Abstract
Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice.
In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated.
Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer.
For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.
References
Passalacqua G, Bousquet J, Bachert C, et al. The clinical safety of H1-receptor antagonists: an EAACI position paper. Allergy 1996 Oct; 51(10): 666–75
Woodward JK. Pharmacology of antihistamines. J Allergy Clin Immunol 1990 Oct; 86 (4 Pt 2): 606–12
Marone G. Milestones in the biology and pharmacology of H1-receptor antagonists. Allergy 1997; 52 (34 Suppl.): 7–13
Index Nominum: International Drug Directory [computer program]. Windows version. Swiss Pharmaceutical Society:medpharm, Sci Pub 1994–1998. Englewood (CO): Micromedex
Simons FE, Simons KJ. Pharmacokinetic optimisation of histamine H1-receptor antagonist therapy. Clin Pharmacokinet 1991 Nov; 21(5): 372–93
Desager JP, Horsmans Y. Pharmacokinetic-pharmacodynamic relationships of H1-antihistamines. Clin Pharmacokinet 1995 May; 28(5): 419–32
White MV. The role of histamine in allergic diseases. J Allergy Clin Immunol 1990 Oct; 86 (4 Pt 2): 599–605
Rimmer SJ, Church MK. The pharmacology and mechanisms of action of histamine Hi-antagonists. Clin Exp Allergy 1990 Aug; 20 Suppl. 2: 3–17
Casale TB. The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor-binding sites. J Allergy Clin Immunol 1989 Apr; 83(4): 771–6
van Wauwe JP, Goossens JG. Arabinogalactan- and dextran-induced ear inflammation in mice: differential inhibition by H1-antihistamines, 5-HT-serotonin antagonists and lipoxy-genase blockers. Agents Actions 1989 Aug; 28(1-2): 78–82
Campoli-Richards DM, Buckley MM, Fitton A. Cetirizine: a review of its pharmacological properties and clinical potential in allergic rhinitis, pollen-induced asthma, and chronic urticaria. Drugs 1990 Nov; 40(5): 762–81
Masuo M, Shimada T, Kitazawa T. Mechanism of inhibitory effects of azelastine on smooth muscle contraction. J Pharmacol Exp Ther 1992 Mar; 260(3): 1300–8
Naclerio RM. The effect of antihistamines on the immediate allergic response: a comparative review. Otolaryngol Head Neck Surg 1993 Jun; 108(6): 723–30
Eda R, Sugiyama H, Hopp RJ, et al. Effect of loratadine on human eosinophil function in vitro. Ann Allergy 1993 Oct; 71(4): 373–8
Okada C, Eda R, Miyagawa H, et al. Effect of cetirizine on human eosinophil Superoxide generation, eosinophil chemotaxis and eosinophil peroxidase in vitro. Int Arch Allergy Immunol 1994; 103(4): 384–90
Eda R, Townley RG, Hopp RJ. Effect of terfenadine on human eosinophil and neutrophil chemotactic response and generation of Superoxide. Ann Allergy 1994 Aug; 73(2): 154–60
Benavides J, Schoemaker H, Dana C, et al. In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in the rodent. Arzneimittel Forschung 1995 May; 45(5): 551–8
Roberts DJ. A preclinical overview of ebastine: studies on the pharmacological properties of a novel histamine H1 receptor antagonist. Drugs 1996; 52 Suppl. 1: 8–14
Howarth PH. Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy 1990 Aug; 20 Suppl. 2: 31–41
Raud J, Thorlacius J, Xie X, et al. Interactions between histamine and leukotrienes in the microcirculation: aspects of relevance to acute allergic inflammation. Ann N Y Acad Sci 1994 Nov 15; 744: 191–8
Wasserfallen JB, Leuenberger P, Pecoud A. Effect of cetirizine, a new H1 antihistamine, on the early and late allergic reactions in a bronchial provocation test with allergen. J Allergy Clin Immunol 1993 Jun; 91(6): 1189–97
Spector SL, Nicodemus CF, Corren J, et al. Comparison of the bronchodilatory effects of cetirizine, albuterol, and both together versus placebo in patients with mild-to-moderate asthma. J Allergy Clin Immunol 1995 Aug; 96(2): 174–81
Malick A, Grant JA. Antihistamines in the treatment of asthma. Allergy 1997; 52 (34 Suppl.): 55–66
Paton DM, Webster DR. Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet 1985 Nov–Dec; 10(6): 477–97
Simons FE, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med 1994 Jun 9; 330(23): 1663–70
Du Buske LM. Clinical comparison of histamine H1-receptor antagonist drugs. J Allergy Clin Immunol 1996 Dec; 98 (6 Pt 3): S307–18
Brogden RN, McTavish D. Acrivastine: a review of its pharmacological properties and therapeutic efficacy in allergic rhinitis, urticaria and related disorders. Drugs 1991 Jun; 41(6): 927–40
Gibson JR, Manna VK. Salisbury J. Acrivastine: a review of its dermatopharmacology and clinical activity. J Int Med Res 1989; 17 Suppl. 2: 28B–34B
Richards DM, Brogden RN, Heel RC, et al. Astemizole: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1984 Jul; 28(1): 38–61
McTavish D, Sorkin EM. Azelastine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1989 Nov; 38(5): 778–800
Matzke GR, Yeh J, Awni WM, et al. Pharmacokinetics of cetirizine in the elderly and patients with renal insufficiency. Ann Allergy 1987 Dec; 59 (6 Pt 2): 25–30
Yamaguchi T, Hashizume T, Matsuda M, et al. Pharmacokinetics of the Hi-receptor antagonist ebastine and its active metabolite carebastine in healthy subjects. Arzneimittel Forschung 1994 Jan; 44(1): 59–64
Markham A, Wagstaff AJ. Fexofenadine. Drugs 1998 Feb; 55(2): 269–274
Grant SM, Goa KL, Fitton A, et al. Ketotifen: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders. Drugs 1990 Sep; 40(3): 412–48
Haria M, Fitton A, Peters DH. Loratadine: a reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Drugs 1994 Oct; 48(4): 617–37
Clissold SP, Sorkin EM, Goa KL. Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1989 Jan; 37(1): 42–57
Pinquier JL, Caplain H, Cabanis MJ, et al. Inhibition of histamine-induced skin wheal and flare after 5 days of mizolastine. J Clin Pharmacol 1996 Jan; 36(1): 72–8
Rosenzweig P, Caplain H, Chaufour S, et al. Comparative wheal and flare study of mizolastine vs terfenadine, cetirizine, loratadine and placebo in healthy volunteers. Br J Clin Pharmacol 1995 Nov; 40(5): 459–65
McTavish D, Goa KL, Ferrill M. Terfenadine: an updated review of its pharmacological properties and therapeutic efficacy. Drugs 1990 Apr; 39(4): 552–74
Sorkin EM, Heel RC. Terfenadine: a review of its pharmaco-dynamic properties and therapeutic efficacy. Drugs 1985 Jan; 29(1): 34–56
Simons FE, Murray HE, Simons KJ. Quantitation of H1-receptor antagonists in skin and serum. J Allergy Clin Immunol 1995 Mar; 95(3): 759–64
Hey JA, del Prado M, Kreutner W, et al. Cardiotoxic and drug interaction profile of the second generation antihistamines ebastine and terfenadine in an experimental animal model of torsade de pointes. Arzneimittel Forschung 1996 Feb; 46(2): 159–63
Simons FE. H1-receptor antagonists: does a dose-response relationship exist? Ann Allergy 1993 Dec; 71(6): 592–7
Juhlin L. A comparison of the pharmacodynamics of H1-receptor antagonists as assessed by the induced wheal-and-flare model. Allergy 1995; 50 (24 Suppl.): 24–30
Frossard N, Melac M, Benabdesselam O, et al. Consistency of the efficacy of cetirizine and ebastine on skin reactivity. Ann Allergy Asthma Immunol 1998 Jan; 80(1): 61–5
Nickelsen JA, Georgitis JW, Reisman RE. Lack of correlation between titers of serum allergen-specific IgE and symptoms in untreated patients with seasonal allergic rhinitis. J Allergy Clin Immunol 1986 Jan; 77 (1 Pt 1): 43–8
Small P, Biskin N. Barrett D. Does nasal provocation play a role in the diagnosis and management of ragweed-induced allergic rhinitis? Ann Allergy 1992 Mar; 68(3): 274–8
Spector SL. The placebo effect is nothing to sneeze at. J Allergy Clin Immunol 1992 Dec; 90 (6 Pt 2): 1042–3
Monroe EW. Nonsedating H1 antihistamines in chronic urticaria. Ann Allergy 1993 Dec; 71: 585–91
Henauer S, Hugonot L, Hugonot R, et al. Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever. J Int Med Res 1987 Jul–Aug; 15(4): 212–23
Stern MA, Rosenberg RM, Smith R, et al. A comparative study of terfenadine at two dose levels in the management of hay-fever. Br J Clin Pract 1990 Sep; 44(9): 359–63
Rosario NA. Comparison of terfenadine once daily with terfenadine twice daily for the treatment of perennial allergic rhinitis. J Int Med Res 1991 Mar–Apr; 19(2): 112–20
Renton R, Fidler C, Rosenberg R. Multicenter, crossover study of the efficacy and tolerability of terfenadine, 120mg, versus cetirizine, 10mg, in perennial allergic rhinitis. Ann Allergy 1991 Oct; 67(4): 416–20
Day JH, Briscoe MP, Welsh A, et al. Onset of action, efficacy, and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit. Ann Allergy Asthma Immunol 1997 Dec; 79(6): 533–40
Berstein DI, Schoenwetter WF, Nathan RA. et al. Efficacy and safety of fexofenadine hydrochloride for treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 1997 Nov; 79(5): 443–8
Simons FE, McMillan JL, Simons KJ. A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects. J Allergy Clin Immunol 1990 Oct; 86 (4 Pt 1): 540–7
DuBuske L. Dose-ranging comparative evaluation of cetirizine in patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 1995 Apr; 74(4): 345–54
Jobst S, vanden Wijngaart W, Schubert A, et al. Assessment of the efficacy and safety of three dose levels of cetirizine given once daily in children with perennial allergic rhinitis. Allergy 1994 Sep; 49(8): 598–604
Pearlman D, Lumry WR, Winder JA, et al. Once-daily cetirizine effective in the treatment of seasonal allergic rhinitis in children aged 6 to 11 years: a randomized, double-blind, placebo-controlled study. Clin Pediatr (Phila) 1997 Apr; 36(4): 209–15
Leynadier F, Bousquet J, Murrieta M, et al. Efficacy and safety of mizolastine in seasonal allergic rhinitis: the Rhinase Study Group. Ann Allergy Asthma Immunol 1996 Feb; 76(2): 163–8
Simons FE, Watson WT, Simons KJ. Lack of subsensitivity to terfenadine during long-term terfenadine treatment. J Allergy Clin Immunol 1988 Dec; 82(6): 1068–75
Bousquet J, Chanal I, Skassa-Brociek W, et al. Lack of sub-sensitivity to loratadine during long-term dosing during 12 weeks. J Allergy Clin Immunol 1990 Aug; 86(2): 248–53
Bousquet J, Chanal I, Murrieta M, et al. Lack of subsensitivity to mizolastine over 8-week treatment. Allergy 1996 Apr; 51(4): 251–6
Spaeth J, Klimek L, Mosges R, et al. Sedation in allergic rhinitis is caused by the condition and not by antihistamine treatment. Allergy 1996 Dec; 51(12): 893–906
Hindmarch I. Psychometric aspects of antihistamines. Allergy 1995; 50 (24 Suppl.): 48–54
Simons FE, Fraser TG, Reggin JD, et al. Individual differences in central nervous system response to antihistamines (H1-receptor antagonists). Ann Allergy Asthma Immunol 1995 Dec; 75 (6 Pt 1): 507–14
Moser L, Huther KJ, Koch-Weser J, et al. Effects of terfenadine and diphenhydramine alone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings. Eur J Clin Pharmacol 1978 Dec 18; 14(6): 417–23
Seidel WF, Cohen S, Bliwise NG, et al. Cetirizine effects on objective measures of daytime sleepiness and performance. Ann Allergy 1987 Dec; 59 (6 Pt 2): 58–62
Simons FE. H1-receptor antagonists: comparative tolerability and safety. Drug Saf 1994 May; 10(5): 350–80
Nolen TM. Sedative effects of antihistamines: safety, performance, learning, and quality of life [discussion 2–3]. Clin Ther 1997 Jan–Feb; 19(1): 39–55
Simons FE, Fraser TG, Reggin JD, et al. Comparison of the central nervous system effects produced by six H1-receptor antagonists. Clin Exp Allergy 1996 Sep; 26(9): 1092–7
Cetirizine prescribing information. New York: Pfizer, 1997
Azelastine prescribing information. Cranberry (NJ): Wallace Laboratories, 1997
Eltze M, Mutschler E, Lambrecht G. Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at muscarinic receptor subtypes Ml, M2 and M3. Eur J Pharmacol 1992 Feb 18; 211(3): 283–93
Wihl JA, Petersen BN, Petersen LN, et al. Effect of the non-sedative Hi-receptor antagonist astemizole in perennial allergic and nonallergic rhinitis. J Allergy Clin Immunol 1985 Jun; 75(6): 720–7
Kailasam V, Mathews KP. Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema. J Am Acad Dermatol 1987 Apr; 16(4): 797–804
Chervinsky P, Georgitis J, Banov C, et al. Once daily loratadine versus astemizole once daily. Ann Allergy 1994 Aug; 73(2): 109–13
Ulbrich E, Nowak H. Long-term multicentre study with azelastine in patients with intrinsic asthma. Arzneimittel Forschung 1990 Nov; 40(11): 1225–30
Craft TM. Torsade de pointes after astemizole overdose. BMJ (Clin Res Ed) 1986 Mar 8; 292(6521): 660
Davies AJ, Harindra V, McEwan A, et al. Cardiotoxic effect with convulsions in terfenadine overdose. BMJ 1989 Feb 4; 298(6669): 325
Monahan BP, Ferguson CL, Killeavy ES, et al. Torsades de pointes occurring in association with terfenadine use. JAMA 1990 Dec 5; 264(21): 2788–90
MacConnell TJ, Stanners AJ. Torsades de pointes complicating treatment with terfenadine. BMJ 1991 Jun 15; 302(6790): 1469
Zimmermann M, Duruz H, Guinand O, et al. Torsades de pointes after treatment with terfenadine and ketoconazole. Eur Heart J 1992 Jul; 13(7): 1002–3
Zechnich AD, Haxby DG. Drug interactions associated with terfenadine and related nonsedating antihistamines. West J Med 1996 Jan; 164(1): 68–9
Honig PK, Woosley RL, Zamani K, et al. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin. Clin Pharmacol Ther 1992 Sep; 52(3): 231–8
Woosley RL, Chen Y, Freiman JP, et al. Mechanism of the cardiotoxic actions of terfenadine. JAMA 1993 Mar 24-31; 269(12): 1532–6
Berul CI, Morad M. Regulation of potassium channels by nonsedating antihistamines. Circulation 1995 Apr 15; 91(8): 2220–5
Woosley RL. Cardiac actions of antihistamines. Annu Rev Pharmacol Toxicol 1996; 36: 233–52
Hey JA, del Prado M, Egan RW, et al. Terfenadine, astemizole, and ebastine produce QTc interval prolongation in an experimental model predictive of adverse clinical ECG effects [letter]. Ann Allergy Asthma Immunol 1996 May; 76(5): 476
Hey JA, del Prado M, Sherwood J, et al. Comparative analysis of the cardiotoxicity proclivities of second generation antihistamines in an experimental model predictive of adverse clinical ECG effects [see comments]. Arzneimittel Forschung 1996 Feb; 46(2): 153–8
Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother 1995 Jun; 29(6): 619–24
Riesenman C. Antidepressant drug interactions and the cytochrome P450 system: a critical appraisal. Pharmacotherapy 1995 Nov; 15 (6 Pt 2): 84S–99S
Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents: drug interactions of clinical significance. Drug Saf 1998 Feb; 18(2): 83–97
Faber TS, Zehender M, Just H. Drug-induced torsade de pointes: incidence, management and prevention. Drug Saf 1994 Dec; 11(6): 463–76
Astemizole prescribing information. Titusville (NJ): Janssen Pharmaceutica, 1997
Terfenadine prescribing information. Kansas City (MO): Hoechst Marion Roussel, 1996
Food and Drug Administration. Seldane labeling changes. FDA Talk Paper 1997; T97–47
Bedford TA, Rowbotham DJ. Cisapride: drug interactions of clinical significance. Drug Saf 1996 Sep; 15(3): 167–75
Einarson A, Bailey B, Jung G, et al. Prospective controlled study of hydroxyzine and cetirizine in pregnancy. Ann Allergy Asthma Immunol 1997 Feb; 78(2): 183–6
Hubert J, Radwanski E, Affrime MB, et al. Excretion of loratadine in human breast milk. J Clin Pharmacol 1988 Mar; 28(3): 234–9
Lucas Jr BD, Purdy CY, Scarim SK, et al. Terfenadine pharma-cokinetics in breast milk in lactating women. Clin Pharmacol Ther 1995 Apr; 57(4): 398–402
Howarth PH, Holgate ST. Comparative trial of two non-sedative H1 antihistamines, terfenadine and astemizole, for hay fever. Thorax 1984 Sep; 39(9): 668–72
Girard JP, Sommacal-Schopf D, Bigliardi P, et al. Double-blind comparison of astemizole, terfenadine and placebo in hay fever with special regard to onset of action. J Int Med Res 1985; 13(2): 102–8
Bruttmann G, Pedrali P. Loratadine (SCH29851) 40mg once daily versus terfenadine 60 mg twice daily in the treatment of seasonal allergic rhinitis. J Int Med Res 1987 Mar–Apr; 15(2): 63–70
Gutkowski A, Bedard P, Del Carpio J, et al. Comparison of the efficacy and safety of loratadine, terfenadine, and placebo in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1988 May; 81 (5 Pt 1): 902–7
Del Carpio J, Kabbash L, Turenne Y, et al. Efficacy and safety of loratadine (10mg once daily), terfenadine (60mg twice daily), and placebo in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1989 Nov; 84 (5 Pt 1): 741–6
Oei HD. Double-blind comparison of loratadine (SCH 29851), astemizole, and placebo in hay fever with special regard to onset of action. Ann Allergy 1988 Dec; 61(6): 436–9
Meltzer EO, Weiler JM, Widlitz MD. Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis. J Allergy Clin Immunol 1996 Feb; 97(2): 617–26
Day JD, Briscoe M, Widlitz MD. Cetirizine, loratadine or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit. J Allergy Clin Immunol 1998 May; 101(5): 638–45
Lockey RF, Widlitz MD, Mitchell DQ, et al. Comparative study of cetirizine and terfenadine versus placebo in the symptomatic management of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 1996 May; 76(5): 448–54
Day JH, Briscoe MP, Clark RH, et al. Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of allergic rhinitis. Ann Allergy Asthma Immunol 1997 Aug; 79(2): 163–72
Spector SL, Toshener D, Gay I, et al. Beneficial effects of propylene and polyethylene glycol and saline in the treatment of perennial rhinitis. Clin Allergy 1982 Mar; 12(2): 187–96
Lemanske Jr RF. A review of the current guidelines for allergic rhinitis and asthma. J Allergy Clin Immunol 1998 Feb; 101 (2 Pt 2): S392–6
International Rhinitis Management Working Group. International consensus report on the diagnosis and management of rhinitis. Allergy 1994; 49 (19 Suppl.): 1–34
Rachellefsky GS. Pharmacologic management of allergic rhinitis. J Allergy Clin Immunol 1998 Feb; 101 (2 Pt 2): S367–9
Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 1998 Dec 12; 317: 1624–9
Juniper EF, Guyatt GH, Ferrie PJ, et al. First-line treatment of seasonal (ragweed) rhinoconjunctivitis: a randomized management trial comparing a nasal steroid spray and a nonsedating antihistamine. Can Med Assoc J 1997 Apr; 156(8): 1123–31
Meltzer EO, Tyrell Jr RJ, Rich D, et al. A pharmacologic continuumin the treatment of rhinorrhea: the clinician as economist. J Allergy Clin Immunol 1995 May; 95 (5 Pt 2): 1147–52
Meltzer EO. The prevalence and medical and economic impact of allergic rhinitis in the United States. J Allergy Clin Immunol 1997 Jun: 99 (6 Pt 2): S805–28
Boggs PB, Ellis CN, Grossman J, et al. Double-blind, placebo-controlled study of terfenadine and hydroxyzine in patients with chronic idiopathic urticaria. Ann Allergy 1989 Dec; 63 (6 Pt 2): 616–20
Kalivas J, Breneman D, Tharp M, et al. Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo. J Allergy Clin Immunol 1990 Dec; 86 (6 Pt 2): 1014–8
Breneman D, Bronsky EA, Bruce S, et al. Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial. J Am Acad Dermatol 1995 Aug; 33 (2 Pt 1): 192–8
Breneman DL. Cetirizine versus hydroxyzine and placebo on chronic idiopathic urticaria. Ann Pharmacother 1996 Oct; 30(10): 1075–9
Kalis B. Double-blind multicentre comparative study of ebastine, terfenadine and placebo in the treatment of chronic idiopathic urticaria in adults. Drugs 1996; 52 Suppl. 1: 30–4
Salo OP, Harvey SG, Calthrop JG, et al. A comparison of acrivastine versus hydroxyzine and placebo in the treatment of chronic idiopathic urticaria. J Int Med Res 1989; 17 Suppl. 2: 18B–21B
Kobza-Black A, Aboobaker J, Gibson JR, et al. Acrivastine versus hydroxyzine in the treatment of cholinergic urticaria: a placebo-controlled study. Acta Derm Venereol 1988; 68(6): 541–4
van Joost T, Blog FB, Westerhof W, et al. A comparison of acrivastine versus terfenadine and placebo in the treatment of chronic idiopathic urticaria. J Int Med Res 1989; 17 Suppl. 2: 14B–7B
Ormerod AD. Urticaria: recognition, causes and treatment. Drugs 1994 Nov; 48(5): 717–30
Juhlin L. Nonclassical clinical indications for H1-receptor antagonists in dermatology. Allergy 1995; 50 (24 Suppl.): 36–40
Barata LT, Ying S, Meng Q, et al. IL-4 and IL-5-positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Allergy Clin Immunol 1998 Feb; 101 (2 Pt 1): 222–30
Hannuksela M, Kalimo K, Lammintausta K, et al. Dose ranging study: cetirizine in the treatment of atopic dermatitis in adults. Ann Allergy 1993 Feb; 70(2): 127–33
La Rosa M, Ranno C, Musarra I, et al. Double-blind study of cetirizine in atopic eczema in children. Ann Allergy 1994 Aug; 73(2): 117–22
Yoshida H, Nimura M, Ueda H, et al. Clinical evaluation of ketotifen syrup on atopic dermatitis: a comparative multicenter double-blind study of ketotifen and clemastine. Ann Allergy 1989 Jun; 62(6): 507–12
Falk ES. Ketotifen in the treament of atopic dermatitis: results of a double blind study. Riv Eur Sci Med Farmacol 1993 Mar; 15(2): 63–6
Monroe EW. Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria and atopic dermatitis. Clin Ther 1992 Jan–Feb; 14(1): 17–21
Langeland T, Fagertun HE, Larsen S. Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis: a multi-crossover-designed study. Allergy 1994 Jan; 49(1): 22–6
Roquet A, Raud J, Hallden G, et al. Effects of loratadine on anti-IgE-induced inflammation, histamine release, and leukocyte recruitment in skin of atopics. Allergy 1995 May; 50(5): 414–20
Brunijnzeel-Koomen C, Storz E, Menz G, et al. Skin eosinophilia in patients with allergic and nonallergic asthma and atopic dermatitis. J Allergy Clin Immunol 1992 Jan; 89 (1 Pt 1): 52–9
Bruijnzeel PL, Kuijper PH, Rihs S, et al. Eosinophil migration in atopic dermatitis: increased migratory responses to N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4. J Invest Dermatol 1993 Feb; 100(2): 137–42
Hoshiko K, Chapman ID, Morley J. Histamine (H1) antagonists and airway hyperreactivity in the guinea-pig. Agents Actions Suppl 1991; 34: 323–33
Levrier J, Duval D, Prouteau M, et al. Anti-anaphylactic activity of the novel selective histamine H1 receptor antagonist mizolastine in the rodent. Arzneimittel Forschung 1995 May; 45(5): 559–68
Berth-Jones J, Graham-Brown RA. Failure of terfenadine in relieving the pruritus of atopic dermatitis. Br J Dermatol 1989 Nov; 121(5): 635–7
Wahlgren CF, Hagermark O, Bergstrom R. The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitis. Br J Dermatol 1990 Apr; 122(4): 545–51
Leung DY, Hanifin JM, Charlesworth EN, et al. Disease management of atopic dermatitis: a practice parameter. Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Work Group on Atopic Dermatitis. Ann Allergy Asthma Immunol 1997 Sep; 79(3): 197–211
Clee MD, Ingram CG, Reid PC, et al. The effect of astemizole on exercise-induced asthma. Br J Dis Chest 1984 Apr; 78(2): 180–3
Patel KR. Terfenadine in exercise induced asthma. BMJ 1984 May 19; 288(6429): 1496–7
Bentley AM, Walker S, Hanotte F, et al. A comparison of the effects of oral cetirizine and inhaled beclomethasone on early and late asthmatic responses to allergen and the associated increase in airways hyperresponsiveness. Clin Exp Allergy 1996 Aug; 26(8): 909–17
Grant JA, Nicodemus CF, Findlay SR, et al. Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol 1995 May; 95 (5 Pt 1): 923–32
Aaronson DW. Evaluation of cetirizine in patients with allergic rhinitis and perennial asthma. Ann Allergy Asthma Immunol 1996 May; 76(5): 440–6
Azelastine-Asthma Study Group. An evaluation of the efficacy and safety of azelastine in patients with chronic asthma. J Allergy Clin Immunol 1996 Jun; 97(6): 1218–24
Canny GJ, Reisman J, Levison H. Does ketotifen have a steroid-sparing effect in childhood asthma? Eur Respir J 1997 Jan; 10(1): 65–70
Hoshino M, Nakamura Y, Shin Z, et al. Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma. Allergy 1997 Aug; 52(8): 814–20
Aaronson DW. Side effects of rhinitis medications. J Allergy Clin Immunol 1998 Feb; 101 (2 Pt 2): S379–82
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Slater, J.W., Zechnich, A.D. & Haxby, D.G. Second-Generation Antihistamines. Drugs 57, 31–47 (1999). https://doi.org/10.2165/00003495-199957010-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199957010-00004