Objective
Interactions between supplements and drugs may potentially increase the risk of bleeding in patients with cancer. However, studies on drug interactions and bleeding risk in cancer patients in a real-world setting are limited. This study investigates supplement-drug interactions associated with bleeding risk using data from the UK Biobank database (https://www.ukbiobank.ac.uk).

Methods
Participants included in this study had a cancer diagnosis and had completed supplement-use assessment after their diagnosis. Potential supplement-drug interactions associated with bleeding were identified using four tertiary databases. Logistic regression was used to investigate the association between potential clinical predictors and the use of supplement-drug pairs with interactions that potentially increase the bleeding risk. Exploratory analysis utilized log-binomial regression to examine the association between potentially interacting supplement-drug pairs and the incidence rates of five major bleeding outcomes (gastrointestinal hemorrhage, intracranial hemorrhage, hematuria, hemorrhage from respiratory passages, and postmenopausal bleeding). All analyses were adjusted for relevant factors.

Results
This study analyzed data from 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) of the participants reported using supplements after their cancer diagnosis. Among those using both supplements and drugs, one-third (n = 4970/14,308, 34.7%) were taking potentially interacting pairs that increase bleeding risk. Younger age at cancer diagnosis, longer time since diagnosis, specific cancer types, and comorbidities were associated with the use of these interacting pairs. Exploratory analyses found no significant associations between the use of potentially interacting supplement-drug pairs and the incidence of major bleeding events (all P > 0.05), although the risk of minor bleeding cannot be ruled out.

Conclusion
Approximately one-third of cancer patients who used supplements and drugs had a potential risk for bleeding due to supplement-drug interactions, suggesting the need to raise awareness about bleeding risks among patients and healthcare providers. Further pharmacovigilance monitoring and prospective cohort studies are needed to better understand the clinical impact of specific interactions.

Key words: Drug interactions, Dietary supplements, Cancer, Bleeding, Hemorrhage