ARC-520 + diphenhydramine

ARC-520 + diphenhydramine is an unbranded combination of two drugs: ARC-520, an investigational RNA interference (RNAi) therapeutic developed for **chronic hepatitis B infection (HBV)**, and diphenhydramine, a well-known **antihistamine**. - **ARC-520** consists of two synthetic, double-stranded, cholesterol-conjugated small interfering RNAs (siRNAs), delivered with a hepatocyte-targeted peptide-polymer excipient. ARC-520 reduces hepatitis B viral proteins by targeting and degrading covalently closed circular DNA (cccDNA)-derived HBV mRNA, thereby lowering viral antigen and DNA levels. - **Diphenhydramine** is a first-generation H1 histamine receptor antagonist used mainly to prevent or treat allergic reactions. In clinical trials of ARC-520, diphenhydramine (or a similar oral antihistamine) was used as prophylaxis to counteract ARC-520-induced mast cell degranulation and histamine release, which could lead to hypersensitivity reactions[1]. Developed clinical interest in this combination is based on using diphenhydramine to increase the safety of ARC-520, not as a co-formulated single pharmaceutical product.