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Safety of Rupatadine Administered Over a Period of 1 Year in the Treatment of Persistent Allergic Rhinitis

A Multicentre Open-Label Study in Spain


Background: Rupatadine (Rupafin®), a novel antihistamine approved recently in Europe for the treatment of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged ≥12 years, has been shown to be highly efficacious, and as safe and well tolerated as other commonly employed antihistamines in the treatment of allergic disease. There are, however, few data on the long-term safety of these antihistamines derived in accordance with the clinical safety recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA) and the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline.

Objective: To assess the safety and tolerability of treatment with rupatadine 10 mg/day for 12 months in subjects with persistent AR (PER).

Methods: A multicentre, open-label, phase IV study in patients recruited from 33 centres in Spain, from September 2002 to November 2005. The study enrolled 324 male and female patients (aged 12–70 years) with a medical history of PER for at least 12 months and a documented positive skin-prick test to an appropriate allergen. On 4 of the 7 days prior to start of treatment, the patients were required to have a minimum total nasal symptom score (TNSS [for sneezing, rhinorrhoea, nasal obstruction/congestion and nasal itching]) of ≥5. Of the 324 eligible patients starting treatment, 120 needed to be treated for more than 6 months and were followed up until the end of 12 months. All patients received rupatadine 10 mg/day and were allowed to continue their normal concomitant medication for all conditions, other than rhinitis, for up to 6 or 12 months. Safety was assessed by means of adverse events (AEs) reported by patients or detected by investigators, scheduled centralized ECG with special attention to Bazzet corrected QT interval (QTcB) and standard laboratory investigations.

Results: Assessment of treatment compliance rates indicated 90% and 83% of patients to be compliant during the 1–6 months and 1–12 months treatment periods, respectively, with compliance rates >80% being associated with the majority of the study population reporting at least one AE. Overall, 74.1% and 65.8% of the patients reported at least one AE during the 1–6 months and 1–12 months treatment periods, respectively, compared with 20.4% and 10.8% of patients reporting at least one treatment-related AE during these periods. Disorders of the nervous system and respiratory thoracic and media-stinal system, in particular headache, somnolence and catarrh, were the three most common AEs reported by >5% of the patients during both treatment periods. Detailed ECG assessments demonstrated no clinically relevant abnormal ECG findings, nor any QTcB increases >60 msec or QTcB values >470 msec for any patient at any time during treatment. Serious AEs were reported in seven patients, of whom six were considered as unlikely to be related to rupatadine treatment, whereas one involving increased blood enzyme levels was considered as possibly related to rupatadine treatment.

Conclusion: This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER.

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  1. Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001; 108 (5 Suppl.): S147–334

    Article  PubMed  CAS  Google Scholar 

  2. Dykewicz MS, Fineman S. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1998; 81: 478–518

    Article  PubMed  CAS  Google Scholar 

  3. Sly RM. Changing prevalence of allergic rhinitis and asthma. Ann Allergy Asthma Immunol 1999; 82: 233–48

    Article  PubMed  CAS  Google Scholar 

  4. Gelfand EW, Plaut M, Washington T, et al. Current trends in allergic reactions: a multidisciplinary approach to patient management. Interdisciplinary Med 2003; 5: 1–12

    Google Scholar 

  5. Bousquet J, Annesi-Maesano I, Carat F, et al. Characteristics of intermittent and persistent allergic rhinitis: DREAMS study group. Clin Exp Allergy 2005; 35: 728–32

    Article  PubMed  CAS  Google Scholar 

  6. Bousquet J, Neukirch F, Bousquet PJ, et al. Severity and impairment of allergic rhinitis in patients consulting in primary care. J Allergy Clin Immunol 2006; 117: 158–62

    Article  PubMed  Google Scholar 

  7. Van Hoecke H, Vastesaeger N, Dewulf L, et al. Classification and management of allergic rhinitis patients in general practice during pollen season. Allergy 2006; 61: 705–11

    Article  PubMed  Google Scholar 

  8. Baroody FM. Allergic rhinitis: broader disease effects and implications for management. Otolaryngol Head Neck Surg 2003; 128: 616–31

    Article  PubMed  Google Scholar 

  9. Schoenwetter WF, Dupclay L, Appajosyula S, et al. Economic impact and quality of life burden of allergic rhinitis. Curr Med Res Opin 2004; 20: 305–17

    Article  PubMed  Google Scholar 

  10. Thompson AK, Juniper E, Meltzer EO. Quality of life in patients with allergic rhinitis. Ann Allergy Asthma Immunol 2000; 85: 338–47

    Article  PubMed  CAS  Google Scholar 

  11. Bachert C. The role of histamine in allergic disease: re-appraisal of its inflammatory potential. Allergy 2002; 57: 287–96

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Scannell RT, Differding E, Talaga P. Dual acting antihistaminergic agents. Mini Rev Med Chem 2004; 4: 923–33

    Article  PubMed  CAS  Google Scholar 

  14. Piwinski JJ, Wong JK, Green MJ, et al. Dual antagonists of platelet activating factor and histamine: identification of structural requirements for dual activity of N-Acyl-4-(5, 6-dihydro-11H-benzo[5,6]cyclohepta-[1,2-b]pyridin-11-ylidene)piperidines. J Med Chem 1991; 34: 457–61

    Article  PubMed  CAS  Google Scholar 

  15. Page CP. The role of platelet activating factor in allergic respiratory disease. Br J Clin Pharmacol 1990; 30 Suppl. 1: 99–106S

    Article  Google Scholar 

  16. Prescott SM, Zimmerman GA, McIntyre TM. The production of platelet-activating factor by cultured human endothelial cells: regulation and function. In: Synder F, editor. Platelet activating factor and related lipid mediators. New York: Plenum Press, 1987: 323–40

    Chapter  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Donado E, García O, Pérez I, et al. Cardiac safety of rupatadine according to the new ICH guideline: a thorough QT/QTc study [abstract no. 760]. XXV Congress of the European Academy of Allergology and Clinical Immunology; 2006 Jun 10–14; Vienna

  19. Holgate ST, Canonica GW, Simons FE, et al. Consensus Group on New-Generation Antihistamines (CONGA): present status and recommendations. Clin Exp Allergy 2003 Sep; 33(9): 1305–24 42

    Article  PubMed  CAS  Google Scholar 

  20. DuBuske LM. Second-generation antihistamines: the risk of ventricular arrhythmias. Clin Ther 1999; 21(2): 281–95

    Article  PubMed  CAS  Google Scholar 

  21. European Agency for the Evaluation of Medicinal Products (EMEA). Committee for Medicinal Products for Human Use: guideline on the clinical development of medicinal products for the treatment of allergic rhinoconjunctivitis. London: Committee for Medicinal Products from EMEA, 2005

    Google Scholar 

  22. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Topic E1A note for guidance: population exposure: the extent of population exposure to assess clinical safety. Geneva: ICH, 1995

  23. Meyboom RHB, Hekster YA, Egberts ACG, et al. Causal or casual? The role of causality assessment in pharmacovigilance. Drug Saf 1997; 17: 374–89

    Article  PubMed  CAS  Google Scholar 

  24. International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline. Clinical safety data management: definitions and standards for expedited reporting. Geneva: ICH, 1994 Oct

  25. Report of CIOMS Working Group V. Current challenges in pharmacovigilance: pragmatic approaches. Geneva: CIOMS, 2001

  26. Ulbrich E, Nowak H. Long-term multicentric study with azelastine in patients with asthma. Arzneimittelforschung 1990 Nov; 40(11): 1225–30

    PubMed  CAS  Google Scholar 

  27. Casale TB, Blaiss MS, Gelfand E, et al. First do no harm: managing antihistamine impairment in patients with allergic rhinitis. J Allergy Clin Immunol 2003; 111: S835–42

    Article  PubMed  Google Scholar 

  28. Philpot EE. Safety of second generation antihistamines. Allergy Asthma Proc 2000; 21: 15–20

    Article  PubMed  CAS  Google Scholar 

  29. Bachert C, Bousquet J, Canonica GW, et al. Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis. J Allegry Clin Immunol 2004; 114: 838–44

    Article  CAS  Google Scholar 

  30. Rinne J, Simola M, Malmberg H, et al. Early treatment of perennial rhinitis with budesonide or cetirizine and its effect on long-term outcome. J Allergy Clin Immunol 2002; 109: 426–32

    Article  PubMed  CAS  Google Scholar 

  31. Scadding GK, Tasman AJ, Murrieta-Aguttes M, et al. Mizolastine is effective and well tolerated in long-term treatment of perennial allergic rhinoconjunctivitis: Riperex Study Group. J Int Med Res 1999; 27: 273–85

    PubMed  CAS  Google Scholar 

  32. Nathan RA, Mason J, Bernstein DI, et al. Long-term tolerability of fexofenadine in healthy volunteers. Clin Drug Invest 1999; 18: 317–28

    Article  CAS  Google Scholar 

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The authors thank J. Uriach y Compañía (Barcelona, Spain) for financial support for this study. This study was partially supported by the National Scientific Research Program of the Spanish Minister of Science and Technology.

Drs Valero and del Cuvillo report receiving consulting fees from J. Uriach y Compañía S.A. Drs Borja, Donado and Mola are medical advisors for J. Uriach y Compañía S.A. and Dr Izquierdo is head of Clinical Development and the Medical Advisory Department.

The authors thank the following investigators who participated in the study: Dr César Picado (Hospital Clínic I Provincial de Barcelona), Dr Joan Serra (Hospital General de Vic), Dr Anna Cisteró (Institut Dexeus), Dr Fernando Duce (Hospital Lozano Blesa), Dr Ana Maria Navarro (Hospital El Tomillar), Dr Anselmo Sanchez (Hospital Insular), Dr Juan García (Hospital Carlos Haya), Dr Tamim Malek (Hospital de Castelló), Dr Alvaro Cadahía (Hospital Vall d’Hebron), Dr Joan Miró (Centre Mèdic Teknon), Dr Teresa Cerdà (Hospital Josep Trueta), Dr Javier Fernandez (Hosptial d’Elx), Dr Esperanza Raga (Clínica Plató), Dr Enric Martí Guadaño (Hospital Sant Pere Claver), Dr Albert Roig (Hospital Tries i Pujol), Dr Alfons Malet (Al.lergocenter), Dr Jesús Pola (Policlínica Sagasta), Dr Montserrat de Molina (Hospital de la Creu Roja de l’Hospitalet), Dr José Fernando Florido López (Complejo Hospitalario Ciudad de Jaén), Dr Antonio Conejero (Hospital Cruz-Roja Sevilla-Reina Victoria), Dr José Conde (Complejo Hospitalario Virgen de la Macarena), Dr Miguel Armengot (Hospital General Universitario de Valencia), Dr Rosa Viñas (CAP Sta. Eulàlia Sud), Dr Josep María Bordas (ABS Gótic), Dr M. Mesa Serrano (Hospital de Viladecans) and Dr Olga Ferrer (Hospital de Sant Boi de Llobregat).

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Correspondence to Oriol Molà.

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Valero, A., de la Torre, F., Castillo, J.A. et al. Safety of Rupatadine Administered Over a Period of 1 Year in the Treatment of Persistent Allergic Rhinitis. Drug-Safety 32, 33–42 (2009).

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  • Allergic Rhinitis
  • Allergic Rhinitis
  • Cetirizine
  • Compliance Rate
  • Desloratadine