Disproportionality analysis of data from VigiBase and other global product safety databases on toxicity of iron chelating agents

ABSTRACT

Background

Iron chelators; deferasirox, deferiprone and deferoxamine, used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions.

Research design and methods

This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020.

Results

Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. 45 new potential signals with different associative values were suggested.

Conclusion

The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

KEYWORDS:

• Disproportionality analysis
• Iron chelators
• signal detection
• deferasirox
• deferiprone
• deferoxamine

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Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

All authors contributed to the study. The Uppsala Monitoring Center provided the data, based on the search strategy defined by all authors. Corresponding author performed the analysis for datasets from FAERS. All authors approved the article.

Data availability statement

Data obtained from World Health Organization used during this study, including disproportionality analysis results, were only provided to author in order to conduct this analysis, hence they are not available to share. Data obtained.

Ethics statement

Ethical approval was waivered as the data is from an online database.

Aknowldegments

We would like to extend our deepest gratitude to Prof. Dr. Ahmet Aydin, ERT for continuously supporting us with his coordination to establish an agreement between WHO and Yeditepe University

Article Highlights

• Three AEs with different types and frequencies, headache (common),blurred vision (rare) and sepsis (serious),  were selected to be compared.

• Headache was only associatedwith Deferiprone, as per FAERS data.  

• Blurred vision may beassociated with Deferoxamine as per FAERS and Vigibase data, blurred vision mayalso be associated with Deferasirox as per FAERS data.

• Sepsis may be associated withDeferiprone as per VigiBase and FAERS data, sepsis may also be associated withDeferasirox and Deferoxamine as per  VigiBase data.

Additional information

Funding

This work was performed during author’s PhD study in Pharmaceutical Toxicology in Yeditepe University. Costs of datasets were funded by Yeditepe University upon an agreement with World Health Organization on August 3rd, 2022. No other financial assistance was required.