Purpose <p>Coagulopathy associated with SARS-CoV-2 infection leads to the formation of abnormal blood clots even in tiny blood vessels, which can lead to severe life-threatening conditions like organ damage, heart attack, and stroke. The objective of this study was to develop a solid oral fixed-dose combination (FDC) of molnupiravir (MPV) as an extended-release core (MPV-XR) with rivaroxaban (RIV) active coating for the management of viral infections with coagulopathy-related complications. While MPV-XR helps reduce viral infection along with daily pill burden, RIV simultaneously minimises coagulopathy-related complications.</p> Method <p>We strategically selected the manufacturing process of RIV active coating on MPV-XR core tablets as an efficient, fast, and cost-effective method for large-scale formulation manufacturing. Both the MPV-XR core and the RIV-coated MPV-XR finished dosage form were characterised by various instrumental and pharmacopoeial studies.</p> Results <p>The composition of the P2 batch was found to be the optimum for the MPV-XR core tablet, and the RIV coating with 5% w/w solid content showed the best active-coated tablets with the minimum unit-to-unit content variation (AV, 5.5%). A scale-up batch was executed to evaluate the impact of batch magnification on product quality.</p> Conclusion <p>FDC of MPV-XR with RIV coating was manufactured, and appropriate characterisation was performed. The scale-up batch samples also showed promising quality in terms of drug content and drug release. Thus, the novel formulation approach showed proven quality characteristics for specific use in coagulopathy associated with SARS-CoV-2 infection. However, detailed clinical study needs to be conducted before its large scale manufacturing and commercialization.</p> Graphical Abstract <p></p>