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Table of Contents
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 101-102

Clobutinol: An effective antitussive drug for captopril-induced cough

Department of Pediatric Nephrology, Sevome Shaban Hospital, Tehran, Iran

Date of Web Publication27-Dec-2018

Correspondence Address:
Majid Malaki
Sevome Shaban Hospital, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJPN.AJPN_31_18

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How to cite this article:
Malaki M. Clobutinol: An effective antitussive drug for captopril-induced cough. Asian J Pediatr Nephrol 2018;1:101-2

How to cite this URL:
Malaki M. Clobutinol: An effective antitussive drug for captopril-induced cough. Asian J Pediatr Nephrol [serial online] 2018 [cited 2021 Sep 19];1:101-2. Available from: https://www.ajpn-online.org/text.asp?2018/1/2/101/248644


The antitussive clobutinol hydrochloride, marketed in 1950s, was withdrawn from the worldwide market due to its potential to prolong the QT interval and a risk of inducing torsades de pointes, attributed to anaphylaxis. Later, clobutinol was reclassified as a drug that may prolong the QT interval and should be avoided in patients with congenital long QT syndrome rather than one with risk of torsades de pointes. Hence, it continues to be available commercially outside the United States and the European Union.[1],[2]

Angiotensin-converting enzyme (ACE) inhibitors are used commonly in patients with congestive heart failure, hypertension, or proteinuria.[3] These drugs induce cough in 5%–35% patients due to bradykinin-induced sensitization of airway sensory nerves.[4] Cough induced by ACE inhibitors may pose diagnostic challenge or aggravate previous respiratory symptoms. Cough usually resolves within 1–4 weeks of cessation of therapy but may persist for up to 3 months.[4] Drugs that have been effective in such cases include sodium cromoglycate, theophylline, sulindac, indomethacin, ferrous sulfate, and picotamide.

A 4-year-old boy, presenting with steroid resistant nephrotic syndrome and anasarca requiring intravenous albumin infusions daily, was initiated on captopril at 0.5 mg/kg/dose to limit proteinuria. After two days, he developed a persistent dry cough that was not associated with hypoxia, auscultatory findings or radiographic changes. The cough persisted despite the use of mucolytics, salbutamol, and diphenhydramine and did not reduce despite the addition of methylxanthine (theophylline elixir). These therapies were withheld, and empiric therapy with clobutinol (60 mg/ml; 8 mg eight hourly) was initiated while monitoring the QT interval on electrocardiography. The cough reduced dramatically on the first day of administration and cough suppressants could be withdrawn. The dose of captopril was incrementally increased to 2 mg/kg/day, but the cough remained suppressed with the continued use of clobutinol; cardiac monitoring did not show QT prolongation.

As demonstrated by this case, clobutinol is a rapidly acting antitussive agent[5] that is effective in inhibiting cough induced by ACE inhibitors. Controlled studies should prospectively evaluate the efficacy of clobutinol for this indication and reexamine its safety particularly with respect to its arrhythmogenic potential.

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Conflicts of interest

There are no conflicts of interest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

  References Top

Balbani AP. Cough: Neurophysiology, methods of research, pharmacological therapy and phonoaudiology. Int Arch Otorhinolaryngol 2012;16:259-68.  Back to cited text no. 1
Bellocq C, Wilders R, Schott JJ, Louérat-Oriou B, Boisseau P, Le Marec H, et al. A common antitussive drug, clobutinol, precipitates the long QT syndrome 2. Mol Pharmacol 2004;66:1093-102.  Back to cited text no. 2
Jackson M, Edwin K. Renin and angiotensin. In: Brunton L, Parker K, editors. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill; 2006. p. 726-43.  Back to cited text no. 3
Dicpinigaitis PV. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 2006;129:169S-173S.  Back to cited text no. 4
Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, et al. Antitussive drugs – past, present, and future. Pharmacol Rev 2014;66:468-512.  Back to cited text no. 5


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