Angiooedema and urticaria with angiotensin converting enzyme inhibitors

To review reports of angiooedema and urticaria associated with angiotensin converting enzyme inhibitors (ACEI) in the New Zealand Centre for Adverse Reactions Monitoring and Intensive Medicines Monitoring Programme (IMMP) database.

Adverse reaction reports describing angiooedema and/or urticaria between April 1981 and December 1994 were examined. Captopril, enalapril and lisinopril were intensively monitored on the IMMP during this period.

Of a total of 116 reports there were 68 reports of angiooedema and 37 of urticaria alone and 11 where angiooedema and urticaria occurred in the same patient. The total number of patients is unknown, but cohorts of patients on captopril, enalapril and lisinopril in the IMMP were 16342, 25686 and 11235, totalling 53263 patients. There were 63 reports of angiooedema/urticaria in patients monitored on the IMMP, giving a reported rate of 1.2/1000 (0.9-1.5). Forty seven reactions occurred between 3 weeks and 4 years after commencement of therapy. Severe angiooedema occurred in 9 patients with early-onset angiooedema and 6 with late-onset angiooedema. There were no deaths. Seventeen patients had up to 12 episodes before diagnosis. Angiooedema/ urticaria occurred without gender preference. Although a dose relationship was not apparent, 3 patients developed angiooedema or urticaria after an increase in dose.

Although reactions are more common shortly after initiation of ACEI therapy, late onset reactions may be less well recognised. Clinicians should be reminded, and ACEI data sheets should emphasise, that onset may be delayed for weeks or months, that patients may have multiple episodes with long symptom free intervals, and that angiooedema may occur with or without urticaria.