Pharmacotherapy of non-productive cough: What should a therapist know?
Abstract. Dry (non-productive) cough is one of the most common reasons for seeking medical care. Undoubtedly, to eliminate cough syndrome, it is first and foremost necessary to directly address its etiology. However, in some cases, the cause remains unclear for a long time, or an excruciating dry cough causes significant discomfort to the patient. It is worth noting that in most cases, a dry cough resolves on its own, without the need for antitussive medications. The main indications for antitussive therapy include pneumothorax, postoperative period, pertussis, a nagging cough that significantly worsens the patient’s condition, and preparation for bronchoscopy performing. The most effective and safe antitussive medications currently used in clinical practice are levodropropizine, prenoxdiazine, and butamirate.A.V. Budnevsky, S.N. Avdeev, E.S. Ovsyannikov, S.N. Feigelman, Ya.V. Ivashkina
Keywords
non-productive cough
acute respiratory viral infection
antitussive medications
References
1. Будневский А.В., Авдеев С.Н., Овсянников Е.С., Фейгельман С.Н., Чопоров О.Н., Максимов А.В., Перцев А.В. Спектральный анализ звуков кашля у больных COVID-19. Пульмонология. 2022;32(6):834–841. (Budnevsky AV, Avdeev SN, Ovsyannikov ES, Feygelman SN, Choporov ON, Maximov AV, Pertsev AV. Spectral analysis of cough sounds of patients with COVID-19. Pul'monologiya = Pulmonology. 2022;32(6):834–841 (In Russ.))
EDN: LJKOGO. https://doi.org/10.18093/0869-0189-2022-32-6-834-841
2. Климова Е.А., Самошкина Е.С. Сухой кашель. Инфекционные болезни: Новости. Мнения. Обучение. Журнал имени академика Н.Д. Ющука. 2013;2(3):39–44. (Klimova EA, Samoshkina ES. Dry cough. Infektsionnyye bolezni: Novosti. Mneniya. Obucheniye Zhurnal imeni akademika N.D. Yushchuka = Infectious Diseases: News. Opinions. Training. Journal named after academician N.D. Yushchuk. 2013;2(3):39–44 (In Russ.)). EDN: SFLEJR.
3. Joo YH, Kim HJ, Jeon YJ, Kim SW. Postnasal drip syndrome: A new definition and successful oral gargling treatment. Am J Otolaryngol. 2025;46(4):104617.
PMID: 40339213. https://doi.org/10.1016/j.amjoto.2025.104617
4. Зайцев А.А., Оковитый С.В., Мирошниченко Н.А., Крюков Е.В. Кашель. Методические рекомендации для врачей. М.: ФГБУ «Главный военный клинический госпиталь имени академика Н.Н. Бурденко» Министерства обороны Российской Федерации. 2021; 84 с. (Zaitsev AA, Okovityi SV, Miroshnichenko NA, Kryukov EV. Cough. Methodological recommendations for doctors. Moscow: Main Military Clinical Hospital named after academician N.N. Burdenko of the Ministry of Defence of the Russian Federation. 2021; 84 pp. (In Russ.)).
EDN: ISFFXZ. ISBN: 978-5-6045500-5-2
5. Wang N, Zhang Q, Wei JF. Cough syncope: A familiar stranger. Kaohsiung J Med Sci. 2024;40(7):685–86.
PMID: 38761411. PMCID: PMC11895576. https://doi.org/10.1002/kjm2.12830
6. O’Doherty DS. Tussive syncope and its relation to epilepsy. Neurology. 1953;3(1):16–21.
PMID: 13013494. https://doi.org/10.1212/wnl.3.1.16
7. Dickinson O, Akdemir B, Puppala VK, Krishnan B, Detloff BLS, Sakaguchi S et al. Blunted chronotropic response to hypotension in cough syncope. JACC Clin Electrophysiol. 2016;2(7):818–24.
PMID: 29759766. https://doi.org/10.1016/j.jacep.2016.02.017
8. Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014;108(2):244–51.
PMID: 24238768. https://doi.org/10.1016/j.rmed.2013.10.020
9. Будневский А.В., Авдеев С.Н., Овсянников Е.С., Фейгельман С.Н. Современный взгляд на патофизиологию кашля. Туберкулез и болезни легких. 2024;102(6):118–126. (Budnevskiy AV, Avdeev SN, Ovsyannikov ES, Feygelman SN. A modern view of cough pathophysiology. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Diseases. 2024;102(6):118–126 (In Russ.)).
http://doi.org/10.58838/2075-1230-2024-102-6-118-126
10. Аполлонова А.Д. Курение как социально-экономическая проблема в России и Китае. Историческая социология и современное социальное развитие в России и Китае: Сборник статей XVIII российско-китайской социологической конференции, Санкт-Петербург, 13–14 мая 2022 г. Санкт-Петербург: Центр научно-производственных технологий «Астерион». 2022; с. 278–79. (Apollonova AD. Smoking as a socio-economic problem in Russia and China. Historical Sociology and Modern Social Development in Russia and China: Collection of Articles of the XVIII Russian-Chinese Sociological Conference, St. Petersburg, May 13–14, 2022. Saint Petersburg: Asterion Research and Production Technology Center.2022; pp. 278–279 (In Russ.)).
11. Kotz D, Batra A, Kastaun S. Smoking cessation attempts and common strategies employed. Dtsch Arztebl Int. 2020;117(1–2):7–13.
PMID: 32008606. PMCID: PMC7008148. http://doi.org/10.3238/arztebl.2020.0007
12. Schmidt HD, Rupprecht LE, Addy NA. Neurobiological and neurophysiological mechanisms underlying nicotine seeking and smoking relapse. Mol Neuropsychiatry. 2019;4(4):169–89.
PMID: 30815453. PMCID: PMC6388439. http://doi.org/10.1159/000494799
13. Smith ML, Gotway MB, Crotty Alexander LE, Hariri LP. Vaping-related lung injury. Virchows Arch. 2021;478(1):81–88.
PMID: 33106908. PMCID: PMC7590536. http://doi.org/10.1007/s00428-020-02943-0
14. Harris KK, Zopey M, Friedman TC. Metabolic effects of smoking cessation. Nat Rev Endocrinol. 2016;12(5);299–308.
PMID: 26939981. PMCID: PMC5021526. http://doi.org/10.1038/nrendo.2016.32. Erratum in: Nat Rev Endocrinol. 2016;12(11):684. PMID: 26939981. PMCID: PMC5021526. http://doi.org/10.1038/nrendo.2016.171
15. Budnevsky AV, Ovsyannikov ES, Feigelman SN, Kitoyan AG, Budnevskaya SA. Effectiveness of peripheral antitussives in patients with dry postinfectious cough. Indian J Med Spec. 2025;16(1):29–34.
http://doi.org/10.4103/injms.injms_50_24
16. Будневский А.В., Овсянников Е.С., Фейгельман С.Н. Исследование эффективности Левопронта в лечении непродуктивного кашля. Практическая пульмонология. 2021;(2):65–74. (Budnevsky AV, Ovsyannikov ES, Feigelman SN. Investigation of the effectiveness of Levopront in the treatment of unproductive cough. Prakticheskaya pul’monologiya = Practical Pulmonology. 2021;(2):65–74 (In Russ.)).
EDN: VMAKUE. http://doi.org/10.24412/2409-6636-2021-12693
17. Инструкция по медицинскому применению лекарственного препарата Левопронт®. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=841da703-273d-4f59-8f71-e8a09672c9fb (дата обращения – 19.02.2026). (Instructions for medical use of the medicinal product Levopront®. The State Register of Medicines of the Ministry of Healthcare of Russia. URL: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=841da703-273d-4f59-8f71-e8a09672c9fb (date of access – 19.02.2026) (In Russ.))
18. Lavezzo A, Melillo G, Clavenna G, Omini C. Peripheral site of action of levodropropizine in experimentally-induced cough: Role of sensory neuropeptides. Pulm Pharmacol. 1992;5(2):143–47.
PMID: 1611233. http://doi.org/10.1016/0952-0600(92)90033-d
19. Оковитый С.В., Суханов Д.С., Зайцев А.А. Кашель при новой коронавирусной инфекции (COVID-19): рациональные подходы к фармакотерапии. Пульмонология. 2022; 32(2):232–238. (Okovityi SV, Sukhanov DS, Zaicev AA. Cough associated with the new coronavirus infection (COVID-19): Rational approaches to pharmacotherapy. Pul'monologiya = Pulmonology. 2022;32(2):232–238 (In Russ.)).
EDN: UJRDPD. http://doi.org/10.18093/0869-0189-2022-32-2-232-238
20. Инструкция по медицинскому применению лекарственного препарата Либексин®. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=feecc727-47ea-4cb9-a3a1-f348143c391c (дата обращения – 19.02.2026) (Instructions for medical use of the drug Libexin®. The State Register of Medicines of the Ministry of Healthcare of Russia. URL: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=feecc727-47ea-4cb9-a3a1-f348143c391c (date of access – 19.02.2026) (In Russ.))
21. Gardiner SJ, Chang AB, Marchant JM, Petsky HL. Codeine versus placebo for chronic cough in children. Cochrane Database Syst Rev. 2016;7(7):CD011914.
PMID: 27405706. PMCID: PMC6457872. http://doi.org/10.1002/14651858.CD011914.pub2
22. Lee SP, Lee SM, Lee BJ, Kang SY. Effectiveness and safety of codeine and levodropropizine in patients with chronic cough. J Korean Med Sci. 2022;37(36):e275.
PMID: 36123964. PMCID: PMC9485064. http://doi.org/10.3346/jkms.2022.37.e275
23. Rajput R, Al Harakeh K, Figueras G, Mahi A, Minhas M, Sobolevskaia D et al. Dextromethorphan as an opioid-sparing analgesic in postoperative pain. Clin Neuropharmacol. 2025;48(4):109–11.
PMID: 40198711. http://doi.org/10.1097/WNF.0000000000000638
24. Ashwin JV, Shahi MK, Singh A, Kumar ST. Efficacy and safety of dextromethorphan-bupropion combination (AXS-05) in the treatment of depression: A systematic review and network meta-analysis. Indian J Pharmacol. 2025;57(4):262–68.
PMID: 40686359. PMCID: PMC12370225. http://doi.org/10.4103/ijp.ijp_907_24
25. Инструкция по медицинскому применению лекарственного препарата Омнитус®. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=4837d56b-0e75-4347-a4c1-5af1ecc179b7 (дата обращения – 19.02.2026) (Instructions for medical use of the medicinal product Omnitus®. The State Register of Medicines of the Ministry of Healthcare of Russia. URL: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=4837d56b-0e75-4347-a4c1-5af1ecc179b7 (date of access – 19.02.2026) (In Russ.))
26. Cortijo J, Villagrasa V, Pons R, Berto L, Martí-Cabrera M, Martinez-Losa M et al. Bronchodilator and anti-inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes. Br J Pharmacol. 1999;127(7):1641–51.
PMID: 10455321. PMCID: PMC1566148. http://doi.org/10.1038/sj.bjp.0702702
27. Инструкция по медицинскому применению лекарственного препарата Бронхолитин®. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=3f1066a2-42d1-46d7-a867-02b1cc631e16 (дата обращения – 19.02.2026) (Instructions for medical use of the drug Broncholitin®. The State Register of Medicines of the Ministry of Healthcare of Russia. URL: https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=3f1066a2-42d1-46d7-a867-02b1cc631e16 (date of access – 02.19.2026) (In Russ.))
28. David A, Leith-Ross F, Vallance DK. Antitussive and other pharmacological properties of the diethylaminoethoxyethyl ester of alpha alpha-diethylphenylacetic acid, (oxeladin). J Pharm Pharmacol. 1957;9(7);446–58.
PMID: 13439531. http://doi.org/10.1111/j.2042-7158.1957.tb12297.x
29. Morice A, Kardos P. Comprehensive evidence-based review on European antitussives. BMJ Open Resp Res. 2016;3(1):e000137.
PMID: 27547407. PMCID: PMC4985807. http://doi.org/10.1136/bmjresp-2016-000137
30. Будневский А.В., Авдеев С.Н., Овсянников Е.С., Фейгельман С.Н. Комплексные эффекты лекарственного препарата Эладис в терапии инфекционного кашля. Респираторная медицина. 2025;1(3):72–78. (Budnevsky AV, Avdeev SN, Ovsyannikov ES, Feigelman SN. Complex effects of Eladis drug in the treatment of infectious cough. Respiratornaya meditsina = Journal of Respiratory Medicine. 2025;1(3):72–78 (In Russ.)).
EDN: YKMKTS. https://doi.org/10.17116/respmed2025103172
31. Leung SY, Niimi A, Williams AS, Nath P, Blanc FX, Dinh QT, Chung KF. Inhibition of citric acid- and capsaicin-induced cough by novel TRPV-1 antagonist, V112220, in guinea-pig. Cough. 2007;3:10.
PMID: 18154688. PMCID: PMC2262090. http://doi.org/10.1186/1745-9974-3-10
32. Patel HJ, Birrell MA, Crispino N, Hele DJ, Venkatesan P, Barnes PJ et al. Inhibition of guinea-pig and human sensory nerve activity and the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation. Br J Pharmacol. 2003;140(2):261–68.
PMID: 12970104. PMCID: PMC1574031. http://doi.org/10.1038/sj.bjp.0705435
33. McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J et al.; COUGH-1 and COUGH- 2 Investigators. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): Results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022;399(10328):909–23.
PMID: 35248186. http://doi.org/10.1016/S0140-6736(21)02348-5
34. Smith J, Allman D, Badri H, Miller R, Morris J, Satia I, Wood A, K Trower M. The neurokinin-1 receptor antagonist orvepitant is a novel antitussive therapy for chronic refractory cough: Results from a phase 2 pilot study (VOLCANO-1). Chest. 2020;157(1):111–18.
PMID: 31421110. http://doi.org/10.1016/j.chest.2019.08.001
About the Authors
Andrey V. Budnevsky, MD, Dr. Sci. (Medicine), professor, head of the Department of faculty therapy, N.N. Burdenko Voronezh State Medical University, Voronezh, Russian Federation.E-mail: budnev@list.ru
ORCID: https://orcid.org/0000-0002-1171-2746. eLibrary SPIN: 7381-0612
Sergey N. Avdeev, MD, Dr. Sci. (Medicine), professor, academician of RAS, head of the Department of pulmonology of N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
E-mail: serg_avdeev@list.ru
ORCID: https://orcid.org/0000-0002-5999-2150. eLibrary SPIN: 1645-5524
Evgeny S. Ovsyannikov, MD, Dr. Sci. (Medicine), associate professor, professor of the Department of faculty therapy, N.N. Burdenko Voronezh State Medical University, Voronezh, Russian Federation.
E-mail: ovses@yandex.ru
ORCID: https://orcid.org/0000-0002-8545-6255. eLibrary SPIN: 7999-0433
Sofya N. Feigelman, MD, PhD (Medicine), assistant at the Department of faculty therapy, N.N. Burdenko Voronezh State Medical University, Voronezh, Russian Federation.
E-mail: s.feygelman@gmail.com
ORCID: https://orcid.org/0000-0003-4128-6044. eLibrary SPIN: 1645-1203
Yana V. Ivashkina, MD, general practitioner of the Department of therapy, Voronezh City Clinical Emergency Hospital No. 1, Voronezh, Russian Federation.
Email: yanusik-p@mail.ru
ORCID: https://orcid.org/0009-0002-6157-4748
Similar Articles
