People who take a commonly prescribed class of heart and blood-pressure medication have been warned about a dangerous side effect that can appear months or even years after they first take the drug.

ACE inhibitors are widely prescribed for conditions including high blood pressure, heart failure, recovery following a heart attack, diabetic kidney disease and the prevention of cardiovascular problems.

The patient information leaflets supplied with the tablets - including ramipril, lisinopril, enalapril and perindopril - will soon include strengthened warnings about the risk of delayed-onset angioedema.

Angioedema causes swelling in the deeper layers beneath the skin or in the tissues lining parts of the body. In patients taking ACE inhibitors, it has been seen to develop weeks, months or even years after treatment begins.

There are two different forms of angioedema. One is caused by an allergic reaction involving histamine, while the other is caused by a build-up of a substance called bradykinin.

The bradykinin-related form usually develops without an itchy rash or hives and may come on more slowly than an allergic reaction, causing the lips, tongue, face or throat to swell.

Either type can be fatal if the swelling blocks the airway.

The guidance, issued by the Medicines and Healthcare products Regulatory Agency (MHRA), also reminds doctors that the two types are distinct and require different treatments.

It reads: 'ACE inhibitors: Be aware of the distinction between bradykinin- and histamine-mediated angioedema, as treatment strategies differ significantly.

'The product information for all ACE inhibitors is being updated to strengthen the warnings on the risk of delayed-onset angioedema, which may still occur after weeks to years of use.

'Healthcare professionals, particularly in emergency departments, should be aware of the potential for delayed onset of angioedema and the distinction between bradykinin- and histamine-mediated cases, as treatment strategies differ significantly and bradykinin-mediated angioedema does not respond to standard treatment.'

The MHRA updated its advice after reviewing reports submitted through the UK Yellow Card scheme up to 10 June 2026.

The review found that around half of cases with a recorded time of onset developed at least 30 days after treatment began.

Information supplied by manufacturers suggested that approximately 20 to 30 per cent of reported cases occurred after patients had taken the medicine for a month or longer.

Delayed reactions are more commonly associated with bradykinin-related angioedema. Although deaths are rare, fatal cases have occurred when the swelling blocked the airway, including among people who had been taking ACE inhibitors for a long time.

Published research has recorded cases developing anywhere from several weeks to many years after treatment began.

Bradykinin-related angioedema does not reliably improve with standard treatments for a severe allergic reaction, such as adrenaline. 

Doctors should consider this form of the condition when the usual treatments do not work.

Ramipril is one of the most commonly prescribed medicines in the UK, with tens of millions of NHS prescriptions issued each year.

It is estimated to be among the five most commonly prescribed drugs in the health service.

ACE inhibitor-related angioedema is uncommon or rare, but some people may face a higher risk. These include older adults, women, smokers and people of Black or African-Caribbean heritage.

Anyone suspected of developing angioedema while taking an ACE inhibitor should stop taking the medicine immediately and must not restart it.