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Rupatadin — Wirksamkeit und Sicherheit eines nichtsedierenden Antihistaminikums mit PAF-antagonisierender Wirkung

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Zusammenfassung

Rupatadin ist ein modernes, nichtsedierendes H1-Antihistaminikum mit zusätzlicher, Plättchenaktivierender-Faktor (PAF)-antagonisierender Wirkung. Rupatadin ist unter den Handelsnamen Rupafin® und Urtimed® in Deutschland zur Behandlung der Rhinitis allergica und der Urtikaria für Erwachsene und Jugendliche ab zwölf Jahren zugelassen. In der folgenden Übersicht wird die bisher verfügbare Literatur zum pharmakologischen Profil und der klinischen Anwendung von Rupatadin zusammengefasst und mit konventionellen Antihistaminika verglichen. Schlussendlich werden die Nebenwirkungen, die Sicherheit sowie die Wechselwirkungen von Rupatadin betrachtet. Aufgrund des Cytochrome-P450-Metabolismus sollte eine Verabreichung von Rupatadin zusammen mit Erythromycin, Ketoconazol und Grapefruitsaft vermieden werden. In zahlreichen Studien konnte die klinische Wirksamkeit und Sicherheit von Rupatadin bei saisonaler, perennialer und persistierender Rhinitis sowie chronisch idiopathischer Urtikaria bestätigt werden.

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Abb. 1

Abbreviations

ARIA:

Allergic rhinitis and its impact on asthma

AUC:

Area under the curve

Cmax:

Maximale Plasmakonzentration

CTZ:

Cetirizin

CYP:

Cytochrom P450

DLQI:

Dermatology life quality index

EEG:

Elektroenzephalogramm

EKG:

Elektrokardiogramm

EMEA:

European Medicines Agency

GM-CSF:

Granulocyte macrophage colony-stimulating factor

HERG:

Human ether-a-go-go related gene

HUVEC:

Humane umbilikale venöse Endothelzellen

IC50:

Mittlere inhibitorische Konzentration

ICH:

International Conference on Harmonisation

IL:

Interleukin

Ki:

Dissoziationskonstante

LCT:

Levocetirizin

LOR:

Loratadin

mDTSS:

Mittlerer täglicher Gesamtsymptom-Score

MNW:

Mean number of wheals score

MPS:

Mean pruritus severity score

NF-κB:

Nuclear factor ‚κ-light-chain-enhancer‘ of activated B-cells

nM:

Nanomolar

OLP:

Olopatadin

PAF:

Plättchenaktivierender Faktor

PAR:

Perenniale allergische Rhinitis

PL:

Placebo

RQLQ:

Rhinoconjunctivitis quality of life questionnaire

RU:

Rupatadin

SAR:

Saisonale allergische Rhinitis

t1/2:

Plasmahalbwertszeit

tmax:

Zeit bis zur Maximalwirkung

Tmax:

Zeitpunkt der maximalen Plasmakonzentration

TNF-α:

Tumornekrosefaktor α

Literatur

  1. Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 2011; 128: 1139–50

    Article  CAS  PubMed  Google Scholar 

  2. Merlos M, Giral M, Balsa D, Ferrando R, Queralt M, Puigdemont A et al. Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther 1997; 280: 114–21

    Google Scholar 

  3. Vuurman E, Theunissen E, Oers A van, Leeuwen C van, Jolles J. Lack of effects between rupatadine 10 mg and placebo on actual driving performance of healthy volunteers. Hum Psychopharmacol 2007; 22: 289–97

    Article  CAS  PubMed  Google Scholar 

  4. Izquierdo I, Merlos M, García-Rafanell J. Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis. Drugs Today (Barc) 2003; 39: 451–68

    Article  CAS  Google Scholar 

  5. Merckle Recordati GmbH (Hrsg). Rupafin® Fachinformation; 2009

  6. Cuvillo A del, Mullol J, Bartra J, Dávila I, Jáuregui I, Montoro J et al. Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol 2006; 16: 3–12

    PubMed  Google Scholar 

  7. Katiyar S, Prakash S. Pharmacological profile, efficacy and safety of rupatadine in allergic rhinitis. Prim Care Respir J 2009; 18: 57–68

    PubMed  Google Scholar 

  8. Mullol J, Bousquet J, Bachert C, Canonica WG, Gimenez-Arnau A, Kowalski ML et al. Rupatadine in allergic rhinitis and chronic urticaria. Allergy 2008; 63 (Suppl 87): 5–28

    Article  PubMed  Google Scholar 

  9. Izquierdo I, Nieto C, Ramis J, Cooper M, Dewland P, Forn J. Pharmacokinetics and dose linearity of rupatadine fumarate in healthy volunteers. Methods Find Exp Clin Pharmacol 1997; 19 (Suppl A): 189–203

    Google Scholar 

  10. Ring J. Angewandte Allergologie. 3. Aufl. München: Urban & Vogel; 2004

  11. Ring J, Brockow K, Ollert M, Engst R. Antihistamines in urticaria. Clin Exp Allergy 1999; 29 (Suppl 1): 31–7

    Article  PubMed  Google Scholar 

  12. Brockow K, Kiehn M, Riethmüller C, Vieluf D, Berger J, Ring J. Efficacy of antihistamine treatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol 1997; 100: 458–63

    Article  CAS  PubMed  Google Scholar 

  13. Church MK. Efficacy and tolerability of rupatadine at four times the recommended dose against histamine- and platelet- activating factor-induced flare responses and ex vivo platelet aggregation in healthy males. Br J Dermatol 2010; 163: 1330–2

    Article  CAS  PubMed  Google Scholar 

  14. Queralt M, Brazís P, Merlos M, Puigdemont A. Inhibitory effects of rupatadine on mast cell histamine release and skin wheal development induced by Ascaris suum in hypersensitive dogs. Drug Development Research 1998; 44: 49–55

    Article  CAS  Google Scholar 

  15. Merlos M, Ramis I, Balsa D, Queralt M, Brazis P, Puigdemont A. Inhibitory effect of rupatadine on TNF alpha release from human monocytes and mast cell line MHC-1. Allergy Clin Immunol 2000; 105: s62

    Article  Google Scholar 

  16. Queralt M, Merlos M, Giral M, Puigdemont A. Dual effect of a new compound, rupatadine, on edema induced by platelet-activating factor and histamine in dogs: comparison with antihistamines and PAF antagonists. Drug Dev Res 1996; 39: 12–18

    Article  CAS  Google Scholar 

  17. Merlos M, Balsa D, Giral M, Ferrando R, Garcia-Rafanell J, Forn J. Inhibition of rat peritoneal mast cell exocytosis by rupatadine fumarate: a study with different secretagogues. Methods Find Exp Clín Pharmacol 1997; 19 (Suppl A): 148

    Google Scholar 

  18. Queralt M, Brazís P, Merlos M, De Mora F, Puigdemont A. In vitro inhibitory effect of rupatadine on histamine and TNF-α release from dispersed canine skin mast cells and the human mast cell line HMC-I. lnflamm Res 2000; 49: 355–60

    Article  CAS  Google Scholar 

  19. Merlos M, Ramis I, Balsa D, Queralt M, Brazis P, Pugidemont A. Inhibitory effect of rupatadine on TNF-α release from human monocytes and mast cell line HMC-1. J Allergy Clin lmmunol 2000; 105 (Suppl 1): S62

    Article  Google Scholar 

  20. Barrón S, Ramis I, Merlos M. Rupatadine inhibits the inflammatory component of allergic response: cytokine release, adhesion molecule expression and inflammatory cell recruitment. In: Proceedings of the 23rd EAACI Congress, 12–16 June 2004, Amsterdam

  21. Ramis I, Giral M, Ferrando R, Merlos M. Inhibition of PAFand LTB4-induced human neutrophil chemotaxis by rupatadine using a new fluorescent chemotaxis assay. Allergy 2000; 55 (Suppl 63): 94–5

    Google Scholar 

  22. Barrón S, Roman J, Michelena P, Ramis I, Merlos M. Rupatadine inhibits cytokine production and NF-κB activity by histamine H1 receptor-dependent mechanism. Rev Rinol 2006; 6: 18

    Google Scholar 

  23. Bousquet J, Van Cauwenberge P, Bachert C, Canonica GW, Demoly P, Durham R et al. Requirements for medications commonly used in the treatment of allergic rhinitis. Allergy 2003; 58: 192–7

    Article  PubMed  Google Scholar 

  24. Bousquet J, Van Cauwenberge P, Khaled NA, Bachert C, Baena-Cagnani CE, Bouchard J et al. Pharmacologic and anti-IgE treatment of allergic rhinitis (ARIA) update (in collaboration with GA2LEN). Allergy 2006; 61: 1086–96

    Article  CAS  PubMed  Google Scholar 

  25. Izquierdo I, Valero A, García O, Pérez I, Mullol J, Van Cauwenberge P. Clinical efficacy of rupatadine in allergic rhinitis under ARIA criteria: pooled analysis. Allergy Clin Immunol Int 2005; 1: 271

    Google Scholar 

  26. Stuebner P, Horak F, Zieglmayer R, Arnáiz E, Leuratti C, Pérez I et al. Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol 2006; 96: 37–44

    Article  CAS  PubMed  Google Scholar 

  27. Valero A, Bartra J, Serrano C, Donado E, Gracia O, Izquierdo I. Rupatadine reduces nasal obstruction in allergen-induced rhinitis. Allergy 2007; 62: 137–8

    Article  Google Scholar 

  28. Izquierdo I, Paredes I, Lurigados C, Sospedra E, Cooper M, Thomas H. A dose ranging study of rupatadine fumarate in patients with seasonal allergic rhinitis. Allergy 2000; 55: 275

    Google Scholar 

  29. Guadaño EM, Serra-Batlles J, Meseguer J, Castillo JA, De Molina M, Valero A et al. Rupatadine 10 mg and ebastine 10 mg in seasonal allergic rhinitis: a comparison study. Allergy 2004; 59: 766–71

    Article  PubMed  Google Scholar 

  30. Maiti R, Rahman J, Jaida J, Allala U, Palani A. Rupatadine and levocetirizine for seasonal allergic rhinitis: a comparative study of efficacy and safety. Arch Otolaryngol Head Neck Surg 2010; 136: 796–800

    Article  PubMed  Google Scholar 

  31. Martínez-Cócera C, De Molina M, Martí-Guadaño E, Pola J, Conde J, Borja J et al. Rupatadine 10 mg and cetirizine 10 mg in seasonal allergic rhinitis: A randomised, doubleblind parallel study. J Invest Allergol Clin Immunol 2005; 15: 22–9

    Google Scholar 

  32. Fantin S, Maspero J, Bisbal C, Agache I, Donado E, Borja J et al. A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis. Allergy 2008; 63: 924–31

    Article  CAS  PubMed  Google Scholar 

  33. Saint-Martin F, Dumur JP, Pérez I, Izquierdo I. A randomized, double-blind, parallel-group study, comparing the efficacy and safety of rupatadine (20 and 10 mg), a new PAF and H1 receptor-specific histamine antagonist, to loratadine 10 mg in the treatment of seasonal allergic rhinitis. J Investig Allergol Clin Immunol 2004; 14: 34–40

    CAS  PubMed  Google Scholar 

  34. Maiti R, Jaida J, Rahman J, Gaddam R, Palani A. Olopatadine hydrochloride and rupatadine fumarate in seasonal allergic rhinitis: a comparative study of efficacy and safety. J Pharmacol Pharmacother 2011; 2: 270–6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Perez I, De La Cruz G, Villa M, Iz-Quierdo I. Rupatadine in allergic rhinitis: pooled analysis of efficacy data. Allergy 2002; 57: 245

    Google Scholar 

  36. Marmouz F, Giralt J, Izquierdo I. Morning and evening efficacy evaluation of rupatadine (10 and 20 mg), compared with cetirizine 10 mg in perennial allergic rhinitis: a randomized, double-blind, placebo-controlled trial. J Asthma Allergy 2011; 4: 27–35

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Fantin S, Maspero J, Bisbal C, Agache I, Donado E, Borja J et al; international Rupatadine study group. A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis. Allergy 2008; 63: 924–31

    Article  CAS  PubMed  Google Scholar 

  38. Mion Ode G, Campos RA, Antila M, Rapoport PB, Rosario N, Mello Junior JF deet al. Futura study: evaluation of efficacy and safety of rupatadine fumarate in the treatment of persistent allergic rhinitis. Braz J Otorhinolaryngol 2009; 75: 673–9

    Article  PubMed  Google Scholar 

  39. Gimenez-Arnau A, Izquierdo I, Maurer M. The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo-controlled treatment with rupatadine 10 and 20 mg. J Eur Acad Dermatol Venereol 2009; 23: 1088–91

    Article  CAS  PubMed  Google Scholar 

  40. Gimenez-Arnau A, Pujol RM, Ianosi S, Kaszuba A, Malbran A, Poop G et al. Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebocontrolled multicentre study. Allergy 2007; 62: 539–46

    Article  CAS  PubMed  Google Scholar 

  41. Dubertret L, Zalupca L, Cristodoulo T, Benea V, Medina I, Fantin S et al. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double- blind, placebo-controlled study. Eur J Dermatol 2007; 17: 223–8

    CAS  PubMed  Google Scholar 

  42. Maiti R, Jaida J, Raghavendra BN, Goud P, Ahmed I, Palani A. Rupatadine and levocetirizine in chronic idiopathic urticaria: a comparative study of efficacy and safety. J Drugs Dermatol 2011; 10: 1444–50

    CAS  PubMed  Google Scholar 

  43. Kim H, Lynde C. Impact of Desloratadine on symptoms and quality of life in subjects with chronic idiopathic urticaria: a multicenter, practice-based study. Arch Drug Inf 2008; 1: 63–9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Metz M, Scholz E, Ferran M, Izquierdo I, Giménez-Arnau A, Maurer M. Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria. Ann Allergy Asthma Immunol 2010; 104: 86–92

    Article  CAS  PubMed  Google Scholar 

  45. Picado C. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders. Expert Opin Pharmacother 2006; 7: 1989–2001

    Article  CAS  PubMed  Google Scholar 

  46. Valero A, Torre F de la, Castillo JA, Rivas P, Cuvillo A del, Antépara I et al. Safety of rupatadine administered over a period of 1 year in the treatment of persistent allergic rhinitis. Drug Safety 2009; 32: 33–42

    Article  CAS  PubMed  Google Scholar 

  47. European Medicines Agency; Committee for Medicinal Products for Human Use (CHMP), eds. Guideline on the clinical development of medicinal products for the treatment of allergic rhinoconjunctivitis. 2004; http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003554.pdf (access: January 2008)

  48. Fidan V, Fidan T. Fixed drug eruption against rupatadine fumarate. J Craniofac Surg 2011; 22: 1682–3

    Article  PubMed  Google Scholar 

  49. Dávila I, Sastre J, Bartra J, Cuvillo A del, Jáuregui I, Montoro J et al. Effect of H1 antihistamines upon the cardiovascular system. J Investig Allergol Clin Immunol 2006; 16(Suppl 1): 13–23

    PubMed  Google Scholar 

  50. Hove-Madsen L, Llach A, Molina CE, Prat-Vidal C, Farré J, Roura S et al. The proarrhythmic antihistaminic drug terfenadine increases spontaneous calcium release in human atrial myocytes. Eur J Pharmacol 2006; 553: 215–21

    Article  CAS  PubMed  Google Scholar 

  51. Thorn C, Pfaar O, Hörmann K, Klimek L. Rupatadin - Pharmakologie, klinische Wirksamkeit und therapeutische Sicherheit eines neuen Antihistamins mit zusätzlicher, PAFantagonisierender Wirkung. Allergologie 2010; 33: 429–40

    Article  Google Scholar 

  52. Keam SJ, Plosker GL. Rupatadine: a review of its use in the management of allergic disorders. Drugs 2007; 67: 457–74

    Article  CAS  PubMed  Google Scholar 

  53. Giral M, Merlos M, Balsa D, Ferrando R, Garcia-Rafanell J, Forn J. Effects of rupatadine on cardiovascular profile in rats and guinea pigs: comparison with other nonsedating antihistamines. Allergy 1997; 52: 44–5

    Article  Google Scholar 

  54. Giral M, Balsa D, Ferrando R, Merlos M, Garcia-Rafanell J, Forn J. CNS activity profile of rupatadine fumarate, a new dual receptor antagonist of platelet-activating factor (PAF) and histamine. Allergy 1998; 53: 131

    Article  Google Scholar 

  55. Barbanoj MJ, García-Gea C, Antonijoan R, Izquierdo I, Donado E, Pérez I et al. Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers. Hum Psychopharmacol 2006; 21: 13–26

    Article  CAS  PubMed  Google Scholar 

  56. Barbanoj MJ, García-Gea C, Morte A, Izquierdo I, Pérez I, Jané F. Central and peripheral evaluation of rupatadine, a new antihistamine/platelet-activating factor antagonist, at different doses in healthy volunteers. Neuropsychobiology 2004; 50: 311–21

    Article  CAS  PubMed  Google Scholar 

  57. Jáuregui I, Mullol J, Bartra J, Cuvillo A del, Dávila I, Montoro J et al. H1 antihistamines: psychomotor performance and driving. J Investig Allergol Clin Immunol 2006; 16: 37–44

    PubMed  Google Scholar 

  58. Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau A et al. EAACI/GA(2)LEN/ EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1417–26

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Biedersteiner Straße 29, 80802, München, Deutschland

    Soja Shamizadeh, Knut Brockow &  Johannes Ring

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  1. Soja Shamizadeh
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  2. Knut Brockow
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  3. Johannes Ring
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Correspondence to Johannes Ring.

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Shamizadeh S, Brockow K, Ring J. Rupatadine: efficacy and safety of a non-sedating antihistamine with PAFantagonist effects. Allergo J Int 2014; 23: 87–95 DOI: 10.1007/s40629-014-0011-7

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Shamizadeh, S., Brockow, K. & Ring, J. Rupatadin — Wirksamkeit und Sicherheit eines nichtsedierenden Antihistaminikums mit PAF-antagonisierender Wirkung. Allergo J 23, 27–35 (2014). https://doi.org/10.1007/s15007-014-0555-3

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