Use with caution in unstented unilateral/bilateral renal artery stenosis (this use is generally avoided due to elevated risk of deterioration in renal function, unless possible benefits outweigh risks). A rare toxicity associated with ACEIs includes cholestatic jaundice, which may progress to fulminant hepatic necrosis. Angioedema may occur rarely with ACEIs, and may involve head and neck or intestine (African-Americans and patients with idiopathic or hereditary angioedema may be at increased risk). Use in previous angioedema associated with ACEI therapy contraindicated. A dry, hacking, nonproductive cough usually occurs within first few months of treatment and should generally resolve within 1-4 weeks after discontinuation of ACEI. Use with caution in pre-existing renal insufficiency. Dosage adjustments needed in hepatic cirrhosis. Another ACEI, captopril, associated with rare cases of agranulocytosis, neutropenia or leukopenia with myeloid hypoplasia. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease are at even higher risk of developing neutropenia. Hyperkalemia may occur with ACEIs (use cautiously, if at all, with these agents). Anaphylactic/anaphylactoid reactions can occur with ACEIs. Rare cases of anaphylactoid reactions reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACEIs. Use with caution in hypertrophic cardiomyopathy and outflow tract obstruction (reduction in afterload may worsen symptoms). Symptomatic hypotension with or without syncope can occur with ACEIs; effects most often observed in volume-depleted patients. Trandolapril may be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow whose glomerular filtration rate is dependent on efferent arteriolar vasoconstriction by angiotensin II. Use with caution in severe aortic stenosis (may reduce coronary perfusion resulting in ischemia), in ischemic heart disease or cerebrovascular disease (due to potential consequences posed by falling blood pressure), in collagen vascular disease, especially with concomitant renal impairment (may be at increased risk for hematologic toxicity), and before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACEIs perioperatively will blunt angiotensin II formation and may result in hypotension.