Postmarketing nutrivigilance safety profile: a line of dietary food supplements containing red yeast rice for dyslipidemia

IntroductionIn the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).Material and methodsWe report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004 to 31st December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.ResultsThe total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical.ConclusionsThis nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement’s labeling.

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

Drug Safety ◽

10.1007/s40264-018-0661-3 ◽

2018 ◽

Vol 41 (8) ◽

pp. 745-752 ◽

Cited By ~ 11

Author(s):

Emanuel Raschi ◽

Anna Girardi ◽

Elisabetta Poluzzi ◽

Emanuele Forcesi ◽

Francesca Menniti-Ippolito ◽

...

Keyword(s):

Comparative Analysis ◽

Adverse Events ◽

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast ◽

Reporting Systems

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Safety of Moxibustion: A Systematic Review of Case Reports

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/783704 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

Ji Xu ◽

Hongyong Deng ◽

Xueyong Shen

Keyword(s):

Systematic Review ◽

Basal Cell Carcinoma ◽

Adverse Events ◽

Medical Treatment ◽

Cell Carcinoma ◽

Premature Birth ◽

Adverse Reactions ◽

Case Reports ◽

Fetal Distress ◽

The World

Moxibustion is a traditional medical treatment originating in China. It involves using the heat of burning moxa to stimulate acupoints. It is considered safe and effective and is widely used throughout the world. The increasing use of moxibustion has drawn attention to the procedure’s adverse events (AEs). This review covers a total of 64 cases of AEs associated with moxibustion in 24 articles, reported in six countries. Some evidence of the risks of moxibustion has been found in these cases. AEs include allergies, burns, infection, coughing, nausea, vomiting, fetal distress, premature birth, basal cell carcinoma (BCC), ectropion, hyperpigmentation, and even death. The position, duration, distance between moxa and skin, proficiency of the practitioners, conditions of the patients, presence of smoke, and even the environment of treatment can affect the safety of moxibustion. Improving practitioner skill and regulating operations may reduce the incidence of adverse reactions and improve the security of moxibustion.

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Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis

Heart Asia ◽

10.1136/heartasia-2019-011191 ◽

2019 ◽

Vol 11 (2) ◽

pp. e011191 ◽

Cited By ~ 4

Author(s):

Shannon Marantelli ◽

Robert Hand ◽

Jonathan Carapetis ◽

Andrea Beaton ◽

Rosemary Wyber

Keyword(s):

Heart Disease ◽

Adverse Events ◽

Rheumatic Heart Disease ◽

Adverse Reactions ◽

Case Reports ◽

Penicillin G ◽

Alternative Mechanism ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Rheumatic Heart

ObjectiveSecondary prophylaxis through long-term antibiotic administration is essential to prevent the progression of acute rheumatic fever to rheumatic heart disease (RHD). Benzathine penicillin G (BPG) has been shown to be the most efficacious antibiotic for this purpose; however, adverse events associated with BPG administration have been anecdotally reported. This study therefore aimed to collate case reports of adverse events associated with BPG administration for RHD prophylaxis.Study designA literature review was used to explore reported adverse reactions to BPG and inform development of a case report questionnaire. This questionnaire was circulated through professional networks to solicit retrospective reports of adverse events from treating physicians. Returned surveys were tabulated and thematically analysed. Reactions were assessed using the Brighton Collaboration case definition to identity potential anaphylaxis.ResultsWe obtained 10 case reports from various locations, with patients ranging in age from early-teens to adults. All patients had clinical or echocardiogram-obtained evidence of valvular disease. The majority of patients (80%) had received BPG prior to the event with no previous adverse reaction. In eight cases, the reaction was fatal; in one case resuscitation was successful and in one case treatment was not required. Only three cases met Level 1 Brighton criteria consistent with anaphylaxis.ConclusionThese results indicate that anaphylaxis is not a major cause of adverse reactions to BPG. An alternative mechanism for sudden death following BPG administration in people with severe RHD is proposed.

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A quantitative UHPLC-MS/MS method for citrinin and ochratoxin A detection in food, feed and red yeast rice food supplements

World Mycotoxin Journal ◽

10.3920/wmj2015.1971 ◽

2016 ◽

Vol 9 (3) ◽

pp. 343-352 ◽

Cited By ~ 10

Author(s):

J.A.L. Kiebooms ◽

B. Huybrechts ◽

C. Thiry ◽

E.K. Tangni ◽

A. Callebaut

Keyword(s):

Risk Assessment ◽

Ochratoxin A ◽

High Performance ◽

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast ◽

Relative Standard ◽

Future Data ◽

Food And Feed ◽

Feed Samples

Mycotoxins may cause deleterious effects (among others nephrogenic, hepatogenic, carcinogenic, teratogenic, neurogenic) in animals and humans, therefore they have been intensely studied and monitored over the years. For citrinin (CIT), a nephrotoxic mycotoxin, however, this has not yet been the case. According to the latest European Food Safety Authority report, a correct risk assessment of CIT was not possible due to the lack of occurrence data. Besides, traces of CIT or its metabolite, dehydrocitrinone are widely (in up to 90% of samples) present in human urine according to recent Belgian and German scientific reports, which might imply chronic exposure. Only recently, a European maximum limit has been set for CIT in cholesterol reducing food supplements including red yeast fermented rice (RYR). During production of RYR through fungal (among others Monascus purpureus) fermentation of rice other components, like CIT, as well as nephrotoxic ochratoxin A (OTA) may form. Consequently, the present work attempted develop to a robust and routinely applicable ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS/MS) method for the analysis of CIT and OTA in food, feed and in RYR food supplements. The method was successfully validated based on EU/657/2002 and EU/519/2014 in RYR food supplements and wheat flour, achieving respective limits of quantification (LOQ) for CIT of 0.4 μg/kg and 0.1 μg/kg and for OTA of 15 μg/kg and 0.4 μg/kg. The average between-day recoveries varied from 72 to 110% with relative standard deviations ≤16%. Single-day validation in rice, curry and apple matrices showed LOQs ranging from 0.3-1.0 μg/kg. Next, the occurrence of CIT/OTA was surveyed in 138 RYR, food and feed samples, proving the potential of this method for future data acquisition within a risk assessment framework specifically for CIT, while also gaining information about the (co-)occurrence of OTA in edible matrices.

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1443Safety of red yeast rice supplementation: a systematic review and meta-analysis of randomized controlled trials

European Heart Journal ◽

10.1093/eurheartj/ehz748.0078 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Fogacci ◽

M Banach ◽

D P Mikhailidis ◽

E Bruckert ◽

P P Toth ◽

...

Keyword(s):

Adverse Events ◽

Meta Analysis ◽

Lipid Lowering ◽

Forest Plot ◽

Tolerability Profile ◽

Red Yeast Rice ◽

Monacolin K ◽

Randomized Controlled ◽

Red Yeast ◽

Increased Risk

Abstract Background Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Purpose Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve the lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Methods Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, <3–5 and >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Results Data were pooled from 52 RCTs comprising 110 treatment arms, which included 8503 subjects, with 4421 in the RYR arm and 4287 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio [OR]=0.94, 95% confidence interval [CI] 0.53,1.65). (Figure below presents the forest plot comparing the RYR associated risk of MuD in the entire population). Moreover, we found a reduced risk of Non-MuD (OR=0.59, 95% CI 0.50, 0.69) and SAE (OR=0.54, 95% CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: −0.10; 95% CI: −0.17, −0.03; two-tailed p<0.01). Forest plot on RYR link with MuD risk. Conclusions Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large population of moderately hypercholesterolaemic subjects. Acknowledgement/Funding None

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Food supplements with red yeast rice: More regulations are needed

European Journal of Preventive Cardiology ◽

10.1177/2047487317716500 ◽

2017 ◽

Vol 24 (13) ◽

pp. 1429-1430 ◽

Cited By ~ 8

Author(s):

Guy G De Backer

Keyword(s):

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast

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Safety of Acupuncture Practice in Japan: Patient Reactions, Therapist Negligence and Error Reduction Strategies

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nem086 ◽

2008 ◽

Vol 5 (4) ◽

pp. 391-398 ◽

Cited By ~ 22

Author(s):

Hitoshi Yamashita ◽

Hiroshi Tsukayama

Keyword(s):

Adverse Events ◽

Clinical Training ◽

Adverse Reactions ◽

Case Reports ◽

Feedback System ◽

Minor Bleeding ◽

Serious Adverse Events ◽

Continued Education ◽

Reduction Strategies ◽

Almost All

Evidence-based approach on the safety of acupuncture had been lagging behind both in the West and the East, but reliable data based on some prospective surveys were published after the late 1990s. In the present article, we, focusing on ‘Japanese acupuncture’, review relevant case reports and prospective surveys on adverse events in Japan, assess the safety of acupuncture practice in this country, and suggest a strategy for reducing the therapists’ error. Based on the prospective surveys, it seems reasonable to suppose that serious adverse events are rare in standard practice by adequately trained acupuncturists, regardless of countries or modes of practice. Almost all of adverse reactions commonly seen in acupuncture practice—such as fatigue, drowsiness, aggravation, minor bleeding, pain on insertion and subcutaneous hemorrhage—are mild and transient, although we should be cautious of secondary injury following drowsiness and needle fainting. After demonstrating that acupuncture is inherently safe, we have been focusing on how to reduce the risk of negligence in Japan, as well as educating acupuncturists more about safe depth of insertion and infection control. Incident reporting and feedback system is a useful strategy for reducing therapist errors such as forgotten needles. For the benefit of acupuncture patients in Japan, it is important to establish mandatory postgraduate clinical training and continued education system.

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NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

Chinese Medicine ◽

10.1186/1749-8546-7-8 ◽

2012 ◽

Vol 7 (1) ◽

pp. 8 ◽

Cited By ~ 23

Author(s):

Dirk W Lachenmeier ◽

Yulia B Monakhova ◽

Thomas Kuballa ◽

Sigrid Löbell-Behrends ◽

Sibylle Maixner ◽

...

Keyword(s):

Food Supplements ◽

Red Yeast Rice ◽

Hmg Coa Reductase ◽

Red Yeast ◽

Coa Reductase

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Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis

10.21203/rs.2.11268/v1 ◽

2019 ◽

Author(s):

Trygve Holmøy ◽

Børre Fevang ◽

David Benee Olsen ◽

Olav Spigset ◽

Lars Bø

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Case Reports ◽

Fatal Outcome ◽

Significant Proportion ◽

Multiple Organ ◽

European Medicines Agency ◽

Immune Mediated ◽

Suspected Adverse Reactions ◽

Fatal Adverse Events

Abstract Objective Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality. Results We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.

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