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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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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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). https://doi.org/10.2165/00002018-200932010-00003
- Allergic Rhinitis
- Allergic Rhinitis
- Compliance Rate