A Benefit Risk Review of Pediatric Use of Hydrocodone/Chlorpheniramine, a Prescription Opioid Antitussive Agent for the Treatment of Cough

Hydrocodone/chlorpheniramine is a prescription opioid licensed in the USA for the relief of cough and upper respiratory symptoms associated with allergy or cold in adults, previously contraindicated in children aged < 6 years. We present findings from a modern benefit risk review of hydrocodone/chlorpheniramine use as an antitussive agent in patients aged 6 to < 18 years. A cumulative search of the manufacturer’s pharmacovigilance database covering 1 January 1900–7 August 2017 identified all individual case safety reports (ICSRs) associated with product family name “hydrocodone/chlorpheniramine.” The search was inclusive of all MedDRA system organ classes, stratified by age (< 18 years). A comprehensive review of the scientific literature was conducted on safety and efficacy of opioids for pediatric treatment of cough. Three hundred and ninety-one ICSRs associated with hydrocodone/chlorpheniramine were identified; 35/391 ICSRs were in patients < 18 years of age; 18 were considered serious. Four fatalities were reported in patients 6 to < 18 years; two fatalities involved co-suspect medication azithromycin and two were poorly documented. Our literature search identified no robust efficacy data for hydrocodone/chlorpheniramine in the relief of cough and upper respiratory symptoms associated with allergy or cold in patients aged 6 to < 18 years. As we found no evidence of hydrocodone/chlorpheniramine efficacy in the pediatric population, we conclude that the benefit risk profile is unfavorable. This evidence contributed to the US Food and Drug Administration’s (FDA’s) recent decision that hydrocodone-containing cough and cold medications should no longer be indicated for treatment of cough in patients < 18 years, highlighting the value of proactive re-evaluation of the benefit risk profile of older established drugs.