Safety of rupatadine administered over a period of 1 year in the treatment of persistent allergic rhinitis: a multicentre, open-label study in Spain.

Department of Pneumology and Respiratory Allergy, Hospital Clinic i Provincial, Barcelona, Spain.
Drug Safety (Impact Factor: 2.62). 02/2009; 32(1):33-42. DOI: 10.2165/00002018-200932010-00003
Source: PubMed

ABSTRACT Rupatadine (Rupafin), a novel antihistamine approved recently in Europe for the treatment of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged>or=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.
To assess the safety and tolerability of treatment with rupatadine 10 mg/day for 12 months in subjects with persistent AR (PER).
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 >or=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.
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 mediastinal 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.
This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Rupatadine fumarate is a second-generation antihistamine provided with a potent, long-lasting and balanced in vivo dual platelet-activating factor (PAF) and histamine antagonist activity and it uniquely combines both activities at a high level of potency. Rupatadine has a rapid onset of action and a long-lasting effect, so a once-daily dosing is permitted, moreover is well tolerated by young adults and the elders. Rupatadine does not present the side effects of first-generation H1-antihistamines, such as somnolence, fatigue, headache, impaired memory and learning, sedation, increased appetite, dry mouth, dry eyes, visual disturbances, constipation, urinary retention and erectile dysfunction. Areas covered: This study evaluates the effectiveness and safety of rupatadine in chronic urticaria (CU) and acquired cold urticaria (ACU), through a systematic review of the literature. Expert opinion: Patients affected by urticaria are often discouraged because frequently their disease does not recognize a cause and it is unresponsive to treatments. Patients can control their symptoms assuming second-generation H1-antihistamines, such as rupatadine. Several randomized, double-blind, placebo-controlled trials testify effectiveness and safety of rupatadine in CU and ACU. However, further clinical trials to evaluate the efficacy of rupatadine in different urticaria subtypes and to test the safety of doses higher than 20 mg are encouraged.
    Expert Opinion on Pharmacotherapy 06/2013; DOI:10.1517/14656566.2013.813481 · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate(®) assay. Generalized Linear Models (GLM) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and homeostatic model assessment (HOMA)); and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL, and HOMA≥3.8) according to ADIPOQ genotype under a dominant inheritance model. Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (p=0.038) and percentages of TC≥200 mg/dL (p=0.022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (Arithmetic mean ratio (AMR)=0.92 ((95%CI=0.85; 0.99) p=0.024) and low likelihood of TC≥200 mg/dL (Odds ratio (OR)=0.32 ((95%CI=0.11; 0.88) p=0.027). When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR= 0.89; p= 0.027), LDL-C (AMR= 0.85; p= 0.039), and non-HDL-C (AMR= 0.86; p= 0.015). No significant associations were found between rs2241766 and HOMA values. The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV coinfected patients with steatosis. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 05/2014; 44(5):453-62. DOI:10.1111/eci.12250 · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The term compliance simply indicates how much doses of the prescribed medication are taken, whereas the term adherence implies also an agreement between patient and physician about the therapeutic plan, and it is therefore preferred. Adherence is a main problem in all long-term treatments. Thus, it represents a problem also in the case of rhinitis, expecially concerning specific immunotherapy that must be assumed continuously for several years. Many factors can affect the adherence, depending on patient, on treatment itself and on the healthcare context, and all those factors usually interact. The adherence measured in controlled trials is usually good, but this does not reflect what happens in real life, where adherence should be preferably measured. There are few data on the adherence in real life for pharmacological treatments of allergic rhinitis (e.g. nasal steroids or antihistamines), whereas more data are available for specific immunotherapy. In this latter case, in real life, adherence seems to be far from optimal, for both sublingual and subcutaneous immunotherapy, although the recent studies agree on the fact that some interventions (i.e. patients' education, strict follow-up, regular contacts) could effectively improve the adherence. In this article, the literature concerning the adherence to pharmacological treatments and immunotherapy in allergic rhinitis was searched and reviewed.
    Clinical & Experimental Allergy 01/2013; 43(1):22-8. DOI:10.1111/j.1365-2222.2012.04052.x · 4.32 Impact Factor