Priapism, an emerging complication in ß-thalassemia intermedia patients.

The increase in survival rate of ß-thalassemia (ß-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in ß-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with ß-thal intermedia (ß-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.

Efficacy of Triprolidine in the Treatment of Temporary Sleep Disturbance.

Triprolidine, a first-generation antihistamine for allergic rhinitis, has a shorter half-life and fewer persistent effects relative to other antihistamines and may be useful in the treatment of temporary sleep disturbance. Patients aged ≥18 years old were randomized 1:1:1 to receive either triprolidine 2.5 mg (n = 65), triprolidine 5 mg (n = 66), or placebo (n = 67) on 3 consecutive nights. Sleep disturbance index was monitored via wrist actimeter. Subjective measures were assessed via diary card. Triprolidine 2.5 mg had a significantly lower sleep disturbance index versus placebo on night 1 (P = .02); however, when adjusted for outliers, sleep disturbance index did not significantly differ between either dose of triprolidine versus placebo on night 1. Adjusted sleep disturbance index was significantly lower with triprolidine 2.5 and 5 mg versus placebo on night 3 (P = .0017 and P = .011, respectively) and for the mean of all 3 nights (P = .01 and P = .015, respectively). Sleep latency was significantly improved for triprolidine 2.5 mg versus placebo on nights 2 and 3 and for the mean of all 3 nights and for triprolidine 5 mg versus placebo for the mean of all 3 nights. Subjective measures showed those on both doses of triprolidine felt more refreshed on awakening versus placebo for the mean of all 3 nights, with no increase in daytime sleepiness. The frequency of adverse events was similar across groups. The optimum dose of triprolidine for treatment of temporary sleep disturbance was 2.5 mg. There were improvements in both objective and subjective measures of sleep quality versus placebo, with no safety concerns raised.

Bivariate or composite plots of endpoints.

Clinical trials often identify two endpoints or response measures of interest. Depending on the drugs and the disease, the endpoints may be correlated or uncorrelated, reflect efficacy or safety, or one or both may be considered as primary. For visualization, plots of each endpoint from baseline to the end of the trial are presented for each treatment group. This paper illustrates the usefulness of developing bivariate, composite plots of both endpoints jointly. Two applications are presented: one of a fixed combination drug for treating allergic rhinitis, and the other of a dose comparison trial in duodenal ulcer.

The butterbur extract petasin has no effect on skin test reactivity induced by different stimuli: a randomized, double-blind crossover study using histamine, codeine, methacholine, and aeroallergen solutions.

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

Acrivastine. A review of its pharmacological properties and therapeutic efficacy in allergic rhinitis, urticaria and related disorders.

Acrivastine is a short acting histamine H1-receptor antagonist with a rapid onset of action. Double-blind clinical trials have shown acrivastine (usually 8mg three times daily) to be an effective and well tolerated antihistamine in the treatment of chronic urticaria and allergic rhinitis. Acrivastine was more effective than placebo and similar in efficacy to clemastine or terfenadine in the treatment of seasonal allergic rhinitis. In the treatment of dermatoses in which histamine has a pathogenetic role, the efficacy of acrivastine was superior to that of placebo and similar to that of usual dosages of clemastine, hydroxyzine, chlorpheniramine, cyproheptadine or terfenadine. Acrivastine caused less drowsiness than clemastine, the incidence of adverse effects being indistinguishable from that with placebo or terfenadine. Thus, acrivastine is an effective addition to drugs currently available for the treatment of patients with allergic diseases in whom a histamine H1-receptor antagonist is indicated. Because of its rapid onset of action acrivastine will be particularly useful for 'on demand' therapy in patients with intermittent symptoms.

Randomized single-blind trial in general practice comparing the efficacy and palatability of two cough linctus preparations, 'Pholcolix' and 'Actifed' Compound, in children with acute cough.

Two hundred and seventeen patients between 6 and 12 years of age suffering from acute cough took part in a randomized, single-blind study comparing 'Pholcolix' and 'Actifed' Compound. No significant difference in efficacy was demonstrated but analysis of palatability components (taste, smell, aftertaste and feeling in the mouth) showed numerical superiority for 'Pholcolix' for all parameters, with a high degree of significance for overall taste. 'Pholcolix' caused significantly fewer side-effects, with 'Actifed' Compound causing markedly more drowsiness after daytime dosage.

The new H1 antihistamines. Treatment of urticaria and other clinical problems.

The new H1 antihistamines are a major therapeutic advancement in the treatment of allergic disorders such as urticaria and allergic rhinitis. Their efficacy combined with greatly reduced sedating and anticholinergic side effects makes the new class of H1 antihistamines the first-line treatment in the management of urticaria and mild angioedema. The choice of a particular low-sedating H1 antihistamine depends on pharmacokinetic considerations, the severity of the problem (systemic steroids and epinephrine are the first-line treatment for severe angioedema), and the requirement for limiting the frequency of administration. The efficacy of the new H1 antihistamines in the treatment of itch due to atopic eczema and systemic disease remains uncertain, and further controlled clinical trials are needed to elucidate their possible role in these conditions.

Inhibition of histamine or allergen-induced wheals by a single dose of acrivastine, fexofenadine or cetirizine.

Certirizine, a potent H1-blocking agent, is often recommended as an emergency drug in anaphylactic reactions because of its well documented fast onset of action. In this randomized, cross-over study we compared the onset of action after a single dose of two recently introduced antihistamines, acrivastine and fexofenadine, with that of cetirizine. The inhibition of the wheal-and-flare reaction produced by skin prick test with histamine in 20 healthy volunteers and with a relevant pollen allergen in 20 atopic patients, respectively, were measured before and at regular intervals up to 60 min after the ingestion of acrivastine (8 mg and 16 mg), fexofenadine (120 mg) and cetirizine (10 mg and 20 mg). Wheal-and-flare reaction were significantly inhibited 20 min after the intake of 16 mg acrivastine in atopic patients and 30 min after intake of 8 mg acrivastine in healthy volunteers, whereas cetirizine produced a significant inhibition of the wheal-and-flare reaction within 40-60 min. No significant inhibition could be observed within 60 min after fexofenadine intake. Therefore, in clinical settings when a fast onset of the H1-blocking action is mandatory (e.g., after insect stings or for short-term prophylaxis) we recommend acrivastine.

Clinical and therapeutic aspects of sinusitis in children with bronchial asthma.

Eighty children between 4 and 14 years of age suffering from bronchial asthma were investigated. Fifty-five of them showed clinical and radiological findings of sinusitis. Of these, 13 patients with purulent postnasal drip were treated with ampicillin, phenylephrine and triprolidine (therapy A) and for the other 42 ampicillin was replaced by beclomethasone (therapy B). Thirty-four of 55 children showed improvement in sinus X-rays; 20 children had a considerable decrease in the severity of asthma and many symptoms cleared up after the therapy for sinusitis (P less than 0.001). In conclusion, owing to the high prevalence of sinusitis in children with bronchial asthma, all asthmatic children should be investigated to check for a sinus disease.

Acrivastine: a review of its dermatopharmacology and clinical activity.

The general human and skin pharmacology of acrivastine, its clinical utility and some important concepts of the use of H1-antihistamines in dermatology are discussed. The drug has potent H1-antihistamic activity yet a low sedative profile as compared with first generation agents. Acrivastine is rapidly absorbed with peak inhibition of flare areas occurring at 90 min and peak activity against weals at 120 min after drug administration. No accumulation of the drug following multiple dosing has been demonstrated. Due to these effects the drug has a high level of patient acceptability and a high level of useful activity in a range of histamine-mediated dermatoses.

Acrivastine in allergic rhinitis: a review of clinical experience.

Acrivastine is an antihistamine with reduced sedating potential. This comprehensive review of clinical experience with acrivastine in allergic rhinitis considers all currently available data both published and, as yet, unpublished. Unequivocal evidence of the efficacy of 8 mg acrivastine three times daily for the control of symptoms of seasonal allergic rhinitis has been provided by 11 placebo-controlled studies involving almost 1000 patients. Additional trials have generated further supportive data as well as evidence for the use of acrivastine in the treatment of perennial allergic rhinitis. In common with most antihistamines, acrivastine alone has limited effect on the symptom of blocked nose. In a further series of 11 studies, mainly conducted in the USA, the combination of 8 mg acrivastine plus 60 mg pseudoephedrine was found to control not only the histamine-mediated symptoms of allergic rhinitis but also blocked nose. There were few adverse events associated with the use of acrivastine and the small increase in incidence of drowsiness over that found with placebo was similar to that observed for terfenadine. The marked absence of other signs of significant depression of the central nervous system (or anticholinergic activity) suggests that acrivastine will be an important addition for the antihistaminic control of symptoms of allergic rhinitis.

A comparison of acrivastine versus hydroxyzine and placebo in the treatment of chronic idiopathic urticaria.

A total of 21 patients with a diagnosis of chronic idiopathic urticaria were assessed in a fully randomized, double-blind, crossover study to investigate the efficacy of 8 mg acrivastine versus 20 mg hydroxyzine and placebo administered three times daily. Both acrivastine and hydroxyzine were found to be effective, and significantly better than placebo, in controlling signs and symptoms of urticaria. No significant differences were found between the active preparations. Hydroxyzine was associated with significantly more reports of drowsiness than was placebo.

A comparison of acrivastine versus terfenadine and placebo in the treatment of chronic idiopathic urticaria.

Patients (n = 56) with a diagnosis of chronic idiopathic urticaria were assessed in a fully randomized, double-blind, crossover study to investigate the efficacy of acrivastine at two doses (8 and 4 mg) versus 60 mg terfenadine and placebo administered three times daily. All three active preparations were found to be effective, and significantly better than placebo, in controlling the signs and symptoms of urticaria. No significant differences were found between the active preparations, although in some cases efficacy trends favoured 8 mg acrivastine and terfenadine over 4 mg acrivastine. No significant differences were noted between the active treatments and placebo with regard to reports of drowsiness.

A comparison of acrivastine versus clemastine and placebo in the treatment of patients with chronic idiopathic urticaria.

Twenty patients of mean age 41.3 years, with a diagnosis of chronic idiopathic urticaria were assessed in a fully randomized, double-blind, crossover study to investigate the efficacy of acrivastine at two doses (8 mg and 4 mg) versus 1 mg clemastine and placebo, given three times per day. All active preparations were found to be effective, and significantly better than placebo, in controlling the signs and symptoms of urticaria. There was a higher incidence of sedation with clemastine than with either acrivastine or placebo, although this difference did not achieve statistical significance in this small study.

A comparison of acrivastine versus chlorpheniramine in the treatment of chronic idiopathic urticaria.

A total of 20 patients with a diagnosis of chronic idiopathic urticaria were entered into a fully randomized, double-blind, crossover study to investigate the efficacy of 8 mg acrivastine versus 4 mg chlorpheniramine three times daily. Data from 16 patients were available for analysis. Both acrivastine and chlorpheniramine were found to be effective in relieving the signs and symptoms of urticaria. There were no significant differences between the two treatments, although efficacy trends were generally in favour of acrivastine over chlorpheniramine throughout the study.

Acrivastine--an evaluation of initial and peak activity in human skin.

Twenty-four healthy volunteers were entered into a double-blind, crossover study conducted to establish the time of onset of action and the time to peak activity of acrivastine in suppressing the weal and flare responses to intradermally injected histamine. Volunteers received single doses of 8 mg acrivastine and placebo according to a fully randomized, balanced treatment plan. Acrivastine significantly (P less than 0.001) reduced both the weal and flare responses induced by histamine challenge 30 min after oral dosing, as compared with placebo. Peak inhibition of the flare response was seen at 90 min, and maximal suppression of the weal response occurred at 120 min after administration of acrivastine.

Prolonged treatment with acrivastine for seasonal allergic rhinitis.

In a double-blind, placebo-controlled multicentre study, the antihistamine acrivastine, was used over prolonged periods for the treatment of seasonal allergic rhinitis. After the initial treatment period of 10 days, 8 mg acrivastine three times daily was significantly superior to placebo in controlling the symptoms of sneezing, itchy nose, running nose, watery eyes, itchy eyes and itchy throat. The benefit from acrivastine was also apparent in the second (14 days) and third (28 days) treatment periods, although the difference no longer reached statistical significance. This was probably due to the large proportion of non-responders in the placebo group who withdrew from the study owing to lack of efficacy. The investigators rated symptom control with acrivastine to be 'good' in comparison to 'poor' control with placebo treatment (P = 0.01) for all three periods. There were no significant differences between acrivastine and placebo in the incidence of adverse experiences at the end of each treatment period. Acrivastine is effective and well tolerated over prolonged periods (up to 52 days) for the treatment of seasonal allergic rhinitis.

Acrivastine versus terfenadine in the treatment of symptomatic dermographism--a double-blind, placebo-controlled study.

Twelve patients with symptomatic dermographism were entered into a double-blind, crossover study. Patients received 8 mg acrivastine three times daily, 60 mg terfenadine three times daily or placebo, according to a fully randomized balanced treatment plan. Subjective clinical assessments were performed and the response to experimentally induced dermographism was assessed. Both active treatments were well tolerated and were shown to be significantly more effective than placebo in the treatment of symptomatic dermographism and in reducing the signs and symptoms of wealing induced by a dermographometer.

Acrivastine in seasonal allergic rhinitis: two randomized crossover studies to evaluate efficacy and safety.

In two randomized crossover studies, the antihistamine, acrivastine, was evaluated for the treatment of seasonal allergic rhinitis. One study on 31 patients found both 4 and 8 mg acrivastine given three times daily to be significantly better than placebo for alleviating hay fever. There were no significant differences in symptom scores between the two doses, although more patients (63%) favoured 8 mg acrivastine over the 4 mg dose (46%) or placebo (35%). The other study found the higher dosage regimen to be similar in efficacy to 1 mg clemastine given three times daily. Both dosages were significantly better than placebo for reducing symptom scores in all 18 evaluable patients. The incidence of adverse experiences was low in both studies; there being no dose-related effects of acrivastine. In the second study, drowsiness, probably or possibly treatment related, occurred on seven occasions during clemastine treatment and once with acrivastine. These studies indicate that 8 mg acrivastine given three times daily is both well tolerated and of equal efficacy to clemastine for the treatment of seasonal allergic rhinitis.

A double-blind controlled evaluation of Actifed and its individual constituents in allergic rhinitis.

Pseudoephedrine and triprolidine, administered every 6 hours as a combination, made separate and distinct contributions to the treatment of allergic rhinitis. Furthermore, the combination was perceived by the patients as being clinically superior to either of its components or placebo.