A knowledge-based approach is proposed that is employed for the construction of a framework suitable for the management and effective use of knowledge on Adverse Drug Event (ADE) prevention. The framework has as its core part a Knowledge Base (KB) comprised of rule-based knowledge sources, that is accompanied by the necessary inference and query mechanisms to provide healthcare professionals and patients with decision support services in clinical practice, in terms of alerts and recommendations on preventable ADEs. The relevant Knowledge Based System (KBS) is developed in the context of the EU-funded research project PSIP (Patient Safety through Intelligent Procedures in Medication). In the current paper, we present the foundations of the framework, its knowledge model and KB structure, as well as recent progress as regards the population of the KB, the implementation of the KBS, and results on the KBS verification in decision support operation.