In the annual report of China's Adverse Drug Reaction Monitoring, it is pointed out that medical institutions are the main source of ADR reports in China. From 2011 and 2022, the total number of ADRs reported by this tertiary hospital reached 7,367, with the number of reported cases increasing year by year. Strengthening the monitoring of adverse drug reactions is an important measure to ensure the safety of drug use for patients. With the implementation of the monitoring system, the awareness of medical staff and pharmacists on the reporting of adverse drug reactions is also increasing.
Among the total 7367 ADR patients, the male-to-female ratio was approximately 1:1.12, female is basically higher than that of males. The number of patients hospitalized for adverse reactions in a Swiss hospital is also slightly higher in women than in men [7]. This may be related, on the one hand, to the differences in pharmacokinetic parameters (such as oral bioavailability, absorption, hepatic and intestinal metabolism, and renal elimination) between men and women, as well as the higher rate of drug combination in women [11]. On the other hand, sex differences in structural genomics, cellular regulatory pathways, and physiological functions may also directly or indirectly affect drug absorption, distribution, metabolism, and elimination, leading to ADRs [12].
Among the total 7367 ADR patients, the male-to-female ratio was approximately 1:1.12, female is basically higher than that of males. The number of patients hospitalized for adverse reactions in a Swiss hospital is also slightly higher in women than in men7. This may be related, on the one hand, to the differences in pharmacokinetic parameters (such as oral bioavailability, absorption, hepatic and intestinal metabolism, and renal elimination) between men and women, as well as the higher rate of drug combination in women 11. On the other hand, sex differences in structural genomics, cellular regulatory pathways, and physiological functions may also directly or indirectly affect drug absorption, distribution, metabolism, and elimination, leading to ADRs12. From the perspective of age distribution, ADRs can occur in all age groups, in the past 10 years, the incidence of ADRs in infants and young children aged 0-3 years old has become a decreasing trend in this tertiary hospital, indicating that the use of drugs for infants is more cautious; while patients over 80 years old, the incidence of ADRs has become an upward trend. One reason is that patients in this age group have decreased immune function, are prone to various diseases, and suffer from multiple diseases at the same time. In treatment, multiple drugs are often used together, and drug interactions increase the incidence of ADR [13]. The other reason may be that the liver and kidney function of patients in this age group is weakened, and the metabolism and tolerance of drugs are reduced, which makes it easy for drugs to accumulate, and thus leads to the occurrence of ADRs [14]. The physiological condition of patients and the situation of multidrug concomitant use should be fully considered in clinical drug therapy, and it is necessary to focus on the monitoring of drug use by age group and adjust the dosage of drug administration accordingly.
From the perspective of age distribution, ADRs can occur in all age groups, in the past 10 years, the incidence of ADRs in infants and young children aged 0-3 years old has become a decreasing trend in this tertiary hospital, indicating that the use of drugs for infants is more cautious; while patients over 80 years old, the incidence of ADRs has become an upward trend. One reason is that patients in this age group have decreased immune function, are prone to various diseases, and suffer from multiple diseases at the same time. In treatment, multiple drugs are often used together, and drug interactions increase the incidence of ADR13. The other reason may be that the liver and kidney function of patients in this age group is weakened, and the metabolism and tolerance of drugs are reduced, which makes it easy for drugs to accumulate, and thus leads to the occurrence of ADRs14. The physiological condition of patients and the situation of multidrug concomitant use should be fully considered in clinical drug therapy, and it is necessary to focus on the monitoring of drug use by age group and adjust the dosage of drug administration accordingly.
Among the ADR reports, intravenous infusion has the highest ADR reporting rate, followed by oral route of administration. Intravenous infusion may be prone to ADRs because of pyrogenic reactions caused by unstrict aseptic handling of the drug; Intravenous administration allows the drug to enter the bloodstream directly and thus exerts its therapeutic effect quickly without first-pass effect, thus resulting in a higher clinical use rate and a higher incidence of ADRs. In addition, the rate of ADR reported by oral administration increased slightly over the years, while intravenous administration did the opposite. In the rational use of clinical medication, physicians and clinical pharmacists are required to select reasonable medications as well as administration methods for patients, optimize the use of intravenous infusion15, reduce the probability of ADRs, and ensure the health of patients.
From the ADR reports from 2011 to 2022, damage to the skin and its adnexa was the most frequent, which was consistent with the adverse reactions reported in a tertiary hospital in Brazil 16. This may be since the clinical manifestations of skin and adnexal damage are commonly rash and itching, which are easy to be observed by patients and their families, and generally appear before other symptoms of organ damage; in addition, the digestive system also accounted for the highest proportion of ADRs, as its symptoms, such as vomiting, are also clinically evident. For some delayed and insidious ADRs, they are not easy to be detected clinically. The reported rate of hematological system damage is increasing year by year, especially after 2020, which may be related to the higher reported rate of ADRs in antineoplastic drugs from 2020 onwards.
In terms of the drug categories in which ADRs occurred, antibacterial drugs had the highest overall reported rate, which was related to the widespread or excessive clinical use of antibacterial drugs17. However, the overall antimicrobial drug ADR reporting rate showed a decreasing trend, which may be attributed to the fact that from 2011, the China Food and Drug Administration carried out a special campaign to begin to strengthen the management of antimicrobial drugs18 and to reduce the misuse of antimicrobial drugs. The hospital strictly follows the Guiding Principles for the Clinical Application of Antimicrobial Drugs, standardizes the use of antimicrobial drugs19. Before antibiotic treatment, it is necessary to clarify the signs of infection as far as possible and do a good job of pharmaceutical care, and formulate an individualized medication plan to avoid unreasonable dosage and drug selection.
The reported rate of ADRs for antineoplastic drugs has basically been on an upward trend from 2011 to 2022, especially by 2022 the reported rate of ADRs for antineoplastic drugs has been the highest, which may be due to the increasing incidence of tumors year by year 20, which makes the application of antineoplastic drugs more widely. And among the reported antineoplastic drugs with ADRs, chemotherapeutic drugs such as antimetabolites, platinum and plant alkaloids are the categories with the highest reported rates. The chemical structure of anti-metabolic drugs is similar to that of some metabolites in the body, which can interfere with nucleic acid and cause tumor cell death after entering the body. The toxic and side effects of such drugs may be aggravated when used in combination with multiple drugs, mainly including blood toxicity, stomatitis, nausea, vomiting and other adverse reactions21. Platinum drugs mainly exert antitumour effects by affecting the DNA structure due to their molecular structure characteristics. With the wide application of platinum drugs in antitumour therapy, the incidence of platinum adverse drug events (ADEs) remains high, and the occurrence of different platinum ADEs is inconsistent, with cisplatin having stronger digestive and nephrotoxicity, carboplatin haematotoxicity being obvious, and neurotoxicity being more common with oxaliplatin22. Plant alkaloids and natural medicines have a broad antitumour spectrum and good antitumour activity, but because of widespread clinical use makes adverse reactions also increasing, most natural product-based anticancer drugs have adequate adverse reactions, mainly haematotoxicity, alopecia toxicity, neurotoxicity and cardiotoxicity23.Therefore, when using antineoplastic drugs, it is necessary to fully understand the characteristics of the drug and the possible toxic side effects, to strictly follow the instructions of the drug to formulate the dosing plan and take appropriate pretreatment measures, and to do good monitoring during the use of the drug as well as preparing for the treatment of ADRs when they are detected.
Overall, the research has both strengths and limitations. In terms of strengths, the study included adverse drug reactions spontaneously reported to the National Centre for Adverse Reactions (NCAR) by a tertiary hospital between 2011 and 2022, and statistically analyzed the trends in the age of the patients with adverse reactions, the severity of the adverse drug reactions, the status of the reporting personnel, the types of medicines in which the adverse reactions occurred, and the organs involved in the adverse reactions over the past 10 years or more, which provides relevant data for the future monitoring and management of adverse reactions. However, there are some limitations. Only the adverse drug reactions in this hospital were counted, so it is difficult to extrapolate the situation in China. In addition, the study did not further analyze the rate of hospitalization caused by adverse drug reactions. There were also a number of cases that were not detailed, such as how many serious ADRs lead to readmission or prolonged hospitalization, and what types of ADRs were associated with the antimicrobials, which will be the next step in the process of refinement and research.