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 Adverse Cases

Back Reported Adverse Drug Reaction Cases
Angioedema - still a problem with ACE inhibitors

Of the over 7,000 reports of angioedema received by ADRAC since 1970, ACE inhibitors account for 916 (12.6%). Angioedema may present with acute onset of soft-tissue swelling of part or all of the face (periorbital, peri-oral, lips), tongue, pharynx and neck. Oedema of the gastrointestinal tract resulting in attacks of abdominal pain, vomiting and diarrhoea has also been rarely reported with ACE inhibitors.1 Angioedema can be life-threatening, and may require prompt parenteral administration of adrenaline if the airway is compromised. The cause may not always be obvious as the first occurrence may be after months or even years of ACE inhibitor therapy. Angioedema may also occur episodically with long symptom-free intervals.

In a case recently reported to ADRAC, an elderly female who had been taking ramipril for a year without adverse effect experienced several episodes of unilateral swelling of the face, lips, jaw line and cheek each lasting 2-3 days over a 4-month period. She made a complete recovery after withdrawal of ramipril. In another case, the patient had 20 episodes of angioedema in 12 months before an association was made with perindopril.

ADRAC first advised of the risk of angioedema with ACE inhibitors in 19932 and noted its occurrence with angiotensin II antagonists in 1999.3 ADRAC now has 119 reports with angiotensin II antagonists. With ACE inhibitors the reaction is thought to be associated with potentiation of bradykinin, causing increased vascular permeability and vasodilation.4 The mechanism with the angiotensin II antagonists is unclear but it has also been postulated to be by bradykinin activation.4,5 Individuals with a history of angioedema with ACE inhibitors may occasionally develop it with an angiotensin II antagonist as well.4,5

  1. Chase MP, Fiarman GS, Scholz FJ, MacDermott RP. Angioedema of the small bowel due to an angiotensin-converting enzyme inhibitor. J Clin Gastroenterology 2000;31:254-7.
  2. Angioedema. Aust Adv Drug Reactions Bull 1993;12:3.
  3. Angiotensin II receptor antagonists - new drugs with some old problems and some new problems. Aust Adv Drug Reactions Bull 1999;18:2.
  4. Howes LG, Tran D. Can angiotensin receptor antagonists be used safely in patients with previous ACE inhibitor-induced angioedema. Drug Safety 2002;25:73-6.
  5. Abdi R, Dong VM, Lee CJ, Ntoso KA. Angiotensin II receptor blocker-associated angioedema: on the heels of ACE inhibitor angioedema. Pharmacotherapy 2002;22:1173-5.
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Australian Adverse Drug Reactions Bulletin
Volume 24, Number 2, April 2005
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