-7

760128

DTXSID9022655

Colorless to faintly yellow oil

R - Respiratory system

121

1.2

Liquid

1.096±0.06 g/cm3(Predicted)

649.0±55.0 °C(Predicted)

346.3ºC

1.495

soluble in most organic solvents except aliphatic hydrocarbons

Commercially available benzonatate liquid-filled capsules should be stored in tight, light-resistant containers at a controlled room temperature of 15-30 deg C.

4.22X10-14 mm Hg at 25 deg C (est)

LD50 oral in mouse: 400mg/kg

pKa = 3.03 (est)

Hydroxyl radical reaction rate constant = 1.49X10-10 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

Xi

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H412

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including benzonatate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

This material is assumed to be combustible.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials. ... As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing vapor. Ventilate area and wash spill site. Place spillage in appropriately labeled container for disposal.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Engineering controls such as exhaust ventilation are recommended.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

The lowest published toxic dose (TDLo) from oral administration in man is 51 mg/kg. The oral LD50 is 400 mg/kg and the subcutaneous LD50 is 100 mg/kg in mice. The signs and symptoms of overdose are typically observed within 15 to 20 minutes and can lead to neurological and cardiovascular toxicity, which is related to blocked sodium channels. Intentional and unintentional death from overdose may occur. The risk of overdose is highest in children and toxicity may result from the ingestion of 1 or 2 capsules in this age group. If capsules are chewed or dissolved in the mouth, oropharyngeal anesthesia will develop rapidly, which may cause choking and a compromised airway function. Symptoms arising from CNS stimulation include restlessness and tremors, which may lead to clonic convulsions followed by profound CNS depression. Within 1 hour following ingestion, convulsions, coma, cerebral edema and cardiac arrest leading to death have been reported. Evacuation of gastric contents and administration of copious amounts of activated charcoal is advised. It is important to note that cough and gag reflexes may be significantly depressed even in conscious patients with overdose; special attention is needed to protect against aspiration of gastric contents. When intravenously administering short-acting barbiturates to treat convulsions, the dose should be carefully titrated for the smallest effective dose. Overdose should be managed with supportive care with continuous monitoring of neurologic and cardiovascular status. Intensive support of respiration and cardiovascular-renal function should be initiated for severe intoxication. Because benzonatate is structurally similar to local anesthetic agents, the use of intravenous lipid emulsion therapy in response to life-threatening cardiovascular collapse is also suggested.

Benzonatate is chemically related to anesthetic agents of the para-amino-benzoic acid class (e.g. procaine; tetracaine) and has been associated with adverse CNS effects possibly related to a prior sensitivity to related agents or interaction with concomitant medication.

Safety and effectiveness in children below the age of 10 have not been established. Accidental ingestion resulting in death has been reported in children below age 10. Keep out of reach of children.

There is limited information on the protein binding profile of benzonatate.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 197 workers (59 of these were female) were potentially exposed to benzonatate in the US(1).

Benzonatate is indicated for the symptomatic relief of cough.

Antitussive Agents|Tessalon is indicated for the symptomatic relief of cough. /Included in US product label/

Accidental ingestion of Tessalon resulting in death has been reported in children below age 10. Signs and symptoms of overdose have been reported within 15-20 minutes and death has been reported within one hour of ingestion. If accidental ingestion occurs, seek medical attention immediately|Safety and effectiveness in children below the age of 10 have not been established. Accidental ingestion resulting in death has been reported in children below age 10. Keep out of reach of children.|Severe hypersensitivity reactions (including bronchospasm, laryngospasm and cardiovascular collapse) have been reported which are possibly related to local anesthesia from sucking or chewing the capsule instead of swallowing it. Severe reactions have required intervention with vasopressor agents and supportive measures.|Benzonatate is chemically related to anesthetic agents of the para-amino-benzoic acid class (e.g. procaine; tetracaine) and has been associated with adverse CNS effects possibly related to a prior sensitivity to related agents or interaction with concomitant medication.|For more Drug Warnings (Complete) data for Benzonatate (8 total), please visit the HSDB record page.

Benzonatate suppresses cough associated with both acute and chronic respiratory conditions. Its works by desensitizing the pulmonary stretch receptors involved in the cough reflex. There are limited clinical trials of benzonatate; however, earlier studies demonstrated inhibition of experimentally-induced cough and subjectively-measured pathological cough by benzonatate. Benzonatate has no inhibitory effects on the respiratory center in recommended dosage. Its onset of action is within 15 to 20 minutes following administration and its duration of effect is about 3 to 8 hours.

Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally. (See all compounds classified as Antitussive Agents.)

Following oral administration, benzonatate enters the systemic circulation via gastrointestinal absorption. The Cmax of benzonatate following oral administration of 100 mg in healthy Chinese volunteers was 1063 ± 460 ng/mL.|There is limited information on the route of elimination of benzonatate.|There is limited information on the volume of distribution of benzonatate.|There is limited information on the clearance of benzonatate.

Benzonatate is hydrolyzed to the major metabolite 4-(butylamino)benzoic acid (BABA) by plasma butyrylcholinesterase (BChE).

The half life of benzonatate following oral administration of 100 mg in healthy Chinese volunteers was 1.01 ± 0.41 h.

Benzonatate is a local anesthetic drug that acts peripherally by anesthetizing and reducing the activity of vagal stretch receptors or nerve fibres located in the respiratory passages, lungs, and pleura. Once the stretch receptors are stimulated, they send impulses to the cough centre located in the medulla via an afferent pathway consisting of sensory nerve fibres or the vagus nerve. The efferent signal is then generated that sends impulses to the expiratory muscles to produce a cough. Anesthetizing these receptors by benzonatate results in the inhibition of the cough reflex activity and cough production. Benzonatate also inhibits the transmission of impulses of the cough reflex in the vagal nuclei of the medulla. There are several proposed mechanisms of benzonatate; it is also a potent voltage-gated sodium channel inhibitor.|Benzonatate apparently inhibits cough production by anesthetizing stretch receptors of vagal afferent fibers in the bronchi, alveoli, and pleura that mediate the cough reflex; the drug also suppresses transmission of the cough reflex at the level of the medulla where the afferent impulse is transmitted to the motor nerves. The relationship between local anesthetic action and peripheral action on sensory nerve endings is not clear.

In case of overdose, seek medical attention immediately. Evacuate gastric contents and administer copious amounts of activated charcoal slurry. Even in the conscious patient, cough and gag reflexes may be so depressed as to necessitate special attention to protection against aspiration of gastric contents and orally administered materials. Convulsions should be treated with a short-acting barbiturate given intravenously and carefully titrated for the smallest effective dosage. Intensive support of respiration and cardiovascular-renal function is an essential feature of the treatment of severe intoxication from overdosage. Do not use CNS stimulants.|Emergency and supportive measures. Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, arrhythmias, and anaphylaxis if they occur. ... Monitor vital signs and ECG for at least 6 hours /Anesthetics, local/.|Decontamination. Parenteral exposure: Decontamination is not feasible. Ingestion:. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestins if activated charcoal can be given promptly. /Anesthetics, local/.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for Benzonatate (6 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ The signs and symptoms of overdose of benzonatate have been reported within 15-20 minutes. If capsules are chewed or dissolved in the mouth, oropharyngeal anesthesia will develop rapidly, which may cause choking and airway compromise. CNS stimulation may cause restlessness and tremors which may proceed to clonic convulsions followed by profound CNS depression. Convulsions, coma, cerebral edema and cardiac arrest leading to death have been reported within 1 hour of ingestion.|/SIGNS AND SYMPTOMS/ Accidental ingestion of Tessalon resulting in death has been reported in children below age 10. Signs and symptoms of overdose have been reported within 15-20 minutes and death has been reported within one hour of ingestion. If accidental ingestion occurs, seek medical attention immediately|/CASE REPORTS/ A 12-month-old male presented to the emergency department of a rural hospital following ingestion of an unknown amount of benzonatate. Upon arrival, the child was seizing and in full cardiac arrest. Resuscitative measures were unsuccessful and the child died shortly after arriving at the emergency department.|/CASE REPORTS/ A 17-year-old woman with no previous medical history presented to the Emergency Department (ED) status post cardiac arrest. One to two hours prior, the patient had ingested at least ten 200 mg Tessalon capsules as part of a suicide attempt. The patient was sedated, intubated, and given magnesium as prophylaxis against recurrent dysrhythmias. Emergent gastric lavage was performed and well tolerated. A 24 hr hypothermia protocol with 6 hr cooling period was initiated. Toxicological studies, chest radiograph, and a computed tomography scan of the head were all unremarkable. The patient was admitted to the Pediatric Intensive Care Unit for further work-up and supportive care. The patient was extubated and able to follow some commands 1 week post-admission. The patient developed blindness and experienced generalized confabulations, which did not resolve. Ingestion of Tessalon, a seemingly innocuous and widely prescribed antitussive, may pose a risk to patients due to its potential for the rapid development of life-threatening adverse events and limited treatment options in the overdose setting.|For more Human Toxicity Excerpts (Complete) data for Benzonatate (7 total), please visit the HSDB record page.

benzonatate

Table: Benzonatate Preparations [Table#7782]

Analyte: benzonatate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: benzonatate; matrix: chemical identification; procedure: liquid chromatography with ultraviolet detection comparison to standards|Analyte: benzonatate; matrix: chemical purity; procedure: reflux with sodium hydroxide; cool; add water and bromothymol blue; titrate with hydrochloric acid; perform a blank determination|Analyte: benzonatate; matrix: benzonatate capsules; procedure: liquid chromatography with ultraviolet detection at 310 nm and comparison to standards (chemical identification)|Analyte: benzonatate; matrix: benzonatate capsules; procedure: mixture of hydroxylamine hydrochloride and sodium hydroxide; add hydrochloric acid and ferric chloride; infrared absorption spectrophotometry with comparison to standards (chemical purity)

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