Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey

• Published in: PloS one 2011-07, Vol.6 (7), p.e22792
• Main Authors: Mallet, Pauline, Mourdi, Nadjette, Dubus, Jean-Christophe, Bavoux, Françoise, Boyer-Gervoise, Marie-José, Jean-Pastor, Marie-Josèphe, Chalumeau, Martin
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - adverse effects; Age; Bronchitis; Bronchospasm; Carbocysteine - adverse effects; Child; Child, Preschool; Children; Cough; Database industry; Drug development; Drug dosages; Drug therapy; Drugs; Dyspnea; Edema; Expectorants - adverse effects; Exposure; Family medical history; Female; France - epidemiology; Health Surveys; Humans; Independent regulatory commissions; Infant; Infants; Librarians; Licenses; Male; Medical personnel; Medicine; Mucus; Parents; Patients; Pediatric pharmacology; Pediatrics; Pharmaceutical industry; Pharmacists; Pharmacology; Pharmacovigilance; Physicians; Physiology; Prolongation; Public opinion; Regulatory agencies; Respiration; Respiratory system; Respiratory tract; Respiratory tract diseases; Respiratory Tract Diseases - drug therapy; Side effects; Surveys; Vomiting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022792

To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.