Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial.

OBJECTIVES: Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR. MATERIALS AND METHODS: Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18-65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter. RESULTS: Evaluation of TNSS revealed significant difference (P < 0.05) when compared from baseline to 4th week in both groups. The mean change of TNSS, i.e., 9.46 was significant (P < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group. CONCLUSION: The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.

Assessing the chiral switch: approval and use of single-enantiomer drugs, 2001 to 2011.

OBJECTIVES: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid. STUDY DESIGN: Retrospective analysis. METHODS: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period. RESULTS: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs. CONCLUSIONS: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.

Patented drug extension strategies on healthcare spending: a cost-evaluation analysis.

BACKGROUND: Drug manufacturers have developed "evergreening" strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole ("spillover effect"). METHODS AND FINDINGS: We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. "Extra costs" were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community. Estimated "extra costs" over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover "extra cost" of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in "extra costs" of €503,600 (95% CI 444,500; 563,100). CONCLUSIONS: Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.

Levocetirizine for chronic idiopathic urticaria: a review.

Only recently available on the US market, levocetirizine has emerged as an effective new option in the treatment of chronic idiopathic urticaria (CIU). Levocetirizine is the active isomer of cetirizine and demonstrates twice the affinity for the H1 receptor compared with the parent compound. In the treatment of CIU, levocetirizine has consistently demonstrated high response rates, fast onset, and a favorable side effect profile.

Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.

This article reports on a systematic literature review of the costs of allergic rhinitis (AR), the economic value of pharmacotherapy of AR, and the factors affecting costs and economic value of pharmacotherapy. Included studies had carried out a cost-of-illness analysis, cost analysis, cost-effectiveness, cost-utility or cost-benefit analysis. Allergic rhinitis imposes a substantial economic burden on society, with indirect costs of productivity loss being larger than the direct healthcare costs. Cost estimates were biased because of difficulties of diagnosis; exclusion of patients who do not seek healthcare; exclusion of over-the-counter medication; difficulties in estimating productivity loss. There is limited evidence on costs of seasonal/perennial and intermittent/persistent AR. Little is known of the economic value of pharmacotherapy of AR, although levocetirizine appears to be cost-effective as compared with placebo. Economic evaluations suffered limitations from small sample sizes, short trial duration, lack of standardized effectiveness measure, restricted scope of costs. Finally, the economic value of pharmacotherapy of AR is influenced by the perspective of the economic evaluation, relative effectiveness and costs of available drugs, patient compliance with treatment.

Cost effectiveness of levocetirizine in chronic idiopathic urticaria : a pooled analysis of two randomised controlled trials.

BACKGROUND: Chronic idiopathic urticaria is a distressing condition that severely affects patients' quality of life. The overall costs associated with this disease, both for the healthcare payer and society, are unknown. The objective of this study was to evaluate the cost effectiveness of levocetirizine, a first-line treatment for urticaria. METHODS: Data were collected from two placebo-controlled trials and from official French databases. The effectiveness of the treatment was assessed by the mean number of pruritus-free days experienced by the patient within a 30-day period (PFD30). Direct cost parameters were medications used, medical procedures and hospitalisations for urticaria or treatment of adverse events. Productivity cost parameters were the workdays lost, defined as absenteeism and/or presenteeism, resulting from urticaria. The costing was performed using a French societal perspective. Costs were reported in euro (2002 values) and were standardised to a 30-day month. Whenever possible, incremental cost-effectiveness ratios (ICERs) were derived from these data. RESULTS: The pooled sample contained 294 patients. Compared with placebo, patients in the levocetirizine group experienced an additional mean 6.5 (95% CI 3.8, 9.3) pruritus-free days per month (p < 0.001). Considering only direct medical costs, the incremental cost of treatment with levocetirizine was totally offset by the reduction in other medical costs (i.e. reduced cost of additional medications, medical procedures and hospitalisations). From the perspective of society, treatment with levocetirizine was cost saving, with a net gain of Euro 91.93 per patient per month. CONCLUSION: Treating chronic idiopathic urticaria with levocetirizine is a dominant strategy for society since it is more effective (in terms of pruritus-free days gained) and less costly than placebo.

Immunotherapy for patients with persistent allergic rhinitis unsatisfied with free chronic pharmacotherapy.

BACKGROUND: Chronic pharmacotherapy is recommended to patients with persistent moderate-severe (PM-S) allergic rhinitis (AR). The cost of pharmacotherapy is the main barrier to achieve symptoms control. AIMS OF THE STUDY: To determine the benefits of mite subcutaneous immunotherapy (SIT) in patients with PM-S AR not satisfied with chronic pharmacotherapy received free of charge. METHODS: Open study with seven (7) patients with PM-S AR not satisfied with chronic pharmacotherapy. Prior to enrollment patients had received monthly for more than five months and free of charge, optimal pharmacotherapy. We compared, off pharmacotherapy, symptoms and quality of life (QOL) before and during SIT. RESULTS: Mite SIT improved nasal symptoms, non nasal symptoms and QOL. Off pharmacotherapy patients reported adequate control of symptoms and were satisfied. CONCLUSIONS: Not all patients with PM-S AR are satisfied with chronic pharmacotherapy, even if medication is received free of charge. SIT control symptoms and satisfies patients with PM-S AR unsatisfied with free chronic pharmacotherapy.

Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis.

BACKGROUND: Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis, like asthma, by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma. OBJECTIVES: Two primary objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations at 1 week and 3, 4.5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic assessment, comorbidities, and a safety evaluation. METHODS: The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/d or placebo. RESULTS: A total of 421 patients completed the full study. Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from week 1 to 6 months (all P values <.001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the levocetirizine group compared with the placebo group. Treatment cessation because of lack of effect, comorbidities, and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group. CONCLUSION: Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.

Review of cetirizine hydrochloride for the treatment of allergic disorders.

Cetirizine hydrochloride is an orally-active and selective histamine (H(1))-receptor antagonist. It is a second-generation antihistamine and a human metabolite of hydroxyzine. Therefore, its principal effects are mediated via selective inhibition of peripheral H(1) receptors. The antihistaminic activity of cetirizine has been documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth has been seen more commonly with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for receptors other than H(1) receptors. Auto-radiographical studies with radiolabelled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H(1) receptors. Impairment of CNS function is comparable to other low-sedating antihistamines at the recommended dose of 10 mg/day for adults. It has anti-inflammatory properties that may play a role in asthma management. It does not interact with concomitantly administered medications, it has no cardiac adverse effects, and it does not appear to be associated with teratogenicity. Cetirizine is predominantly eliminated by the kidneys with a mean elimination half-life is 8.3 h. It is rapidly absorbed, and significant clinical inhibition of a wheal and flare response occurs in infants, children and adults within 20 min of a single oral dose and persists for 24 h. No tolerance to the wheal and flare response occurs even after 1 month of daily treatment. The clinical efficacy of cetirizine for allergic respiratory diseases has been established in numerous trials. There is evidence that cetirizine improves symptoms of urticaria. Concomitant use of cetirizine also decreases the duration and amount of topical anti-inflammatory preparations needed for the treatment of atopic dermatitis. Interestingly, several clinical studies suggest that cetirizine may be useful in the treatment and prevention of mild asthma.