Abstract: Objective To study the connotation of the eighteen incompatible (Shibafan), a core concept of safety of clinical medication in traditional Chinese medicine (TCM), construct a modern framework for theoretical interpretation, and provide data for safe medication and in-depth research on compatibility in TCM. Methods The origin and semantic evolution of the character “fan” (incompatibility) were explored via historical textual research and semantic analysis. By combining empirical analysis and systematic evaluation and integrating modern pharmacopeial standards, clinical trials, and basic experimental research, the toxicity-efficacy transformation mechanism of incompatible medicaments under the syndrome microenvironment was analyzed. Results A multidimensional and clinically-applicable decision tree model was established that involved constitution identification, dosage thresholds, and compatibility with adjuvant herbs. Research indicated that the “eighteen incompatible medicaments” were not absolute compatibility contraindications, but rather an unconventional clinical medication regimen that conformed to the dialectical thinking of TCM. Conclusion Clinical applications of the “eighteen incompatible medicaments” are clearly applicable under specific conditions. In the future, real-world studies (RWS) and N-of-1 randomized crossover trials should be leveraged to provide higher-level evidence-based evidence.

Key words: Eighteen Incompatible (Shibafan), Drug Compatibility Contraindications, Medication Contraindications, Trational Chinese Medicine, Medicinal Properties