Clinical data | |
---|---|
Trade names | Tessalon, others |
Other names | Benzononatine; Egyt-13; KM-65 [1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682640 |
License data |
|
Routes of administration | By mouth |
Drug class | Antitussives; Local anesthetics; Sodium channel blockers |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Onset of action | 15–20 minutes [3] [5] |
Elimination half-life | 1 hour [6] [ unreliable medical source? ] |
Duration of action | 3–8 hours [3] [5] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.002.904 |
Chemical and physical data | |
Formula | C30H53NO11 |
Molar mass | 603.750 g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
Benzonatate, sold under the brand name Tessalon among others, is a medication that is used for the symptomatic relief of cough. [7] [8] A 2023 systematic review found that there is inadequate evidence to support the effectiveness and 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]
Side effects include sleepiness, dizziness, headache, upset stomach, skin rash, hallucinations, and allergic reactions. [7] Overdosage can result in serious adverse effects including seizures, irregular heartbeat, cardiac arrest, and death. [10] [11] Overdose of only a small number of capsules can be fatal. [11] Chewing or sucking on the capsule, releasing the drug into the mouth, can also lead to laryngospasm, bronchospasm, and circulatory collapse. [7] It is unclear if use in pregnancy or breastfeeding is safe. [12] Benzonatate is a local anesthetic and voltage-gated sodium channel blocker. [6] [ unreliable medical source? ] It is theorized to work by inhibiting 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. [5] [7] It is available as a 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]
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 systematic review of the literature of benzonatate for cough was published in 2023. [9] The review identified 37 relevant articles including 21 cohort studies, 5 experimental studies, and 11 case studies and series. [9] The data were of very low quality. [9] Most of the studies on benzonatate are decades old and were conducted shortly after its introduction. [13] The systematic review concluded that there is inadequate evidence to support the effectiveness and 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]
Benzonatate has been reported to have use in the suppression of hiccups. [8]
Benzonatate acts as a local anesthetic and the liquid inside the capsule can be applied in the mouth to numb the 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]
Benzonatate is available in the form of 100, 150, and 200 mg oral capsules. [5] [3] [20]
Hypersensitivity to benzonatate or any related compounds is a contraindication to its administration. [3]
Benzonatate is generally well-tolerated[ vague ] if the liquid-capsule is swallowed intact. [7] Potential adverse effects of benzonatate include:
Benzonatate is structurally related to anesthetic medications of the para-aminobenzoic acid (PABA) class which includes procaine and tetracaine. [3] [22] [13] Procaine and tetracaine, previously used heavily in the fields of dentistry and anesthesiology, have fallen out of favor due to allergies associated with their metabolites. [22] Similarly, severe hypersensitivity reactions to benzonatate have been reported and include symptoms of laryngospasm, bronchospasm, and cardiovascular collapse. [3] [23] These reactions are possibly associated with chewing, sucking, or crushing the capsule in the mouth. [3] [22]
Benzonatate should be swallowed whole. [3] Crushing or sucking on the liquid-filled capsule, or "softgel," will cause release of benzonatate from the capsule and can produce a temporary local anesthesia of the oral mucosa. [3] Rapid development of numbness of the tongue and choking can occur. [3] [22] In severe cases, excessive absorption can lead to laryngospasm, bronchospasm, seizures, and 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]
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]
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]
It is not known if benzonatate can cause fetal harm to a pregnant woman or if it can affect reproduction capacity. [3] [12] Animal reproductive studies have not been conducted with benzonatate to evaluate its teratogenicity. [3]
It is not known whether benzonatate is excreted in human milk. [3] [12]
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. [22] Toxicity above the therapeutic dose is relatively low and ingestion of a small handful of pills can cause symptoms of overdose. [22] [19] Children are at an increased risk for toxicity, which have occurred with administration of only one or two capsules. [24] [25] [19] Following cardiopulmonary collapse with benzonatate overdose, most people have significant 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]
Benzonatate is chemically similar to other local anesthetics such as tetracaine and procaine, and shares their pharmacology. [22]
Similar to other local anesthetics, benzonatate is a potent voltage-gated sodium channel blocker. [22] 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. [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]
The antitussive effect of benzonatate begins within 15 to 20 minutes after oral administration and typically lasts between 3 and 8 hours. [3] [5] 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 routes, including rectal administration, subcutaneous injection, intramuscular injection, and intravenous infusion. [5]
Benzonatate is a butylamine, para-amino-benzoic acid, or long-chain polyglycol, structurally related to other ester local anesthetics such as procaine and tetracaine. [22] [6] [ unreliable medical source? ] [13] The 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]
Benzonatate was first synthesized in 1956 and was introduced as an antitussive in the United States in 1958. [5]
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. [24] [25] There are a variety of prescription opioid-based cough relievers, such as hydrocodone and codeine, but have unwanted side effects and potential of abuse and diversion. [22] However, benzonatate is currently the only prescription non-opioid antitussive and its usage has been rapidly increasing. [22] [19] The exact reasons of this increase are unclear. [19]
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]
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]
Benzonatate is available in the United States and Mexico. [13] [15]
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.
A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.
Cold medicines are a group of medications taken individually or in combination as a treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The term encompasses a broad array of drugs, including analgesics, antihistamines and decongestants, among many others. It also includes drugs which are marketed as cough suppressants or antitussives, but their effectiveness in reducing cough symptoms is unclear or minimal.
Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of the trade name Novocain or Novocaine, in some regions, procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker. Today, it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects.
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.
A drug overdose is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Typically it is used for cases when a risk to health will potentially result. An overdose may result in a toxic state or death.
Benadryl is a brand of various antihistamine medications used to stop allergies, whose content varies in different countries, but which includes some combination of diphenhydramine, acrivastine, and/or cetirizine.
An anesthetic or anaesthetic is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.
Fluticasone/salmeterol, sold under the brand name Advair among others, is a fixed-dose combination medication containing fluticasone propionate and salmeterol. It is used in the management of asthma and chronic obstructive pulmonary disease (COPD). It is used by inhaling the medication into the lungs.
Dexmethylphenidate, sold under the brand name Focalin among others, is a potent central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours. It is the more active enantiomer of methylphenidate.
Vicks DayQuil is an over-the-counter combination medication product used for the temporary relief of common cold and flu symptoms. DayQuil is available in several formulations.
Guaifenesin, also known as glyceryl guaiacolate, is an expectorant medication taken by mouth and marketed as an aid to eliminate sputum from the respiratory tract. Chemically, it is an ether of guaiacol and glycerine. It may be used in combination with other medications. A 2014 study found that guaifenesin has no effect on sputum production or clearance in upper respiratory infections.
Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive and local anaesthetic effects. The drug has been taken off the market in Europe and the US due to concerns of fatal overdoses and heart arrhythmias. It is still available in Australia, albeit with restrictions after an application by its manufacturer to review its proposed banning. Its onset of analgesia is said to be 20–30 minutes and peak effects are seen about 1.5–2.0 hours after oral administration.
Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD. It can be taken in various ways including by mouth, injection into a muscle, and inhalation.
Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease feeling in a specific area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of epinephrine to increase the duration of its action. It typically begins working within 15 minutes and lasts for 2 to 8 hours.
Dextromethorphan (DXM) is a cough suppressant used in many cough and cold medicines. It affects serotonin, norepinephrine, NMDA, and sigma-1 receptors in the brain, all of which have been implicated in the pathophysiology of depression. In 2022, the FDA approved the combination dextromethorphan/bupropion to serve as a rapid acting antidepressant in patients with major depressive disorder.
Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist. It was approved for use by the Food and Drug Administration in the United States in 2018.
A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.
An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that can cause hypoxia from slow and shallow breathing. Other symptoms include small pupils, and unconsciousness; however, its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.
Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. The most common symptoms of overdose include central nervous system (CNS) depression, impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of benzodiazepine overdose. There is an antidote, flumazenil, but its use is controversial.