Benzonatate

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Benzonatate
Clinical data
Trade namesTessalon, others
Other namesBenzononatine; Egyt-13; KM-65[1]
AHFS/Drugs.comMonograph
MedlinePlusa682640
License data
Antitussives; Local anesthetics; Sodium channel blockers
ATC code
Legal status
Legal status
Pharmacokinetic data
Onset of action15–20 minutes[3][5]
Elimination half-life1 hour[6][unreliable medical source?]
Duration of action3–8 hours[3][5]
Identifiers
  • 2,5,8,11,14,17,20,23,26-Nonaoxaoctacosan-28-yl 4-(butylamino)benzoate
JSmol)
  • O=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCOC)c1ccc(NCCCC)cc1
  • InChI=1S/C30H53NO11/c1-3-4-9-31-29-7-5-28(6-8-29)30(32)42-27-26-41-25-24-40-23-22-39-21-20-38-19-18-37-17-16-36-15-14-35-13-12-34-11-10-33-2/h5-8,31H,3-4,9-27H2,1-2H3 checkY
  • Key:MAFMQEKGGFWBAB-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Benzonatate, sold under the brand name Tessalon among others, is a

safety of benzonatate for cough and highlighted rising safety concerns.[9] Benzonatate is taken by mouth.[7][5] Effects generally begin within 20 minutes and last 3 to 8 hours.[7][3]

stretch receptors in the lungs, in turn suppressing the cough reflex in the brain.[6][unreliable medical source?][7] Benzonatate is structurally related to other local anesthetics like procaine and tetracaine.[13][6][unreliable medical source?
]

Benzonatate was discovered in 1956 and was approved for medical use in the United States in 1958.

generic medication.[10] Availability worldwide is limited, with the drug remaining marketed only in the United States and Mexico.[14][13][15] In 2021, it was the 158th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[16][17]

Medical uses

100mg generic Benzonatate capsules
100 mg generic benzonatate capsules

Cough

Benzonatate is a prescription non-opioid alternative for the symptomatic relief of cough.[7][10] It has been found to improve cough associated with a variety of respiratory conditions including asthma, bronchitis, pneumonia, tuberculosis, pneumothorax, opioid-resistant cough in lung cancer, and emphysema.[7][5][18]

Benzonatate also reduces the consistency and volume of sputum production associated with cough in those with chronic obstructive pulmonary disease (COPD).[5]

Compared to codeine, benzonatate has been reported to be more effective in reducing the frequency of induced cough in experiments.[7]

Benzonatate does not treat the underlying cause of the cough.[19]

According to a 2001 literature review, more than 29 clinical studies have assessed benzonatate for the treatment of cough in more than 2,100 patients.[5]

A

safety of benzonatate and emphasized rising safety concerns surrounding the drug.[9] It further concluded that there is a need for large observational studies or randomized trials to assess the place of benzonatate in modern medicine.[9]

Hiccups

Benzonatate has been reported to have use in the suppression of hiccups.[8]

Intubation

Benzonatate acts as a

oropharynx for awake intubation.[7] However, there can be life-threatening adverse effects when the medication is absorbed by the oral mucosa, including choking, hypersensitivity reactions, and circulatory collapse.[7]

Available forms

Benzonatate is available in the form of 100, 150, and 200 mg oral capsules.[5][3][20]

Contraindications

Hypersensitivity to benzonatate or any related compounds is a contraindication to its administration.[3]

Side effects

Benzonatate is generally well-tolerated[vague] if the liquid-capsule is swallowed intact.[7] Potential adverse effects of benzonatate include:

  • Constipation, dizziness, fatigue, stuffy nose, nausea, headache are frequently reported.[21]
  • Sedation, a feeling of numbness in the chest, sensation of burning in the eyes, a vague "chilly" sensation, itchiness, and rashes are also possible.[7][3]
  • Ingestion of a small handful of capsules has caused
    seizures, cardiac arrhythmia, and death in adults.[22]

Hypersensitivity reactions

Benzonatate is structurally related to

cardiovascular collapse.[3][23] These reactions are possibly associated with chewing, sucking, or crushing the capsule in the mouth.[3][22]

Improper use

Benzonatate should be swallowed whole.

circulatory collapse.[3][22] This may be due to a hypersensitivity reaction to benzonatate or a systemic local anesthetic toxicity, both of which have similar symptoms.[22] 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.[22]

Psychiatric effects

Isolated cases of bizarre behavior, mental confusion, and visual hallucinations have been reported during concurrent use with other prescribed medications.[3] Central nervous system effects associated with other para-aminobenzoic acid (PABA) derivative local anesthetics, for example procaine or tetracaine, could occur with benzonatate and should be considered.[7]

Children

Safety and efficacy in children below the age of ten have not been established.[3] Accidental ingestion resulting in death has been reported in children below the age of ten.[3] Benzonatate may be attractive to children due to its appearance, a round-shaped liquid-filled gelatin capsule, which looks like candy.[23][24] Chewing or sucking of a single capsule can cause death of a small child.[3][24] Signs and symptoms can occur rapidly after ingestion (within 15–20 minutes) and include restlessness, tremors, convulsions, coma, and cardiac arrest.[24] Death has been reported within one hour of ingestion.[21][24]

Pregnancy and breast feeding

It is not known if benzonatate can cause fetal harm to a pregnant woman or if it can affect reproduction capacity.

teratogenicity.[3]

It is not known whether benzonatate is excreted in human milk.[3][12]

Overdose

Benzonatate is chemically similar to other local anesthetics such as tetracaine and procaine, and shares their pharmacology and toxicology.[22]

Benzonatate overdose is characterized by symptoms of restlessness, tremors,

seizures, abnormal heart rhythms (cardiac arrhythmia), cerebral edema, absent breathing (apnea), fast heart beat (tachycardia), and in severe cases, coma and death.[7][3][25][19] Symptoms develop rapidly, typically within 5 minutes to 1 hour of ingestion.[3][19][11][6][unreliable medical source?] Treatment focuses on removal of gastric contents and on managing symptoms of sedation, convulsions, apnea, and cardiac arrhythmia.[3]

Despite a long history of safe and appropriate usage, the safety margin of benzonatate is reportedly narrow.

neurological deficits or other end-organ damage.[11]

Due to increasing usage of benzonatate and rapid onset of symptoms, there are accumulating cases of benzonatate overdose deaths, especially in children.[19][11]

Pharmacology

Benzonatate is chemically similar to other local anesthetics such as tetracaine and procaine, and shares their pharmacology.[22]

Pharmacodynamics

Similar to other

lower airway and lung.[7][8] This dampens their activity and reduces the cough reflex.[7][3] Benzonatate also has central antitussive activity on the cough center in central nervous system at the level of the medulla.[7][5] However, there is minimal inhibition of the respiratory center at a therapeutic dosage.[3]

Pharmacokinetics

The

elimination half-life of benzonatate has been reported to be 1 hour.[6][unreliable medical source?
]

Benzonatate is hydrolyzed by plasma butyrylcholinesterase (BChE) to the metabolite 4-(butylamino)benzoic acid (BABA) as well as polyethylene glycol monomethyl ethers.[22] Like many other local anesthetic esters, the hydrolysis of the parent compound is rapid.[22] 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.[22]

Aside from oral administration, benzonatate has also been used by a variety of other

intravenous infusion.[5]

Chemistry

Benzonatate is a

molecular weight of benzonatate is 603.7 g/mol.[3] However, the reference standard for benzonatate is a mixture of n-ethoxy compounds, differing in the abundance of 7 to 9 repeating units, with an average molecular weight of 612.23 g/mol.[22] There is also evidence that the compound is not uniform between manufacturers.[22]

History

Benzonatate was first synthesized in 1956 and was introduced as an antitussive in the United States in 1958.[5]

Society and culture

Benzonatate was first made available in the United States in 1958 as a prescription medication for the treatment of cough in individuals over the age of 10.

antitussive and its usage has been rapidly increasing.[22][19] The exact reasons of this increase are unclear.[19]

Economics

In the United States between 2004 and 2009, prescriptions increased 50% from 3.1 million to 4.7 million, the market share of benzonatate among antitussives increased from 6.3% to 13%, and the estimated number of children under the age of 10 years receiving benzonatate increased from 10,000 to 19,000.[22][19] Throughout this same period, greater than 90% of prescriptions were given to those 18 or older.[19] The majority of prescriptions were given by general, family, internal, and physicians with pediatricians account for about 3% of prescribed benzonatate.[19]

In 2021, it was the 158th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[16][17]

Brand names

Tessalon is a brand name version of benzonatate manufactured by Pfizer.[22][19] It is available as perles (capsules).[3] Zonatuss was a brand name manufactured by Atley Pharmaceuticals, Inc. and Vertical Pharmaceuticals, Inc.[26][27] Other brand names of benzonatate include Exangit, Tessalin, Tesalon, Tusical, Tusitato, and Ventussin.[1]

Availability

Benzonatate is available in the United States and Mexico.[13][15]

References

  1. ^
    ISBN 978-1-4757-2085-3
    . Retrieved 12 January 2024.
  2. FDA
    . Retrieved 22 October 2023.
  3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac "Tessalon - benzonatate capsule". DailyMed. 20 November 2019. Retrieved 21 April 2020.
  4. ^ "Benzonatate capsule". DailyMed. 3 January 2024. Retrieved 20 February 2024.
  5. ^
    S2CID 25881426
    .
  6. ^ a b c d e f g "Benzonatate".
  7. ^ a b c d e f g h i j k l m n o p q r s "Benzonatate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 23 March 2019.
  8. ^
    PMID 21174569
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  9. ^
    S2CID 256102939
    .
  10. ^
    PMID 30625123
    .
  11. ^
    S2CID 235735410
    .
  12. ^ a b c "Benzonatate Use During Pregnancy". Drugs.com. 10 October 2019. Retrieved 20 February 2020.
  13. ^
    PMID 18771744
    .
  14. ISBN 9781437721942
    .
  15. ^
    ISBN 978-3-88763-075-1
    . Retrieved 12 January 2024.
  16. ^ a b "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  17. ^ a b "Benzonatate - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  18. PMID 16302303
    .
  19. ^
    S2CID 35165660
    .
  20. ^ "Tessalon, Tessalon Perles (benzonatate) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 29 February 2024.
  21. ^ a b "Benzonatate (Professional Patient Advice)". Drugs.com. 4 March 2020. Retrieved 21 April 2020.
  22. ^
    PMID 28334901
    .
  23. ^
    PMID 30625123
    .
  24. ^ a b c d e f "FDA Drug Safety Communication: Death resulting from overdose after accidental ingestion of Tessalon (benzonatate) by children under 10 years of age". U.S. Food and Drug Administration (FDA). 28 June 2019. Retrieved 22 April 2020.
  25. ^
    PMID 21304443
    .
  26. ^ "Zonatuss (Benzonatate Capsules USP, 150 mg)". DailyMed. 2 June 2010. Retrieved 20 August 2020.
  27. ^ "Zonatuss (Benzonatate Capsules USP, 150 mg)". DailyMed. 31 October 2016. Retrieved 20 August 2020.