Safety of fexofenadine in children treated for seasonal allergic rhinitis.

BACKGROUND: The incidence of allergic rhinitis in children is increasing. OBJECTIVE: To evaluate the safety of fexofenadine HCI in children ages 6 through 11 years for treatment of seasonal allergic rhinitis. METHODS: Two large, double-blind, randomized, placebo-controlled, parallel studies with identical protocols included patients with a positive skin test to fall allergen(s) and allergic rhinitis symptoms. Patients were randomized to receive fexofenadine 15, 30, or 60 mg or placebo twice daily for 2 weeks after a 1-week placebo lead-in. Safety was evaluated through adverse event reporting, electrocardiograms, and pre- and posttreatment laboratory panels and physical examinations. RESULTS: A total of 875 patients from both studies were eligible for safety analyses. Ten patients (5 on placebo, 5 on fexofenadine) discontinued because of an adverse event; no event that resulted in discontinuation was judged to be caused by study medication. Incidence of adverse events was similar in active and placebo groups, and did not increase with increasing fexofenadine dose: 36.2% (83 of 229) in the placebo group versus 35.3% (79 of 224), 36.8% (77 of 209), and 34.7% (74 of 213) in the 15, 30, and 60 mg twice-daily fexofenadine groups, respectively. Headache was the most commonly reported adverse event (6.6%, 8.0%, 7.2%, and 9.4% in the placebo, 15, 30, 60 mg twice-daily fexofenadine groups, respectively). Clinical, vital sign, electrocardiogram, and laboratory measures were similar in active and placebo groups. There was no statistically significant mean change from baseline in any electrocardiogram parameter after fexofenadine treatment. CONCLUSIONS: Fexofenadine, 15, 30, and 60 mg twice daily, was safe and well tolerated in this large pediatric patient population.

Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.

BACKGROUND: Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI). OBJECTIVE: MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma. METHODS: Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study. RESULTS: At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables. CONCLUSIONS: MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Venom immunotherapy: when to start, when to stop.

Over the past 25 years, major advances have been made in the diagnosis and treatment of insect sting allergy. Controlled clinical trials have demonstrated the efficacy of venom immunotherapy (VIT) in the prevention of subsequent systemic reactions in allergic individuals. We have refined our criteria for selection of patients for VIT. Studies on selections of venoms, rush immunotherapy, and interval between VIT injections have been performed. Finally, much work has been done to try to define criteria for the discontinuation of VIT.

New therapies for allergic rhinitis.

New therapies for allergic rhinitis are more effective and have fewer side effects than older medications. Antihistamines, decongestants, and cromolyn sodium nasal sprays are often tried first. Second generation prescription antihistamines have fewer side effects than over-the-counter ones. Steroid nasal sprays are extremely effective and safe for the entire range of allergy symptoms. Immunotherapy requires a lengthy course of injections, but it can bring long-term relief for severe allergies.

Stinging insect hypersensitivity in children.

In the past two decades, many advances have been made in the treatment of patients with insect venom sensitivity. An effective treatment (venom immunotherapy) has been developed and indications for therapy refined. In the past year, reports concerning fatal toxic reactions to multiple stings, Africanized ("killer") bees, bumblebee venom allergy and treatment, and reactions to fire ant stings have been published. Papers have also appeared on the use of sting challenges in the diagnostic evaluation of insect sting allergy, laboratory investigations of the mechanism of action of venom immunotherapy, and the outcome of discontinuing venom treatment after 5 years in insect-allergic patients.

Allergic and nonallergic rhinitis. Directing medical therapy at specific symptoms.

Rhinitis is a common complaint, especially during the allergy season. Physicians can often identify the probable allergen or irritant with history taking, and skin tests may be helpful in confirming the clinical impression. Often, environmental control measures can provide significant relief. Successful drug treatment hinges on selection of the proper class of medication for a given patient's type and severity of symptoms. Antihistamines remain a mainstay for reducing sneezing, itching, and nasal discharge. New oral agents are nonsedating, and an eyedrop form is available for bothersome eye symptoms. Decongestants reduce nasal blockage and are often especially beneficial when used in combination with antihistamines, In moderate to severe rhinitis, intranasal corticosteroids are the most effective treatment.

Comparison of triamcinolone acetonide nasal inhaler with astemizole in the treatment of ragweed-induced allergic rhinitis.

BACKGROUND: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids. OBJECTIVE: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis. METHODS: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated. RESULTS: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p

Tilarin in combination with astemizole.

This multicentre double-blind, placebo controlled study had a practical objective, based on the expectation that many patients with seasonal allergic rhinitis will be prescribed oral antihistamine monotherapy by their primary care physician, whereas allergy specialists are more likely to prescribe combination therapy including antiinflammatories. The specific question was, "Will the addition of nedocromil sodium 1% nasal spray to astemizole tablets improve control of symptoms of seasonal allergic rhinitis induced by ragweed pollen, as compared to astemizole therapy alone?'. Following a one-week baseline, planned to coincide with the start of the local ragweed pollen season, patients (aged 12-64) were randomly assigned to four weeks' double-blind test treatment with either nedocromil sodium 1% nasal spray four times daily (QID) + astemizole (n = 146) or placebo nasal spray + astemizole (n = 148) or double-dummy (nasal spray + capsules) placebo (n = 71). Patient diary cards were kept throughout the five weeks, and clinic visits were made before and after baseline and after one and four weeks' treatment. During the 10-day peak pollen period, the diary card rhinitis symptom summary score (0-4 severity scale) was significantly reduced in patients receiving either astemizole alone (p < 0.001) or the combination therapy (p < 0.001) as compared with placebo. Direct comparison of the active treatments further showed that symptoms were significantly less severe (p < 0.01) with the combined therapy than with astemizole alone, and this despite significantly greater reliance on permitted rescue medications (p < 0.05 for pseudoephedrine usage) in the astemizole group. Clinical assessments of rhinitis made during the peak pollen visit, after the first week of test treatment, were also significantly (p < 0.05 - p < 0.01) in favour of combined therapy with nedocromil sodium 1% nasal spray + astemizole rather than astemizole alone, and at the same time this preference was confirmed by physician (p = 0.011) and patient (p = 0.003) opinions of symptom control. In conclusion, this antiinflammatory + antihistamine treatment proved superior to antihistamine alone for effective management of allergic rhinitis. The combined therapy worked quickly and was well-tolerated, with no serious adverse events or untoward effects on blood or urine variables.

Insect sting allergy: analysis of a cohort of patients who initiated venom immunotherapy from 1978 to 1986.

BACKGROUND: The proper duration of venom immunotherapy remains uncertain. OBJECTIVE: We report our experience with a cohort of patients who started venom immunotherapy from 1978 to 1986. METHODS: In a midwestern allergy practice, the cohort of 204 stinging insect-allergic patients who commenced venom immunotherapy from 1978 to 1986 were identified and evaluated by retrospective chart analysis and patient telephone inquiry. RESULTS: Only 12 patients remain on venom treatment. The majority of patients have discontinued venom immunotherapy either by self-determination (35 patients) or upon physician advice (80 patients). There was no relationship between the severity of the initial sting reaction and the length of time patients received therapy. After cessation of venom treatment, there were 148 re-stings in 117 patients with only two re-sting reactions, both of which occurred in patients with severe initial sting reactions. CONCLUSIONS: Most patients who have received four to 6 years of venom immunotherapy continue to tolerate insect stings after cessation of treatment.

Detection of beta-blocker use in people with asthma.

Although there have been numerous reports of adverse outcomes for people with asthma who are placed on beta-blockers, there has been no description of how often people with asthma receive prescriptions for beta-blockers. Despite the fact that pharmacy claims are available and can be used for clinical evaluation, there has been no description of a practical surveillance or warning system to recognize and reduce the rate of beta-blocker use in people with asthma. This study used administrative claims data to estimate the prevalence of patients with asthma who also had prescriptions for beta-blockers. Chart audit was used to supplement our understanding of the causes of the problem and its consequences. In the calendar year 1989, in a large midwestern group practice that contracts with a single health maintenance organization (HMO), 3,170 HMO patients presumed to have asthma were identified. Of those 3,170 patients, 44 or 1.4% also had filled prescriptions for beta-blockers. The occurrence of beta-blocker use varied by age group: from less than 1% in patients below 30 years of age, rising to 8.9% in patients aged 60 to 69. Two of the patients with asthma who had prescriptions for beta-blockers were hospitalized for asthma in the study period. In 61% of the cases, different physicians managed the asthma care from those who prescribed the beta-blockers. In the remaining 39%, one physician was responsible for both the asthma care and beta-blocker prescription. We conclude prescribing beta-blockers for individuals with asthma is not uncommon. Current systems of administrative claims data permit the development of warning systems to help avert adverse outcomes.

The value of immunotherapy with venom in children with allergy to insect stings.

BACKGROUND: The treatment of patients allergic to insect stings with insect-venom injections has been shown to be 97 percent effective in reducing the risk of sting-induced anaphylaxis. However, the frequency of systemic reactions to subsequent stings in unimmunized adults with previous reactions is approximately 60 percent. To determine which factors, in addition to a history of reaction and evidence of venom-specific IgE antibody, predispose patients to future insect-sting reactions, we studied a venom-sensitive group of children who were deemed to be at relatively low risk for severe reactions; 28 percent of them received venom therapy. METHODS: We studied 242 children, 2 through 16 years of age, each of whom had had a systemic allergic reaction, affecting only the skin, to an insect sting. Each child had a positive skin-test reaction to one or more of five hymenopteran venoms. Sixty-eight children received immunotherapy with insect venom and 174 did not; about half were randomly assigned to treatment groups, and the rest were assigned on the basis of the patient's (or the parents') choice. The results of accidental stings during four years of observation were evaluated. RESULTS: In the treated group, 84 stings in 36 patients resulted in one systemic reaction (1.2 percent of stings). In contrast, 196 stings in 86 untreated children resulted in 18 systemic reactions (9.2 percent of stings, P less than 0.001). Sixteen of these 18 reactions were judged to be milder than the patient's reaction to the first sting, 2 were similar in severity, and none were more severe. CONCLUSIONS: These data confirm that immunotherapy with insect venom prevents recurrences of systemic reactions after subsequent insect stings. Because of the surprisingly low rate of reactions among untreated children, we could not identify any characteristics that were predictive of repeat reactions. Since only 9.2 percent of stings in the untreated children led to a systemic reaction and since there was no progression to a more severe reaction, we conclude that venom immunotherapy is unnecessary for most children who are allergic to insect stings.

Stinging insect allergy. How management has changed.

The state of the art for insect allergy has undergone significant changes over the last two decades. Epinephrine, which is indispensable to treat all but the mildest reactions, is available in portable kits and can be used by the patient when medical help is not readily available. Venom immunotherapy has proven to be safe and effective for those patients who require it, and the concern that lifelong therapy would be necessary is likely to be unwarranted.

Venom immunotherapy during pregnancy.

A patient who received venom immunotherapy during pregnancy without complications delivered a healthy term infant. Venom-specific IgG antibodies were similar in the mother and infant at birth and then fell to undetectable levels by six months of age. Although the mother had elevated venom-specific IgE levels, they were not detectable in the infant at birth or six months of age. Therefore, venom immunotherapy during pregnancy did not lead to allergic sensitization of this child.

Assessment of prolonged venom immunotherapy in children.

Venom immunotherapy was initiated in 94 children from April 1977 to October 1979. As of February 1983, 66 children had continued receiving treatment and had recent immunologic evaluation. Assessment of prolonged venom treatment included analysis of immunologic parameters, efficacy of treatment, and long-term safety. Venom skin tests, venom-specific IgE antibody levels, and venom-specific IgG antibody levels comprised the immunologic parameters evaluated. A decrease in allergic sensitivity was demonstrated over time in the skin and serum. Forty-three of 57 (75%) children had less positive vespid venom skin tests, and the mean venom-specific IgE antibody level declined to less than the pretreatment value with 3 or more years of yellow jacket venom therapy. Venom-specific IgG antibody measurements rose rapidly after the initiation of venom injections and were maintained for the duration of this evaluation. During a 3- to 6-year period, 200 stings in 49 treated children resulted in only four mild systemic reactions (98% efficacy). The benign nature of interval histories, physical examinations, and laboratory analyses in these children argues optimistically for the safety of prolonged venom immunotherapy.

A prospective study of the natural history of large local reactions after Hymenoptera stings in children.

Large local reactions are a frequent occurrence after insect stings. We prospectively studied the demography, immunology, and significance of these reactions in the pediatric age group. Most children (83%) who have had large local reactions have positive skin test results to one or more venoms. Elevated amounts of venom-specific IgE antibody are usually present. Over 3 to 5 years, allergic sensitivity declines, as evidenced by less positive skin test results and lower levels of antivenom IgE antibodies. Most significantly, of 113 repeat stings, only 2% resulted in a systemic reaction.