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Dose-response relationship with increasing doses of dextromethorphan for children with cough
Ian M Paul1, Michele L Shaffer, Katharine E Yoder
1Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. ipaul@psu.edu
Insights
Dextromethorphan (DM) may offer improved cough relief in children at higher doses, but further research is needed to balance efficacy and adverse events. A dose of 0.5 mg/kg is suggested for future pediatric studies.
Area of Science:
- Pediatric Pharmacology
- Clinical Therapeutics
- Cough Medicine Research
Background:
- Dextromethorphan (DM) is frequently used for pediatric cough despite uncertain efficacy and lack of AAP support.
- Current DM dosing in children is age-based, leading to significant weight-based dose variability.
Purpose of the Study:
- To investigate a potential dose-response relationship for dextromethorphan (DM) in children with acute cough.
- To evaluate the efficacy of a single nocturnal dose of DM for cough associated with upper respiratory tract infections in pediatric patients.
Main Methods:
- A subset of children from a double-blind, placebo-controlled trial received DM at manufacturer-recommended, age-based doses (0.35-0.94 mg/kg).
- Parental assessments of cough and sleep were recorded using a 7-point Likert scale comparing post-medication symptoms to baseline.
- Three dose ranges (low, medium, high) were analyzed to compare treatment effects.
Main Results:
- No statistically significant differences in cough or sleep outcomes were observed across different DM dose ranges.
- A trend suggested better symptomatic relief with medium (0.45 to <0.60 mg/kg) and high-dose (0.60-0.94 mg/kg) DM compared to low-dose (0.35 to <0.45 mg/kg).
- Adverse events were most frequent in the high-dose DM group.
Conclusions:
- While not statistically significant, findings indicate a potential for improved cough symptom control with higher DM doses in children.
- A dose of 0.5 mg/kg of DM is proposed for future pediatric studies to optimize symptomatic relief while minimizing adverse events.
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 antitussive. 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 medication). 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 findings 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.
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