Background: Rupatadine, a dual H1-histamine and platelet-activating factor antagonist, has shown promise in allergic rhinitis (AR), but its overall efficacy and safety remain variably reported. This systematic review aimed to evaluate the therapeutic effectiveness and tolerability of rupatadine in adults with seasonal and perennial AR. Methods: Following PRISMA guidelines, PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to April 2025 for randomized controlled trials (RCTs) comparing rupatadine with placebo after registration on PROSPERO (CRD42025065190). Data on nasal symptom reduction, quality of life, and adverse events were pooled using a random-effects model, expressed as standardized mean differences (SMD) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB-2 tool. Results: Eight RCTs comprising 2442 participants were included. Rupatadine significantly reduced total nasal symptom scores (SMD = −1.36; P = 0.001) and improved nasal congestion (SMD = −0.60; P = 0.008), rhinorrhea (SMD = −1.17; P < 0.001), sneezing (SMD = −1.23; P < 0.001), and nasal itching (SMD = −1.02; P < 0.005) compared with placebo. A dose-response trend favored 20 mg over 10 mg in most outcomes. Quality-of-life improvements were statistically inconclusive (SMD = −1.52; P = 0.24). No serious adverse events were reported; somnolence was the most common adverse drug reaction. Conclusion: Rupatadine is an effective, well-tolerated therapy for AR, providing significant relief from key nasal symptoms, particularly at higher doses. Although quality-of-life benefits were modest, the findings support rupatadine’s role as a safe and potent antihistamine option, warranting further long-term and real-world evaluation.
Rehman et al. (Mon,) studied this question.