Journal of Respiratory Diseases

Journal of Respiratory Diseases

Current Issue Volume No: 1 Issue No: 3

Review-article Article Open Access
  • Available online freely Peer Reviewed
  • A Newer Approach In The Management Of Cough: A Review On Levodropropizine

    1 Apollo Clinic, 105, GN Chetty Road, T Nagar, Chennai, Tamil Nadu, India 

    2 Professor, Paediatrics, Dr. D. Y. Patil Medical College, Pimpri, Pune, India; 

    3 Vohra ENT Care Centre, Malakpet, Hyderabad, India 

    4 Cluster Head, Medical Affairs, Dr. Reddy's Laboratories Ltd, Hyderabad, India 

    5 Medical Advisor, Dr. Reddy's Laboratories Ltd, Hyderabad, India 

    Abstract

    Safe and effective antitussive therapy remains a significant area of unmet need for cough management. Antitussive drugs are commonly used cough suppressants and include centrally acting (opioids and non-opioids) cough suppressants and peripherally acting antitussives. Authors searched PubMed, Google Scholar and additional studies from reference lists via cross-referencing to identify studies assessing levodropropizine for the treatment of cough. Of the 748 studies identified, 13 were included. Recent clinical evidence, guideline recommendations and findings from this review suggest that levodropropizine is a peripheral antitussive which reduces cough intensity, frequency, and nocturnal awakenings in children and adults and provides better efficacy outcomes with a more favourable risk/benefit ratio compared to centrally acting antitussive agents which pose greater safety concerns and present an unacceptable risk-benefit profile. This review is aimed at Indian primary care physicians for making effective cough management decisions where the clinical evidence needs to be translated to clinical practice.

    Key Messages

    The usage of currently available centrally acting antitussive agent is greatly limited by their central depressing action and frequent side effect. The findings of this review indicate that levodropropizine is an effective antitussive agent and well tolerated in the management of cough in patients of all ages.

    Author Contributions
    Received Apr 20, 2023     Accepted Apr 26, 2023     Published May 23, 2023

    Copyright© 2023 Prasanna K Thomas, et al.
    License
    Creative Commons License   This work is licensed under a Creative Commons Attribution 4.0 International License. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Competing interests

    Dr. Prasanna K Thomas, Dr. Pramod Jog, Dr. Nitin R Vohra, have no competing interests. Dr. Krishna C Veligandla and Dr. Anup U Petare are Dr. Reddy's Laboratories Ltd employees.

    Funding Interests:

    Citation:

    Prasanna K Thomas, Pramod Jog, Nitin R Vohra, Krishna C Veligandla, Uttam Anup Petare et al. (2023) A Newer Approach In The Management Of Cough: A Review On Levodropropizine Journal of Respiratory Diseases. - 1(3):1-14
    DOI 10.14302/issn.2642-9241.jrd-23-4566

    Introduction

    Introduction

    Coughing is a vital defensive reflex that allows clearance of excessive airway secretions and prevents the entry of foreign bodies into the respiratory tract. 1 Cough is classified into three categories based on its duration: acute (<3 weeks), subacute (3-8 weeks), and chronic (>8 weeks in adults and >4 weeks in children). 234 Acute cough episodes are mainly related to upper respiratory tract infections (URTI). The other underlying causes of acute cough are pneumonia, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) exacerbation, aspiration, and pulmonary embolism. 5

    The American College of Chest Physicians (ACCP) defines subacute cough as cough that resolves spontaneously on its own, with negative chest radiography ruling out pneumonia4 Chronic cough can be caused by many diseases including asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, bronchiectasis, and postnasal drip.6 Cough can also be categorized based on the sputum volume as dry and wet cough. Wet cough is also known as productive cough and is defined as sputum volume >10 mL per day.4,7 A dry cough is also known as unproductive cough and is characterized by no mucus production. Chronic cough may indicate a more serious underlying medical condition such as asthma, postnasal drip, and gastric reflux disease.8 Patients with the acute and sub-acute cough usually self-medicate with over the counter (OTC) antitussive drugs, although a careful examination and patient history is required to identify the underlying causes. OTC drugs which include combinations of antihistamines, decongestants, cough suppressants and expectorants are most used preparations for self-medication.9 Current ACCP guidelines recommend nonpharmacologic and pharmacologic treatments based on patient comorbid disease status and underlying chronic cough causes. Pharmacologic treatment usually consists of a bronchodilator, corticosteroid, leukotriene receptor antagonists and inhaled anticholinergic etc. 10 Antitussive drugs are commonly used cough suppressants which include centrally acting (opioids and non-opioids) cough suppressants and peripheral antitussives. Codeine, dextromethorphan and cloperastine are among the most common central agents that act by inhibiting the cough center in the brain.11 Peripherally acting antitussives such as levodropropizine and moguisteine exhibit a very strong antitussive activity. Levodropropizine is an orally administered non-opioid anti-tussive agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels within the respiratory tract.121314 In India, levodropropizine was approved by The Central Drugs Standard Control Organization in 2005 for the treatment of dry cough in adult patient. 15 The current ACCP and ERS guidelines also suggest using alternative antitussive strategy in subset of patients with cough resistant to other treatments.16

    There is a need to find an effective antitussive medication with a high tolerability profile because the usage of the currently available centrally acting antitussive for the treatment of cough is severely restricted by the central depressive action and abusive side effects. 17 This review article aims to summarize the potential mechanism of action, comparative effectiveness, and safety profile of levodropropizine for symptomatic treatment of cough in paediatric and adult population. Its impact on patients’ health-related quality of life (HRQoL) and in managing COVID-19 associated cough have also been discussed.

    Discussion

    Discussion on recommended treatment strategy for cough

    The comparative analysis reported in the efficacy section above for peripherally acting antitussive levodropropizine was found to be safer and more effective to manage the cough. These findings are also consistent with current international recommendations, which recommend the use of peripherally acting antitussive such as levodropropizine for management of cough.5 The ACCP guidelines recommend the use of levodropropizine in adult patients with chronic or acute bronchitis for the short-term symptomatic relief. These guidelines recommended that centrally acting antitussive medications like codeine and dextromethorphan have lower levels of benefit when use to treat acute or chronic bronchitis than levodropropizine (Level of evidence, good; benefit, substantial; grade of recommendation, A).39 Cough is frequently a very distressing symptom that has a significant effect on children's health. Because of the potential for severe sedation, most cough suppressants use by adults have an unfavourable risk-benefit profile for usage in children.18 The use of OTC medications and centrally acting antitussive treatments on paediatric patients with colds and coughs has been challenged by the regulatory bodies such as the United States Food and Drug Administration and the United Kingdom s Medicines and Healthcare products Regulatory Agency. Additionally, the American Academy of Paediatrics has advised against treating children's coughs with dextromethorphan and codeine due to their sedative profile. Respiratory depression slowed or difficult breathing are the most common side effects associated with use of centrally acting antitussive drugs in children. 40,41 The Italian Society of Pediatric Allergy and Immunology advised the use of peripherally acting antitussives such levodropropizine for children and adolescents with cough.16 Indian Environmental Medical Association (EMA) also developed an evidence-based graded clinical guideline to provides recommendation for the management of acute or chronic cough. Risk factors, including smoking, should be addressed in chronic bronchitis (CB) with normal lung function. When compared to dextromethorphan, levodropropizine has a superior benefit/risk profile and can be used to treat such situations. (Level IIB, Strong). 42 EMA has advised the use of antitussives including dextromethorphan, levodropropizine, and levocloperastine for the management of dry cough associated with acute bronchitis case (Level IIB, Strong).42 EMA has also advised to use levodropropizine in non-productive cough associated with primary or metastatic lung cancer (Level IIB; Strong), cough variant asthma (Level IIIC; weak), pulmonary tuberculosis (Level IVB, Strong) and URTI (Level IIB, Strong).42 Although this review provides overall evidence on the efficacy and safety of levodropropizine in both paediatric and adult patients, number of studies in each category of cough medications require further evidence generation with larger sample size, different treatment type, dosing, treatment duration & comparative studies of different antitussives.

    Affiliations:
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