49: Antihistamines and Decongestants

INTRODUCTION

Antihistamines and decongestants rank among the highest prescription and non prescription xenobiotics used in the United States. In 2011, antihistamines and cough and cold preparations ranked respectively 9th and 11th in substance categories most frequently involved in human exposures related calls to US Poison Control centers. Antihistamines ranked 11th place in categories associated with the largest number of fatalities in 2011 (Chap. 136).

Popular mythology suggests that expectorants or decongestants depress cough and relieve congestion, and antihistamines also promote sleep. In an effort to retain selected drugs on the nonprescription market, the US Food and Drug Administration (FDA) developed a nonprescription monograph rule allowing some medications in use before 1972 to remain on the market without new clinical trials. As such, many nonprescription decongestants, antihistamines, and expectorants remained available for children without adequate safety or efficacy data in younger age groups. Between the years 1998 and 2007, 8.7% of US parents surveyed reported to have used an antihistamine or decongestant containing remedy for their children younger than 12 years of age in the past week. The majority of these children were younger than 5 years of age. Pseudoephedrine, brompheniramine, and chlorpheniramine are the three most common ingredients used.¹⁷⁸

Unwanted effects associated with their use have posed significant public health problems particularly in children. Fatality studies associated with nonprescription cough and cold medicines reported that although uncommon, most deaths involved nontherapeutic dosages, administration for sedation purposes, and use in children primarily younger than 2 years of age.³⁴ However, the causality of death by cough and cold medicine is often debated. The data needed to prove this relationship are often incomplete because of such factors as the lack of postmortem drug quantification.¹³³ In 2007, a group of pediatricians and pharmacists petitioned the FDA requesting a change in labeling for children younger than 6 years of age on the basis that safety had never been demonstrated in this age group. This petition alerted the general public of the underestimated adverse effects of these xenobiotics.^143,166 In early 2008, the FDA Public Health Advisory announced that cough and cold products were not recommended for children younger than 2 years of age, and later that same year the Consumer Healthcare Products Association (CHPA), a trade group of generic drug manufacturers, announced that its members were voluntarily modifying product labels for cough and cold medicines to exclude children younger than 4 years of age.¹⁷¹

Despite their widespread use, many reviews of nonprescription medications for cough in adults and children found no evidence for the effectiveness of these xenobiotics.¹⁵⁴ Conclusions are similar regarding the use of antihistamines or decongestants in otitis media.²⁸ Moreover, many well-conducted studies of antihistamines in monotherapy or in combination with a decongestant for patients with upper respiratory illness reported a significant absence of overall symptom improvement.^154,176 It is also suggested that the majority ...