Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: Risk of Serious and Fatal Outcomes

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19 Aug Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: Risk of Serious and Fatal Outcomes

Posted at 20:48h in Safety Alerts 1 by Ntokozo Msiza

19 August 2026

The South African Health Products Regulatory Authority (SAHPRA) wishes to remind healthcare professionals of the risk of angioedema during treatment with angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, trandolaprim). remind healthcare professionals are reminded that ACE inhibitor treatment should be stopped and should never be reintroduced following an initial occurrence of ACE inhibitor-induced angioedema in a patient. A prescribing/dispensing error may result in inadvertent re-exposure which can be potentially fatal. Therefore, to minimise the risk of re-exposure, healthcare professionals should carefully record and communicate a patients’ previous ACE inhibitor induced angioedema. Appropriate alternative antihypertensive treatment should be initiated, where clinically indicated.

BACKGROUND

ACE inhibitors are a class of medicines indicated for the treatment of essential hypertension, renovascular hypertension, asymptomatic left ventricular dysfunction and heart failure. This class of medicines prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This results in vasodilation and reduction in blood pressure. ACE also plays an important role in the degradation of bradykinin which is a vasodilator. Inhibition of ACE therefore results in increased bradykinin levels, which may cause angioedema in susceptible individuals. ACE-inhibitor associated angioedemamay also be histamine-related. Importantly, angioedema can occur at any time during ACE-inhibitor treatment, including after weeks to years of use.

Angioedema due to ACE inhibitors may involve the face, extremities, lips, tongue, glottis and/or larynx. Involvement of the tongue and upper airway is of particular concern because it can result in airway obstruction and may be life-threatening.

ADVICE TO HEALTHCARE PROFESSIONALS

Healthcare professionals should be aware of the difference between bradykinin and histamine mediated angioedema. Bradykinin mediated angioedema does not present with urticaria or skin rash. Bradykinin mediated angioedema may not respond to standard anaphylaxis treatments such as adrenaline, antihistamines, and glucocorticoids. Thus, if a patient develops angioedema that does not respond to antihistamines and adrenaline, healthcare professionals should consider alternative measures to support ventilation. Effective treatment plans have included the use of bradykinin B2 receptor antagonists e.g., icatibant, marketed as Firazyr® in South Africa, and plasma kallikrein inhibitors, which are not registered in South Africa.

ADVICE FOR HEALTHCARE PROFESSIONALS TO PROVIDE TO PATIENTS

Patients prescribed ACE inhibitors should be counselled about the risk of angioedema, including its potential to cause life-threatening airway obstruction. Counselling should emphasise early recognition of symptoms and the need to seek urgent medical attention, particularly if swelling of the lips, tongue, mouth or throat occurs.

REPORT SUSPECTED ADVERSE DRUG REACTIONS

Healthcare professionals and members of the public are urged to report suspected adverse drug reactions (ADRs), including ACE inhibitor-induced angioedema, to SAHPRA. It is important to report all suspected cases to SAHPRA, even when a causal relationship has not been established.

Report conveniently using the Med Safety App

The Med Safety App provides a simple and convenient way to report suspected adverse reactions directly to SAHPRA. Download the app from Google Play or the Apple App Store and submit your report using your mobile device.

Other reporting options

Suspected ADRs can also be reported through SAHPRA’s eReporting system via the SAHPRA website or by completing an ADR reporting form and emailing it to adr@sahpra.org.za.

Report suspected ADRs, even when a causal relationship has not been established. Every report contributes to safer medicines.

SAHPRA remains committed to ensuring the safety of medicines available in South Africa and will update the public if new scientific evidence changes current recommendations.

REFERENCES

Klabunde RE. Angiotensin converting enzyme (ACE) inhibitors [Internet]. Cardiovascular Pharmacology Concepts; 2023 [cited 2026 Aug 13]. Available from: https://cvpharmacology.com/vasodilator/ace

Obtułowicz K. Bradykinin-mediated angioedema. Pol Arch Med Wewn. 2016;126(1-2):76-85. doi:10.20452/pamw.3273.

Agah R, Bandi V, Guntupalli KK. Angioedema: the role of ACE inhibitors and factors associated with poor clinical outcome. Intensive Care Med. 1997;23(7):793-6. doi:10.1007/s001340050413.
Day C, Mapahla L, Ribeiro M, Deetlefs M, McDougall C, Engelbrecht A, et al. Risk factors for angiotensin converting enzyme inhibitor angioedema in a South African population. Front Allergy. 2025;6:1664354. doi:10.3389/falgy.2025.1664354.