Global patterns of adverse drug reactions related to doxorubicin, epirubicin and methotrexate: analysis of individual case safety reports in Vigibase

Abstract

Introduction: Cancer is one of the leading causes of death, globally. Chemotherapy drugs are revolutionary in the treatment of cancer. However, their use is associated with a high incidence of adverse drug reactions (ADRs) due to the intrinsic toxicity of the drugs. Pharmacovigilance is essential in oncology as it plays a significant role in evaluating the safety of drugs and protecting patients from potentially harmful effects of medicines. This study aimed to analyze the global patterns of ADRs associated with commonly used chemotherapy drugs, doxorubicin, epirubicin, and methotrexate reported to VigiBase, the World Health Organization ADR database.

Method: A quantitative secondary analysis was conducted on ADR reports in VigiBase. A total of 184,318 anonymized individual case safety reports were extracted from VigiBase into spreadsheets on Microsoft Excel. Only reports for doxorubicin, epirubicin, and methotrexate as "suspect” or "interacting” drugs were included in the study. Descriptive statistics were conducted in Microsoft Excel, and data were summarized using frequencies and percentages. Pearson chisquared test was done to establish associations between ADRs and demographic factors (significance level of p<0.05), while binary logistic regression analysis determined the magnitude of association using Stata software.

Results: Blood and lymphatic, general and administration site, and gastrointestinal disorders were commonly reported ADR categories for doxorubicin and epirubicin, while general and administration site condition was the most predominant category for methotrexate. The likelihood of having a therapeutic product effect incomplete was 29% higher in males (OR:1.29 95% CI: 1.16-1.42) and 17% higher in the age group 45-64 years (OR:1.17, 95% CI: 1.06-1.29). Also, children (ages 2-11 years) showed 3.33 times higher odds of developing pyrexia (OR:3.33, 95% CI: 1.55-7.18). A comparison between the ADRs found on the drug package inserts in South Africa and the VigiBase data revealed that certain ADRs were not labeled on the package inserts. The main findings were off-label use, disease progression, constipation, decreased appetite, pulmonary embolism, pain, pneumonia, nervous system disorders, and drug therapy issues.

Conclusion: This study contributes to the knowledge of ADRs associated with commonly used chemotherapy drugs. It can assist in minimizing ADR risks and enhancing cancer patient safety.