Rupatadine: efficacy and safety of a non-sedating antihistamine with PAF-antagonist effects

Shamizadeh, Soja; Brockow, Knut; Ring, Johannes

doi:10.1007/s40629-014-0011-7

Cited by 46 publications

(64 citation statements)

References 42 publications

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“…The pharmacokinetic profile of rupatadine and its main metabolites in healthy Japanese subjects, also assessed in this clinical trial, has been recently reported by Taubel et al . The PK parameters in Japanese subjects were shown to be in close agreement with the results exhibited by several white Caucasian studies …”

Section: Discussionsupporting

confidence: 81%

“…Recently Rupafin in tablet form and as pediatric oral solution have also been approved by Health Canada. As part of rupatadine's drug development program, its safety has been extensively investigated in several nonclinical and clinical studies …”

mentioning

confidence: 99%

“…The main biotransformation pathways of rupatadine include different oxidative processes, namely, oxidation of the pyridine methyl group to the carboxylic acid, hydroxylation in the 3, 5, and 6 positions in the tricyclic ring system, and N‐dealkylation of the piperidine nitrogen. Two of its main metabolites, desloratadine and 3‐hydroxylated desloratadine, retain antihistaminic properties that may contribute to the overall efficacy of the drug . In vitro metabolism studies in human liver microsomes indicate that rupatadine is mainly metabolized by cytochrome P450 (CYP) 3A4, and a genetic polymorphism in its biotransformation is unlikely .…”

mentioning

confidence: 99%

“…Two of its main metabolites, desloratadine and 3‐hydroxylated desloratadine, retain antihistaminic properties that may contribute to the overall efficacy of the drug . In vitro metabolism studies in human liver microsomes indicate that rupatadine is mainly metabolized by cytochrome P450 (CYP) 3A4, and a genetic polymorphism in its biotransformation is unlikely . The concomitant administration of rupatadine with potent CYP3A4 inhibitors (like ketoconazole and erythromycin) should be avoided, and comedication with moderate CYP3A4 inhibitors should be used with caution .…”

mentioning

confidence: 99%

“…As part of rupatadine's drug development program, its safety has been extensively investigated in several nonclinical and clinical studies. [15][16][17][18] Rupatadine is almost completely metabolized when administered orally, with very little of the drug being recovered unmetabolized. The main biotransformation pathways of rupatadine include different oxidative processes, namely, oxidation of the pyridine methyl group to the carboxylic acid, hydroxylation in the 3, 5, and 6 positions in the tricyclic ring system, and N-dealkylation of the piperidine nitrogen.…”

mentioning

confidence: 99%

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Cardiac Safety of Rupatadine in a Single‐Ascending‐Dose and Multiple‐Ascending‐Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments—Comparison With the Previous White Caucasian Thorough QT Study

Täubel

Ferber

Fernandes³

et al. 2017

Clinical Pharm in Drug Dev

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A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that rupatadine has no proarrhythmic potential and raised no cardiac safety concerns. The present phase 1 study aimed to confirm the cardiac safety of rupatadine in healthy Japanese subjects. In this randomized, double-blind, placebo-controlled study, 27 healthy Japanese subjects were administered single and multiple escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate electrocardiogram (ECG) recordings were performed on days −1, 1, and 5 at several points, and time-matched pharmacokinetic samples were also collected. Concentration-effect analysis based on the change in the QT interval corrected using Fridericia's formula (QTcF) from average baseline was performed. Data from the formal TQT study in white Caucasian subjects was used for a comparison analysis. The ECG data for rupatadine at doses up to 40 mg did not show an effect on the QTc interval of regulatory concern. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a significant shortening of QTcF on days 1 and 5 four hours after a standardized meal. The data from this study exhibited no statistically significant differences in the QTc effect between Japanese and white Caucasian subjects. Keywords rupatadine, Japanese, cardiac safety, food effect, assay sensitivityThe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline E14 recommends that the QTprolonging potential of a drug be evaluated primarily by a specific "thorough QT" (TQT) study. 1 In 2005, when the ICH was first adopted, it was not expected that the results of a TQT would be influenced by ethnic factors. However, emerging clinical experience has suggested that interethnic differences can be of particular relevance when assessing the safety of some drugs. 2 Since 2010, when the ICH E14 was fully adopted in Japan, the suitability of foreign data to provide proarrhythmic liability information concerning the Japanese population is still under assessment. Nevertheless, more efficient approaches to reduce the associated costs and alternatives to a conventional TQT study have been extensively discussed to modify the current regulatory requirements now allowing thorough QT assessments in other trials.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cardiac Safety of Rupatadine in a Single‐Ascending‐Dose and Multiple‐Ascending‐Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments—Comparison With the Previous White Caucasian Thorough QT Study

Täubel

Ferber

Fernandes³

et al. 2017

Clinical Pharm in Drug Dev

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Platelet‐activating factor as an endogenous cofactor of food anaphylaxis

Pałgan,

Tretyn

2023

BioFactors

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Anaphylaxis is a severe, acute, life‐threatening generalized or systemic hypersensitivity reaction. The incidence of anaphylaxis is increasing worldwide, with medications and food contributing to most cases. Physical exercise, acute infections, drugs, alcohol, and menstruation are the external cofactors associated with more severe systemic reaction. The aim of this review is to show that platelet‐activating factor contributes to the development of severe anaphylactic reaction, and even to anaphylactic shock.

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Efficacy of increased dose of rupatadine up to 20 mg on itching in Japanese patients due to chronic spontaneous urticaria, dermatitis, or pruritus: A post hoc analysis of phase III clinical trial

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Suzuki

Tanaka

et al. 2019

J Cutaneous Imm & Allergy

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Objectives The effect of rupatadine, a novel H1 antihistamine with platelet‐activating factor antagonist activity, had been demonstrated for itching in Japanese patients with chronic spontaneous urticaria, dermatitis, or pruritus in a 12‐month, open‐label clinical trial (JapicCTI‐152787). However, patients could have received an updose at various timings due to distinct reasons in the study; timing of updose was not evaluated. This study aimed to elucidate the relationship between performance of rupatadine and timing of updose. Methods For 206 enrolled patients was evaluated the total pruritus score (TPS) to Week 2 with 10 mg rupatadine. From Week 3 to Week 52, rupatadine was updosed to 20 mg accordingly. Subpopulation was categorized by absence/presence of updosing and timing of updose (Week 3 or ≥Week 5). Results Reduction of TPS from baseline to Week 2 in patients updosed at Week 3 was significantly lower than those given an updose at ≥Week 5 and fixed dose. However, significant improvement in the change in mean TPS from 1 week pre‐updose to the second week post‐updose was achieved regardless of updose timing, scoring −0.903 for Week 3 and −0.983 for ≥Week 5 (P < 0.001). Conclusions The results inferred the inclusivity of patients who either updosed during the earlier phase due to lack of efficacy, or later due to aggravation of symptoms. The results of this subgroup analysis produced evidence of appropriateness for using 10 mg rupatadine as the starting dose, and evaluating the necessity of updose to 20 mg during the first 2 weeks for nonresponsive patients.

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Rupatadine: efficacy and safety of a non-sedating antihistamine with PAF-antagonist effects

Cited by 46 publications

References 42 publications

Cardiac Safety of Rupatadine in a Single‐Ascending‐Dose and Multiple‐Ascending‐Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments—Comparison With the Previous White Caucasian Thorough QT Study

Cardiac Safety of Rupatadine in a Single‐Ascending‐Dose and Multiple‐Ascending‐Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments—Comparison With the Previous White Caucasian Thorough QT Study

Platelet‐activating factor as an endogenous cofactor of food anaphylaxis

Efficacy of increased dose of rupatadine up to 20 mg on itching in Japanese patients due to chronic spontaneous urticaria, dermatitis, or pruritus: A post hoc analysis of phase III clinical trial

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