MHRA Drug Safety Update: ACE-inhibitors

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.

ACE inhibitors are indicated for the treatment of hypertension, heart failure, post-myocardial infarction management, diabetic nephropathy, and cardiovascular risk reduction.

Angioedema is characterised by localised swelling of subcutaneous or submucosal tissues. Unlike histamine-mediated (allergic) angioedema, bradykinin-mediated angioedema usually occurs without urticaria and typically has a slower onset. Symptoms may involve the tongue, lips, and upper airway, and can be life-threatening.

Although uncommon or rare, ACE inhibitors are associated with both histamine-mediated and bradykinin-mediated angioedema. Certain populations, including older adults, women, people who smoke and patients of Black  or African Caribbean ethnicity, may be at increased risk of angioedema.

Advice for Healthcare Professionals

• angioedema is a known uncommon or rare side-effect of ACE inhibitor treatment. This can either be allergic (histamine-mediated) or less commonly non-allergic (bradykinin-mediated). Healthcare professionals should consider bradykinin-mediated mechanisms as a cause when standard anaphylaxis treatment is ineffective
• angioedema can occur at any time during treatment, including after weeks to years of use
• swelling of the tongue, lip, face, or larynx which may cause difficulty in breathing or swallowing may progress and can lead to airway compromise. Other symptoms can include gastrointestinal pain and cramps^{[footnote 1]}
• bradykinin-mediated angioedema is unlikely to respond to standard anaphylaxis treatments including adrenaline (epinephrine)
• lack of response to standard anaphylaxis treatments should prompt consideration of bradykinin-mediated angioedema, with treatment informed by clinical protocols
• if angioedema is suspected in a patient taking an ACE inhibitor, discontinue the ACE inhibitor immediately and do not restart

Advice for Healthcare Professionals to Provide to Patients

• although uncommon or rare, angioedema (swelling of the face, lips, tongue, or throat) can occur at any time while taking an ACE inhibitor, even if you have been taking it for a long period without problems
• seek urgent medical attention if you develop swelling of the face, lips, tongue, or throat, or experience difficulty breathing or swallowing whilst taking ACE inhibitors
• do not take further doses of your ACE inhibitor if angioedema is suspected and inform a healthcare professional immediately
• inform healthcare professionals if you have ever experienced angioedema, including while taking an ACE inhibitor.  Please be aware that angioedema can occur for other reasons, and a healthcare professional may still recommend an ACE inhibitor for you in these instances

For further details, please view the full Drug Safety Update here.