Drug-induced tumoral disease: A global pharmacovigilance database analysis
1Service de pharmacologie médicale et clinique, faculté de médecine, centre hospitalier universitaire, 37, allées Jules-Guesde, 31000 Toulouse, France.
Introduction:
Cancer remains a worldwide threat, having caused almost 10 million deaths in 2020. The American Cancer Society has identified both known and probable carcinogens, including commonly used drugs. The aim of this study is to describe the drugs most frequently reported in the occurrence of cancer.
Methods:
Among all individual case safety reports (ICSRs) in the global pharmacovigilance database VigiBase, we searched for the 50 most reported drugs with an adverse drug reaction term belonging to the query "Malignant or unspecified tumors" until June 30, 2023. Then, we extracted the disproportionality measurement data, information component (IC), and reporting odds ratio (ROR) in order to assess a disproportionality signal.
Results:
Among all ICSRs in VigiBase, 871,925 contained an ADR belonging to the SMQ "Malignant or unspecified tumors". Ranitidine was the drug with the most reported ADRs related to cancer (n=106,484), followed by lenalidomide (n=13,466), and etanercept (n=8014). The drugs with the highest IC were ranitidine (IC=5.2, 95% confidence interval [95% CI]=5.2-5.2), pioglitazone (1353 ICSRs, IC=4.2, 95% CI=4.2-4.2), and regorafenib (1272 ICSRs, IC=2.8, 95% CI=2.8-2.8).
Discussion:
Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these drugs may be required. Further studies are needed to assess the risk with certain drugs in this ranking.
Insights
Ranitidine, pioglitazone, and regorafenib were most frequently linked to cancer reports in pharmacovigilance data. Special monitoring of patients exposed to these and other drugs may be required due to potential carcinogenic mechanisms.
Area of Science:
- Pharmacovigilance
- Drug Safety
- Oncology
Background:
- Cancer is a significant global health burden, causing millions of deaths annually.
- Certain commonly used medications have been identified as potential carcinogens.
- Understanding drug-associated cancer risks is crucial for patient safety.
Purpose of the Study:
- To identify and describe drugs most frequently reported in association with cancer occurrence.
- To analyze pharmacovigilance data for signals of drug-induced carcinogenicity.
Main Methods:
- Searched the global pharmacovigilance database VigiBase for individual case safety reports (ICSRs).
- Identified the 50 most reported drugs associated with 'Malignant or unspecified tumors' adverse drug reactions (ADRs).
- Utilized disproportionality measures, including Information Component (IC) and Reporting Odds Ratio (ROR), to assess safety signals.
Main Results:
- Over 871,000 ICSRs related to malignant tumors were identified.
- Ranitidine showed the highest number of cancer-related ADRs (n=106,484).
- Other drugs with significant signals included lenalidomide, etanercept, pioglitazone, and regorafenib.
Conclusions:
- Identified drugs exhibit potential carcinogenic mechanisms, including N-nitrosodimethylamine formation (ranitidine), gene activation (pioglitazone), immunosuppression, and unclear oncogenic pathways (protein kinase inhibitors).
- Hormone antagonists like tamoxifen and letrozole were also implicated.
- Special patient monitoring and further research are recommended for drugs with identified cancer risks.
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