Allergic reaction to opioid

Scottish Palliative Care Guidelines
Healthcare Improvement Scotland

Histamine reactions such as itch are seen not uncommonly, without development of features of an allergic reaction.

True opioid allergy is very rare. As with any allergic reaction, this has the potential to result in life-threatening anaphylaxis and rapid ABCDE assessment (Airway, Breathing, Circulation, Disability, Exposure) using Resuscitation Council UK algorithms may be needed.

Following initial management of the allergic response, it is important to discuss the reaction with specialist palliative care prior to administration of any further opioid. This is a highly complex situation as the five different classes of opioids used pose varying degrees of risk cross-reactivity.

Assessment and immediate management

Assess using an ABCDE (Airway, Breathing, Circulation, Disability, Exposure) standard approach:

  • if anaphylaxis, proceed to anaphylaxis guidance as per the Resuscitation Council UK Anaphylaxis algorithm 2021.pdf
  • if non-life threatening but clear immune-mediated allergy, treat as per local allergy guidelines.

In all cases of suspected opioid allergy immediately discontinue the opioid if possible (ie assess for and remove all patches, pause and remove IV or subcutaneous infusions, and deprescribe any regular or as-required (prn) opioids to ensure no further doses are given in error).

Future opioid selection

Seek advice from specialist palliative care before administering any further opioids.

If it is a true allergy to opioid, switching to a different class of opioid is a common approach depending on which opioid caused the reaction. If there is ongoing skin reaction it may be necessary to avoid transdermal patches because of the risk of increased absorption or further skin irritation from the adhesive.

Chemical classes of opioids

Morphinans

Benzomorphans

Piperidine derivatives

Diphenylheptanes

Other

Codeine

Pentazocine

Fentanils*

Dextropropoxyphene

Tramadol

Dextromethorphan

 

Diphenoxylateb

Methadone

Tapentadol

Dihydrocodeine

 

Loperamideb

 

 

Hydrocodone

 

Pethidinea

 

 

Morphine

 

 

 

 

Diamorphine

 

 

 

 

Buprenorphine

 

 

 

 

Hydromorphine

 

 

 

 

Oxycodone

 

 

 

 

Oxymorhpone

 

 

 

 

a not recommended for use in palliative care

b diphenoxylate and loperamide also contain a diphenyl group.

*fentanils refers to alfentanil, fentanyl, remifentanil, sufentanil

Reproduced with permission from: Wilcock A et al. (eds), Palliative Care Formulary. [online] London: Pharmaceutical Press, http://www.medicinescomplete.com/, (accessed on 12 Mar 2025)

How this guideline was developed

This guideline was published in 2025. The update is based on expert opinion and was authored by Dr Anna Sutherland, Chair Scottish Palliative Care Guidelines.

The author made a declaration of interest.

Consultation

The draft guideline was approved by the following organisations:

 

Editorial

As a final quality control check, the guideline was reviewed by an editorial group. The editorial group for this guideline was as follows:

Dr Roberta James

SIGN Programme Lead, Healthcare Improvement Scotland

Dr Safia Qureshi

Director of Evidence and Digital, Healthcare Improvement Scotland

Dr Angela Timoney

Chair of SIGN, Healthcare Improvement Scotland