Overview

Intravenous iron-containing products are indicated for treatment of iron deficiency.

Background

The National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) on the association of intravenous iron-containing products with the risk of Kounis syndrome. Iron sucrose, iron dextran and iron isomaltoside are in the scope of EMA’s review.¹

Kounis syndrome is defined as acute coronary syndromes with mast cell and platelet activation caused by allergic, hypersensitivity or anaphylactoid reactions.² It is not considered a rare disease but it is a condition which is infrequently diagnosed clinically.

Based on all available evidence from clinical trials, post-market reports, and literature, EMA concluded that all product registration holders of iron-containing products under the review would need to update their product information with the risk of Kounis syndrome.¹

Adverse Drug Reaction Reports

NPRA has received 162 reports with 368 adverse events, 322 reports with 755 adverse events, and 11 reports with 28 adverse events suspected to be related to iron sucrose, iron dextran and iron isomaltoside respectively. To date, no event related to Kounis syndrome has been reported locally.³

Advice for Healthcare Professionals

• Advise patients to inform their doctor immediately if they experience chest pain, which could be a sign of a potentially serious allergic reaction.
• Be alert on the risk of Kounis syndrome associated with the use of intravenous iron-containing products.
• Consider the diagnosis of Kounis syndrome if patients simultaneously develop hypersensitivity reaction and acute coronary syndromes during or after intravenous iron therapy.
• Report all suspected adverse events associated with iron-containing products to the NPRA.

References:

1. European Medicine Agency (2019). PRAC recommendations on signals. EMA/PRAC/580132/2019. Retrieved from: https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-28-31-october-2019-prac-meeting_en.pdf
2. Li et al. (2018): Acute coronary syndrome secondary to allergic coronary vasospasm (Kounis Syndrome): A case series, follow-up and literature review. BMC Cardiovascular Disorders 18:42. Retrieved from: https://doi.org/10.1186/s12872-018-0781-9
3. The Malaysian Adverse Drug Reaction database, NPRA [Accessed: January 2020]

DISCLAIMER:

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.