CLINICAL THERAPEUTICS®/VoL. 26, No. 9, 2004 Dose-Response Relationship with Increasing Doses of Dextromethorphan for Children with Cough Ian M. Paul, MD, MSc, 1,2 Michele L. Shaffer, PhD, 2 Katharine E. Yoder, BA, 1 Sarah A. Sturgis, RN, CRNP, 1 Mark S. Baker, MD, 1 and Cheston M. Berlin, Jr, MD 1 ~Department of Pediatrics and 2Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania ABSTRACT Background: The efficacy of dextromethorphan (DM) for treating acute cough is uncertain, and its use is not supported by the American Academy of Pediatrics. Nevertheless, DM is often administered to children as an anti- tussive. DM dosages are based on age rather than body weight, resulting in substantial variability in the relative amount of drug administered. Objective: The aim of this work was to determine whether a dose-response relationship existed among a group of children administered a single nocturnal dose of DM for cough due to an upper respiratory tract infection. Methods: As part of a larger double-blind, placebo-controlled trial of over-the-counter cough medications, children received DM. The administered doses (per manufacturer recommendations) were as follows: ages 2 to 5 years, 7.5 mg; ages 6 to 11 years, 15 mg; and ages 12 to 18 years, 30 mg. This resulted in a range of 0.35 to 0.94 mg/kg per dose. Subjective parental assessments of cough and sleep were obtained using a 7-point Likert- type scale that compared symptoms after medication with symptoms during the prior night (without medica- tion). Three dose ranges were compared as a subset analysis of the group that received DM. Results: Thirty-three patients (19 girls, 14 boys; median [interquartile range] age, 4.90 [2.90-6.80] years; age range, 2.10-16.50 years) received DM and completed the study. No significant differences were found for any of the outcome measures when comparing the effects of different doses of DM, but our observations suggested somewhat more symptomatic relief for patients receiving medium-dose DM (0.45 to <0.60 mg/kg per dose) or high-dose (HD) DM (0.60-0.94 mg/kg per dose) compared with low-dose DM (0.35 to <0.45 mg/kg per dose). Adverse events occurred most often in the HD group. Conclusions: Although no statistically significant differences were detectable for the outcomes studied, our observations suggest the potential for improved clinical symptom control with increasing doses of DM. Our find- ings may further suggest that a dose of 0.5 mg/kg should be considered in future assessments of the antitussive effect of DM in pediatric studies, to balance symptomatic relief with the avoidance of adverse events. (Clin Ther. 2004;26:1508-1514) Copyright © 2004 Excerpta Medica, Inc. Key words: dextromethorphan, dose-response, cough, sleep, upper respiratory infection. This work was presented as an abstract at the American Society of Clinical Pharmacology and Therapeutics Annual Meeting, March 24-27, 2004, Miami, Florida. AcceptedJor publicationdune 23, 2004. Printed in the USA. Reproduction in whole or part is not permitted. doi:l O. I016/j.clinthera.2004.09.004 0149 2918/04/$19.00 ~508 Copyright © 2004 Excerpta Nedica, Inc.