⚠ ANGIOEDEMA – Life-Threatening Reaction#

Angioedema involving the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients receiving ACE inhibitors, including lisinopril, at any time during treatment. Angioedema can occur with the first dose and can progress to life-threatening airway obstruction. Patients with involvement of the tongue, glottis, or larynx are at particular risk for airway obstruction, especially those with prior airway surgery. ACE inhibitors are associated with a higher rate of angioedema in Black than in non-Black patients. Fatalities have been reported. Manufacturer notes: Discontinue lisinopril immediately and provide appropriate emergency therapy including epinephrine 1:1000 solution (0.3-0.5 mL subcutaneous) and measures to ensure patent airway.

⚠ ANGIOEDEMA – Life-Threatening Reaction#

Angioedema involving the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients receiving ACE inhibitors, including lisinopril, at any time during treatment. Angioedema can occur with the first dose and can progress to life-threatening airway obstruction. Patients with involvement of the tongue, glottis, or larynx are at particular risk for airway obstruction, especially those with prior airway surgery. ACE inhibitors are associated with a higher rate of angioedema in Black than in non-Black patients. Fatalities have been reported.Manufacturer notes: Discontinue lisinopril immediately and provide appropriate emergency therapy including epinephrine 1:1000 solution (0.3-0.5 mL subcutaneous) and measures to ensure patent airway.

⚠ INTESTINAL ANGIOEDEMA#

Intestinal angioedema has been reported in ACE inhibitor-treated patients presenting with abdominal pain (with or without nausea or vomiting). In some cases, there was no prior history of facial angioedema and C-1 esterase inhibitor levels were normal. Diagnosis has been made via abdominal CT scan, ultrasound, or at surgery. Symptoms resolved after discontinuation of the ACE inhibitor.

⚠ ANAPHYLACTOID REACTIONS DURING DIALYSIS#

Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes (e.g., AN69®) and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines. Consider using a different dialysis membrane or different antihypertensive class in ACE inhibitor-treated dialysis patients.

⚠ HYPERKALEMIA – Dangerous Potassium Elevation#

Serum potassium greater than 5.7 mEq/L occurred in approximately 2.2% of hypertensive patients and 4.8% of heart failure patients treated with lisinopril. Hyperkalemia can cause serious, sometimes fatal, cardiac arrhythmias. Risk factors include renal insufficiency (creatinine clearance <30 mL/min), diabetes mellitus, and concomitant use of potassium-sparing diuretics (spironolactone, amiloride, triamterene), potassium supplements, or potassium-containing salt substitutes. Monitor serum potassium periodically, especially in patients with renal impairment or diabetes. Advise patients not to use salt substitutes without physician consultation.

⚠ RENAL FUNCTION IS CRITICAL – CAN CAUSE ACUTE RENAL FAILURE#

Lisinopril is not metabolized; entirely renin-dependent elimination. Renal impairment increases drug accumulation and hyperkalemia risk. Dose adjustment essential for GFR <30 mL/min. Monitor creatinine and potassium. Patients whose renal function depends on the activity of the renin-angiotensin system are at particular risk, including those with: renal artery stenosis (unilateral or bilateral), chronic kidney disease, severe congestive heart failure, post-myocardial infarction state, or volume depletion.

⚠ SYMPTOMATIC HYPOTENSION – Severe Blood Pressure Drop#

Excessive hypotension (blood pressure drop) can occur, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Patients at risk of excessive hypotension include those with: heart failure with systolic blood pressure <100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high-dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion. Drug is generally not recommended to be initiated in acute MI patients at risk of further hemodynamic deterioration after vasodilator therapy (e.g., systolic BP ≤100 mmHg) or cardiogenic shock. In heart failure patients, dose adjustment or diuretic reduction may be necessary.

⚠ AGRANULOCYTOSIS & BONE MARROW DEPRESSION#

Another ACE inhibitor (captopril) has been shown to cause agranulocytosis (severe reduction in white blood cells) and bone marrow depression, particularly in patients with renal impairment or collagen vascular disease. Available data are insufficient to show that lisinopril does not have a similar risk. Cases of leukopenia and neutropenia have been reported with lisinopril marketing experience. Periodic monitoring of white blood cell counts is advisable in patients with collagen vascular disease and renal disease, particularly at the beginning of therapy. Patients should report any signs of infection (fever, sore throat).

⚠ HEPATIC FAILURE & CHOLESTATIC JAUNDICE#

ACE inhibitors have been associated with a syndrome starting with cholestatic jaundice or hepatitis and progressing to fulminant hepatic necrosis and sometimes death. The mechanism is not understood. Patients receiving lisinopril who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug immediately and receive appropriate medical supervision.