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. Plain Language Summary People often use medicines containing
opioids to treat
cough symptoms. The US Food and Drug Administration (FDA) recently decided that
cough medicines containing
opioids should not be used by children under 18 years old. Part of this decision was a review of the benefits and risks of using
cough medicines that contain the
opioid hydrocodone in children.Why was this review carried out? Most
cough medicines that doctors can prescribe were approved several decades ago. Since then, rules for the approval of medicines have become stricter. In this review, researchers looked at the safety of
hydrocodone, and how well this
opioid relieves
cough symptoms in children. Up-to-date information and modern research methods were used.The two key pieces of evidence found were: We could not locate any clinical trials providing robust evidence for the use of
hydrocodone for
cough relief in children under 18 years of age. (Outside the scope of this review, a number of clinical trials of
hydrocodone-containing
cough medicines in adults aged 18 years and over have shown the medicine to be effective in these patients.)
Cough medicines containing
opioids can cause harmful side effects in children such as breathing problems. In the research reported here, ten children died after taking a
hydrocodone-containing
cough medicine. Nine of these deaths were due to overdose. This evidence was used to draw the following conclusions: In children under 18 years of age, the risks of using
hydrocodone for
cough relief are greater than any benefits. Older medicines should be reviewed regularly to look at their safety and how well they are working using up-to-date evidence.