Treatment of allergic rhinoconjunctivitis: a review of the role of topical levocabastine

Review Paper Mediators of Inflammation LCOCABASTINE is an extremely potent and highly selective HI-receptor antagonist which has been specifically developed as eye drops and nasal spray for the treatment of allergic rhinoconjunctivitis. Clinical experience to date suggests that this topical antihistamine is at least as effective as other cm-nt first-line therapeutic approaches for the treatment of this condition, including oral Hi-receptor antagonists and sodium cromoglycate. Onset of action is rapid, with clinical effects apparent within minutes of instillation. Moreover, duration of action is sufficiently long to permit a convenient twice-daily dosing regimen. Topical levocabastine is well tolerated with an adverse-effect profile comparable with that of placebo and sodium cromoglycate. As might be expected from the route of drug administration, application site reactions are the most frequent adverse effect associated with levocabastine eye drops and nasal spray with an incidence comparable with that seen in placebotreated controls. The availability of effective and well-tolerated topical antihistamines, such as levocabastine, is an important advance which broadens the range of therapeutic approaches available for the clinical management of allergic rhinoconjunctivitis. Levocabastine appears to be an attractive alternative to oral antihistamines as a first-line therapeutic option for the treatment of this atopic condition. 4, $31-$38 (1995) Treatment of allergic rhinoconjunctivitis" a review of the role of topical levocabastine R. Gerth van Wijk Academisch Ziekenhuis Dijkzigt, Rotterdam, The Netherlands Key words: Allergic rhinoconjunctivitis, Hi-receptor antagonist, Histamine, Levocabastine, Topical antihistamine Epidemiology and Aim of Therapy Mlergic rhinoconjunctivitis is a common atopic condition which is frequently encountered in clinical practice, with current estimates suggesting that as many as 22% of the general population may be affected. Available epidemiological data suggest that the incidence of this atopic disorder is increasing,’12 particularly in urban areas, possibly as a result of environmental pollution. 2-4 The relationship between air pollution and the prevalence of allergic disease is, however, complex. Analysis of the prevalence of respiratory diseases and atopic disorders in German children has revealed that the prevalence of allergic disorders was lower in the former East Germany than in West Germany in spite of higher pollution levels. 5 Characteristic clinical manifestations include nasal itching, sneezing, rhinorrhoea and congestion, often accompanied by ocular symptoms of lacrimation, redness and itching. Causative allergens are diverse and include grass, tree and weed pollens, fungal spores, house dust mite and animal dander. (C) 1995 Rapid Communications of Oxford Ltd The medical and socioeconomic impact of allergic rhinoconjunctivitis is often underestimated. Although rarely associated with longterm clinical complications, symptoms may be sufficiently severe to impact on the patient’s quality of life, with almost all patients experiencing a degree of sleep impairment, limitation of normal daily activities and emotional distress. 6 These findings are supported by data from the US Department of Health which reveal that allergic rhinoconjunctivitis accounts for more than 2 million lost school days and 3.5 million lost work days every year in the USA alone. 7 Treatment of allergic rhinoconjunctivitis should not only be aimed at direct amelioration of symptoms. The subsequent inflammation after allergen exposure may induce non-specific hyperreactivity and nasal priming. ’9 Reduction of this inflammation may therefore be expected to interrupt the vicious circle of early and late sequelae of allergen exposure, including nasal hyperreactivity. Indeed, it has been demonstrated that treatment of the nose may have a beneficial effect on lung function and bronchial hyperMediators of Inflammation Vol 4 (Supplement) 1995 S31 R. G. van Wijk responsiveness in patients with concurrent asthma. 1’11 The fundamental approach to the treatment of allergic rhinoconjunctivitis is environmental control, combined with appropriate antiallergic drug therapy and, in selected cases, specific immunotherapy. Levocabastine is a novel H1receptor antagonist which has been specifically developed for the topical treatment of allergic rhinoconjunctivitis. The aim of this paper is to review the clinical experience of this topical antihistamine available to date, with particular reference to the implications for patient management, Pathophysiology: the Role of Histamine Our understanding of the pathophysiology of allergic rhinoconjunctivitis has increased considerably in recent years revealing a number of potential targets for pharmacological intervention, Therapeutic approaches available for the clinical management of this atopic condition include H1receptor antagonists, vasoconstrictors, cortico- steroids, and mast cell stabilizers, such as sodium cromoglycate. Although multiple inflammatory mediators have been implicated in the pathogenesis of allergic rhinoconjunctivitis, histamine appears to play a prominent role. 12 Experimental allergen challenge studies have revealed that histamine is the only mediator which produces the full spectrum of clinical manifestations of the acute allergic reaction when applied to the nasal and ocular mucosa. The available pathophysiological evidence therefore supports the current clinical practice for use of Hi-receptor antagonists as a primary treatment option. 1 The efficacy and tolerability of oral antihistamines in the treatment of allergic rhinoconjunctivitis is well documented..14 However, although the reported incidence of adverse reactions such as sedation is minimal with newer drugs of this class, the potential for unwanted systemic effects, as exemplified by the arrhythmic effects seen with certain oral antihistamines, clearly exists. 5 In addition, as might be expected from the route of drug administration, onset of action with oral antihistamines is relatively slow. Peak antihistaminic activity typically not observed for several hours, 4 necessitating administration prior to allergen exposure for maximum clinical benefit. ils Rationale for Topical Therapy Treatment for allergic rhinoconjunctivitis need not necessarily be systemic. Topical therapy is possible due to the accessibility of the affected tissues. A topical agent may be expected to have S32 Mediators of Inflammation Vol 4 (Supplement)- 1995 a number of advantages over an orally administered drug, including a faster onset of action, since it is applied directly to the affected site, and a reduced potential for systemic adverse effects. Until recently, however, topical administration of Hi-receptor antagonists has not been feasible as the available agents have not been sufficiently potent to permit single agent therapy. Topical treatment for all (...truncated)