Introduction: The accurate categorization of drugs is a prerequisite for decision support rules. The manual process of creating drug classes can be laborious and error-prone. Methods: All 142 drug classes currently used at Regenstrief Institute for drug interaction alerts were extracted. These drug classes were replicated as fully-defined concepts in our local instance of the NDFRT knowledge base. The performance of these two strategies (manual classification vs. NDFRT-based queries) was compared, and the sensitivity and specificity of each was calculated. Results: Compared to existing manual classifications, NDFRT-based queries made a greater number of correct class-drug assignments: 1528 vs. 1266. NDFRT queries have greater sensitivity (74.9% vs. 62.1%) to classify drugs. However, they have less specificity (85.6% vs. 99.8%). Conclusion: The NDFRT knowledge base shows promise for use in an automated strategy to improve the creation and update of drug classes. The chief disadvantage of our NDFRT-based approach was a greater number of false positive assignments due to the inclusion of non-systemic doseforms.