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Delayed-onset angioedema is a known uncommon or rare side-effect of angiotensin-converting enzyme (ACE) inhibitor treatment, and healthcare professionals should consider bradykinin-mediated mechanisms as a cause when standard anaphylaxis treatment is ineffective, the Medicines and Healthcare products Regulatory Agency (MHRA) has warned.
In a drug safety update issued on 17 June 2026, the MHRA told clinicians that ACE inhibitors should be discontinued immediately if angioedema — which can present as swelling of the tongue, lip, face or larynx, or gastrointestinal pain and cramps — is suspected in a patient taking an ACE inhibitor.
Older adults, women, people who smoke and patients of Black or African Caribbean ethnicity may be at increased risk of angioedema, which carries a risk of life-threatening airway complications, the MHRA said.
It added that angioedema can either be allergic (i.e. histamine-mediated) or less commonly non-allergic (i.e. bradykinin-mediated) and can occur at any time during ACE inhibitor treatment, including after weeks to years of use.
The agency continued that ACE inhibitors are a leading cause of bradykinin-mediated angioedema, which usually occurs without urticaria (i.e. hives) and typically has a slower onset than histamine-mediated angioedema.
Bradykinin-mediated angioedema is unlikely to respond to standard anaphylaxis treatments, including adrenaline (i.e. epinephrine), it said. The MHRA highlighted that if this happens, clinicians should consider treatment for bradykinin-mediated angioedema, in line with clinical protocols.
Current clinical guidance for bradykinin-mediated angioedema emphasises prompt discontinuation of the ACE inhibitor, close airway monitoring and early specialist involvement in severe or life-threatening cases, the MHRA said.
It also said that additional investigations, such as C4 level testing, may support identification of non-allergic causes and help guide management.
According to the drug safety update, clinicians should advise patients that although uncommon or rare, angioedema can occur at any time while taking an ACE inhibitor, even if they had been taking it for a long period without problems.
Patients should also inform healthcare professionals if they have ever experienced angioedema, including while taking an ACE inhibitor, it said. Although the drug safety update noted that if angioedema had occurred for another reason, patients may still be prescribed an ACE inhibitor.
Gurvinder Najran, pharmacist at the Dudley Primary Care Network (PCN), told The Pharmaceutical Journal: “The drug safety alert will improve awareness and management of delayed angioedema risks associated with ACE inhibitors.
“Pharmacists are essential in educating patients about these risks during consultations and medication reviews. Given that around 50% of cases occur 30 or more days after starting treatment [according to UK Yellow Card data], increased awareness is crucial. As a PCN pharmacist, I have seen delayed angioedema cases, and this alert will significantly enhance patient safety by facilitating timely interventions.”
Kate Ryan, patient safety manager at the Royal College of Pharmacy, commented: “[Pharmacists should] underline the importance of identifying the cause when standard anaphylaxis treatment is ineffective, so patients can receive the right care.”
