Pharmacovigilance system is an extension of the original adverse drug reactions monitoring and reporting system as well as an internationally recognized basic system that must be matched with the whole life cycle supervision of drugs. European Union(EU)pharmacovigilance system, World Health Orgnization(WHO) Uppsala Monitoring Center system and ICH system are internationally recognized pharmacovigilance systems. They all have their own pharmacovigilance characteristics and could provide guarantee for clinical safe drug use. With the deepening of international communication, pharmacovigilance has also been developed in China. Pharmacovigilance of Chinese medicine is a new concept based on the existing pharmacovigilance system of chemical medicine and the characteristics of Chinese medicine. In ancient China, Chinese medicine also had its own ways of early warning. Ancient medical books have records on the toxicity classification, clinical pharmacovigilance and intoxication rescue of Chinese medicine. With the increase of public recognition of Chinese medicine in recent years, especially since the government issued the 13 th Five-Year Plan for the development of Chinese medicine, the pharmaceutical industry in China has paid more and more attention to the pharmacovigilance of Chinese medicine.However, the pharmacovigilance system of Chinese medicine has not yet been established, and it still needs to be explored and improved.Therefore, it is very necessary to develop the system to standardize pharmacovigilance-related activities of Chinese medicine. In this context, this study analyzed and learned the characteristics of pharmacovigilance systems of EU, ICH, and WHO Uppsala Monitoring Center, so as to provide some enlightenment for the establishment and improvement of pharmacovigilance system of Chinese medicine.
Adverse Drug Reaction Reporting Systems ; Books ; Drug-Related Side Effects and Adverse Reactions/epidemiology* ; European Union ; Humans ; Medicine, Chinese Traditional ; Pharmacovigilance

OBJECTIVE: To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance. METHODS: A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed. RESULTS: There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion. CONCLUSIONS Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.
Adult ; Adverse Drug Reaction Reporting Systems ; Chemical and Drug Induced Liver Injury/etiology* ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Male ; Middle Aged ; Pharmacovigilance ; Retrospective Studies

BACKGROUND: Taxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world. METHODS: Taxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI). RESULTS: A total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09). CONCLUSIONS The results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.
Adverse Drug Reaction Reporting Systems ; Bayes Theorem ; Bridged-Ring Compounds ; Taxoids/adverse effects* ; United States ; United States Food and Drug Administration

In order to understand the characteristics of adverse drug reaction/adverse event(ADR/AE) of Ginkgo biloba Dropping Pills and evaluate the safety of clinical use after marketing, 407 ADR/AE case report data of Ginkgo biloba Dropping Pills collected by National Center for ADR Monitoring System during 2009-2018 was systematically analyzed, and its general characteristics were analyzed using descriptive statistical methods. The results showed that among the 407 cases of spontaneous reporting system(SRS) data, 401 cases were general ADR/AE, accounting for 98.5%, and 6 cases were severe ADR/AE, accounting for 1.5%; there were more females than males(171/150) in ADR/AE, and they were mainly middle-aged and elderly people aged 45-64 years(152 cases, accounting for 37.35%); gastrointestinal system(23.89%) was mostly involved in ADR/AE. The top ten clinical symptoms were nausea(15.49%), dizziness(9.88%), vomiting(8.11%), rash(5.60%), chest tightness(5.46%), palpitations(5.31%), pruritus(4.72%), headache(4.57%), abdominal distension(3.83%), gastric dysfunction(3.54%); proportional reporting ratio(PRR) and Bayesian confidence progressive neural network method(BCPNN) were adopted to mine ADR/AE warning signals. Due to the small sample size, there were only 0-2 ADR/AE cases with various symptoms in many quarters, with no warning signal by PRR and BCPNN methods. The findings suggest that ADR/AE of Ginkgo biloba Dropping Pills based on SRS system was not recorded in the package insert, and further active monitoring studies shall be conducted to improve relevant ADR/AE information and pay attention to its clinical drug safety issues.
Adverse Drug Reaction Reporting Systems ; Aged ; Bayes Theorem ; Drug-Related Side Effects and Adverse Reactions ; Female ; Ginkgo biloba ; Humans ; Male ; Middle Aged ; Neural Networks, Computer ; Pharmacovigilance

In recent years, the safety problems and events of traditional Chinese medicine represented by liver injury have occurred frequently. In particular, Polygonum multiflorum has been widely used and considered as a "non-toxic" tonic traditional Chinese medicine for thousands of years. However, in recent years, frequent reports of liver injury events have attracted widespread attention at home and abroad, which has made unfavorable impacts on traditional Chinese medicine and its international development. Some scho-lars have found that susceptible genes of P. multiflorum on liver injury lay a scientific foundation for formulating rational comprehensive prevention and control measures for liver injury risk of P. multiflorum and its relevant preparations. But what are the risk signals of adverse reactions of P. multiflorum in clinical application? Spontaneous reporting system is an important way to monitor and find adverse drug reaction(ADR) signals after the drug is launched in the market. It can find the ADR signals in time and effectively, and then effectively prevent and avoid the occurrence of adverse drug events. At present, the data mining technique has gradually become the main method of ADR/adverse event(AE) report analysis and evaluation at home and abroad. Specifically, Bayesian confidence propagation neural network in Bayesian method is a commonly used risk signal early warning analysis method. In this paper, BCPNN method was used to excavate the risk signals of adverse reactions of Xinyuan Capsules, a traditional Chinese medicine preparation containing P. multiflorum, such as nausea, diarrhea, rash, dizziness, vomiting, abdominal pain, headache, liver cell damage, so as to provide evidence-based evidence for clinical safe and rational use of drugs.
Adverse Drug Reaction Reporting Systems ; Bayes Theorem ; Capsules ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Neural Networks, Computer

To explore the general characteristics of adverse drug reactions/adverse events(ADR/AE) in patients after using Shujin Jianyao Pills, and explore risk warning signals, this study analyzed 166 cases of ADR/AE reports of Shujin Jianyao Pills collected from 2005 to 2017 based on the National Center for ADR Monitoring spontaneous reporting system(SRS). And the descriptive statistical method was used to analyze general characteristics. The results showed that among the 166 ADR/AE cases, 106 cases were female patients, accounting for 63.86%. Middle-aged and elderly people aged 45 to 64 accounted for the largest proportion(82 cases, 49.40%), which were followed by elderly aged 65 and over(48 cases, 28.91%). ADR/AE involved a wide range of systems and organs, of which skin and its accessories were the most damaged(30 cases, 12.93%), which were followed by systemic damage(27 cases, 11.64%). The top 10 ADR/AE manifestations were rash(15 cases, 6.33%), nausea(14 cases, 5.91%), dizziness(14 cases, 5.91%), abdominal pain(12 cases, 5.06%), pruritus(11 cases, 4.64%), low back pain(11 cases, 4.64%), vomiting(10 cases, 4.22%), hepatocyte damage(9 cases, 3.80%), headache(9 cases, 3.80%), and diarrhea(7 cases, 2.95%). Bayesian confidence propagation neural network(BCPNN) was used to mine the ADR/AE risk early warning signal of Shujin Jianyao Pills, and the propensity score method was used to control the balance of confounding factors. The results suggested warning signs for nausea, diarrhea, rash, and dizziness, vomiting, abdominal pain, headache, liver cell damage. This study provides a basis for the post-marke-ting safety evaluation of Shujin Jianyao Pills, and can provide guidance for its rational clinical use and risk management.
Adverse Drug Reaction Reporting Systems ; Aged ; Bayes Theorem ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; Female ; Humans ; Middle Aged ; Pharmacovigilance ; Risk Management

To understand the characteristics of adverse reactions and find early warning signs after intake of Guizhi Fuling Capsules. The 1 500 adverse reaction(ADR) cases of Guizhi Fuling Capsules obtained by spontaneous reporting system(SRS) from 2008 to 2017 were analyzed by proportional reporting ratios method(PRR), Bayesian confidence propagation neural network method(BCPNN) and propensity score method. The number of ADR reports increased year by year, and reached the peak in the fourth quarter of 2014. A total of 1 500 ADR cases were monitored, including 10 severe ADR cases. There were a total of 934 cases aged between 18-44 years old, accounting for 62.27%. All patients were orally administered. Among them, 1 398 patients received a single dose according to the package insert, and 57.4% had ADR within 24 h. The top five clinical manifestations of ADR were gastric dysfunction, abdominal pain, nausea, vomiting and rash, which mainly damaged the digestive system. The ADR signals were analyzed. PRR suggested that "gastric dysfunction" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. BCPNN suggested that "nausea" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. After the propensity score weighting method was used to control the confounding factors, the warning signals remained unchanged. The results show that Guizhi Fuling Capsules has fewer adverse reactions and is relatively safe. This study provides a basis for studying ADR of Guizhi Fuling Capsules, and guidance for drug vigilance and risk management of Guizhi Fuling Capsules.
Adolescent ; Adult ; Adverse Drug Reaction Reporting Systems ; Bayes Theorem ; Capsules ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Risk Management ; Young Adult

In 2013,China pharmaceutical regulatory department issued guiduance on postmarketing drug safety monitoring for industry. It aimed to encourage industry to carry out postmarketing drug safety monitoring including hospital-based intensive monitoring of postmarketing Chinese patent medicine. Subsequently,more and more such kind of studies have been performed all over China. However,in view of the current situation in this field,the development of hospital-based intensive monitoring of postmarketing Chinese patent medicine lacks standardization,such as unreasonable design,omission of reports about adverse drug reactions,inadequate process of quality control,non-standardized interpretation of adverse reactions,etc. Therefore,it is necessary to formulate relevant technical specifications to guide this area. The developing of this technical specification refered to the international post-marketing safety monitoring model and advanced design concepts and methods. We developed it under the guidance of relevant laws,regulations and technical documents in China. Meanwhile the characteristics of Chinese patent medicines and the real situation in this area were considered. The aim of this technical specification is to obtain the incidence,type,degree and clinical manifestation of adverse drug reactions of Chinese patent medicines,to find new risk signals of adverse reactions,to identify risk factors,and to provide a basis for the formulation of risk management and control plans. This specification has been approved by China association of Chinese medicine which is numbered T/CACM011-2016.
Adverse Drug Reaction Reporting Systems ; China ; Hospitals ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Product Surveillance, Postmarketing

There are no drugs without the risk of potential adverse reactions. All pharmacologically active substances can cause adverse drug reactions (ADRs). This paper aims at introducing recent trends in pharmacosurveillance systems for ADRs, which can be broadly classified into type A and B reactions. Since type A reactions are associated with drug pharmacology, they are usually dose-dependent and predictable. Whereas, type B reactions occur in some susceptible individuals, regardless of the pharmacological action of drug. Drug hypersensitivity reactions are typical examples of type B reactions and are subclassified according to the underlying pathomechanism. Recent advancements in pharmacogenomics have enlightened the understanding of individual differences in drug efficacy and susceptibility to ADRs. Therefore, expectations for safe personalized medicines are higher than ever before. However, premarketing clinical trials are too small and too short to uncover rare but serious ADRs and detect long-standing ADRs. In the past, post-marketing surveillance systems mainly focused on passive ADR monitoring systems, based on spontaneous reports. Recently, the importance of active pharmacovigilance systems, which use big data, is growing with recent advancements in medical informatics. Thus, regarding ADRs, suspecting and detecting the causative drug using causality assessment based on data science may contribute to decrease suffering induced by ADRs.
Adverse Drug Reaction Reporting Systems ; Drug Hypersensitivity ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Individuality ; Medical Informatics ; Pharmacogenetics ; Pharmacology ; Pharmacovigilance

BACKGROUND: Adverse cutaneous drug reactions (ACDRs) are common and are responsible for increased morbidity, mortality, and socioeconomic costs. OBJECTIVE: The purpose of our study was to investigate the common drugs and clinical patterns related to ACDRs using an electronic drug adverse reaction reporting system at a single secondary referral center. METHODS: We conducted a retrospective analysis of the ACDR database between January 2014 and April 2016 at the Ilsan Paik Hospital. RESULTS: The study analyzed 320 patients with ACDRs (male:female ratio=93:227; mean age 50.8±17.8 years). Using a Korean causality evaluation algorithm, the percentage of drugs with a possible relationship with ACDRs was calculated to be 50.6%, while the percentage with a probable relationship was 44.7%. Antibiotics (44.0%), radiocontrast media (15.1%), and non-steroidal anti-inflammatory drugs (NSAIDs) (14.3%) were the most commonly implicated drugs. Antibiotics, including cephalosporins (30.6%) and quinolones (10.2%), were responsible for the majority of the ACDRs. Acetic acid (5.9%) and propionic acid (5.9%) derivatives of NSAIDs were also common causative agents. The most common clinical presentations were maculopapular exanthema (33.4%), pruritus (30.9%), and urticaria (25.7%). Severe ACDRs were significantly associated with older age, eosinophilia, and underlying heart and renal diseases (p<0.05). CONCLUSION: Antibiotics, radiocontrast media, and NSAIDs were identified as common causes of ACDRs. Older age, eosinophilia, heart disease, and renal disease were associated with severe ACDRs.
Acetic Acid ; Adverse Drug Reaction Reporting Systems ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Cephalosporins ; Contrast Media ; Diethylpropion ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Heart ; Heart Diseases ; Humans ; Mortality ; Pruritus ; Quinolones ; Retrospective Studies* ; Secondary Care Centers* ; Urticaria