Impaired Renal Function: APO-ENALAPRIL (enalapril maleate) should be used with caution in patients with renal insufficiency as they may require reduced or less frequent doses (See Dosage & Administration). Close monitoring of renal function during therapy should be performed as deemed appropriate in those with renal insufficiency. In the majority, renal function will not alter, or may improve.
Renal failure has been reported in association with enalapril, mainly in patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis. If recognized promptly and treated appropriately, renal failure, when associated with enalapril therapy, is usually reversible.
Some hypertensive patients, with no apparent preexisting renal disease, have developed increases in blood area and creatinine when enalapril has been given concurrently with in diuretic. Dosage reduction and/or discontinuation of the diuretic and/or APO-ENALAPRIL may be required.
Renal function should be assessed before initiating therapy with APO-ENALAPRIL.
Hemodialysis Patients: Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (eg: polyacrylonitrile (PAN) and treated concomitantly with an ACE inhibitor. Dialysis should be stopped immediately if symptoms such as nausea, abdominal cramps, burning, angioedema, shortness of breath and severe hypotension occur. Symptoms are not relieved by antihistamines. In these patients, considerations should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.
Hyperkalemia: Elevated serum potassium (greater than 5.7 mEq/L) was observed in approximately one percent of hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in 028% of hypertensive patients. Risk factors for the development of hyperkalemia may include renal insufficiency, diabetes mellitus, and the concomitant use of agents to treat hypokalemia (See Adverse Reactions).
Valvular Stenosis: There is a concern on theoretical grounds that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction.
Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, enalapril blocks angiotensin II formation, secondary to compensatory renin release. If hypotension occurs an is considered to be due to this mechanism, it can be corrected by volume expansion.
Patients with Impaired Liver Function: Hepatitis (hepatocellular and/or cholestatic) elevations of liver enzymes and/or serum bilirubin have occurred during therapy with enalapril in patients with or without pre-existing liver abnormalities. In most cases the changes were reverse on discontinuation of the drug.
Should the patient receiving enalapril experience any unexplained symptoms (See Patient Counselling Information), particularly during the first weeks or months of treatment, it is recommended that a full set of liver function tests and any other necessary investigation be carried out. Discontinuation of enalapril should be conside red when appropriate.
There are no adequate studies in patients with cirrhosis and/or other liver dysfunction. Enalapril should be used with particular caution in patients with pre-existing liver abnormalities. In such patients, baseline liver function tests should be obtained before administration of the drug and close monitoring of response and metabolic effects should apply.
Cough: A dry, persistent cough, which usually disappears only after withdrawal or lowering of the dose of enalapril has been reported. Such possibility should be considered as part of the differential diagnosis of the cough.
Nursing Mothers: In rats, it has been shown that enalapril is excreted in milk.
It is not known whether this drug is excreted in human milk. Caution should be exercised when enalapril is administered to a nursing mother and in general, nursing should be interrupted.
Pediatric Use: Enalapril has not been studied in children and therefore, use in this age group is not recommended.