Adverse Drug Events (ADEs) are currently considered as a major public health issue, endangering patients' safety and causing significant healthcare costs. Several research efforts are currently concentrating on the reduction of preventable ADEs by employing Information Technology (IT) solutions, which aim to provide healthcare professionals and patients with relevant knowledge and decision support tools. In this context, we present a knowledge engineering approach towards the construction of a Knowledge-based System (KBS) regarded as the core part of a CDSS (Clinical Decision Support System) for ADE prevention, all 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 knowledge sources considered in PSIP and the implications they pose to knowledge engineering, the methodological approach followed, as well as the components defining the knowledge engineering framework based on relevant state-of-the-art technologies and representation formalisms.