Adverse event reporting patterns of concomitant botanical dietary supplements with CYP3A4 interactive & CYP3A4 non-interactive anticancer drugs in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

ABSTRACT

Background: To examine the adverse event (AE) reporting patterns for concomitant Botanical Dietary Supplements (BDS) and anticancer drugs.

Research design and methods: Using the 2004–2015 U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, AEs involving commonly used BDS and anticancer drugs (categorized into CYP3A4 interactive and CYP3A4 non-interactive) were examined. Disproportionality analyses using reporting odds ratios (RORs) assessed the relative reporting rates of 1) serious AEs (i.e., mortality and morbidity) with concomitant use of BDS (overall and by type) and anticancer drugs compared to anticancer drugs only; and 2) AEs by specific System Organ Classes (SOCs).

Results: A total of 3,264 AEs were reported involving concomitant BDS and CYP3A4 interactives, and 3,885 involving concomitant BDS and non-interactive anticancer drugs. ROR of serious AEs with concomitant all BDS and anticancer drugs compared to anticancer drugs alone showed a potential protective signal (ROR = 0.65, 95% CI = 0.62,0.68), but ROR for açaí and non-interactive anticancer drugs indicated potential risk (ROR = 1.70, 95% CI = 1.01,2.86). Heterogeneity of reporting patterns of AEs related to certain SOCs was observed for use of BDS along with anticancer drugs.

Conclusion: This study identified potential protective and risk signals for AEs with concomitant use of BDS and anticancer drugs.

KEYWORDS:

• Adverse drug events
• anticancer drugs
• botanical dietary supplements
• cytochrome P450 CYP3A4
• pharmacovigilance
• system organ class

Author contributions

S.M. Fahim: Acquisition, analysis, and interpretation of data; writing–initial draft; and writing–review and editing. A.U. Mishuk: Acquisition, analysis, and interpretation of data; writing–review and editing. N. Cheng: Data analysis; and writing–review and editing. R.A. Hansen: Study concept and design; acquisition, analysis, and interpretation of data; and writing–review and editing. A.I. Calderon: Study concept and design; interpretation of data; and writing–review and editing. J. Qian: Study concept and design; acquisition, analysis, and interpretation of data; writing–initial draft; writing–review and editing; and study supervision.

Declaration of interest

These findings were presented at (1) the American Pharmacists Association (APhA) Annual Meeting, March 15–19, 2018, Nashville, TN; and (2) the 34TH ICPE: International Conference on Pharmacoepidemiology & Therapeutic Risk Management. Prague, Czech Republic. August 22–26, 2018.

R. Hansen has provided expert testimony for Daiichi Sankyo and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the Auburn University Research Initiative in Cancer (AURIC).