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Ebastine is a long-acting nonsedating second generation histamine H1 receptor antagonist which binds preferentially to peripheral H1 receptors in vivo. It has shown antihistamine and antiallergic activity in healthy volunteers and patients with allergies, and protected against histamine-induced bronchoconstriction in patients with asthma.
Significant symptom improvement is observed in patients with seasonal or perennial allergic rhinitis or chronic idiopathic urticaria following administration of ebastine 10 mg/day, or 20 mg/day in severe rhinitis. In clinical trials, the efficacy of ebastine 10 or 20 mg/day was generally similar to standard dosages of terfenadine, cetirizine, astemizole and loratadine in patients with seasonal allergic rhinitis, astemizole, terfenadine and ketotifen in patients with chronic idiopathic urticaria, and ketotifen, terfenadine, chlorpheniramine and mequita-zine in patients with perennial allergic rhinitis.
The most frequent adverse events reported during ebastine therapy are drowsiness, headache and dry mouth, the incidence being similar to that reported in placebo recipients. Serious adverse cardiac events, observed on rare occasions with some other histamine H receptor antagonists, have not been reported with ebastine, and there has been no evidence of QTc interval prolongation related to ebastine therapy.
Thus, once-daily ebastine offers an effective and well-tolerated alternative to other second generation antihistamines in current use for the first-line treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria.
Ebastine significantly inhibited histamine-induced wheal and flare compared with placebo. The extent of inhibition was dose-dependent with single doses of ebastine between 1 and 30mg. Onset of antihistaminic action was evident within 1 to 3 hours of ebastine administration, peaked between 3 and 12 hours, and was sustained for at least 24 hours. In a comparative study of antihistaminic activity (inhibition of wheal and flare reactions) in patients with allergic rhinitis ebastine 10mg was similar to terfenadine 60mg, superior to loratidine 10mg and less active than terfenadine 120mg or cetirizine 10mg 3 hours after drug administration. 24 hours after administration the antihistaminic activity of ebastine 10mg was similar to that of astemizole 10mg and greater than that of loratadine 10mg and terfenadine 120mg in one study. The activity of ebastine was similar to or greater than that of cetirizine.
Dose-dependent protection against histamine-induced bronchoconstriction in patients with asthma has been demonstrated after administration of ebastine 10 or 30 mg/day for 3 days.
Ebastine showed significant antiallergic activity (determined by allergen skin prick tests and nasal challenge) compared with placebo in adults and children with allergies to pollen.
Ebastine does not readily cross the blood-brain barrier and in murine studies the concentration of the drug required to inhibit [3H]mepyramine binding to cerebral H1 receptors in vitro was about 5-fold higher than that of terfenadine, and 1500-fold higher than that of chlorpheniramine. No significant effects on the CNS have been observed in healthy volunteers given doses of ebastine 10 to 30mg, and the drug did not potentiate the depressant effects of alcohol or diazepam-induced impairment of psychomotor performance.
Preclinical findings suggest that ebastine may have less potential to induce cardiovascular adverse events than terfenadine. Phase I/II clinical studies in healthy elderly and young adult volunteers found no effect of ebastine on cardiac parameters including the QTc interval. In addition, no effect on the QTc interval was observed when plasma concentrations of ebastine were increased as a result of coadministration of the drug with erythromycin or ketoconazole.
Ebastine is a prodrug which is extensively metabolised by first-pass metabolism to its active carboxylic acid metabolite carebastine. Peak plasma concentrations (Cmax) of carebastine are reached in about 3 to 6 hours in healthy adult volunteers after administration of single oral doses of ebastine, and steady-state plasma concentrations are reached by day 3 to 5 of multiple-dose administration. Cmax and the area under the plasma concentration-time curve for carebastine increased in a dose-dependent manner following administration of ebastine 10 to 90mg, Cmax being about 0.1 mg/L after a single 10mg dose. The bioavailability of carebastine is increased when ebastine is administered with food. Carebastine is about 98% plasma protein bound and has a large volume of distribution (approximately 90 to 140L). The terminal elimination half-life is between 13 and 16 hours, carebastine being eliminated predominantly in the urine.
The pharmacokinetic properties of carebastine in healthy elderly volunteers and children aged 6 to 12 years appear to be similar to those in healthy adults. Hepatic or severe renal impairment did not affect the bioavailability of carebastine but significantly increased the terminal elimination half-life of the drug.
The metabolism of a single dose of ebastine 20mg was significantly slowed and the elimination half-life significantly prolonged in healthy volunteers when coadministered with multiple doses of ketoconazole or erythromycin.
Clinical trials have shown that ebastine 5 to 20mg once daily is effective in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria.
A dosage of 20 mg/day appeared to be more effective than 10 mg/day in the treatment of severe symptoms of seasonal allergic rhinitis; however, both dosages sustained symptom improvement throughout study periods of up to 4 months. Efficacy has been demonstrated in children (aged 2 to 15 years) with seasonal allergic rhinitis with dosages of ebastine 2.5 to 20 mg/day and in adolescents (aged 12 to 17 years) with perennial allergic rhinitis (5 or 10 mg/day).
In comparative studies with other antihistamines, ebastine 10mg once daily provided similar symptom relief to that achieved with terfenadine 60mg twice daily or cetirizine 10 mg/day in patients with seasonal allergic rhinitis. Ebastine 10 mg/day generally showed similar efficacy to that of astemizole 10 mg/day, although the latter was more effective against nasal blockage. The higher dosage of ebastine 20 mg/day tended to be more effective than either cetirizine or lorata-dine 10 mg/day.
Ebastine 5 mg/day was at least as effective as ketotifen 2 mg/day in improving symptoms in patients with perennial allergic rhinitis, and unpublished findings indicate that ebastine 10mg once daily is as effective as terfenadine 60mg twice daily, chlorpheniramine 6mg twice daily or mequitazine 5mg twice daily in the treatment of this condition.
In patients with chronic idiopathic urticaria, astemizole 10 mg/day initially appeared more effective in providing symptom relief than ebastine 5 or 10 mg/day; however, after 4 week’ treatment, similar efficacy was achieved with both drugs. Ebastine 10 mg/day was at least as effective as terfenadine 120 mg/day, and showed similar efficacy to ketotifen 2 mg/day.
Symptom improvement was sustained for 12 months in patients with chronic idiopathic urticaria treated with ebastine 20 mg/day.
Ebastine 5 to 20 mg/day was well tolerated in clinical trials, the incidence of adverse events being similar to that reported in placebo recipients. The most common adverse events were drowsiness, headache and dry mouth, which were mild to moderate in most affected patients. Other less common adverse events included asthenia, gastrointestinal discomfort, nausea/vomiting, increased appetite, diarrhoea, constipation and agitation. In long term studies (up to 1 year) the most common adverse events were headache and gastrointestinal disturbance.
Comparative studies have found ebastine to be at least as well tolerated as other histamine H1 receptor antagonists including astemizole, terfenadine, cetirizine and loratadine. Analysis of pooled ECG data from large clinical trials did not reveal any adverse cardiovascular effects in over 800 patients with allergic rhinitis treated with ebastine 1 to 30 mg/day.
Further clinical experience is warranted to confirm the apparent lack of cardiac events during therapy with ebastine.
Dosage and Administration
A single daily dose of oral ebastine 10mg is effective for the treatment of adults with allergic rhinitis or chronic idiopathic urticaria. The recommended dosage in children is 5mg once daily. A higher dosage of 20 mg/day may provide additional symptom relief in adults with more severe symptoms, and administration in the morning provides maximal benefit.
Ebastine should be administered with caution in patients with an established prolongation of the QTc interval, or hepatic or renal insufficiency.
KeywordsAdis International Limited Allergic Rhinitis Terfenadine Cetirizine Loratadine
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- 1.Kontou-Fili K. H1-receptor antagonists in the management of allergic rhinitis: a comparative review. Clin Immunother 1994 Nov; 2: 352–75Google Scholar
- 2.Krause HF. Pharmacotherapy of perennial and seasonal allergic rhinitis. Clin Immunother 1995; 3: 308–24Google Scholar
- 4.Kukita A, Kawashima M, Harada S, et al. Clinicopharmacological study of LAS-90: inhibitory effect on wheal and erythema induced by intradermal injection of histamine [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 103–11Google Scholar
- 5.Buchmeier A, Nelson HS, Bucher B, et al. Dose-response of prick skin test (PST) suppression by ebastine [abstract]. J Allergy Clin Immunol 1994 Jan; 92: 163Google Scholar
- 7.Almeda E, Daza JC, Reyes L, et al. A comparative study of ebastine and cetirizine effect on in vivo test on children who are sensitive to olea pollen [abstract]. Allergy 1992; 47(12) Suppl.: 99Google Scholar
- 8.Almeda E, Daza JC, Reyes L, et al. A comparative study of ebastine and loratadine effect on in vivo test of children sensitive to olea pollen [abstract]. Allergy Clin Immunol News 1994 Suppl. 2: 389Google Scholar
- 11.Torrent Farnells J, Segura J. Study of the antihistamine effect of LAS W090 (INN ebastine) in healthy volunteers. Single oral administration of LAS W-090 (10mg) in human volunteers and a pharmacokinetic study of its acid metabolite. Rhone-Poulenc Rorer (Collegeville), 1984. Report no. Clin 1/5 and Bio 3/2. (Data on file)Google Scholar
- 12.Carrenca FJ, Farnells JT, Pulido II, et al. Study of safety, pharmacokinetics and antihistamine effects of LAS W-090 at repeated doses in healthy volunteers. Rhône-Poulenc Rorer (Collegeville), 1986. Report No. Clin 1/7. (Data on file)Google Scholar
- 15.Fernández L, Fernández del Cotero JN, Rodriguez F, et al. Protective effect of ebastine on the conjunctival provocation test with histamine [abstract no. P-0300]. Allergy 1995; 50 Suppl.: 182Google Scholar
- 16.Llupiá J, Bou J, Fernández AG, et al. Antihistamine, anti-allergic and related pharmacological properties of ebastine, a new selective histamine H1-receptor antagonist. Drugs Today 1992; 28 Suppl. B: 11–21Google Scholar
- 17.Chanal I, Maudino G, Campbell AM, et al. Efficacy of ebastine assessed by nasal challenge in a double-blind placebo-controlled study [abstract]. J Allergy Clin Immunol 1994 Jan; 93: 272Google Scholar
- 18.Campbell AM, Crampette L, Lebel B, et al. In Vitro inhibition of PGD2 and LTC4 release from human nasal polyp cells by ebastine and carebastine [abstract no. P-0335]. Allergy 1995; 26 Suppl.: 194Google Scholar
- 19.Puigdemont A, Queralt M, Llenas J. Suppressive effect of ebastine on histamine, PAF and allergen induced wheals in hypersensitive dogs [abstract no. P-0352]. Allergy 1995; 5 Suppl. 26: 199Google Scholar
- 20.Berga P, Puig J, Fernández AG, et al. Preclinical safety studies with ebastine. I. Pharmacological effects on the central nervous system. Drugs Today 1992; 28 Suppl. B: 23–7Google Scholar
- 21.Aoki Y, Funabashi H, Terada Y, et al. Reproductive and developmental toxicity studies of ebastine (2): teratogenicity study in rats [in Japanese]. Yakuri to Chiryo 1994 Mar; 22: 1193–215Google Scholar
- 22.Nakashima M, Uematsu T, Kanamaru M. Phase I study of LAS-90 (1st report): single oral administration in healthy volunteers [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 3–21Google Scholar
- 26.Barbanoj MJ, Torrent J, Azcona O, et al. Psychomotor performance after different single oral doses of a new non-sedating H1 antihistamine in healthy subjects. Rhône-Poulenc Rorer (Collegeville). (Data on file)Google Scholar
- 28.Azcona O, Barbanoj MJ, Gich I, et al. Evaluation of CNS effects of repeated doses of ebastine and their interaction with ethanol in healthy subjects [abstract no. 100]. J Psychopharmacol 1992 Suppl.: A25Google Scholar
- 30.Rolf LN. Important drug warning. Marion Merrell Dow Inc. 1990, Aug 6.Google Scholar
- 35.Llenas J, Bou J, Massingham R. Preclinical safety studies with ebastine. II. Pharmacological effects on the cardiovascular system. Drugs Today 1992; 28 Suppl. B: 29–34Google Scholar
- 36.Llenas J, Cardelus I, Gristwood RW. Terfenadine, but not ebastine, increases the force of contraction of guinea pig ventricular strips by an action on histamine receptors [abstract no.120]. Br J Pharmacol 1985; 87: 91PGoogle Scholar
- 37.Investigator’s Brochure. Rhône-Poulenc Rorer (Collegeville), 1995. (Data on file)Google Scholar
- 38.Geary III WJ, Garcia JD, Dockhorn RJ. Electrocardiographic safety of 10mg of ebastine in healthy elderly and young adult volunteers [abstract no. P-0351]. Allergy 1995; 50(26) Suppl.: 199Google Scholar
- 39.Wilson J, Huang M-Y, Garcia J, et al. AN open-label interaction study between a single dose of ebastine and multiple doses of ketoconazole on the cardiac function and pharmacokinetic profile in healthy adult male volunteers. Rhône-Poulenc Rorer (Collegeville), 1994. Report No. EBA 127. (Data on file)Google Scholar
- 40.Wilson J, Huang M-Y, Garcia J, et al. An open-label interaction study between a single dose of ebastine and a multiple dose of erythromycin stearate on the cardiac function and pharmacokinetic profile in healthy adult male volunteers. Rhône-Poulenc Rorer (Collegeville), 1994. Report no. EBA 130. (Data on file)Google Scholar
- 41.Martínez-Tobed A, Tarrús E, Segura J, et al. Pharmacokinetic studies of ebastine in rats, dogs and man. Drugs Today 1992; 28 Suppl. B: 57–67Google Scholar
- 44.Nakamura T, Mizorogi Y, Matsuda M, et al. Pharmacokinetics of ebastine in the elderly. Rinsho Iyaku 1994; 10(9): 47–54Google Scholar
- 45.Huang M-Y, Wilson J, Argenti D, et al. Comparative pharmacokinetics of ebastine/carebastine in liver cirrhosis and healthy volunteers following administration of a 10mg ebastine tablet. Pharm Res 1993; 10(10 Suppl.): S-390Google Scholar
- 46.Huang M-Y, Argenti D, Wilson J, et al. Single dose and steady-state pharmacokinetics of carebastine following administration of 10mg ebastine tablets once daily in healthy elderly and young adults. Pharm Res 1993; 10(10 Suppl.): S-391Google Scholar
- 47.Dorr MB, Huang M-Y, Heald D, et al. Effect of food on the bioavailability of carebastine in healthy male volunteers. Pharm Res 1993; 10(10 Suppl.): S-306Google Scholar
- 50.Moreland TA, Pears JS, Mills MJ, et al. The effect of ebastine on warfarin kinetics and dynamics. 5th World Conference on Clinical Pharmacology & Therapeutics: 1992 Jul 26-31; Yokohama, JapanGoogle Scholar
- 51.Kukita A, Harada S, Yoshida H, et al. Clinical study of LAS-90 on eczema/dermatitis, prurigo and pruritus cutaneous [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 73–88Google Scholar
- 52.Czarny D, Gillis D, Katelaris C, et al. A double-blind randomized controlled multicentre phase III efficacy and safety trial to assess the effect of ebastine (RP 64305) 10mg (o.d.) versus terfenadine 60mg (b.i.d.) and placebo given for a period of three weeks in the treatment of adult patients with seasonal allergic rhinitis. Rhône-Poulenc Rorer (Collegeville). Report No. 59 (Pt IV.B.l). (Data on file)Google Scholar
- 54.Ankier SI, Fay L, Warrington SJ. Report on a placebo-controlled study in general practice to compare the efficacy and tolerability of ebastine and astemizole 10mg against the symptoms of hay fever. Rhône-Poulenc Rorer (Collegeville). Report No. 61 (Pt IV.B.l). (Data on file)Google Scholar
- 55.Luria X, Robert M, Antepara I, et al. A double-blind placebo controlled study of the efficacy and tolerability of ebastine and loratidine in seasonal allergic rhinitis patients [abstract no. P-0350]. Allergy 1995; 50: 199Google Scholar
- 56.Antépara I, Basomba, Castillo, et al. Double-blind randomised parallel clinical trial to compare the efficacy and tolerability of ebastine 20mg once daily with loratidine 10mg once daily and placebo in the treatment of seasonal allergic rhinitis. Rhône-Poulenc Rorer (Collegeville). Report No. 72 (Pt IV.B.2). (Data on file)Google Scholar
- 57.Castro E, Molina E, Prieto L, et al. A comparative study of the efficacy and tolerability of ebastine (LAS W 0-90) and terfenadine in the treatment of seasonal allergic rhinitis. Rhône-Poulenc Rorer (Collegeville). Report No. 60 (Pt IV.B.l). (Data on file)Google Scholar
- 58.de Molina M, Cadahia L, Cano L, et al. Efficacy and tolerability of ebastine at two dose levels in the treatment of seasonal allergic rhinitis. Drug Invest 1989; 1(1): 40–6Google Scholar
- 59.Gehannol P, Brémard-Oury C, Zeisser P. A double-blind multi-center randomized study comparing once daily oral administration of ebastine 20mg, ebastine 10mg, and cetirizine 10mg for the treatment of seasonal allergic rhinitis in adults. Rhône-Poulenc Rorer (Collegeville). (Data on file)Google Scholar
- 60.Banov CH, Chervinsky P, Munk ZM, et al. Multicenter double-blind parallel-group randomized comparisons of ebastine and placebo in patients with seasonal allergic rhinitis. Rhône-Poulenc Rorer (Collegeville), 1992. Report no. EBA 124. (Data on file)Google Scholar
- 62.Morris RJ, Garcia JD, Tobey RE. Multicenter trial of ebastine for seasonal allergic rhinitis [abstract]. Ann Allergy 1994 Jan; 72: 58Google Scholar
- 63.Luria X, Raga E, Molina M, et al. Resultados del ensayo clinico de la prevention de aparición de síntomas de rinitis alérgica estacional de ebastina vs astemizol [abstract no. 116]. Rev Espanola Alergol Immunol Clin 1992; 7 Suppl. 2: 86Google Scholar
- 64.Nevot S, Sierra JI, Marco MT, et al. Resultados del ensayo clinico de ebastina en niños de 2 a 5 afios de edad [abstract]. Rev Espanola Alergol Immunol Clin 1992; 7 Suppl. 2: 57Google Scholar
- 65.Teran-Ortiz L, Sandoval GF, Solano MO, et al. Ebastina vs terfenadina en la rinitis alérgica. Rev Alergica México 1993; 40(4): 82–5Google Scholar
- 67.Baba S, Ito H, Takagi I, et al. Early phase II study of LAS-90 on perennial allergic rhinitis [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 113–24Google Scholar
- 68.Baba S, Takagi I, Saito Y, et al. Clinical evaluation of LAS-90 on Japanese cedar pollinosis [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 147–61Google Scholar
- 69.Baba S, Takagi I, Okuda M, et al. Phase II study of LAS-90 on perennial allergic rhinitis: optimal dose finding study by double-blind technique [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 125–45Google Scholar
- 70.Baba S, Mamiya S, Sakakura Y, et al. Clinical trial of LAS-90 on perennial allergie rhinitis: a double blind study in comparison with ketotifen fumarate [in Japanese]. Rinsho Iyaku 1994; 10 (5): 1143–62Google Scholar
- 71.Cadahia A, Picado C, Cistero A, et al. Efficacy and tolerability of the H1-antihistamine ebastine in the treatment of perennial allergic rhinitis. Laboratorios Almirall, Barcelona. (Data on file)Google Scholar
- 72.de Molina M, Garcia P. A study of the efficacy and tolerability of ebastine (LAS W-090) at two therapeutic dose levels in the treatment of perennial allergic rhinitis in adolescents. Rhône-Poulenc Rorer (Collegeville), 1988. Report no. CLIN 2/8. (Data on file)Google Scholar
- 73.Kukita A, Harada S, Yoshida H, et al. Early phase II study of LAS-90 on chronic urticaria [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 43–53Google Scholar
- 74.Kukita A, Harada S, Yoshida H, et al. Late phase II study of LAS-90 on chronic urticaria: optimal dose finding study by double-blind technique [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 55–72Google Scholar
- 75.Kalis B, Brémard-Oury C. A 3-month double-blind comparative study of ebastine (10mg o.d.), terfenadine (60mg b.i.d.) and placebo in the treatment of chronic urticaria [abstract no. P-0895]. Allergy 1995; 50 Suppl.: 380Google Scholar
- 77.Kukita A, Harada S, Yoshida H, et al. Phase III study of LAS-90 on chronic urticaria: double blind comparative study with ketotifen fumarate [in Japanese]. Rinsho Iyaku 1994; 10(4): 895–912Google Scholar
- 78.Ledo A, Fonseca E, De Molina G, et al. A study of the efficacy and tolerability of two dose levels of ebastine (LAS W-090) and astemizole in the treatment of chronic urticaria over a four-week period. Rhône-Poulenc Rorer (Collegeville). (Data on file)Google Scholar
- 79.Kukita A, Harada S, Yoshida H, et al. Long-term treatment of LAS-90 on chronic urticaria [in Japanese]. Rinsho Iyaku 1994; 10 Suppl. 1: 89–102Google Scholar
- 80.Double blind randomised parallel clinical trial to determine the safety and tolerability over one month of ebastine 20mg once daily compared to placebo in patients with chronic urticaria. One year follow up of the ebastine 20mg group. Rhône-Poulenc Rorer (Collegeville), 1995. Report no. M-09020.21. (Data on file)Google Scholar
- 81.Thomas K. A long term (one year) safety and efficacy study of ebastine 10mg in the treatment of chronic urticaria in adult patients. Rhône-Poulenc Rorer (Collegeville), 1994. Report no. EBA 020. (Data on file)Google Scholar
- 82.Chico C, Domingo C, de Molina G, et al. A study of the efficacy and tolerability of two therapeutic doses of ebastine compared with placebo in the treatment of perennial allergic rhinitis. Rhône-Poulenc Rorer (Collegeville), 1987. Report no. CLIN 2/7. (Data on file)Google Scholar
- 83.A double-blind placebo-controlled parallel group field study on the onset of action of ebastine 20mg in patients with seasonal allergic rhinitis. Rhône-Poulenc Rorer (Collegeville), 1994. Report no. EBA 133. (Data on file)Google Scholar
- 84.Beaucher WN, Grossman J, Morris RJ, et al. Multicenter double-blind parallel group randomized comparison of ebastine and placebo in patients with perennial allergic rhinitis. Rhône-Poulenc Rorer (Collegeville), 1992. Report no. EBA 109. (Data on file)Google Scholar
- 85.Luria X, Bakke OM. Ebastine (LAS W-090): overview of clinical trials. Drugs Today 1992; 28 Suppl. B: 69–79Google Scholar
- 86.Banov CH, Chervinsky P, Munk ZM, et al. Multicenter open-label long-term safety study of ebastine in patients with pollen induced allergic rhinitis. Rhône-Poulenc Rorer (Collegeville) 1995. Report no. EBA 124LT. (Data on file)Google Scholar
- 90.Busse WW. Role of antihistamines in allergic disease. Ann Allergy 1994; 71: 371–5Google Scholar