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SAFETY PROFILE OF RUPATADINE IN THE TREATMENT OF CHRONIC URTICARIA Giménez-Arnau A1, Malbran A2, Poop G3, Benea V4, Medina I5, Garcia O6, Donado E6 1Hospital del Mar, Dermatology Department, IMAS. Barcelona, Spain.
2Unidad de Alergia, Asma o Inmunología-COM. Buenos Aires, Argentina.
3Dermatological Clinical Practica. Augsburg, Germany.
4Clinical Hospital Prof Scarlat Longhin. Bucharest, Romania.
5Centro Médico Vitae. Buenos Aires, Argentina.
6J. Uriach y Compañía, SA. Barcelona, Spain.
Chronic urticaria is defined by spontaneous wheals long-lasting more than six weeks1. Conventionally, if any apparent etiology was considered, Sample demographic data are summarized in Table I.
chronic urticaria is categorized as idiopathic. Chronic idiopathic urticaria (CIU) is a relatively common skin condition. Wheals and pruritus Global incidence of AEs was 28.02% with placebo-treated group (n=182), 32.86% with rupatadine 5mg-treated group (n=70), 30.11% with rupatadine 10 mg-
are the most prominent sign and symptom1. The symptoms of CIU are mainly associated with dermal mast cells degranulation and histamine treated group (n=186) and 35.20% with rupatadine 20 mg-treated group (n=179). The 11.54%, 14.29%, 11.83% and 20.67% of the AEs respectively were
release. This fact has led to use inverse agonist H1 antihistamines to treat the urticarias2.
related with the treatment.
Chronic urticaria bleaching requires to control of multiple involved factors and also long periods of continuous treatment. Non-
The most frequents reported related AEs were headache 2.75%, 2.86%, 2.69% and 3.91% and somnolence 3.85%, 4.29%, 3.76% and 13.41% for placebo,
sedating H1 antihistamines have been recommended by the EAACI / GA2LEN / EDF guideline as first line of treatment3. One of
rupatadine 5mg, rupatadine 10 mg and rupatadine 20 mg, respectively. Any of these AEs forced to discontinue the treatment.
the reasons for this kind of recommendation is the good safety profile of these drugs.
Just somnolence AEs was significantly higher with rupatadine 20 mg than with placebo or rupatadine 10 mg. The others AEs did not show significant differences
Rupatadine is a new selective long-acting histamine H1 receptor inverse agonist (H1 antihistamine) which is currently approved as a once daily among the treatment groups. (Fig. 2 and 3)
dose of 10 mg, for the treatment of chronic idiopathic urticaria5,6 and allergic rhinitis7.
No clinically relevant AEs were observed related with ECG, blood testing and vital signs studies during rupatadine clinical trials. Concerning ECG no relevant findings were reported.
Any patient showed a QTc value longer than 470 msec and in any case QTc increased 60 or more msec. One asymptomatic and not clinically relevant CPK increased value was reported as SAE.
To assess Rupatadine safety profile in moderate to severe Chronic Urticaria without an identifiable aetiology or “Chronic
Overall headache AE described with 5 mg desloratadine was 15,5% (placebo 10%)8 and 12,6% (placebo 16,8%)9. Other significant AEs observed during desloratadine clinical Idiopathic Urticaria” (CIU) treatment.
trials were nausea, dry mouth, fatigue, upper respiratory tract infection or dizziness.
MATERIAL AND METHODS Figure 2. Incidence of global adverse events
Figure 3. Incidence of related adverse events
(AE) (n<1, at least one) after 4 weeks
(AE) (n<1, at least one) after 4-weeks
Table I. Pooled CIU Demographic data (ITT population)
The pooled data from two randomised, double blind and placebo controlled, 4-week multicentre studies were used for this analysis. The first was a Figure 1. Study design
dose-ranging study comparing the efficacy and safety of placebo or Placebo Rupatadine Rupatadine Rupatadine
rupatadine 5 mg, 10 mg and 20 mg once daily in 283 CIU patients4. The second study compared the efficacy of placebo or rupatadine 10 mg and 20 mg once daily in 334 CIU patients5. Efficacy and safety profile was evaluated over 6 weeks of treatment.
The incidence and type of adverse events (AEs) was assessed based on the patients’ diaries reports, routine laboratory tests results, clinical and physical examinations and ECG, before and at the end of the treatment period. (Fig. 1)
Descriptive statistics was applied. Incidence of AE during the 4-weeks
Age (years)
was calculated. The qualitative parameters were described by treatment group in terms of frequencies and percentages. The initial comparability of the treatment groups concerning to demographic and anthropometric Somnolence: Rupatadine 20 vs. placebo, p<0.001;
Somnolence: Rupatadine 20 versus placebo, p<0.001;
variables was analyzed, as well as clinical characteristics at the time of Rupatadine 20mg vs. Rupatadine 10mg p<0.001 Rupatadine 20mg versus Rupatadine 10mg p<0.001 inclusion by means of T test, Chi square test or Fisher test according Headache: No differences between treatments
Headache: No differences between treatments
to the type of variable.
1. Greaves MW. Chronic Urticaria. N Engl J Med 1995; 322: 1767-1772.
2. Kozel MMA, Sabroe RA. Chronic Urticaria. Etiology,management and current future treatment options. Drugs 2004; 64: 2515-36.
All dosages of rupatadine administered once daily during these two clinical trials showed to be safe and well tolerated.
3. Zuberbier T, Bindslev-Jensen C, Canonica W, Grattan EH, Greaves MW, Henz BM, Kapp A, Kozel MMA, Maurer M, Merk HF, Schäfer T, Simon D, Vena GA, Wedi B. EAACI/ GA2LEN/ EDF guideline: management of urticaria. Allergy
2006; 61: 321-331 Rupatadine can be recommended as first line treatment for moderate-to-severe Chronic Urticaria without an identifiable
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 of
aetiology.
today 2003; 39:451-468.
5. Dubertret L, Zalupca L, Cristodoulo T, Benea V, Medina M, Fantin S, Lahfa M, Pérez P, Izquierdo I, Arnaiz E. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled
study. 2007. In press.
6. Gimenez-Arnau A, Pujol RM, Ianosi S, Kaszuba A, Malbran A, Poop G, Donado E, Perez I, Izquierdo I, Arnaiz E. Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicenter
study. Allergy 2007; 62(5): 539-546.
7. Merlos M, Giral M; Balsa D, Ferrando Q, Queralt M, Puigdement A, García-Rafanell J and Forn J. Ruptadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther 1997;
The authors would like to thank J. Uriach y Compañía S.A. (Barcelona, Spain) for its financial support to this study. This study was partially 8. Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D and the Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: A double-blind, randomized,
placebo-controlled trial. J Am Acad Dermatol 2003; 48: 535-541.
supported by the National Scientific Research Program of the Spanish Minister of Science and Technology.
9. Ring J, Hein R, Gauger A, Bronsky E, Miller B, and the Desloratadine Study Group. International Journal of Dermatology 2001; 40: 1-5.
Hospital del Mar

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