Published: 7 September 2023

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Infusion-related reactions – not all allergy related

Published: 7 September 2023
Prescriber Update 44(3): 61–63
September 2023

The Centre for Adverse Reactions Monitoring (CARM) received a report of a vancomycin infusion-related reaction where the patient developed redness and itch (ID 145998). Previously called ‘Red Man Syndrome’, the clinical presentation of severe vancomycin infusion reaction may mimic that of anaphylaxis.¹

This article highlights examples of medicines that may cause infusion-related reactions.

What are infusion-related reactions?

Infusion-related reactions are potentially serious adverse events associated with parenteral administration of medicines and may have different underlying causes.²

Infusion-related reactions may be allergic or pseudo-allergic.

• Allergic type or hypersensitivity reactions can be classified into types I to IV, depending on the mechanism. Anaphylaxis is the most severe presentation of an immunoglobulin E (IgE)-mediated (type I) medicine reaction.²
• Pseudo-allergic type or nonimmune hypersensitivity reactions are rare, unpredictable reactions to a medicine. The mechanisms underlying most pseudo-allergic reactions are not known. With vancomycin infusion reaction, mast cells are activated independent of IgE and the clinical presentation can mimic an IgE-mediated allergic reaction.²

It may be difficult to distinguish clinically between allergic and pseudo-allergic reactions. However, both types of reaction can be potentially life threatening. If signs and symptoms of anaphylaxis are present, immediately discontinue the infusion and initiate appropriate management.²

Administer medicines with potential for infusion-related reactions in a suitable environment with adequately trained personnel and resuscitation equipment.

Examples of medicines associated with infusion-related reactions

Vancomycin, intravenous iron and monoclonal antibodies are examples of medicines associated with infusion-related reactions (not an exhaustive list).

Vancomycin

Rapid administration of vancomycin may cause vancomycin infusion reaction, a pseudo-allergic reaction.²

To minimise the risk of vancomycin infusion reaction, administer vancomycin at a rate of 500mg/hour or slower, and at an appropriate dilution.³

Symptoms of vancomycin infusion reaction may include hypotension (low blood pressure), flushing, erythema (skin redness), urticaria (skin welts), pruritis (itchiness), or pain and muscle spasm of the chest and back. Stopping the infusion usually stops the symptoms. Rule out other causes such as anaphylaxis.^1,3

Depending on the severity of the vancomycin infusion reaction, it may be possible to restart the infusion at a reduced rate after the symptoms have resolved. Monitor the patient closely for further reactions.^1,3

Intravenous iron

For intravenous administration of iron polymaltose, use a slow infusion rate initially and observe the patient. Increase the rate if the infusion is well tolerated. The approximate infusion time is 5 hours.⁴

Ferric carboxymaltose can be administered via slow intravenous undiluted injection or as a diluted infusion. For 500mg–1,000mg doses, the minimum infusion time should be 15 minutes.⁵

Monitor patients during and after iron administration. If an infusion-related reaction occurs, stop the infusion and take appropriate action.⁶

Mild infusion-related reactions with intravenous iron may include symptoms such as itching, flushing, sensation of heat, slight chest tightness, hypertension or back/joint pains. The reaction may be related to the rate of the infusion, rather than an allergic reaction.⁶ Following resolution of mild symptoms, restart the infusion at a slower rate if clinically appropriate.⁶

Rarely, serious allergic reactions, including anaphylaxis, can occur with intravenous iron.

Monoclonal antibodies

Infusion-related reactions can occur with monoclonal antibodies, with potential to cause a wide spectrum of symptoms.⁷

Rituximab is a monoclonal antibody associated with a high incidence of pseudo-allergic infusion reactions. To reduce this risk, premedicate the patient and administer the first rituximab dose at a slower rate (refer to the data sheet and/or clinical guidelines for premedication recommendations). Patients who have elevated white blood cells are more likely to have severe infusion-related reactions.^7,8

Symptoms of rituximab infusion reactions may include fever, chills, rigors, hypotension, urticaria and angioedema and features of cytokine release syndrome. Symptoms are usually reversible with interruption of the infusion. Decision for retreatment depends on the severity and nature of the reaction.^7,8

Anaphylactic reactions have been reported with rituximab and must be differentiated from other types of infusion reactions.⁷

Further information

Refer to the relevant data sheet for further information about administration and infusion-related reactions.

References

1. Weller P. 2023. Vancomycin hypersensitivity. In: UpToDate 28 April 2023. URL: www.uptodate.com/contents/vancomycin-hypersensitivity (accessed 12 July 2023).
2. Pichler W. 2019. Drug hypersensitivity: Classification and clinical features. In: UpToDate 1 December 2023. URL: www.uptodate.com/contents/drug-hypersensitivity-classification-and-clinical-features (accessed 12 July 2023).
3. Viatris Ltd. 2022. Vancomyin New Zealand Data Sheet 5 August 2022. URL: www.medsafe.govt.nz/profs/Datasheet/v/VancomycinMylaninf.pdf (accessed 12 July 2023).
4. Multichem NZ Ltd. 2020. Ferrosig New Zealand Data Sheet 22 December 2020. URL: www.medsafe.govt.nz/profs/Datasheet/f/ferrosiginj.pdf (accessed 12 July 2023
5. Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2021. Ferinject New Zealand Data Sheet 22 June 2021. URL: www.medsafe.govt.nz/profs/Datasheet/f/ferinjectinj.pdf (accessed 12 July 2023).
6. Auerbach M. 2023. Treatment of iron deficiency anemia in adults. In: UpToDate 13 June 2023. URL: www.uptodate.com/contents/treatment-of-iron-deficiency-anemia-in-adults (accesed 12 July 2023).
7. LaCasce A, Castells MC, Burstein HJ, et al. 2023. Infusion-related reactions to therapeutic monoclonal antibodies used for cancer. In: UpToDate 13 June 2023. URL: www.uptodate.com/contents/infusion-related-reactions-to-therapeutic-monoclonal-antibodies-used-for-cancer-therapy (accessed 12 July 2023).
8. Roche Products (New Zealand) Limited. 2023. MabThera New Zealand Data Sheet 1 February 2023. URL: www.medsafe.govt.nz/profs/datasheet/m/Mabtherainf.pdf (accessed 12 July 2023).