PHARMACOVIGILANCE INSIGHTS: A RARE COHORT STUDY ON HYPERSENSITIVITY REACTIONS TO INTRAVENOUS IRON SUCROSE IN POSTPARTUM ANEMIC WOMEN AT TERTIARY CARE HOSPITAL, TAMILNADU

KRISHNA RAVI; SENTHILKUMAR PALANIAPPAN

doi:10.22159/ajpcr.2025v18i12.57167

Authors

KRISHNA RAVI Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India. https://orcid.org/0000-0001-8663-778X
SENTHILKUMAR PALANIAPPAN Centre for Active Pharmaceutical Ingredients, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India. https://orcid.org/0000-0002-1053-057X

DOI:

https://doi.org/10.22159/ajpcr.2025v18i12.57167

Keywords:

Adverse drug reactions, Hypersensitivity, Iron sucrose, Medication errors, Pharmacovigilance, Postpartum anaemia

Abstract

Objectives: This study aims to investigate the incidence, severity, and timeline of hypersensitivity reactions (HSRs) associated with intravenous (IV) iron sucrose and to evaluate the effectiveness of management strategies in postpartum anemic (PPA) women using a structured pharmacovigilance approach.

Methods: The 2-year, single-center, prospective observational cohort study was conducted in obstetrics and gynecology at a tertiary care hospital in Tamil Nadu. Among 238 PPA women, 129 received a standard dose of iron sucrose and were categorized into adverse drug reaction (ADR, n=11) and non-ADR (n=118) groups. To identify potential risk factors for HSRs, we performed a nested case–control analysis, comparing the 11 cases who experienced HSRs with the 118 controls from the same cohort who did not. A Delphi panel assessed ADRs and graded HSRs using the World Health Organization-Uppsala Monitoring Centre causality scale and Ring–Messmer classification, respectively. The data were analyzed using Fisher’s exact test.

Results: The HSR incidence was 8.5%. Most of the patients experienced Grade 2 HSR (63.64%) moderate ADR, followed by Grade 3, severe, potentially life-threatening (27.27%), requiring emergency management, with no fatalities. Demographics showed no significant association with ADRs (p>0.05). Patients with severe anemia appeared to increase the likelihood of ADRs (odds ratio = 2.77; 95% confidence interval: 0.573–13.42; p=0.204, though statistically non-significant. Over half of HSRs (54.5%) occurred after multiple doses, and 72.7% developed within 15 min of infusion. One medication error caused recurring reactions. Most ADRs (91%) were classified as probable/likely.

Conclusion: This study highlights the critical need for active pharmacovigilance in tracking, managing rare and unpredictable ADRs of IV iron sucrose, necessitating pre- and post‐infusion risk assessments, immediate intervention, and infusion policy optimization in the future.

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References

1. Raj P, Gupta N. A review of the national Family Health survey data in addressing India’s maternal health situation. Public Health Rev. 2022;43:1604825. doi: 10.3389/phrs.2022.1604825, PMID 36387421

2. World Health Organization. Guideline: Iron Supplementation in Postpartum Women. Geneva: World Health Organization; 2016. Available from: https://www.who.int/publications/i/item/9789241549585

3. Benson CS, Shah A, Frise MC, Frise CJ. Iron deficiency anaemia in pregnancy: A contemporary review. Obstet Med. 2021;14(2):67-76. doi: 10.1177/1753495X20932426, PMID 34394714

4. Young MF. Maternal anaemia and risk of mortality: A call for action. Lancet Glob Health. 2018;6(5):e479-80. doi: 10.1016/S2214- 109X(18)30185-2, PMID 29571593

5. US Food and Drug Administration. Drug FDA. FDA- Approved Drugs. Venofer (iron Sucrose Injection) - Prescribing Information. Shirley: American Regent, Inc.; 2000 Available from: https://www.fda.gov/ drugsatfda [Last accessed on 2022 Oct 07].

6. Wang C, Graham DJ, Kane RC, Xie D, Wernecke M, Levenson M, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA. 2015;314(19):2062-8. doi: 10.1001/ jama.2015.15572, PMID 26575062

7. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-9. doi: 10.1016/j.jclinepi.2007.11.008, PMID 18313558

8. Nanjundeswaraswamy TS, Divakar S. Determination of sample size and sampling methods in applied research. Proc Eng Sci. 2021;3(1):25-32. doi: 10.24874/pes03.01.003

9. The Use of the WHO-UMC System for Standardised Case Causality Assessment. Geneva: World Health Organization; 2013. World Health Organization. Available from: https://www.who.int/publications/m/ item/WHO-causality-assessment [Last accessed on 2022 Dec 22].

10. Ring J, Brockow K, Behrendt H. History and classification of anaphylaxis. Novartis Found Symp. 2004;257:6-16. doi: 10.1002/0470861193.ch2, PMID 15025389

11. Saroj K, Shiralee R. Comparative evaluation of efficacy and safety of intravenous ferric carboxymaltose versus iron sucrose complex for the treatment of moderate grade anemia in post caesarean section women: A randomized and prospective study. Asian J Pharm Clin Res. 2023;16(4):128-32. doi: 10.22159/ajpcr.2023.v16i4.46822

12. Louzada ML, Hsia CC, Al-Ani F, Ralley F, Xenocostas A, Martin J, et al. Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study. BMC Hematol. 2016;16:7. doi: 10.1186/ s12878-016-0046-8, PMID 26973791

13. Auerbach M, Ballard H. Clinical use of intravenous iron: Administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program. 2010;2010:338-47. doi: 10.1182/asheducation-2010.1.338, PMID 21239816

14. Critchley J, Dundar Y. Adverse events associated with intravenous iron infusion (low-molecular weight iron dextran and iron sucrose): A systematic review. Transfus Altern Transfus Med. 2007;9(1):8-36. doi: 10.1111/j.1778-428X.2007.00042.x

15. Karwasara V, Prakash P, Datika S, Goyal P. To compare intravenous ferric carboxymaltose versus intravenous iron sucrose in post-partum women with iron-deficiency anemia. Asian J Pharm Clin Res. 2023;16(7):187-90. doi: 10.22159/ajpcr.2023.v16i7.48520

16. Caimmi S, Crisafulli G, Franceschini F, Liotti L, Bianchi A, Bottau P, et al. Hypersensitivity to intravenous iron preparations. Children (Basel). 2022;9(10):1473. doi: 10.3390/children9101473, PMID 36291409

17. Kale MA, Bindu SM, Khadkikar P. Role of antioxidants and nutrition in oxidative stress: A review. Int J Appl Pharm. 2015;7(1):1-4. doi: 10.22159/ijap.2015v7i1.6206

18. Mishra A, Dave N, Viradiya K. Fatal anaphylactic reaction to iron sucrose in pregnancy. Indian J Pharmacol. 2013;45(1):93-4. doi: 10.4103/0253-7613.106446, PMID 23543624

19. Nagaratnam C, Deepika B, Deepalatha C. Drug utilization pattern study in young adult patients of cutaneous adverse drug reactions. Int J Curr Pharm Sci. 2018;10(6):13-5. doi: 10.22159/ijcpr.2018v10i6.30965

20. Parikh A, Agarwal S. Intravenous ferric carboxymaltose versus iron sucrose in iron deficiency anemia of pregnancy. Indian J Obstet Gynecol Res. 2022;9(1):10-4. doi: 10.18231/j.ijogr.2022.003

21. Kamath V, Reddy N, Shettian N. A comparative study of efficacy, safety and compliance of intravenous ferric carboxymaltose versus iron sucrose in the treatment of iron deficiency anaemia of pregnancy. Indian J Obstet Gynecol Res. 2021;8(4):448-53. doi: 10.18231/j. ijogr.2021.094

22. Sharma M, Sanneving L, Mahadik K, Santacatterina M, Dhaneria S, Stålsby Lundborg C. Antibiotic prescribing in women during and after delivery in a non-teaching, tertiary care hospital in Ujjain, India: A prospective cross-sectional study. J Pharm Policy Pract. 2013;6:9. doi: 10.1186/2052-3211-6-9, PMID 25848538

23. WHO Recommendation on Routine Antibiotic Prophylaxis for Women Undergoing Operative Vaginal Birth. Geneva: World Health Organization; 2021. Available from: https://iris.who.int/bitstream/hand le/10665/341862/9789240027992-eng.pdf?sequence=1 [Last accessed on 2023 Mar 18].

24. WHO Recommendation on Prophylactic Antibiotics for Women Undergoing Caesarean Section. Geneva: World Health Organization; 2021. Available from: https://iris.who.int/bitstream/hand le/10665/341865/9789240028012-eng.pdf?sequence=1 [Last accessed on 2024 Aug 23].

25. Girsang BM, Elfira E. Postnatal perineal wound treatment technology: Systematic review. Int J App Pharm. 2024;16(4):17-28. doi: 10.22159/ ijap.2024v16s4.52253