Acetylcysteine and carbocysteine to treat acute upper and lower respiratory tract infections in children without chronic broncho-pulmonary disease

Acetylcysteine and carbocysteine are the most commonly prescribed drugs which aim to change the structure of bronchial secretions. This systematic review assessed their efficacy and safety for treating acute upper and lower respiratory tract infections in children without chronic broncho-pulmonary disease. We also looked in particular at patients younger than two years of age.

Forty-nine trials met the inclusion criteria. Six trials involving 497 participants were included to study efficacy, and compared acetylcysteine or carbocysteine to placebo. Thirty-four trials (including the previous six) were eligible to study safety and involved 2064 paediatric patients.

The results of this review suggest actual but limited efficacy of acetylcysteine and carbocysteine (e.g. reduction of cough at day seven) and good overall safety (except for rare mild gastrointestinal side effects) among children older than two years of age. However, the number of participants included was limited and the methodological quality was questionable. These results should also take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). In children younger than two years, and given strong concerns about safety (increased instead of decreased bronchial secretions), these drugs should only be used for acute upper and lower respiratory tract infections in the context of a randomised controlled trial.

Authors' conclusions: 

The results have to be interpreted with caution because they are based on a limited number of participants included in studies whose methodological quality is questionable. Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be safe in children older than two years. These results should take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). Given strong concerns about safety, these drugs should only be used for acute upper and lower RTIs in the context of a RCT with regards to children younger than two years.

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Background: 

Acetylcysteine and carbocysteine are the most commonly prescribed mucolytic drugs in Brazil and many European and African countries. To our knowledge, no systematic review has been published on their efficacy and safety for acute upper and lower respiratory tract infections (RTIs) in children without chronic broncho-pulmonary disease.

Objectives: 

The objective was to assess the efficacy and safety and to establish a benefit-risk ratio of acetylcysteine and carbocysteine as symptomatic treatments for acute upper and lower RTIs in paediatric patients without chronic broncho-pulmonary disease.

Search strategy: 

We searched CENTRAL (2013, Issue 2), MEDLINE (1966 to February week 3, 2013), EMBASE (1980 to March 2013), Micromedex (2010), Pascal (1987 to 2004) and Science Citation Index (1974 to March 2013).

Selection criteria: 

To study efficacy, we used randomised controlled trials (RCTs) comparing the use of acetylcysteine or carbocysteine versus placebo, either alone or as an add-on therapy. To study safety, we used trials comparing acetylcysteine or carbocysteine versus active treatment or no treatment and case reports.

Data collection and analysis: 

In this review update two review authors (YD, MC), with help from a colleague, extracted data and assessed trial quality. We performed a subgroup analysis of children younger than two years of age.

Main results: 

We included six trials involving 497 participants to study efficacy. They showed some benefit (e.g. reduction of cough at day seven) from mucolytic agents, although differences were of little clinical relevance. No conclusion was drawn about the subgroup of infants younger than two years because data were unavailable. Thirty-four studies, including the previous six trials involving 2064 children, were eligible to study safety. Overall safety was good but very few data were available to evaluate safety in infants younger than two years. However, 59 cases of paradoxically increased bronchorrhoea observed in infants were reported to the French pharmacovigilance system.

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