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Loratadine is a long acting antihistamine which has a high selectivity for peripheral histamine H1-receptors and lacks the central nervous system depressant effects often associated with some of the older antihistamines. Results from controlled clinical trials have shown that loratadine (usually 10mg once daily) is a well-tolerated and effective antihistamine which will be beneficial in patients with allergic rhinitis and chronic urticaria. It was found to be significantly superior to placebo, faster acting than astemizole and as effective as usual dosages of terfenadine, clemastine, mequitazine and azatadine in eliciting relief of symptoms. Importantly, loratadine is associated with a lower incidence of sedation than azatadine, clemastine, chlorpheniramine and mequitazine.
Thus, loratadine, with its convenience of once daily administration, will be a useful addition to those drugs currently available for the treatment of patients with allergic diseases in whom a histamine H1-receptor antagonist is indicated. Indeed, it is likely to find a place as one of the newer ‘agents of choice’ in this setting.
Loratadine is a potent, long acting antihistamine which has a high selectivity for peripheral histamine H1-receptors and low affinity for H1-receptors in the CNS in vitro or in vivo. The drug displays little activity at acetylcholine or α1adrenergic receptors, and is inactive in animal models of assessing anticholinergic effects. Loratadine penetrates poorly into the CNS.
Standard tests of antihistaminic activity in guinea-pigs have shown a greater potency for loratadine than for comparator drugs such as terfenadine, astemizole, promethazine and diphenhydramine, with longer lasting effects (for 18 to 24 hours with loratadine vs 6 to 8 hours with azatadine or terfenadine). In man, suppression of wheal response to intradermally injected histamine was greater with loratadine than with placebo or chlorpheniramine. The magnitude and duration of the response were dose related.
Antiallergic activity has been demonstrated by loratadine in animal models in vivo. In addition, the drug suppressed histamine release from rat mast cells.
A few psychomotor performance studies in small numbers of subjects have shown that, in keeping with its lack of affinity for CNS receptors, loratadine in doses up to 40mg does not impair psychomotor function or potentiate the central effects of drugs such as ethanol or diazepam.
Loratadine is rapidly absorbed after single-dose oral administration, with peak plasma concentrations of 5, 11 and 26 μg/L occurring 1 to 1.5 hours after the ingestion of 10, 20 and 40mg capsules, respectively; thus, for these doses loratadine pharmacokinetics are not dose dependent, but dose proportional. Similar results were obtained when 40mg capsules were given once daily for 10 days to 12 healthy volunteers, indicating little accumulation of loratadine with multiple once-daily administration.
The chief metabolite of loratadine, descarboethoxy-loratadine (DCL), is pharmacologically active. Similar to the parent compound, the pharmacokinetics of DCL are not significantly altered by multiple dosing. Although tissue distribution studies of loratadine in humans have not yet been published, single-dose studies have reported elimination half-lives of 8 to 11 and 17 to 24 hours for loratadine and DCL, respectively. Similar values of 14 and 19 hours, respectively, were documented following multiple once daily administration for 10 days. Loratadine is secreted into breast milk but the amount is minimal.
Loratadine undergoes rapid and extensive biotransformation in humans with large oral clearance values of 12 and 9 L/h/kg reported after single-dose oral administration of 20 and 40mg capsules in healthy volunteers, respectively. Renal impairment and haemodialysis, and administration to geriatric volunteers, appear to have no effect on the disposition kinetics of both loratadine and DCL. In patients with alcoholic liver disease the half-lives of loratadine and DCL are longer, but generally within the range observed in a population of normal subjects.
Loratadine has been evaluated in studies involving patients with allergic rhinitis (seasonal and perennial), acute coryza and chronic idiopathic urticaria. In short term clinical trials in patients with seasonal rhinitis loratadine (usually 10mg once daily) was found to be as effective as histamine H1-receptor antagonists such as terfenadine, clemastine, mequitazine and azatadine, and to be quicker acting than astemizole, as assessed by global evaluation of symptom resolution. A dose of 5 to 10mg once daily was shown to be as effective as chlorpheniramine 2 to 4mg twice daily in 231 children aged from 6 to 12 years. Loratadine 10mg once daily was also as effective as terfenadine 60mg twice daily and clemastine 1mg twice daily in patients with perennial allergic rhinitis treated for up to 6 months; complaints of nasal stuffiness, postnasal drainage and nasal discharge were reduced by approximately 50% in these clinical trials.
A combination tablet containing loratadine 5mg and pseudoephedrine 120mg (administered twice daily) was significantly more effective (p < 0.05 to < 0.01) than its individual components and placebo in relieving symptoms in patients with seasonal allergic rhinitis. Similarly, the combination at the same dosage was significantly (p < 0.05) better than placebo in relieving symptoms such as rhinorrhoea, nasal stuffiness, nasal patency, nasal discharge, sneezing and hyperaemia in a 5-day double-blind clinical trial involving 283 patients with acute head colds (coryza).
Loratadine 10mg once daily produced significantly greater symptomatic improvement (itching, erythema and hives) in patients with chronic idiopathic urticaria than did placebo. Furthermore, it tended to be more effective than terfenadine 60mg twice daily in such patients treated for 28 days.
In studies reported thus far loratadine 5, 10 or 40mg once daily has been extremely well tolerated and seemed to cause a lower incidence of sedation/somnolence than azatadine, clemastine, chlorpheniramine and mequitazine, administered at their usual dosages. Indeed, in these studies loratadine did not appear to cause a significant increase in adverse effects compared with placebo, was not associated with an increased frequency of anticholinergic effects and did not induce any clinically significant changes in laboratory test indices.
Dosage and Administration
The recommended adult dosage of loratadine is 10mg once daily while that of the combination tablet (loratadine 5mg plus pseudoephedrine 120mg) is 1 tablet twice daily.
- Ahn, H-S, Barnett, A (1986) Selective displacement of [3H] mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine. European Journal of Pharmacology 127: pp. 153-155
- Banov CH. Assessment of a new antihistamine/decongestant combination (SCH 434) vs placebo and its individual components in patients with seasonal allergic rhinitis. 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Barnett, A, Iorio, LC, Kreutner, W, Tozzi, S, Ahn, HS (1984) Evaluation of the CNS properties of SCH 29851, a potential non-sedating antihistamine. Agents and Actions 14: pp. 590-597 CrossRef
- Batenhorst, RL, Batenhorst, AS, Graves, DA, Foster, TS, Kung, M (1986) Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo. European Journal of Clinical Pharmacology 31: pp. 247-250 CrossRef
- Bedard, P-M, Carpio, J, Gutkowski, A, Hebert, J, Prevost, M (1985) Comparison of the efficacy and safety of SCH 29851, terfenadine and placebo in the treatment of seasonal rhinitis. Annals of Allergy 55: pp. 233
- Bernstein, IL, Bernstein, DI (1988) The efficacy and safety of loratadine in the management of chronic idiopathic urticaria. Journal of Allergy and Clinical Immunology 81: pp. 211 CrossRef
- Bousquet J. Clinical activity and side effects of loratadine and astemizole in patients with seasonal allergic rhinitis. 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Bousquet, J, Lebel, B, Chanal, I, Morel, A, Michel, FB (1988) Anti-allergic activity of loratadine and terfenadine assessed by nasal challenge. Journal of Allergy and Clinical Immunology 81: pp. 228 CrossRef
- Bradley, CM, Nicholson, AN (1987) Studies on the central effects of the H1-antagonist, loratadine. European Journal of Clinical Pharmacology 32: pp. 419-421 CrossRef
- Bruttmann, G, Pedrali, P (1985) SCH 29851 and the treatment of seasonal allergic rhinitis (pollinosis). Annals of Allergy 55: pp. 233
- Bruttmann, G, Pedrali, P (1987) Loratadine (SCH 29851) 40mg once daily versus terfenadine 60mg twice daily in the treatment of seasonal allergic rhinitis. Journal of International Medical Research 15: pp. 63-70
- Bruttmann G, Charpin D, Germounty J, Horak F, Kunkel G, et al. Evaluation of the efficacy and safety of loratadine in perennial allergic rhinitis. Journal of Allergy and Clinical Immunology, in press, 1988
- Connell JT. Loratadine/decongestant combination (SCH 434) vsplacebo in patients with acute coryza. 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Dockhorn, RJ, Shellenberger, MK (1987) Antihistamines: the new generation. Immunology and Allergy Practice 9: pp. 124-133
- Dockhorn, RJ, Bergner, A, Connell, JT, Falliers, CJ, Grabiec, SV (1987) Safety and efficacy of loratadine (SCH-29851): a new non-sedating antihistamine in seasonal allergic rhinitis. Annals of Allergy 58: pp. 407-411
- Dockhorn, RJ, Shellenberger, MK, Hassanien, R, Trachelman, L (1988) Efficacy of SCH 434 (loratadine plus pseudoephedrine) versus components and placebo in seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 81: pp. 178 CrossRef
- Friedman, HM (1987) Loratadine: a potent, nonsedating, and long-acting H1-antagonist. American Journal of Rhinology 1: pp. 95-99 CrossRef
- Gaillard, AWK, Gruisen, A, Jong, R (1988) The influence of antihistamines on human performance. European Journal of Clinical Pharmacology 35: pp. 1-5 CrossRef
- Giacco, SD, Locci, F, Meloni, G, Montaldo, E, Arangino, V (1988) Perennial allergic rhinitis treated with a non-sedating new anti-histamine loratadine. Allergy 43: pp. 111
- Grossman, J, Schenkel, EC, Bronsky, E, Linzmayer, I, Seiner, J (1987) Double-blind control study of loratadine (L) 5mg plus pseudoephedrine (P) 120mg (SCH434) in seasonal allergic rhinitis. Annals of Allergy 58: pp. 280
- Gutkowski, A, Bedard, P, Carpio, JD, Hébert, J, Prevost, M (1988) Comparison of the efficacy and safety of loratadine, terfenadine, and placebo in the treatment of seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 81: pp. 902-907 CrossRef
- Hébert, J, Bédard, P-M, Carpio, JD, Drouin, M, Gutkowski, A (1988) Loratadine and pseudoephedrine sulfate: a double-blind, placebo-controlled comparison of a combination tablet (SCH 434) and its individual components in seasonal allergic rhinitis. American Journal of Rhinology 2: pp. 71-75 CrossRef
- Hébert, J, Drouin, M, Gutkowski, A, Turenne, Y, Carpio, J (1987) A double-blind, placebo-controlled study of the effect of SCH 434 compared to its components in patients with seasonal allergic rhinitis. Revista Espanola de Alergologia e Immunologia Clinica 2: pp. 137
- Hubert, JM, Matzke, GR, Radwanski, E, Moritzen, V, Luc, V (1987) Loratadine pharmacokinetics in renal impairment. Abstract no 326. Journal of Allergy and Clinical Immunology 79: pp. 206
- Hubert, J, Moritzen, V, Parks, A, Radwanski, E, Perentesis, G (1988) The pharmacokinetics of loratadine in normal geriatric volunteers. Journal of International Medical Research 16: pp. 50-60
- Hubert, J, Radwanski, E, Affrime, MB, Perentesis, G, Symchowicz, S (1988) Excretion of loratadine in human breast milk. Journal of Clinical Pharmacology 28: pp. 234-239
- Hubert, J, Radwanski, E, Weglein, R, Luc, V, Perentesis, G (1987) Pharmacokinetics and dose proportionality of loratadine. Journal of Clinical Pharmacology 27: pp. 694-698
- Horak, F, Bruttmann, G, Charpin, J, Germouty, J, Wittmann, G (1987) Effects of loratadine in patients with perennial allergic rhinitis. Revista Espanola de Alergologia e Immunologia Clinica 2: pp. 323
- Horak, F, Bruttmann, G, Pedrali, P, Weeke, B, Frolund, L (1988) A multicentric study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis. Arzneimittel-Forschung 38: pp. 124-128
- Iorio, LC, Cohen-Winston, M, Barnett, A (1986) Interaction studies in mice of SCH 29851, a potential non-sedating antihistamine, with commonly used therapeutic agents. Agents and Actions 18: pp. 485-493 CrossRef
- Irander, K, Ödkvist, LM, Ohlander, B (1988) Treatment of hay fever with loratadine — a new non-sedating antihistamine. Allergy 43: pp. 111
- Kaminszczik I, Soto-Roman L, Kutwak A, Rodriguez L, Cataldo J, et al. Loratadine vsastemizole: Onset of allergy symptoms relief. XIIIth Congress of the European Academy of Allergology and Clinical Immunology, Budapest, May, 1986
- Kassem, NY, Garvin, PR, Gural, RP, Amkraut, HJ (1985) Inhibition of histamine-induced wheals by SCH 29851. Annals of Allergy 54: pp. 366
- Kassem, N, Roman, I, Gural, R, Dyer, JG, Robillard, N (1988) Effects of loratadine (SCH 29851) in suppression of histamine-induced skin wheals. Annals of Allergy 60: pp. 505-507
- Katchen, B, Cramer, J, Chung, M, Gural, R, Hubert, J (1985) Disposition of 14C-SCH 29851 in humans. Abstract no. 669. Annals of Allergy 55: pp. 393
- Katelaris, CH (1986) A double-blind study of the effect of SCH 29851 in patients with seasonal allergic rhinitis. Asian Pacific Journal of Allergy and Immunology 4: pp. 69
- Kemp, JP, Bahna, SL, Chervinsky, P, Rachelefsky, GS, Seltzer, JM (1987) A comparison of loratadine, a new nonsedating anti-histamine, with clemastine and placebo in patients with fall seasonal allergic rhinitis. American Journal of Rhinology 1: pp. 151-154 CrossRef
- Kemp, JP, Meltzer, EO, Orgel, HA, Welch, MJ, Bahna, SL (1987) A comparison of loratadine, clemastine and placebo in patients with seasonal rhinitis. Journal of Allergy and Clinical Immunology 79: pp. 190 CrossRef
- Kreutner W. Pharmacology of non sedating antihistamines. Presented at the 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Kreutner, W, Chapman, RW, Gulbenkian, A, Siegel, MI (1987) Antiallergic activity of loratadine, a non-sedating antihistamine. Allergy 42: pp. 57-63 CrossRef
- Marks, J, Rawlins, MD Skin diseases. In: Speight, TM eds. (1987) Avery’s Drug Treatment. ADIS Press, Auckland, pp. 439-479
- Meltzer EO. Evaluation of clemastine and a new antihistamine (loratadine) in patients with seasonal allergic rhinitis. 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Monroe EW, Fox RW, Green AW, Izuno GT, Bernstein DI, et al. Efficacy and safety of loratadine in the management of idiopathic chronic urticaria. Cutis, in press, 1988
- Moser L, Plum H, Bückmann M. Lack of potentiation of the effect of alcohol by loratadine. XIIIth Congress of the European Academy of Allergology and Clinical Immunology, Budapest, May, 1986
- Oei, HD, Verheij, E, Schwab, D, Lherminier, M, Bruynzeel, PLB (1987) A comparative study of the efficacy of loratadine (L) and astemizole (A). Journal of Allergy and Clinical Immunology 79: pp. 190
- Ongini, E, Marzanatti, M, Guzzon, V (1987) Comparative effects of loratadine and selected antihistamines on sleep-waking patterns in the cat. Drug Development Research 10: pp. 75-83 CrossRef
- Passaleva, A, Ricci, M (1988) Loratadine, a new antihistamine drug in seasonal allergic rhinitis. Allergy 43: pp. 111
- Paul, E (1988) Loratadine and terfenadine in the treatment of chronic urticaria. Allergy 43: pp. 122
- Pedrali P, Bruttmann G. Efficacy of loratadine in the management of idiopathic chronic urticaria. XIIIth Congress of the European Academy of Allergology and Clinical Immunology, Budapest, May, 1986
- Pleskow WW. Studies of a new antihistamine in the management of perennial allergic rhinitis and chronic idiopathic urticaria. 44th Annual Congress, American College of Allergists, Boston, Nov, 1987
- Radwanski, E, Hilbert, J, Symchowicz, S, Zampaglione, N (1987) Loratadine: multiple-dose pharmacokinetics. Journal of Clinical Pharmacology 27: pp. 530-533
- Richards, DM, Brogden, RN, Heel, RC, Speight, TM, Avery, GS (1984) Astemizole: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 28: pp. 38-61 CrossRef
- Riedel WJ, Schoenmakers EA, O’Hanlon JF. The effects of loratadine alone and in combination with alcohol on actual driving performance. Institute for Drugs, Safety and Behaviour, University of Limburg, Maastricht, 1987
- Roman, LS (1988) Onset of action of loratadine in seasonal allergic rhinitis. Today’s Therapeutic Trends 6: pp. 19-27
- Roman, J, Kassem, N, Gural, RP, Herron, J (1986) Suppression of histamine-induced wheal response by loratadine (Sch 29851) over 28 days in man. Annals of Allergy 57: pp. 253-256
- Roth, T, Roehrs, T, Koshorek, G, Sicklesteel, J, Zorick, F (1987) Sedative effects of antihistamines. Journal of Allergy and Clinical Immunology 80: pp. 94-98 CrossRef
- Skassa-Brociek, W, Bousquet, J, Montes, F, Verdier, M, Schwab, D (1988) Double-blind placebo-controlled study of loratadine, mequitazine, and placebo in the symptomatic treatment of seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 81: pp. 725-730 CrossRef
- Skassa-Brociek, W, O’Quigley, J, Blizard, R, Cougnard, J, Michel, FB (1988) Differentiation between the anti-allergic and anti-histaminic effects of loratadine (L) and astemizole (A) by skin tests. Journal of Allergy and Clinical Immunology 8: pp. 175 CrossRef
- Sorkin, EM, Heel, RC (1985) Terfenadine: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 29: pp. 34-56 CrossRef
- Soto, LD, Falabella, R, Hojyo, T, Múzquiz, D (1987) Estudio multicentrico comparativo entre dos antihistaminicos anti H1en el manejo de dermatosis crónicas pruriginosas. Dermatologia Revista Mexicana 31: pp. 9-14
- Storms, WW, Bodman, SF, Nathan, RA, Trochelman, L, Greenstein, S (1988) SCH 434 (loratadine 5mg plus pseudoephedrine 120mg) versus components in the treatment of seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 81: pp. 173 CrossRef
- Temple, DM, McCluskey, M (1988) Loratadine, an antihistamine, blocks antigen- and ionophore-induced leukotriene release from human lung in vitro. Prostaglandins 35: pp. 549-554 CrossRef
- Villani, FJ, Magatti, CV, Vashi, DB, Wong, J, Popper, TL (1986) N-substituted 11-(4-Piperidylene)-5, 6-dihydro-11H-benzo-[5,6] cyclohepta [1,2-β]. pyridines. Arzneimittel-Forschung/Drug Research 36: pp. 1311-1314
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