Objective

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To evaluate the safety and clinical utilization of traditional Chinese medicine （TCM） formula granules based on real-world data， and to provide evidence for their rational clinical use.

Methods

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A multicenter， prospective， open-label， observational centralized monitoring study was conducted. Participants who received TCM formula granules in 293 medical institutions throughout China from February 5th， 2020 to May 20th， 2025 were consecutively enrolled. The year of data collection was used as the stratification factor. Demographic characteristics （including sex， age， and concomitant medication use）， information on TCM formula granule use （including mean prescribed dosage and inappropriate use）， and adverse event（AE）/adverse drug reaction（ADR） occurrence and related factors were collected and statistically analyzed.

Results

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A total of 42 011 participants were included in the safety set （SS）， with a mean age of （38.34±22.30） years， including 18 693 males and 23 318 females. Among them， 3519 participants （8.38%） had a history of or concomitant diseases. The three most common comorbidities were hypertension （1189 cases， 33.79%）， diabetes mellitus （850 cases， 24.15%）， and coronary heart disease （471 cases， 13.38%）. The top three diagnostic categories were respiratory， thoracic， and mediastinal diseases （7008 cases， 16.68%）， infectious and parasitic diseases （6591 cases， 15.69%）， and gastrointestinal diseases （4580 cases， 10.90%）.Among 41 961 participants with available concomitant medication data， 3332（7.94%） received concomitant medications， and western medicines were the most commonly used concomitant medications （2819 cases， 6.72%）. The mean prescribed dosage of TCM formula granules （expressed as the equivalent dosage of crude herbal pieces） was （158.23±104.86） g in 2020， （131.70±65.84） g in 2021， （130.62±59.96） g in 2022， （86.74±50.61） g in 2023， （118.59±52.01） g in 2024， and （134.38±49.43） g in 2025. The five most frequently prescribed toxic herbs were Kuxingren （

Semen Armeniacae Amarum，

2746 cases， 6.54%）， Xixin （

Radix et Rhizoma Asari，

2193 cases， 5.22%）， processed Kuxingren （862 cases， 2.05%）， Baiqucai （

Herba Chelidonii，

747 cases， 1.78%）， and Wuzhuyu （

Fructus Evodiae，

645 cases， 1.54%）. Prescriptions involving incompatible combinations of the "eighteen antagonisms" and the "nineteen mutual inhibitions" were most frequently observed in 2020 （54 cases， 0.503%）， and then decreased markedly， remaining at zero or an extremely low level thereafter. The overall incidence of adverse drug reactions （ADRs）

associated with TCM formula granules was 0.057% （24 cases）， indicating a rare occurrence. The annual incidence was 0.028% （3 cases） in 2020， 0 in both 2021 and 2022， 0.065% （5 cases） in 2023， 0.158% （15 cases） in 2024， and 0.226% （1 case） in 2025. Among the 24 patients who experienced ADRs， 15 had inappropriate medication use.Five of the 24 patients used toxic herbs， and all five had inappropriate medication. Multivariate logistic regression analysis showed that no history of drug-related adverse reactions ［OR=0.053， 95%CI（0.006， 0.465）］ and no concomitant medication ［OR=0.315， 95%CI（0.109， 0.911）］ were associated with a lower risk of ADRs.

Conclusion

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TCM formula granules are widely used in clinical practice and exhibit a favorable overall safety. Greater attention should be paid to people with a history of drug-related adverse reactions and those receiving concomitant medications to further improve medication safety.