Objective and self-reported evidence of dextromethorphan antitussive efficacy in children, aged 6-11 years, with acute cough due to the common cold.

OBJECTIVE: To determine objective and subjective endpoints most suitable for evaluating antitussive efficacy of dextromethorphan hydrobromide (DXM) in children. Spontaneous resolution of acute cough and large placebo effects are impediments to evaluating antitussive efficacy. Another impediment is paucity of age-appropriate, validated cough assessment tools. METHODS: This was a multiple-dose, double-blind, placebo-controlled, randomized, pilot clinical study in children, aged 6-11 years, with cough due to the common cold. Eligible subjects met entry criteria and qualified by completing a run-in period where coughs were recorded with a cough monitor after they were dosed with sweet syrup. They were subsequently randomized to receive DXM or placebo over 4 days. Coughs were recorded during the initial 24 h; subjective assessments of cough severity and frequency were self-reported daily during treatment. RESULTS: Data from 128 evaluable subjects (67 DXM; 61 placebo) were analyzed. Total coughs over 24-hours (primary endpoint) and cough frequency during daytime were reduced by 21.0% and 25.5%, respectively, with DXM relative to placebo. Also, greater reductions in cough severity and frequency were self-reported with DXM. These findings were statistically significant and medically relevant. No effects were detected between treatments for nighttime cough rates or impact of cough on sleep. Multiple doses of DXM and placebo were generally well-tolerated. CONCLUSION: Evidence of DXM antitussive efficacy was shown in children using objective and subjective assessment tools validated in pediatric populations. Diurnal variation of cough frequency over 24 h reduced the assay sensitivity needed to detect treatment differences at nighttime, as coughs/hour decreased during sleep for both groups.

The use of antihistamines in safety-critical jobs: a meeting report.

The use of sedating agents by aircrew and those with safety-critical occupations has raised serious concern and has been extensively debated for several years. This meeting report summarizes the findings of an international panel of experts in aerospace medicine and allergic rhinitis who were brought together to discuss issues related to the use of antihistamines, in particular the selective, H1-receptor antagonist fexofenadine, in pilots. The presentations covered a wide range of topics including methods for accurately assessing sedation and impairment, and the validity of laboratory testing versus simulator assessments. The panel also examined data on sedation and impairment levels with currently available antihistamines and assessed the impact of these data on their use by pilots and aircrew. It was the consensus of the meeting that fexofenadine can be safely recommended for use in individuals involved in skilled activities, such as pilots, without the concern of sedation above recommended therapeutic doses.

Efficacy and safety profile of fexofenadine HCl: a unique therapeutic option in H1-receptor antagonist treatment.

Results of head-to-head comparative trials suggest that fexo-fenadine might offer distinct advantages compared with other antihistamines. Fexofenadine is highly selective for peripheral H(1)-receptors and does not cross the blood-brain barrier, as shown by positron emission tomography. These data support findings that fexofenadine is nonsedating and does not impair performance or driving ability, even at very high doses. In addition, fexofenadine does not interact with muscarinic receptors, which might offer a potential advantage compared with desloratadine, the recently approved active metabolite of loratadine. Fexofenadine is devoid of adverse cardiac effects, and changes in electrocardiogram parameters are not significantly different from those observed with placebo. Fexofenadine has also been shown to have a favorable effect on nasal congestion. This therapeutic advantage might be related to its significant antiallergic properties, ie, the demonstrated ability of fexofenadine to blunt the inflammatory effects of preformed and de novo synthesized mediators at clinically relevant doses in vivo and in vitro. Cumulatively, these benefits distinguish fexofenadine from other antihistamines and make it an optimum therapeutic option for treating allergy-mediated respiratory and dermatologic diseases.

Effects of fexofenadine, diphenhydramine, and placebo on performance of the test of variables of attention (TOVA).

OBJECTIVE: To determine the effects of diphenhydramine 50 mg and fexofenadine 180 mg on cognitive performance using the Test of Variables of Attention (TOVA), and to ascertain whether the TOVA was sufficiently sensitive to differentiate between the effects of these first- and second-generation H1-receptor antagonists on performance. STUDY DESIGN: The study used a double-blind, placebo-controlled, randomized, crossover design. Forty-two subjects completed four separate TOVA tests: at baseline and after administration of placebo, diphenhydramine 50 mg, and fexofenadine 180 mg. On each occasion, subjects rated subjective feelings of drowsiness on a visual analog scale (VAS) before taking the TOVA. RESULTS: Compared with placebo, diphenhydramine caused an increased response time (P = 0.0230) and more omission errors (P = 0.0398). Diphenhydramine was also associated with increased drowsiness VAS ratings (P = 0.0065) compared with placebo. Diphenhydramine caused significantly more commission errors than fexofenadine (P = 0.0354). Neither placebonor fexofenadine 180 mg caused significant changes in any TOVA or VAS measurements compared with baseline. Fexofenadine was not statistically different from placebo for any evaluation. CONCLUSIONS: The TOVA was sufficiently sensitive to differentiate between the central nervous system effects of fexofenadine and diphenhydramine. Fexofenadine 180 mg had no significant effect on the TOVA measures of performance or on self-reported drowsiness compared with placebo. In contrast, diphenhydramine 50 mg caused significant increases in omission errors and response time on the TOVA and increases in self-reported drowsiness compared with placebo [corrected].

Relative potency of fexofenadine HCl 180 mg, loratadine 10 mg, and placebo using a skin test model of wheal-and-flare suppression.

BACKGROUND: H1-receptor antagonists differ in their ability to produce peripheral H1-blockade. Suppression of histamine-induced flares and wheals is a useful objective test for measuring these differences. OBJECTIVE: To evaluate the relative potency of fexofenadine HCI 180 mg, loratadine 10 mg, and placebo (PBO) in suppressing histamine-induced flares and wheals and compare the onset, duration, and maximum suppression of histamine achieved with each agent. METHODS: Thirty healthy volunteers were enrolled in this randomized, double-blind, single-dose, crossover study. Flares and wheals induced by skin-prick testing with histamine 1.8 mg/mL were measured before treatment, every 20 minutes during the first hour after dosing, and thereafter hourly between 2 and 12 hours and between 23 and 25 hours postdose. RESULTS: Fexofenadine was significantly more effective than loratadine in suppressing the histamine-induced flare response at hours 2 through 7 and 10 through 12 and produced greater flare suppression than did PBO at hours 2 through 25. Onset of flare suppression occurred 2 hours after dosing with fexofenadine and 4 hours after dosing with loratadine. Likewise, fexofenadine was superior to loratadine in suppressing the wheal response from hours 1 through 12 and was more effective than PBO at hours 1 through 12, 24, and 25. Throughout the 25-hour measurement interval, the magnitude of difference in both wheal and flare suppression consistently favored fexofenadine over loratadine. CONCLUSIONS: In a skin test model of wheal-and-flare suppression, fexofenadine showed rapid distribution into the skin compartment with faster onset of action and greater potency vs loratadine.