Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.     

Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.     

A Comparative Study of Dexchlorpheniramine Maleate Sustained Release Tablets and Budesonide Nasal Spray in Seasonal Allergic Rhinitis

It was the aim of the study to compare the efficacy and side effects of oral antihistamine and nasal glucocorticoid therapy in seasonal allergic, rhinitis. In a double blind, double-dummy, group-comparative study, 61 adult grass pollen allergic patients were either treated with dexchlorpheniramine maleate sustained release tablets (6 mg b.d.), or with budesonide nasal spray (200 micrograms b.d.). After a 1-week run-in period, treatment was given for 3 weeks in the grass pollen season. Patients treated with budesonide showed significantly less nasal blockage than those who received dexchlorpheniramine (P less than 0.05), but there was no difference in the number of sneezes and nose blowings. Patients treated with budesonide and a larger quantity of antihistamine-vasoconstrictor eye drops (P less than 0.01). Drowsiness occurred in the group that was treated with dexchlorpheniramine, but mainly during the first week of treatment. The side effects caused by the budesonide spray were few and insignificant. The patients' overall assessment of the treatment favoured the glucocorticoid spray (P = 0.06).     

2000年～2002年杭州地区18家医院抗组胺药物利用分析

目的 :了解杭州地区抗组胺药用药现状和趋势。方法 :调查杭州地区18家医院2000年～2002年抗组胺药的用药金额、生产厂家等信息 ,并进行回顾性分析。结果 :抗组胺药的用药金额2001年较2000年增长17 89 %,2002年较2001年下降4 58 %;西替利嗪和氯雷他定是抗组胺药的首选 ;合资、进口药品占70 %以上市场分额。结论 :抗组胺药品种变化不大 ,用量呈下降趋势。     

应用皮肤试验抑制指数评价阿伐斯汀的起效时间

目的皮肤试验抑制指数(Skin Test Inhibition Index,STII)是评价抗组胺药疗效的一个药效学指标,本试验以阿伐斯汀为例应用STII方法评价抗组胺药阿伐斯汀的起效时间。方法选择27例花粉症病人,分为阿伐斯汀组(24例)和安慰剂组(3例),并分别于服药前及服药30、90min后观察受试者的过敏原皮试反应,计算STII值,并将STII达到10的时间定为起效时间。结果安慰剂组前后过敏原皮试风团无显著差异,而阿伐斯汀组30、90min后,STII值分别为22.2、237.7。故可初步认为阿伐斯汀的起效时间小于30min。结论 STII可做为评价抗组胺药起效时间的客观指标之一。     

Paediatric issues relating to the pharmacotherapy of allergic rhinitis

The prevalence of allergic rhinitis in children has risen significantly over the last two decades. Important comorbidities like asthma have grown in parallel due to a complex mix of environmental and genetic factors. These conditions have similar allergic inflammatory mechanisms, which raises the possibility of treating both conditions by targeting shared inflammatory mediators pharmacologically. The first line treatment for paediatric allergic rhinitis is a topical nasal corticosteroid or a non-sedating antihistamine. Available intranasal corticosteroids show superior symptom control to second-generation antihistamines. However, most topical steroids and non-sedating antihistamines have equivalent clinical efficacy within their respective classes, so the choice of agent depends on safety and tolerability. Ideally, topical nasal steroids should exhibit high local receptor binding affinity and low systemic bioavailability, allied with a lack of long-term growth suppression in children and adolescents. Regular use of topical steroids is advisable, but intermittent and prophylactic use is also effective. Second-generation antihistamines are effective and some have no adverse cardiac or sedative effects. Non-sedating antihistamine treatment can ameliorate rhinitis-induced decrements in learning. α-Adrenergic nasal decongestants provide short-term benefit, but topical agents can cause rebound symptoms. Prophylactic treatment with chromones is safe and effective, but multiple daily dosing is needed. Ipratroprium bromide nasal spray is useful as an intermittent therapy for mild disease or as add-on treatment, but its effect is limited to the control of rhinorrhoea. Children with allergic rhinitis should receive pharmacotherapy if allergen avoidance measures are ineffective, ideally with a topical intranasal steroid or a second-generation antihistamine.     

Low-dose doxepin for the treatment of insomnia: emerging data

Background: Doxepin is a tricyclic compound that has been used extensively for the treatment of depressive and anxiety disorders for approximately thirty years. It was noted early to have sedative effects and assist with the improvement of disrupted sleep patterns, but in higher antidepressant doses it was also noted to have significant anticholinergic and antinoradrenergic properties. These properties led to significant dose-limiting side effects, which at times precluded its effective use. Recently, doxepin has seen renewed interest in low doses as an H1 specific antagonist in sleep disorders. Objective: The review seeks systematically to examine currently published data on the use of doxepin for the treatment of insomnia, and its pharmacological basis. Methods: Medline articles showing from a search of ‘doxepin and insomnia’ were included in the review. Results/conclusion: Currently available data support the use of low-dose doxepin as preferential H1 antagonist for the treatment of primary insomnia. There are likely preferential effects upon sleep maintenance insomnia compared with sleep initiation given the role of histamine in the sleep–wake cycle.     

Efficacy and safety of rupatadine in Japanese adult and adolescent patients with chronic spontaneous urticaria: A double-blind,randomized, multicenter,placebo-controlled clinical trial

Background

Rupatadine, a novel nonsedating second-generation H1-antihistamine with antiplatelet-activating factor activity, has been used in the treatment of allergic rhinitis and urticaria in European countries since 2003. However, its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU) are unknown.

Combining desloratadine and pseudoephedrine in the treatment of seasonal allergic rhinitis

Nonsedating antihistamines are a first-line therapy in the management of allergic rhinitis. They relieve the majority of the histamine-mediated symptoms of the condition, including rhinorrhea, sneezing, and pruritus. The nonsedating antihistamine desloratadine is effective in alleviating the symptoms of both seasonal and perennial allergic rhinitis. It may also have some decongestant properties, and thus help to alleviate nasal congestion. Administering desloratadine in combination with the decongestant pseudoephedrine may offer allergic rhinitis patients with moderate-to-severe nasal congestion the benefits of desloratadine’s effectiveness for alleviating histamine-mediated symptoms plus pseudoephedrine’s relief from nasal congestion. This drug profile reviews a combination therapy containing desloratadine and pseudoephedrine, approved in the USA for the relief of the symptoms of seasonal allergic rhinitis, including nasal congestion.     

One‐year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases

A number of second‐generation non‐sedating antihistamines are used in clinical practices over the world. However, long‐term safety and efficacy have not been proved high level evidence based medicine. We have performed an open‐label, multicenter, phase III study to evaluate the long‐term safety and efficacy of bilastine, a novel non‐sedating H₁‐antihistamine for patients with chronic spontaneous urticaria (CSU) or pruritus associated with skin diseases (trial registration no. JapicCTI‐142528). Patients aged 18–74 years were treated with bilastine 20 mg once daily for up to 52 weeks. Safety and tolerability were assessed on the basis of adverse events (AE), bilastine‐related AE, laboratory tests and vital signs. Efficacy was assessed based on rash score, itch score, overall improvement and quality of life. One hundred and ninety‐eight patients enrolled, 122 of whom (61.6%) completed the 52‐week treatment period. AE were reported in 64.5% and bilastine‐related AE in 2.5% of patients throughout the 52‐week treatment period. All AE were mild to moderate in severity. AE associated with the nervous system occurred in 10 patients (5.1%) including seven patients (3.6%) with headache. Somnolence reported in two of these patients (1.0%) was related to bilastine. All efficacy variables improved during treatment with bilastine. In conclusion, long‐term treatment with bilastine 20 mg once daily for 52 weeks is safe and well tolerated in Japanese patients with CSU or pruritus associated with skin diseases. Bilastine improved disease symptoms of both conditions early in treatment, and the efficacy was maintained throughout the treatment.