Second-generation antihistamine with additional PAF antagonism
Updated · Methodology
First line
First-line for seasonal and perennial allergic rhinitis under ARIA 2020 and 2022, on par with other second-generation antihistamines. Dose 10 mg once daily. Efficacy is comparable to cetirizine and loratadine; PAF antagonism may give an additional benefit on nasal congestion in some trials.
Sources
ICD-10: J30.9 · ICD-11: CA08.0
First line
First-line for chronic spontaneous urticaria under /GA²LEN/EDF/ 2022: second-generation antihistamines at standard dose. With insufficient response, up-dosing rupatadine to 40 mg/day is acceptable (off-label, EAACI consensus). When symptoms persist at quadruple dose, add omalizumab.
Sources
ICD-10: L50.1 · ICD-11: EB00.1
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Rupatadine is a second-generation antihistamine with additional anti–platelet-activating factor activity. It is prescribed for seasonal and perennial allergic rhinitis and urticaria ( 2024, AEMPS Ficha Técnica). Rupatadine is taken for cold-related runny nose and for immunity as a universal anti-allergic agent. The Cochrane review by De Sutter 2015 did not confirm benefit of antihistamines in the common cold. If rupatadine was prescribed for a cold without confirmed allergic rhinitis, consider seeking a second opinion.
Dual antagonist of H1 histamine receptors and platelet-activating factor (PAF) receptors. Minimal blood-brain barrier penetration with low sedative potential. The active metabolite is desloratadine. Additional PAF antagonism theoretically gives a stronger anti-inflammatory effect in urticaria, although the head-to-head advantage over desloratadine or levocetirizine is modest. Developed by Spain's J. Uriach.
Pregnancy data are limited. Per EMA: use only when clearly necessary. Antihistamines with more data – loratadine or cetirizine – are preferred in pregnancy.
Hale L3, insufficient data for RID estimate. Dual H1 + PAF blocker mechanism. Per AEMPS, not recommended during breastfeeding when alternatives are available (loratadine, cetirizine).
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Grapefruit juice raised rupatadine exposure 3.5-fold in the study cited in the Rupafin SmPC, because it blocks the CYP3A4 that breaks rupatadine down. With that much drug in the blood, drowsiness, tiredness, headache and dry mouth increase. The SmPC does not recommend taking rupatadine with grapefruit juice.
Source: AEMPS: Ficha técnica de Rupafin 10 mg comprimidos (rupatadina) (2021)
Verbatim lines from the interaction sections, in the language of the label
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«Interacción con estatinas: Se han notificado excepcionalmente aumentos asintomáticos de CPK con rupatadina en ensayos clínicos. El riesgo de interacción con estatinas, algunas de las cuales se…»AEMPS, section 4.5 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«La administración concomitante con inhibidores potentes del CYP3A4 (p. ej., itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa HIV, claritromicina, nefazodona) debe ser…»AEMPS, section 4.5 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«Puede requerirse el ajuste de la dosis de sustratos susceptibles del CYP3A4 (p. ej., simvastatina, lovastatina) y sustratos del CYP3A4 con estrecho índice terapéutico (p. ej., ciclosporina…»AEMPS, section 4.4 · Open on CIMA
«Interacciones con otros depresores del Sistema Nervioso Central (SNC): Como ocurre con otros antihistamínicos, no puede excluirse la interacción con depresores del Sistema Nervioso Central.»AEMPS, section 4.5 · Open on CIMA
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Rupatadine is evaluated for the following indications with varying evidence strength: Chronic urticaria (evidence tier A), Allergic rhinitis (evidence tier A), Immune support and respiratory infection care (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Rupatadine (≥ 1 in 100): Headache, Drowsiness (~5%), Dry mouth, Fatigue. See the Safety section for uncommon and serious reactions.
Pregnancy data are limited. Per EMA: use only when clearly necessary. Antihistamines with more data – loratadine or cetirizine – are preferred in pregnancy.
Hale L3, insufficient data for RID estimate. Dual H1 + PAF blocker mechanism. Per AEMPS, not recommended during breastfeeding when alternatives are available (loratadine, cetirizine).
Rupatadine is contraindicated in: Rupatadine hypersensitivity; Age under 2 years; Severe hepatic impairment. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Bilastine, Cetirizine, Chloropyramine, Chlorpheniramine, Dexchlorpheniramine, Doxylamine/pyridoxine, Ketotifen, Desloratadine