April 25, 2025
Cough is an adaptive physiologic mechanism which protects the airway from aspiration and expels mucus and debris from the lungs. However, a cough is also bothersome, and families often ask prescribers for cough medications in the setting of upper respiratory infection which brings to the question of efficacy.
There are many options for cough suppressing medications including over the counter medications, prescription medications, and herbal/non-pharmacologic remedies.
Over the counter cough medications primarily consist of dextromethorphan, guaifenesin, and antihistamines1,2. Dextromethorphan, the main ingredient in Robitussin, has not shown efficacy in randomized trials, however, is relatively safe and is found in many combination OTCs. Diphenhydramine and other antihistamines are also available over the counter and have shown mild efficacy, though have unfavorable side-effect profiles including somnolence, hallucinations, and paradoxical reactions.
Prescription medications include codeine, promethazine, and benzonatate. Codeine is an opioid which is no longer used in children due to high risk of respiratory depression and abuse potential. Promethazine is an antihistamine with similarly low efficacy as OTC antihistamines though a higher abuse potential than its cousin drugs. Benzonatate (Tessalon Perles) inhibits pulmonary stretch receptors, though is not very effective. Benzonatate has a high risk for respiratory depression and death, especially in children under 10.
Herbal cold remedies like Echinacea or Pelargonium sidoides (a geranium extract) are generally safe but have very limited evidence. Other non-pharmacologic cough medications such as Zarbees are typically honey or syrup based and work by coating the throat. Interestingly, half a teaspoon of honey is a more effective cough relief than dextromethorphan or diphenhydramine in some studies3,4.
With limited positive impact, what are the risks of anti-tussive medications?
Risks can include death. In one study, adverse effects for all cough medications in children were rare and usually non-fatal (>99%), mostly consisting of tachycardia, somnolence, and hallucinations, and mostly secondary to accidental unsupervised ingestions5. In another study, among accidental exposures of Benzonatate under the recommended 10 years of age, a total of 2.8% of exposures were deemed clinically moderate or severe, including three deaths. The majority in this study had no clinical impact (79%), however the potential cause for death warrants that this medication be locked away from small children5. Prescription codeine and promethazine are very risky and are not recommended for children of any age. Lastly, honey should not be prescribed for infants younger than 12 months old due to risk of infant botulism6.
Ultimately, cough suppressing medications are not very effective and carry a non-zero risk of adverse events, with prescription medications being much riskier especially for children. The risk/benefit suggests honey alone for URI-related cough relief in children >12 months of age7.
Brian Ward, MD, PGY-3, Department of Pediatrics
Well done review by Dr. Ward. Recently, we had a toddler go into cardiac arrest from inadvertent Tessalon Perle (Benzonatate) ingestion. The child had a return of spontaneous circulation but this case highlights the highly dangerous nature of benzonatate in small children. Therefore, if this medication is prescribed at all, it is important that all pharmacists and prescribers ensure patients know to keep this medication up and locked away from children. Benzonatate poisoning should be treated like other sodium channel blocking agents with sodium bicarbonate for widened QRS with or without hypotension, benzodiazepines for seizures, and consideration of lipid emulsion therapy for hemodynamic instability and dysrhythmias. As always, the Tennessee Poison Center is here 24/7/365 to help guide management at 1-800-222-1222.
**Dr. Ward is our Second volunteer to do a Question of the Week! Thank you, Dr. Ward. Please submit more. We welcome any of you to submit a question if you are interested.**
Rebecca Bruccoleri, MD, Medical Director, Tennessee Poison Center
References:
- Lam SHF, Homme J, Avarello J, Heins A, Pauze D, Mace S, Dietrich A, Stoner M, Chumpitazi CE, Saidinejad M. Use of antitussive medications in acute cough in young children. J Am Coll Emerg Physicians Open. 2021 Jun 18;2(3):e12467. doi: 10.1002/emp2.12467. PMID: 34179887; PMCID: PMC8212563.
- Smith SM, Schroeder K, Fahey T. Over‐the‐counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database of System-atic Reviews 2014, Issue 11. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub5.
- Shadkam MN, Mozaffari-Khosravi H, Mozayan MR. A comparison of the effect of honey, dextromethorphan, and diphenhydramine on nightly cough and sleep quality in children and their parents. J Altern Complement Med. 2010 Jul;16(7):787-93. doi: 10.1089/acm.2009.0311. PMID: 20618098.
- Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM. 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. doi:10.1001/archpedi.161.12.1140
- Kim I, Goulding M, Tian F, Karami S, Pham T, Cheng C, Biehl A, Muñoz M. Benzonatate Exposure Trends and Adverse Events. Pediatrics. 2022 Dec 1;150(6):e2022057779. doi: 10.1542/peds.2022-057779. PMID: 36377394; PMCID: PMC9732921.
- Arnon SS, Midura TF, Damus K, Thompson B, Wood RM, Chin J. Honey and other envi-ronmental risk factors for infant botulism. J Pediatr. 1979 Feb;94(2):331-6. doi: 10.1016/s0022-3476(79)80863-x. PMID: 368301.
- Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS; CHEST Expert Cough Panel. Pharma-cologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report. Chest. 2017 Nov;152(5):1021-1037. doi: 10.1016/j.chest.2017.08.009. Epub 2017 Aug 22. PMID: 28837801; PMCID: PMC6026258.