Risk of Angioedema with Olmesartan

Olmesartan carries a low but definite risk of angioedema, which is documented in its FDA drug label as a post-marketing adverse event. 1

Overview of Angioedema Risk with ARBs

Angioedema is listed as a post-marketing adverse event for olmesartan in the FDA drug label, though it occurs less frequently than with ACE inhibitors 1
While ARBs like olmesartan were developed partly to avoid the angioedema risk associated with ACE inhibitors, they can still cause angioedema through alternative pathways 2
The 2017 ACC/AHA hypertension guidelines acknowledge that ARBs can cause angioedema, though they are generally considered safer alternatives for patients who experienced angioedema with ACE inhibitors 3

Unlike ACE inhibitors, which directly increase bradykinin levels (a primary cause of angioedema), ARBs like olmesartan may cause angioedema through secondary stimulation of angiotensin II AT2 receptors, which can increase tissue bradykinin 2
Risk factors that may increase the likelihood of angioedema with olmesartan include:
- History of previous angioedema with any medication 1
- Black race (higher risk noted in studies of ARB-induced angioedema) 4, 5
- Renal impairment (observed in case reports with other ARBs) 4

Olmesartan-induced angioedema typically presents as swelling of the face, neck, and lips 2
Onset can be delayed - in a published case report, angioedema occurred 10 days after initiation of olmesartan therapy 2
Symptoms typically resolve within days after discontinuation of the medication 2

ACE inhibitors have a higher incidence of angioedema (occurs in fewer than 1% of patients but more frequent in blacks) compared to ARBs 3
ARBs like olmesartan are often considered as alternatives for patients who experienced angioedema with ACE inhibitors, but should be used with caution 3
Guidelines state: "Patients with a history of angioedema with an ACE inhibitor can receive an ARB beginning 6 weeks after ACE inhibitor is discontinued" 3

Do not use olmesartan in patients with a history of angioedema with any ARB 3
For patients who develop angioedema while taking olmesartan:
- Immediately discontinue the medication 2
- Monitor for airway compromise, as angioedema can be life-threatening 5
- Consider alternative antihypertensive classes such as calcium channel blockers, thiazide diuretics, or beta-blockers 3
If a patient has experienced angioedema with an ACE inhibitor but requires RAAS blockade, an ARB like olmesartan may be considered after a 6-week washout period, but with careful monitoring 3

A common pitfall is assuming ARBs are completely safe alternatives for patients with ACE inhibitor-induced angioedema 5
Olmesartan-induced angioedema can occur in ACE inhibitor-naïve patients 2
Delayed onset of angioedema is possible with olmesartan, so vigilance should continue beyond the initial days of therapy 2
Recurrent episodes of angioedema can occur if the medication is not discontinued after the initial event 5