Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems

Emanuel Raschi, Anna Girardi, Elisabetta Poluzzi, Emanuele Forcesi, Francesca Menniti-Ippolito, Gabriela Mazzanti, Fabrizio De Ponti

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events.

METHODS: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs.

RESULTS: One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for "general disorders and administration site conditions," whereas CAERS received also a high number of reports for "investigations" and "musculoskeletal and connective tissue disorders". Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44-13.10).

CONCLUSIONS: Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

Original languageEnglish
Pages (from-to)745-752
Number of pages8
JournalDrug Safety
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 2018

Fingerprint

Dietary Supplements
Liver
Hydroxymethylglutaryl-CoA Reductase Inhibitors
United States Food and Drug Administration
Safety
Odds Ratio
Confidence Intervals
Food safety
Rhabdomyolysis
Food Safety
Muscular Diseases
Nutrition
Connective Tissue
red yeast rice
Inspection
Databases
Tissue
Wounds and Injuries
Pharmaceutical Preparations

Keywords

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems/standards
  • Aged
  • Biological Products/adverse effects
  • Child
  • Child, Preschool
  • Dietary Supplements/adverse effects
  • Female
  • Food Safety/methods
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing/methods
  • United States/epidemiology
  • United States Food and Drug Administration/standards
  • Young Adult

Cite this

Adverse Events to Food Supplements Containing Red Yeast Rice : Comparative Analysis of FAERS and CAERS Reporting Systems. / Raschi, Emanuel; Girardi, Anna; Poluzzi, Elisabetta; Forcesi, Emanuele; Menniti-Ippolito, Francesca; Mazzanti, Gabriela; De Ponti, Fabrizio.

In: Drug Safety, Vol. 41, No. 8, 08.2018, p. 745-752.

Research output: Contribution to journalArticle

Raschi, Emanuel ; Girardi, Anna ; Poluzzi, Elisabetta ; Forcesi, Emanuele ; Menniti-Ippolito, Francesca ; Mazzanti, Gabriela ; De Ponti, Fabrizio. / Adverse Events to Food Supplements Containing Red Yeast Rice : Comparative Analysis of FAERS and CAERS Reporting Systems. In: Drug Safety. 2018 ; Vol. 41, No. 8. pp. 745-752.
@article{e3f333c6d7774266989881affabe4c55,
title = "Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems",
abstract = "INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events.METHODS: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95{\%} confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs.RESULTS: One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for {"}general disorders and administration site conditions,{"} whereas CAERS received also a high number of reports for {"}investigations{"} and {"}musculoskeletal and connective tissue disorders{"}. Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95{\%} CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44-13.10).CONCLUSIONS: Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.",
keywords = "Adolescent, Adult, Adverse Drug Reaction Reporting Systems/standards, Aged, Biological Products/adverse effects, Child, Child, Preschool, Dietary Supplements/adverse effects, Female, Food Safety/methods, Humans, Infant, Infant, Newborn, Male, Middle Aged, Product Surveillance, Postmarketing/methods, United States/epidemiology, United States Food and Drug Administration/standards, Young Adult",
author = "Emanuel Raschi and Anna Girardi and Elisabetta Poluzzi and Emanuele Forcesi and Francesca Menniti-Ippolito and Gabriela Mazzanti and {De Ponti}, Fabrizio",
year = "2018",
month = "8",
doi = "10.1007/s40264-018-0661-3",
language = "English",
volume = "41",
pages = "745--752",
journal = "Drug Safety",
issn = "0114-5916",
publisher = "Adis International Ltd",
number = "8",

}

TY - JOUR

T1 - Adverse Events to Food Supplements Containing Red Yeast Rice

T2 - Comparative Analysis of FAERS and CAERS Reporting Systems

AU - Raschi, Emanuel

AU - Girardi, Anna

AU - Poluzzi, Elisabetta

AU - Forcesi, Emanuele

AU - Menniti-Ippolito, Francesca

AU - Mazzanti, Gabriela

AU - De Ponti, Fabrizio

PY - 2018/8

Y1 - 2018/8

N2 - INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events.METHODS: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs.RESULTS: One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for "general disorders and administration site conditions," whereas CAERS received also a high number of reports for "investigations" and "musculoskeletal and connective tissue disorders". Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44-13.10).CONCLUSIONS: Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

AB - INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events.METHODS: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs.RESULTS: One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for "general disorders and administration site conditions," whereas CAERS received also a high number of reports for "investigations" and "musculoskeletal and connective tissue disorders". Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44-13.10).CONCLUSIONS: Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

KW - Adolescent

KW - Adult

KW - Adverse Drug Reaction Reporting Systems/standards

KW - Aged

KW - Biological Products/adverse effects

KW - Child

KW - Child, Preschool

KW - Dietary Supplements/adverse effects

KW - Female

KW - Food Safety/methods

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Middle Aged

KW - Product Surveillance, Postmarketing/methods

KW - United States/epidemiology

KW - United States Food and Drug Administration/standards

KW - Young Adult

U2 - 10.1007/s40264-018-0661-3

DO - 10.1007/s40264-018-0661-3

M3 - Article

C2 - 29582393

VL - 41

SP - 745

EP - 752

JO - Drug Safety

JF - Drug Safety

SN - 0114-5916

IS - 8

ER -