S. Meeves

Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine, 10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic rhinitis

BACKGROUND Previous studies have shown that fexofenadine and cetirizine effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE To compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg, on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR. METHODS In this 2-week multicenter, double-blind, randomized study, 495 subjects with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective (AM, PM) and instantaneous (AM) individual symptoms and total symptom score (TSS) were evaluated. Drowsiness and motivation were recorded daily using visual analog scale at 7 AM, 10 AM, and 3 PM. RESULTS Between-treatment differences in reduction from baseline in AM instantaneous and 24-hour reflective TSS were -0.18 [95% confidence interval (CI), -0.55 to 0.20) and -0.22 (95% CI, -0.59 to 0.15), respectively. Since CIs for reduction in TSS between treatments fell within a 0.7 margin (defined a priori), treatments were considered statistically equivalent. Patients receiving fexofenadine experienced significantly less overall drowsiness vs baseline than those receiving cetirizine [-2.33 (95% CI, -3.80 to 0.86) vs 0.37 (95% CI, -1.10 to 1.84), P = .0110]. There was a trend toward greater improvements in overall motivation with fexofenadine compared with cetirizine [-2.36 (95% CI, -3.83 to 0.90) vs -0.30 (95% CI, -1.76 to 1.17), P = .0504]. CONCLUSIONS Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks caused statistically and clinically equivalent improvement in symptoms and significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in patients with moderate-to-severe SAR.

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.

Onset of action, efficacy, and safety of fexofenadine 60 mg/pseudoephedrine 120 mg versus placebo in the Atlanta allergen exposure unit

BACKGROUND Second-generation antihistamine-decongestant combinations are often used to treat seasonal allergies. However, onset of action and efficacy data for these agents in a controlled setting are limited. OBJECTIVE Determine onset of action of fexofenadine-pseudoephedrine (Allegra-D, Aventis, Bridgewater, NJ) for treating moderate-to-severe seasonal allergies in an allergen exposure unit. METHODS This single-dose, double-blind, placebo-controlled study was conducted during the fall ragweed allergy season. Qualifying subjects attended one to two priming visits; those with sufficient symptom scores returned for treatment and were initially exposed to ragweed pollen for 90 minutes. Symptomatic subjects received fexofenadine-pseudoephedrine or placebo and recorded symptoms for 6 hours postdose. Efficacy variables were major symptom complex (MSC; sneezes, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, stuffy nose), total symptom complex (nose blows, sniffles, postnasal drip, cough, plus all MSC symptoms), and all individual symptoms as well as headache. Onset of action for each efficacy variable was calculated as the earliest time at which a consistent, significant decrease was seen for fexofenadine-pseudoephedrine versus placebo. RESULTS Of 571 screened subjects, 298 were randomized. Onset of relief for fexofenadine-pseudoephedrine (n = 148) was 45 minutes postdose (MSC, P = 0.0127; total symptom complex, P = 0.0380). All individual symptoms were reduced to a greater extent with fexofenadine-pseudoephedrine than with placebo (P < 0.05, not adjusted for multiple comparisons). Decrease in headache with fexofenadine-pseudoephedrine versus placebo began 45 minutes postdose (P = 0.0425). Incidence of treatment-related adverse events was 1.4% for fexofenadine-pseudoephedrine and 3.3% for placebo. CONCLUSIONS Fexofenadine-pseudoephedrine was safe and effective in treating a broad range of allergy symptoms, with a rapid onset of action at 45 minutes.

Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research

SUMMARY Objective: To compare the anti-inflammatory effects of fexofenadine with other H -receptor antagonists in vitro. Data sources: Published literature. Study selection: Recent experimental studies on anti-inflammatory effects of H1-receptor antagonists. Databases searched: Medline, Medscape. Period covered: 1990-2003. Search terms: second-, third-generation antihistamines; sedating, nonsedating antihistamines; in vitro anti-inflammatory activity; cetirizine; ebastine; loratadine; fexofenadine; desloratadine. Results: Second- and third-generation H1-⁁ receptor antagonists may demonstrate significant in vitro anti-inflammatory activity at concentrations considered to be clinically relevant. In some instances, higher (supraclinical) concentrations are required to achieve comparable effects. Conclusions: Experimental research suggests that second- and third-generation H1-receptor antagonists may achieve anti-inflammatory effects in a clinical context. Further studies are required to support this conclusion.

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.

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].

The Use of Antihistamines in Safety-critical Jobs: A Meeting Report *

Summary 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 L 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 of fexofenadine in the prophylactic control of cat allergen-induced allergic rhinitis

BACKGROUND To date, it is unknown whether fexofenadine mitigates the worsening of symptoms induced by the cat allergen Felis domesticus allergen 1. OBJECTIVE To determine the effects of a single dose of fexofenadine hydrochloride, 180 mg, in preventing and controlling cat allergen-induced allergic rhinitis symptoms using the cat room challenge model. METHODS This single-center, randomized, double-blind, placebo-controlled, 2-way crossover study consisted of a screening visit, 1 or 2 qualifying visits, and 2 treatment periods separated by a mean +/- SD washout period of 14 +/- 3 days. Patients were randomized to treatment sequence 1 (placebo followed by fexofenadine) or sequence 2 (fexofenadine followed by placebo). Baseline end points were obtained before study drug administration, and allergen challenges were initiated 1 1/2 hours after dosing. The primary end point was the change from predose baseline in the total symptom score (sum of rhinorrhea, itchy nose/palate/ throat, sneezing, and itchy/watery/red eyes) after 30 minutes of allergen exposure compared with placebo. RESULTS Of 211 patients screened, 66 were randomized and 63 completed the study. Mean change in the total symptom score from predose baseline was significantly less with fexofenadine compared with placebo 30 minutes after initiation of the cat allergen challenge (2 hours after dosing) (P = .03). The overall incidence of treatment-emergent adverse events was low and comparable for both groups. CONCLUSION Prophylactic treatment with a single dose of fexofenadine hydrochloride, 180 mg, significantly mitigated the worsening of allergic rhinitis symptoms induced by exposure to cat allergen compared with placebo use.

Two-week treatment with cetirizine 10 mg is associated with increased drowsiness compared with fexofenadine 180 mg

4 Two-Week Treatment with Cetirizine 10 mg Is Associated with Increased Drowsiness Compared with Fexofenadine 180 mg L. E. Mansfield 1, S. Meeves 2, Y. Liao 2, G. Georges2; IEl Paso Institute for Medical Research and Development, El Paso, TX, 2Aventis Pharmaceuticals, Bridgewater, NJ. RATIONALE: This study compared the effect of treatment with fexofenadine 180 mg and cetirizine 10 mg on drowsiness and motivation in individuals with moderate to severe seasonal allergic rhinitis (SAR). METHODS: This was a multicenter, randomized, double-blind, parallel group study in which 495 subjects with moderate to severe SAR received once-daily treatment at 7 AM with either fexofenadine 180 mg (n=248) or cetirizine 10 mg (n=247) for 14 days. Changes from baseline in drowsiness and motivation were measured using a visual analog scale (VAS), which ranged from 0 (wide awake/highly motivated) to 100 (extremely sleepy/unmotivated). Drowsiness and motivation were assessed independently in patients at 7 AM, 10 AM, and 3 PM daily. RESULTS: Compared with patients treated with cetirizine, patients treated with fexofenadine had significantly less mean daily drowsiness VAS scores overall (33.71 vs. 36.39; P=0.01). Compared with patients treated with cetirizine, patients treated with fexofenadine had a trend toward greater motivation (34.29 vs. 36.75; P=0.05). Analysis of covariance, including terms for treatment and baseline values, also showed a significant difference between fexofenadine and cetirizine for change from baseline in VAS scores for drowsiness (P=0.01). Changes from baseline in mean daily drowsiness VAS scores overall for fexofenadine and cetirizine were ~5.47% and +1.03%, respectively. Changes from baseline in mean daily motivation VAS scores overall for fexofenadine and cetirizine were 6.21% and 1.05% respectively. CONCLUSIONS: tn patients with SAR, treatment with fexofenadine resulted in less drowsiness and improved motivation compared with treatment with cetirizine, as measured by VAS. Funding: Aventis Pharmaceuticals