The South African Health Products Regulatory Authority (SAHPRA) has issued an alert to healthcare professionals of the risk of angioedema during treatment with angiotensin-converting enzyme (ACE) inhibitors (e.g, captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, trandolapril).
It warned that treatment should be stopped and should never be reintroduced in the event of an initial occurrence of ACE inhibitor-induced angioedema: prescribing/dispensing error may result in inadvertent re-exposure, which can be potentially fatal.
To minimise the risk of re-exposure, doctors should record and communicate a patient’s previous ACE inhibitor-induced angioedema, and initiate appropriate alternative antihypertensive treatment, where clinically indicated, it advised.
ACE inhibitors – for the treatment of essential hypertension, renovascular hypertension, asymptomatic left ventricular dysfunction and heart failure – prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in vasodilation and reduction in blood pressure.
ACE also plays an important role in the degradation of bradykinin, a vasodilator. Inhibition of ACE therefore results in increased bradykinin levels, which may cause angioedema in susceptible individuals.
ACE-inhibitor associated angioedema may also be histamine-related. Importantly, angioedema can occur at any time during the treatment, including after weeks to years of use.
It might involve the face, extremities, lips, tongue, glottis and/or larynx – involvement of the tongue and upper airway is particularly concerning because it can result in airway obstruction and be life-threatening.
Differences to note
There are importnat differences 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, alternative measures should be considered to support ventilation.
Effective treatments have included bradykinin B2 receptor antagonists e.g, icatibant, marketed as Firazyr(r) in South Africa, and plasma kallikrein inhibitors, which are not registered in South Africa.
Patients prescribed ACE inhibitors should be counselled about the risk of angioedema, including its potential to cause life-threatening airway obstruction, and warned about early recognition of symptoms and the need to seek urgent medical attention, particularly if swelling of the lips, tongue, mouth or throat occurs.
Suspected adverse drug reactions (ADRs), including ACE inhibitor-induced angioedema, should be reported to SAHPRA, using the Med Safety App, or through SAHPRA’s eReporting system via the website or by completing an ADR reporting form.
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