Levocabastine is a potent and selective histamine H1-receptor antagonist which has been evaluated as a topical treatment (nasal spray and/or eyedrops) for allergic rhinitis and/or conjunctivitis. Data available at the time of the previous review in Drugs, together with more recent results, have clearly demonstrated that levocabastine nasal spray and eyedrops are clinically effective, have a rapid onset of action and are well tolerated in patients with nasal and/or ocular allergic conditions.
Previous evidence indicating that topical levocabastine has efficacy similar to or better than that of topical sodium cromoglycate (cromolyn sodium) has been confirmed in more recent studies. Furthermore, results from a number of controlled clinical trials have also shown that topical levocabastine is at least as effective as oral terfenadine for the treatment of allergic rhinoconjunctivitis. Notably, topical levocabastine appears to be more effective than oral terfenadine in improving the severity of selected symptoms. Limited data indicating efficacy equivalent to that of oral loratadine, oral cetirizine or azelastine nasal spray will need to be confirmed.
Data from several studies have shown that topical levocabastine has a tolerability profile similar to that of placebo, topical sodium cromoglycate or oral terfenadine. The main adverse events seen in patients treated with topical levocabastine are ocular irritation after application of eyedrops, and headache, nasal irritation, somnolence and fatigue after administration of the nasal spray. Administered doses of topical levocabastine, and subsequent plasma concentrations, are low, and the risk of systemic adverse events is therefore expected to be minimal.
Thus, topical administration of levocabastine provides rapid and effective symptom relief with no apparent serious adverse events in patients with allergic rhinitis and/or conjunctivitis. Topical levocabastine is a useful alternative to topical sodium cromoglycate or oral terfenadine. Additional data supporting current evidence that topical levocabastine can provide more effective symptom relief than oral terfenadine, together with clarification of the relative efficacies of these agents in relation to varying pollen exposure, would help to further confirm its clinical potential. However, the results available to date suggest that the topical formulations of levocabastine are a valuable treatment option in patients with allergic rhinitis and/or conjunctivitis.
Overview of Pharmacology
Levocabastine is a potent antagonist of histamine H1-receptors, which has shown little or no affinity for dopaminergic, adrenergic, serotonergic or opiate receptors in vitro. Topical administration of levocabastine (nasal spray or eyedrops) provides fast and relatively long-lasting relief (onset of action within 15 minutes, duration of action up to 12 hours) from the allergic symptoms caused by experimental allergen challenge in healthy volunteers and patients with allergic conditions. In comparative allergen challenge studies, levocabastine nasal spray and/or eyedrops were more effective than topical treatment with placebo, sodium cromoglycate (cromolyn sodium; eyedrops or nasal spray) or nedocromil (nasal spray).
Levocabastine eyedrops were generally similar to placebo eyedrops or oral terfenadine in their pharmacodynamic effects on a range of ophthalmological criteria. Administration of topical levocabastine has not resulted in any clinically significant effects on psychomotor or cognitive function, nor does it appear to potentiate the effects of alcohol or diazepam.
Information on the pharmacokinetic properties of topical levocabastine is somewhat limited. It is absorbed quickly (time to maximum plasma concentration approximately 1 to 4 hours) but incompletely (single-dose systemic bioavailability of 60 to 80% for the nasal spray and 30 to 60% for eyedrops) in healthy volunteers. Peak plasma concentrations after single-dose administration of levocabastine nasal spray (0.2mg) or eyedrops (0.04mg), respectively, were 1.4 to 2.2 μg/L and 0.26 to 0.29 μg/L in healthy volunteers. Steady-state plasma concentrations are reached after 7 to 10 days of topical treatment. The extent of drug absorption from levocabastine nasal spray or eyedrops in patients with allergic symptoms has been reported to be either increased or decreased in comparison with healthy individuals.
Levocabastine is eliminated primarily by the kidneys (elimination half-life of ≈35 to 50 hours), with about 70% of an oral dose being excreted unchanged in the urine. Although direct comparisons with healthy volunteers are lacking, it appears that renal impairment may be associated with reduced elimination of levocabastine.
Since the previous review in Drugs, data from several clinical trials have confirmed earlier results which showed that topical levocabastine is at least as effective as topical sodium cromoglycate in providing symptom relief in patients with allergic rhinitis and/or allergic conjunctivitis. In addition, global evaluations of clinical efficacy were similar for topical levocabastine and oral terfenadine in a number of more recent clinical trials involving patients with allergic rhinoconjunctivitis. Good or excellent ratings for nasal symptoms were reported for 63 to 75% of topical levocabastine recipients compared with 61 to 75% of oral terfenadine recipients; for ocular symptoms, the ranges were 76 to 88% and 75 to 81%, respectively. Although investigators’ assessments of symptom severity were generally similar for both treatments, data from patients’ self assessments of individual symptoms indicated some statistically significant differences in favour of topical levocabastine in 2 studies. In addition, topical levocabastine produced more symptom-free days than oral terfenadine in 115 patients with allergic rhinoconjunctivitis. In contrast, no significant differences in efficacy were observed between topical levocabastine and oral terfenadine in 128 patients with allergic rhinoconjunctivitis.
Definitive data are still required to confirm the relative efficacy of topical levocabastine and oral terfenadine on days when the pollen count is high. However, studies to date have shown that topical levocabastine is at least as effective as oral terfenadine under such conditions.
Levocabastine nasal spray (plus eyedrops as required) produced a faster onset of therapeutic action than oral cetirizine in a study of patients with perennial allergic rhinoconjunctivitis. Global efficacy evaluations were similar for both treatments in this investigation and in a comparative study of topical levocabastine and oral loratadine in patients with seasonal allergic rhinoconjunctivitis. Levocabastine nasal spray was as effective as azelastine nasal spray in a single study in patients with allergic rhinitis.
Headache, nasal irritation, somnolence and fatigue are the most commonly reported adverse events in patients receiving levocabastine nasal spray. Ocular irritation after application is the most frequent adverse event in patients treated with levocabastine eyedrops. Severe adverse events were not reported in patients treated with either formulation of topical levocabastine. Indeed, the incidence of adverse events in patients receiving topical levocabastine is similar to that seen in placebo recipients. Recent data have also confirmed previous reports that topical levocabastine has a tolerability profile similar to that of topical sodium cromoglycate.
Results from a number of well-controlled clinical trials have shown that the incidence, type and severity of adverse events experienced by patients receiving levocabastine nasal spray plus eyedrops are similar to those observed in patients receiving oral terfenadine. Levocabastine nasal spray plus eyedrops did not differ significantly from oral cetirizine or oral loratadine with regard to tolerability profile in patients with allergic rhinoconjunctivitis, although data are available only from a single study for each comparison. Levocabastine nasal spray was at least as well tolerated as azelastine nasal spray in a single clinical trial in patients with allergic rhinitis.
Dosage and Administration
Levocabastine is available as a 0.5 mg/ml nasal spray and 0.5 mg/ml eyedrops; the recommended treatment regimen in adults and children is 2 sprays/nostril and 1 drop/eye twice daily. Treatment frequency may be increased to 3 or 4 times daily. Levocabastine nasal spray should be used with caution in patients with renal impairment, although formal dosage recommendations have not been made. Patients receiving levocabastine eyedrops should not wear soft contact lenses.
- Dechant KL, Goa KL. Levocabastine: a review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergic rhinitis and conjunctivitis. Drugs 1991 Feb; 41: 202–24.
- Dushay ME, Johnson CE. Management of allergic rhinitis: focus on intranasal agents. Pharmacotherapy 1989; 9 (6): 338–50.
- Kontou-Fili K. H1-receptor antagonists in the management of allergic rhinitis: a comparative review. Clin Immunother 1994 Nov; 2: 352–75.
- Abelson MB, Weintraub D. Levocabastine eye drops: a new approach for the treatment of acute allergic conjunctivitis. Eur J Ophthalmol 1994 Apr-Jun; 4: 91–101.
- Awouters F, Niemegeers CJE, Jansen T, et al. Levocabastine: pharmacological profile of a highly effective inhibitor of allergic reactions. Agents Actions 1992 Jan; 35: 12–8.
- Tasaka K, Kamei C, Akagi M, et al. Antiallergic profile of the novel H1-antihistaminic compound levocabastine. Arzneimittel Forschung 1993 Dec; 43: 1331–7.
- Stokes TC, Feinberg G. Rapid onset of action of levocabastine eye-drops in histamine-induced conjunctivitis. Clin Exp Allergy 1993 Sep; 23: 791–4.
- Pazdrak K, Górski P, Ruta U. Inhibitory effect of levocabastine on allergen-induced increase of nasal reactivity to histamine and cell influx. Allergy 1993 Nov; 48: 598–601.
- Abelson MB, George MA, Smith LM. Evaluation of 0.05% levocabastine versus 4% sodium cromolyn in the allergen challenge model. Ophthalmology 1995 Feb; 102: 310–6.
- Chanal I, Bousquet J, Arnaud B, et al. Comparison of new antiallergic eye drops, levocabastine versus NAAGA, by the conjunctival challenge test [in French]. Rev Fr Allergol Immunol Clin 1994 Oct; 34: 420–3.
- Tomiyama S, Ohnishi M, Okuda M. The dose and duration of effect of levocabastine, a new topical H1 antagonist, on nasal provocation reaction to allergen. Am J Rhinol 1993 Mar-Apr; 7: 85–8.
- Bachert C, Schlemm P, Rettig K. A comparison between levocabastine and nedocromil using nasal allergen challenge [in German]. Allergologie 1995; 18 (7): 292–5.
- Falconieri P, Monteleone AM, Mancuso T, et al. Effectiveness of levocabastine eyedrops in children with allergic conjunctivitis: a double-blind study. Pediatr Asthma Allergy Immunol 1994; 8 (2): 111–5. CrossRef
- Pécoud A, Gerber M, Rahm F. Levocabastine, oxymetazoline and their combination in a nasal provocation test with allergen [abstract]. J Allergy Clin Immunol 1991 Jan; 87: 150.
- Remky A, Wolf S, Schulte S, et. al. Influence of levocabastine on accomodation in healthy subjects [abstract]. Allergy 1993; 48 Suppl. 16: 30.
- Reim M, Thiel H-J, Tajerbashi D, et al. Safety of levocabastine eye drops: effects on accommodation and in glaucoma [abstract no. 62]. Allergy Clin Immunol News 1994; Suppl. 2: 17.
- Stokes TC, Feinberg G. The irritancy of levocabastine eye drops containing benzylkonium chloride. Br J Clin Res 1993; 4: 141–3.
- Bahmer FA, Ruprecht KW. Safety and efficacy of topical levocabastine compared with oral terfenadine. Ann Allergy 1994 May; 72: 429–34.
- The Livostin Study Group. A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis. Allergy 1993; 48: 530–4. CrossRef
- Rombaut N, Bhatti JZ, Curran S, et al. Effects of topical administration of levocabastine on psychomotor and cognitive function. Ann Allergy 1991 Jul; 67: 75–9.
- Nicholls A, Janssens M, James R. The effects of levocabastine and ethanol on psychomotor performance in healthy volunteers [abstract]. Allergy 1993; 48 Suppl. 16: 34.
- Merkus FWHM, Schüsler-van Hees MTIW. Influence of levocabastine suspension on ciliary beat frequency and mucociliary clearance. Allergy 1992 Jun; 47: 230–3.
- Heykants J, Van Peer A, Van de Velde V, et al. The pharmacokinetic properties of topical levocabastine; a review. Clin Pharmacokinet 1995 Oct; 29 (4): 221–30. CrossRef
- Okuda M, Tomiyama S, Baba S, et al. Phase I study of R 50547 (levocabastine hydrochloride) nasal spray (1st report) — single administration study [in Japanese]. Jibi to Rinsho 1995; 41 Suppl. 1: 281–300.
- Okuda M, Tomiyama S, Ohnishi M, et al. Phase I study of R 50547 (levocabastine hydrochloride) nasal spray (2nd report) — repeated administration study [in Japanese]. Jibi to Rinsho 1995; 41 Suppl. 1: 301–25.
- Okuda M, Tomiyama S, Ohnishi M, et al. Phase I study of R 50547 (levocabastine hydrochloride) nasal spray (3rd report) — nasal provocation test [in Japanese]. Jibi to Rinsho 1995; 41 Suppl. 1: 326–41.
- Zazgornik J, Huang ML, Van Peer A, et al. Pharmacokinetics of orally administered levocabastine in patients with renal insufficiency. J Clin Pharmacol 1993 Dec; 33: 1214–8.
- International Product Information Document. Livostin Clinical Monograph, Janssen Pharmaceutica, 1995.
- Bende M, Pipkorn U. Topical levocabastine, a selective H1 antagonist, in seasonal allergic rhinoconjunctivitis. Allergy 1987 Oct; 42: 512–5.
- van de Heyning PH, van Haesendonck J, Creten W, et al. Effect of topical levocabastine on allergic and non-allergic perennial rhinitis. A double-blind study, levocabastine vs. placebo, followed by an open, prospective, single-blind study on beclomethasone. Allergy 1988 Jul; 43: 386–91.
- Van Durme P. Levocabastine nasal spray in seasonal allergic rhinitis [abstract no. 01 041]. Schweiz Med Wochenschr 1991; 121 Suppl. 40/I: 18.
- Janssens M, Blockhuys S. Levocabastine vs placebo in the treatment of seasonal allergic rhinitis [abstract]. Allergy 1993; 48 Suppl. 16: 40.
- Busse W, Janssens M, Eisen G, et al. Is there a place for a topical antihistamine/decongestant combination in the treatment of seasonal allergic rhinitis? Draft manuscript, Janssen Pharmaceutica, Belgium, 1995 (Data on file).
- Schuermans V, Lewi PJ, Gypen LM, et al. Meta-analysis of the global evaluation of levocabastine nasal spray versus placebo. Drug Info J 1993 Apr-Jun; 27: 575–84.
- Palma-Carlos AG, Chieira C, Conde TA, et al. Double-blind comparison of levocabastine nasal spray with sodium cromoglycate nasal spray in the treatment of seasonal allergic rhinitis. Ann Allergy 1991 Oct; 67: 394–8.
- Schata M, Jorde W, Richarz-Barthauer U. Levocabastine nasal spray better than sodium cromoglycate and placebo in the topical treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1991 Apr; 87: 873–8.
- Cruz MA, Aguila N. Levocabastine vs sodium cromoglycate in seasonal allergic rhinitis treatment [in Spanish]. Invest Med Int 1993 Dec; 20: 187–92.
- Melluso M, Di Lorenzo G, Mansueto P, et al. Levocabastine vs cromoglycate in patients with seasonal allergic rhinitis [abstract no. 233]. Allergy Clin Immunol News 1994; Suppl. 2: 65.
- Mösges R, Spaeth J, Klimek L. Efficacy and tolerability of levocabastine and azelastine nasal sprays for the treatment of allergic rhinitis. Mediators Inflamm 1995; 4 Suppl. 1: S11–5. CrossRef
- Pacor ML, Biasi D, Girelli D, et al. Topical levocabastine versus orally administered loratadine in seasonal allergic rhinitis [abstract no. P-0076]. Allergy 1995; 50 Suppl. 26: 107.
- Bischoff P, Gerber M. Levocabastine eye drops vs terfenadine in the treatment of allergic conjunctivitis [abstract]. Allergy 1992; 47 (12) Suppl.: 305.
- Drouin MA, Yang WH, Horak F. Faster onset of action with topical levocabastine than with oral cetirizine. Mediators Inflanyn 1995; 4 Suppl., 1: S5–S10. CrossRef
- Søhoel P, Freng BA, Kramer J, et al. Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis. J Allergy Clin Immunol 1993 Jul; 92 (Part 1): 73–81.
- Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Allergy 1994 Sep; 49: 611–5.
- Blockhuys S. Levocabastine eye drops in vernal conjunctivitis [abstract]. Schweiz Med Wochenschr 1991; 121 Suppl. 40/II: 22.
- Bonini St, Pierdomenico R, Bonini S. Levocabastine eye drops in vernal keratoconjunctivitis [abstract]. Allergy 1993; 48 Suppl. 16: 41.
- Howarth PH, Fell P, Selvam A. Levocabastine in allergic conjunctivitis [abstract]. Clin Exp Allergy 1994 Feb; 24: 184.
- Goes F, Blockhuys S, Janssens M. Levocabastine eye drops in the treatment of vernal conjunctivitis. Doc Ophthalmol 1994; 87 (3): 271–81. CrossRef
- Frostad AB, Olsen AK. A comparison of topical levocabastine and sodium cromoglycate in the treatment of pollen-provoked allergic conjunctivitis. Clin Exp Allergy 1993 May; 23: 406–9.
- Azevedo M, Castel-Branco MG, Ferraz Oliveira J, et al. Double-blind comparison of levocabastine eye drops with sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy 1991 Nov; 21: 689–94.
- Davies BH, Mullins J. Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis. Allergy 1993 Oct; 48: 519–24.
- Odelram H, Björkstén B, Klercker TA, et al. Topical levocabastine versus sodium cromoglycate in allergic conjunctivitis. Allergy 1989 Aug; 44: 432–6.
- Tiszler CE, Nowak W, Gluza J. A comparison of levocabastine and sodium cromoglycate in children with allergic conjunctivitis due to house dust mite [abstract]. Allergy Clin Immunol News 1994; Suppl. 2: 16.
- Wüthrich B, Gerber M. Levocabastine eye drops are effective and well tolerated for the treatment of allergic conjunctivitis in children. Mediators Inflamm 1995; 4 Suppl. 1: S16–20. CrossRef
- Wihl JA, Rudblad S, Kjellén H, et al. Levocabastine eye drops versus sodium cromoglycate in seasonal allergic conjunctivitis. Clin Exp Allergy 1991 May; 21 Suppl. 2: 37–8. CrossRef
- Vermeulen J, Mercer M. Comparison of the efficacy and toler- ability of topical levocabastine and sodium cromoglycate in the treatment of seasonal allergic rhinoconjunctivitis in children. Pediatr Allergy Immunol 1994 Nov; 5: 209–13.
- Njaa F, Baekken T, Bjaamer D, et al. Levocabastine compared with sodium cromoglycate eyedrops in children with both birch and grass pollen allergy. Pediatr Allergy Immunol 1992; 3: 39–42. CrossRef
- Howarth PH. A review of the tolerability and safety of levocabastine eyedrops and nasal spray. Implications for patient management. Mediators Inflamm 1995; 4: S26–30. CrossRef
- Eisen G, Janssens M, Creticos P, et al. Levocabastine vs placebo nasal spray in seasonal allergic rhinitis due to weed — a large multicenter US/Canadian study [abstract]. Allergy 1993; 48 Suppl. 16: 40.
- Parys W, Janssens M. The efficacy and tolerability of topical levocabastine and oral terfenadine in seasonal allergic rhinoconjunctivitis: an international study [abstract]. Allergy 1992; 47 (12) Suppl.: 249.
Volume 50, Issue 6 , pp 1032-1049
- Cover Date
- Print ISSN
- Online ISSN
- Springer International Publishing
- Additional Links
- Industry Sectors