Review of the Cough Medications Dextromethorphan and Benzonatate

Cough is the body’s natural reflexive response to irritants in the airways. This automatic mechanism helps clean the lungs to maintain efficient breathing. Mucus normally lines the walls of the airways in the lungs and captures foreign material, such as inhaled smoke and virus particles.[1] Hair-like projections called cilia normally push this material upward and out of the airways. But coughing adds an additional, rapid-fire means of removing unwanted material and excess mucus from the lungs.

A cough is beneficial if it brings up material, such as sputum (phlegm), from the airways and lungs. This is known as a wet or productive cough and often occurs with colds, bronchitis and pneumonia.[2] A dry, hacking, nonproductive cough, on the other hand, can be irritating and interfere with sleep.

Despite its importance in maintaining clear airways and lung health, cough is one of the most common symptoms for which patients seek medical attention and is responsible for millions of doctor visits in the U.S. every year.

Cough management

Cough can be managed in different ways depending on the cause. It typically is the symptom of an underlying medical problem such as an upper respiratory infection, pneumonia, asthma or chronic obstructive pulmonary disease.[3] It also occurs following exposure to inhaled irritants such as cigarette smoke or air pollution. Therefore, it is important to identify and treat the underlying cause of a cough whenever possible.

Cough suppressants have been marketed for decades for the treatment of acute cough that occurs with the common cold and other upper respiratory infections. For many years, we generally have recommended against the use of cough suppressants because they have not been shown to be any more effective than placebo in relieving symptoms. Furthermore, most acute coughs are self-limiting and do not require treatment.

Dextromethorphan

Dextromethorphan is the most commonly used cough suppressant. It is available as an over-the-counter (OTC) single-drug product under the brand name DELSYM and multiple generics for both children and adults. It is also available in multiple combination cold medicine products in both prescription and OTC forms under the brand names BROMFED DM and MUCINEX DM, respectively, and multiple generics.

Since 2004, Public Citizen’s Health Research Group has designated dextromethorphan as Do Not Use.[4] This designation was prompted by a study published in the journal Pediatrics in 2004, which showed that dextromethorphan was not any more effective than placebo in providing nighttime symptomatic relief in children with acute cough, nor did it improve sleep quality in their parents.[5]

This finding was confirmed by a second study published in the Archives of Pediatrics and Adolescent Medicine in 2007,[6] which compared honey, dextromethorphan and no treatment. The investigators found that honey was superior to both dextromethorphan and no treatment in providing nighttime relief of children’s cough and sleep difficulties due to upper respiratory tract infection. Moreover, it was determined that in comparison with no treatment, dextromethorphan treatment did not improve nighttime cough symptoms or sleep.

Additionally, the American Academy of Pediatrics’ Committee on Drugs has not supported the use of dextromethorphan to treat cough primarily because there is a lack of proven benefit and some potential for toxicity and overdose.[7]

In 2005, the Food and Drug Administration (FDA) issued a public advisory warning about the abuse of dextromethorphan after five reported deaths of teenagers who were abusing the drug. Abuse of this medication can lead to death or serious adverse effects such as psychosis, mania, hallucinations, seizures, loss of consciousness, brain damage and abnormal heart rhythms.[8]

In addition to the abuse potential of this drug, dextromethorphan also can have significant adverse effects when taken as intended, particularly when combined with some other medications that strongly increase serotonin effects. This can produce dangerous reactions, such as serotonin syndrome — a rare but serious condition that usually occurs when two or more drugs combine or interact to create too much serotonin in the body. In severe cases, seizures, coma and death can occur.[9]

Benzonatate

Benzonatate (TESSALON) is a prescription drug that was first marketed in the U.S. in 1958 and is approved by the FDA for the symptomatic relief of cough in patients older than 10 years.[10] The safety and effectiveness of benzonatate in children younger than 10 years have not been established. The drug is chemically related to anesthetic agents such as procaine and tetracaine.

In the absence of convincing published research on the value of benzonatate in the management of cough due to upper respiratory tract infection, we do not recommend it for this use. The best therapeutic role for this drug may be in the management of cough due to lung cancer. We therefore have designated benzonatate as Limited Use.

Severe hypersensitivity reactions that include cardiovascular collapse have been reported when the benzonatate capsule is sucked or chewed instead of swallowed. Also, because of the drug’s local anesthetic effect, choking can occur when the capsule is sucked or chewed.

In December 2010, the FDA issued a warning to the public concerning the use of benzonatate in children younger than 10. The warning stated that accidental ingestion of benzonatate by children in this age group could result in death from overdose. Signs and symptoms of benzonatate overdose include restlessness, tremors, convulsions, coma and cardiac arrest. The advisory further stated that these symptoms can occur rapidly after ingestion (within 15-20 minutes) and that deaths in children have been reported within hours of accidental ingestion.[11]

What You Can Do

We recommend against the use of any cough suppressant, including dextromethorphan and benzonatate, in children or adults to treat acute cough, particularly for a productive cough. Cough plays an important role in keeping the lungs healthy, and suppressing a cough may prolong the duration of an illness.[12]

Instead, you should try other ways to manage acute coughs, such as drinking plenty of fluids, using a cool (not warm) mist humidifier or taking a teaspoonful of honey. You also should avoid irritants, such as cigarette smoke, that can exacerbate cough. Call your doctor if your cough lasts eight weeks or longer or if you cough up blood.
 

References

[1] Irwin RS, Boulet LP, Cloutier MM, et al. Managing cough as a defense mechanism and as a symptom. Chest. 1998;114(2):133S-181S.

[2] Martin MJ, Harrison TW. Causes of chronic productive cough: an approach to management. Respir Med. 2015;109(9):1105-1113.

[3] Irwin RS, Boulet LP, Cloutier MM, et al. Managing cough as a defense mechanism and as a symptom. Chest. 1998;114(2):133S-181S.

[4] Worst Pills, Best Pills. Drug profile: dextromethorphan. /monographs/view/206. Accessed October 29, 2019.

[5] Paul IM, Yoder KE, Crowell KR, et al. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004;114(1):e85-90.

[6] Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med. 2007;161(12):1140-1146.

[7] American Academy of Pediatrics, Committee on Drugs. Use of codeine- and dextromethorphan-containing cough remedies in children. Pediatrics. 1997;99(6):918-920. https://pediatrics.aappublications.org/content/pediatrics/99/6/918.full.pdf. Accessed October 10, 2019.

[8] Rosenbaum C, Boyer EW. Dextromethorphan abuse and poisoning: clinical features and diagnosis. Up to Date. Mary 20, 2019.

[9] Ibid.

[10] Pfizer Laboratories. Label: benzonatate (TESSALON) label. January 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8edd07a0-5f5b-9000-bafb-dbf8ff7609d4&type=display. Accessed October 29, 2019.

[11] Food and Drug Administration. FDA drug safety communication: Death resulting from overdose after accidental ingestion of Tessalon (benzonatate) by children under 10 years of age. December 14, 2010. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-death-resulting-overdose-after-accidental-ingestion-tessalon. Accessed October 29, 2019.

[12] Sharma S, Hashmi MF, Alhajjaj MS. Cough. [Updated 2019 Sep 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493221/.