Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma.

Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.

Clinical benefits of switching to an inhaled corticosteroid extrafine aerosol; a case series.

Hydrofluoroalkane beclomethasone dipropionate (HFA-BDP) extrafine aerosol is the first in a new generation of inhaled corticosteroid (ICS) formulations that have an improved deposition profile in comparison with conventional ICS preparations. This reformulation offers potential benefits to patients with asthma in terms of improved symptom control and reduced oropharyngeal adverse effects, such as dysphonia and candidiasis. This article presents four cases that illustrate the clinical benefits that can be obtained following a switch from conventional ICS preparations to treatment with HFA-BDP extrafine aerosol. The patients described were experiencing significant exacerbations of their asthma and increasing asthma symptoms and/or oropharyngeal adverse effects during treatment with conventional ICS preparations. On switching to HFA-BDP extrafine aerosol, the patients experienced an improvement in their asthma control and resolution of any oropharyngeal adverse effects.

The evolution of pharmacotherapy for rhinitis and urticaria.

The efficacy of antihistamines in the treatment of allergic rhinitis and urticaria is compared. In treating allergic rhinitis, the new second- and third-generation antihistamines have multiple advantages including rapid onset of action, extended duration of action, and efficacy for nearly all the symptoms that are produced by allergen sensitization. These include non-nasal and nasal symptoms. These agents are generally nonsedating and can be administered either once or twice daily. There is minimal potentiation for QTC prolongation, and they are safe and effective as first-line therapies for seasonal allergic rhinitis. They are especially effective when combined with topical corticosteroids in reducing the whole constellation of symptomatology of allergic rhinitis. The treatment of chronic idiopathic urticaria should include second- and third-generation antihistamines as primary therapy. Additional therapy may include H2 antagonists, antihistamine-decongestant combinations, tricyclic antidepressants such as doxepin, and beta-adrenergic agonists including albuterol and epinephrine for acute angioedema. Corticosteroids may be required to treat significant exacerbations of chronic urticaria and/or to break a long-standing cycle of urticaria. Miscellaneous therapeutic agents include leukotriene antagonists combined with H1, H2 antagonists, calcium channel antagonists, plasmapheresis, cyclosporin and methotrexate.

Long-term safety and efficacy of a chlorofluorocarbon-free beclomethasone dipropionate extrafine aerosol.

BACKGROUND: Beclomethasone dipropionate (BDP) extrafine aerosol, a newly developed pressurized metered dose inhaler (pMDI) with a hydrofluoroalkane-134a (HFA) propellant (HFA-BDP; Qvar, 3M Pharmaceuticals, St. Paul, MN), has been shown to be effective in controlling asthma symptoms at approximately half the daily dose of chlorofluorocarbon (CFC)-BDP. OBJECTIVE: This study evaluated the long-term efficacy and safety of switching patients with asthma maintained on a stable dose of CFC-BDP pMDI to therapy with HFA-BDP pMDI at approximately half their previous daily dose of CFC-BDP. METHODS: This was an open-label, randomized, parallel-group multicenter trial. Patients with at least a 6-month history of asthma whose symptoms were controlled on CFC-BDP, 400 to 1600 microg daily, during a 2-week run-in period were randomized in a 1:3 ratio to CFC-BDP at the same daily dose or HFA-BDP at approximately half the daily dose of CFC-BDP for 12 months. RESULTS: A total of 473 patients were randomized: 354 to HFA-BDP, 119 to CFC-BDP. There were no statistically significant differences between groups in mean change from baseline in morning (AM) peak expiratory flow rate or forced expiratory volume in one second throughout the study. There were no consistent differences between treatment groups in individual asthma symptoms or daily beta2-agonist use during the study. There was an increase in the percentage of symptom-free days between baseline and month 12 in the HFA-BDP group (11.5%) and the CFC-BDP group (4.6%). No statistically significant differences in serum osteocalcin levels or adverse events were seen during the study or in AM plasma cortisol levels at month 12. CONCLUSIONS: Asthma control was maintained in patients switched from a stable dose of CFC-BDP (400 to 1600 microg daily) to HFA-BDP at approximately half the CFC-BDP dose (200 to 800 microg daily), and was maintained over the next 12 months. HFA-BDP demonstrated a similar safety profile to CFC-BDP; there were no differences between the agents with regard to systemic effects.

Efficacy and tolerability of loratadine versus fexofenadine in the treatment of seasonal allergic rhinitis: a double-blind comparison with crossover treatment of nonresponders.

BACKGROUND: Nonsedating antihistamines are well-established treatment for seasonal allergic rhinitis (SAR), but patients do not always respond to the first antihistamine prescribed. OBJECTIVE: This double-blind, double-dummy, randomized, 2-phase, multicenter study was designed primarily to compare the therapeutic responses to loratadine and fexofenadine in patients who failed initial therapy with the other drug. METHODS: Male and female patients aged 12 to 60 years received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale) subsequently received the alternate medication for 14 days (phase 2). The investigator's rating of relief (complete, marked, moderate, or slight relief of symptoms or treatment failure) at the end of phase 2 was the primary efficacy measure; changes in total symptom severity (TSS) assessed by the investigator (4-point scale) and the patient (11-point visual analog scale) were secondary measures. RESULTS: Mean decreases in TSS were significantly greater with loratadine than with fexofenadine for the 659 patients who completed phase 1 (-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389 patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037; investigator assessment). Of the 389 patients who responded to initial therapy, 61.0% had received loratadine and 57.0% had received fexofenadine. More nonresponders to initial therapy had moderate, marked, or complete relief of symptoms after switching to loratadine than after switching to fexofenadine (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs 21.7%, respectively (P = 0.011). CONCLUSION: Overall, ioratadine provided significantly better therapeutic response than fexofenadine in patients who failed to respond to initial therapy with the other drug.

Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial.

BACKGROUND: Nasal challenge studies have suggested histamine and cysteinyl leukotrienes are important proinflammatory mediators in allergic rhinitis. This study was designed to determine the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, administered alone or concomitantly with loratadine, an H(1)-receptor antagonist, in seasonal allergic rhinitis. OBJECTIVE: The purpose of this study was to determine the effect of concomitant use of montelukast and loratadine in the treatment of seasonal allergic rhinitis. METHODS: In this multicenter (N = 12) double-blind, randomized, parallel-group, placebo-controlled 2-week trial, 460 men and women, aged 15 to 75 years, with spring seasonal allergic rhinitis were randomly allocated to receive 1 of the following 5 treatments: montelukast 10 or 20 mg, loratadine 10 mg, montelukast 10 mg with loratadine 10 mg, or placebo, once daily in the evening. The primary end point was daytime nasal symptoms score (average of congestion, rhinorrhea, itching, and sneezing). Other end points were eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations (patient's and physician's), and rhinoconjunctivitis quality-of-life scores. RESULTS: Concomitant montelukast with loratadine improved the primary end point significantly (P <.001) compared with placebo and each agent alone. Compared with placebo, montelukast with loratadine also significantly improved eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations, and quality of life. Montelukast alone and loratadine alone caused modest improvements in rhinitis end points. All treatments were similarly well tolerated. CONCLUSIONS: Concomitant montelukast with loratadine provided effective treatment for seasonal allergic rhinitis and associated eye symptoms with a safety profile comparable with placebo.

Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

Double-strength beclomethasone dipropionate (84 micrograms/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: The use of intranasally administered corticosteroid sprays is an established treatment option for seasonal allergic rhinitis. METHODS: In this double-blind, placebo-controlled, multicenter study, 438 patients with moderate to severe symptoms of seasonal allergic rhinitis were treated for 4 weeks with double-strength beclomethasone dipropionate (BDP) aqueous nasal spray (84 micrograms/spray: BDP-ds), once daily; regular-strength BDP (42 micrograms/spray: BDP-rs), twice daily; high-strength BDP (336 micrograms/spray: BDP-hs), once daily; or placebo. BDP-hs was included as a safety comparison group. All treatments were given as two sprays per nostril. RESULTS: Physician-rated nasal symptom scores were significantly improved in all three active treatment groups compared with those of the placebo group within the initial 3 days of treatment. Improvement was maintained throughout the 4-week treatment period. BDP-ds and BDP-rs were equivalent at all time points. The BDP-ds, BDP-rs, and BDP-hs groups had greater numbers of patients with a good or excellent therapeutic response at end point than the placebo group. All treatments were well-tolerated, and no unexpected adverse events were reported. No effects on laboratory evaluations or vital signs were evident for any treatment group. CONCLUSIONS: The results of this study show that BDP-ds given once a day and BDP-rs given twice a day in the same total daily dose are comparably safe and effective in the treatment of patients with seasonal allergic rhinitis.

Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial.

BACKGROUND: Azelastine is a chemically novel investigational antiallergy drug with the ability to antagonize the effects of chemical mediators of the early- phase and late phase allergic responses suggesting its usefulness in the treatment of upper and lower airway diseases. OBJECTIVE: The objective of this 4-week, double- bind, multicenter trial was to evaluate the efficacy of azelastine nasal spray in subjects with seasonal allergic rhinitis. METHODS: Two hundred sixty-four subjects 12 years of age and older were randomized to receive either azelastine, 2 sprays/nostril qd; azelastine, 2 sprays/nostril bid; oral chlorpheniramine maleate, 12 mg bid; or placebo. The primary efficacy parameters were the changes in major and total symptom severity scores. RESULTS: Overall, across all 4 weeks of treatment, the mean percent improvements in the total and major symptom complex severity scores in both azelastine treatment groups were greater than those for the placebo group. For the azelastine 2 sprays bid group, the overall results were significant at P = .05 for the major symptom complex score and at .05 < P = .10 for the total symptom complex score versus placebo. For both azelastine treatment groups, improvements in all of the individual rhinitis symptoms were superior to those for the placebo group and, in general were clinically and statistically significant. Azelastine nasal spray was well tolerated; adverse experiences were generally application site reactions, mild to moderate, and not limiting to continued treatment. CONCLUSIONS: Azelastine nasal spray demonstrated broad clinical antirhinitis activity that for the 2 sprays/nostril bid dosage regimen was consistently clinically and statistically significant.

Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol.

In a double-blind, double-dummy, multicenter study, 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were randomized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks. Asthma symptom scores (daytime asthma, nighttime asthma, morning chest tightness, and cough) and peak expiratory flow rate were recorded daily on diary cards. Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge. Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness. Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol. Compared with patients treated with albuterol, patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge. Patients in both groups reduced their as-needed albuterol use. Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol. The study also showed that more frequent use of a beta 2-agonist (for symptom relief or not) did not improve asthma control. Both drugs were well tolerated.

A comparative tolerance study of terfenadine-pseudoephedrine combination tablets and pseudoephedrine tablets in patients with allergic or vasomotor rhinitis.

In this multicentre, double-blind, randomized, parallel group study, 315 patients with allergic or vasomotor rhinitis were treated on a twice daily dosing schedule with either a 60 mg terfenadine-120 mg pseudoephedrine hydrochloride combination or 120 mg pseudoephedrine hydrochloride (extended release) for 2 weeks. No clinically significant differences between the two groups were noted in body weight, temperature, respiration rate or blood pressure following the treatment period. An increase in mean heart rate of approximately 5 beats/min from entry to the final clinic visit was noted in both treatment groups. No clinically significant changes were noted in either treatment group when pre- and post-treatment electrocardiograms were compared. There were also no clinically significant alterations in laboratory values, which included serum chemistry, haematology and urinalysis, within or between either group. The adverse events profiles for both groups were similar. The most frequent adverse event was insomnia, in 40 (25.3%) patients given the terfenadine-pseudoephedrine combination and in 42 (26.8%) of those given pseudoephedrine. No unusual or unexpected adverse events were reported.

Double-blind placebo-controlled trial of intranasal IgE pentapeptide.

The safety and efficacy of intranasal HEPP (IgE pentapeptide) was evaluated in 30 patients with IgE-mediated allergic rhinitis. Statistically and clinically significant differences were observed in the degree of clinical improvement between HEPP and placebo groups. IgE pentapeptide 0.5% intranasal solution appears to be safe and effective in the treatment of allergic rhinitis.

Safety, efficacy and bronchodilator-sparing effects of nebulized cromolyn sodium solution in the treatment of asthma in children.

In a 12-week study 20 children, ages two to seven years, with moderate to severe asthma received 20 mg cromolyn sodium via a power-driven nebulizer four times daily. Entry criteria required that each patient be maintained on at least one bronchodilator on a daily basis prior to the study. By the conclusion of the trial asthmatic symptoms had declined significantly (p less than 0.01), both as scored by the patients and by the physician. These was a 73% reduction in theophylline dosage over-all. No significant adverse reactions occurred, and there were no meaningful changes in clinical chemistry tests hematology or urinalyses.

Neonatal withdrawal syndrome associated with hydroxyzine hydrochloride.

To our knowledge, this is the first report of a neonatal withdrawal syndrome associated with maternal usage of 600 mg daily of hydroxyzine hydrochloride throughout pregnancy. This observation suggests that the use of high doses of this agent in pregnancy should be avoided.