The P-I-E-N-O Parkinsn's List Drug Database
enalapril /EnalaprillatTM , VasotecTM
ANTIHYPERTENSIVE:
ACE Inhibitor:
Description: Enalapril is an oral and parenteral angiotensin- converting enzyme (ACE) inhibitor used in the treatment of hypertension and congestive heart failure. It has become a first- line agent for treating heart failure due to its proven reduction of mortality, and, in November 1993, it was approved for use in the early stages of heart failure to slow progression of the disease. Enalapril is longer-acting than captopril but shorter-acting than other ACE inhibitors and is usually dosed twice daily when given orally. In some patients, once-daily dosing may be acceptable. Neither enalapril nor enalaprilat contains a sulfhydryl group, which has implications regarding the drug's adverse reaction profile. Enalapril was originally approved by the FDA in December 1985. Its patent will expire in February 2000.
Mechanism of Action: Enalapril competes with the natural substrate, angiotensin I, thereby inhibiting its conversion to angiotensin II. Angiotensin II is a potent vasoconstrictor and a negative feedback mediator for renin activity. Thus, when enalapril lowers angiotensin II plasma levels, blood pressure decreases and plasma renin activity increases. In addition, baroreceptor reflex mechanisms are stimulated in response to the fall in blood pressure.
ACE-inhibiting drugs can act locally to reduce vascular tone by decreasing local angiotensin II-induced sympathetic and/or vasoconstrictive activity. ACE inhibitors also can inhibit presynaptic norepinephrine release and postsynaptic adrenergic receptor activity, decreasing vascular sensitivity to vasopressor activity; however, this action may not be clinically evident at usual doses. Decreases in plasma angiotensin II levels also reduce aldosterone secretion, with a subsequent decrease in sodium and water retention.
Enalapril causes arterial dilation, thereby lowering total peripheral vascular resistance. In hypertensive patients, blood pressure is decreased with little or no change in heart rate, stroke volume, or cardiac output. However, in patients with heart failure, enalapril increases cardiac output, cardiac index, stroke volume, and exercise tolerance. The drug also decreases pulmonary wedge pressure, pulmonary vascular resistance, and mean arterial and right atrial pressures in these patients.
Pharmacokinetics: Enalapril is administered orally and parenterally. Enalapril is rapidly absorbed from the GI tract following oral administration. The oral formulation is a prodrug requiring hepatic conversion to generate the more potent metabolite enalaprilat. After oral administration, noticeable cardiovascular effects begin within 1 hour, but maximum effects are delayed due to the necessary metabolic conversion. The parenteral formulation consists solely of the active moeity, enalaprilat.
The distribution pattern of enalapril is not clear, but it does not seem to cross the blood-brain barrier. Both parent and its metabolite are excreted in the urine and the feces; thus half- life is dependent upon renal function. In patients without renal disease, the half-life of enalaprilat is 11 hours. Heart failure and hepatic disease may also prolong the elimination of enalaprilat.
CONTRAINDICATIONS/PRECAUTIONS: Several dozen cases of ACE inhibitor-related fetal and neonatal death have been reported. ACE inhibitors are classified as FDA category C during the first trimester of pregnancy. Risk appears to increase during the second and third trimesters and ACE inhibitors are then considered category D drugs. Every effort should be made to discontinue ACE inhibitors whenever pregnancy is discovered. Enalapril therapy can cause neutropenia or agranulocytosis, and patients who have renal disease, are receiving concomitant immunosuppression, or have collagen-vascular disease or autoimmune disease are at an increased risk of developing this complication. Complete blood counts should be established before and during enalapril therapy when the drug is administered to these patient populations. Enalapril should be used with caution in patients with pre-existing bone marrow depression. The dose of enalapril should be adjusted in patients with renal impairment.
Hypotension can occur if enalapril is administered to patients with hypovolemia or hyponatremia, or to patients receiving diuretics or other antihypertensives. Enalapril should be used cautiously in patients with congestive heart failure (initial doses should be lower than in the treatment of hypertension) because of a greater risk of developing hypotension. Hypotension may aggravate ischemia in patients with coronary artery disease or cerebrovascular disease precipitating a myocardial infarction or cerebrovascular accident.
Patients with renal artery stenosis should not receive enalapril or therapy with any other ACE inhibitor. Because affected kidneys depend on the renin-angiotensin system to maintain GFR, inhibition of the mechanism can lead to renal failure. (Note that enalapril is used therapeutically in the treatment of other types of renal disease.) The dose of enalapril should be adjusted in patients with renal impairment.
Enalapril is a prodrug and its conversion to its active metabolite may be decreased in patients with hepatic disease. Monitoring and dosage adjustments may be necessary in patients with hepatic impairment.
Enalapril should be used with caution patients with hyperkalemia. ACE inhibitors can elevate serum potassium concentrations and could worsen pre-existing condition. Hyperkalemia is associated with serious cardiac arrhythmias.
Enalapril therapy can produce angioedema, which can be fatal. Enalapril is contraindicated in patients with a history of ACE inhibitor-induced angioedema, hereditary angioedema, or idiopathic angioedema.
DRUG INTERACTIONS: Antihypertensive agents or diuretics can enhance the effects of enalapril if given concomitantly. This additive effect can be desirable, but dosages must be adjusted accordingly. Hyponatremia or hypovolemia predispose patients to developing reversible renal insufficiency when enalapril and diuretic therapy are given concomitantly.
Enalapril decreases aldosterone secretion, leading to small increases in serum potassium levels. Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, potassium salts, and heparin, should be given cautiously to patients receiving enalapril.
Nonsteroidal antiinflammatory drugs (NSAIDs) may or may not interact with a given ACE inhibitor. While NSAIDs reduce the antihypertensive activity of captopril, this interaction has not been verified with enalapril. Nonetheless, patients should be monitored for loss of ACE inhibitor activity if an NSAID is added.
Enalapril can decrease the renal elimination of lithium, which can lead to lithium toxicity. Plasma lithium concentrations should be measured carefully during concomitant enalapril therapy.
ADVERSE REACTIONS: Neutropenia, agranulocytosis, pancytopenia, and aplastic anemia are infrequent but serious adverse effects associated with enalapril. These reactions are more common in patients with impaired renal function or collagen vascular disease and in those receiving immunosuppressive therapy. Complete blood counts should be done regularly during the first several months of therapy.
Renal function may decrease during enalapril treatment, but this effect is usually reversible if therapy is discontinued. Renal insufficiency (e.g. azotemia) may be related to hypovolemia, hyponatremia, or preexisting renal artery stenosis. In patients with renal artery stenosis, enalapril therapy must be held. In patients who are either hypovolemic or hyponatremic, correction of these abnormalities may correct the renal dysfunction. Although rare, serious renal effects include ischemic renal tubular necrosis and glomerulonephritis.
Hypotension occurs in about 1-2% of patients receiving enalapril for hypertension, and in about 5-7% of patients receiving the drug for congestive heart failure. Hypotensive symptoms have required discontinuance of enalapril in 2% of patients receiving the drug for congestive heart failure. Hypotension is generally well tolerated but can cause such symptoms as orthostatic hypotension, dizziness, fatigue, headache, syncope, sinus tachycardia, and lightheadedness.
ACE inhibition can result in the accumulation of kinins in the respiratory tract, sometimes causing a persistent, nonproductive cough. This cough may occur more frequently in patients with chronic obstructive pulmonary disease and is often overlooked as a potential adverse effect of enalapril therapy. Dyspnea and bronchospasm also have been reported rarely during enalapril therapy.
Patients receiving drugs that can increase serum potassium, or patients with congestive heart failure or impaired renal function, may be at an increased risk for developing hyperkalemia during enalapril therapy (see Drug Interactions).
The frequency of maculopapular rash may be less with enalapril than with captopril, but rash does occur. Angioedema has occurred in 0.6% of patients receiving enalapril; if it evolves to laryngeal edema, it can be fatal.
PATIENT INFORMATION:
What do enalapril tablets do?
Enalapril (VasotecTM ) is an antihypertensive (blood pressure lowering agent) known as an ACE inhibitor. Enalapril controls high blood pressure (hypertension) by relaxing blood vessels; it is not a cure. High blood pressure levels can damage your kidneys, and may lead to a stroke or heart failure. Enalapril also helps to treat patients with congestive heart failure (heart does not pump strongly enough). Generic enalapril tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take enalapril?
They need to know if you have any of these conditions:
How should I take this medicine?
Take enalapril tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking enalapril except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses. If you take only one dose a day and forget to take it that day, do not take a double dose the next day.
What other medicines can interact with enalapril?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines. What side effects may I notice from taking enalapril?
Serious side effects with enalapril include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with enalapril include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take enalapril?
Visit your doctor for regular checks on your progress. Check your blood pressure regularly while you are taking enalapril. Ask your doctor what your blood pressure should be and when you should contact him or her. Call your doctor if you notice an uneven or fast heart beat. Do not treat yourself for a fever or sore throat; check with your doctor as these may be the result of an enalapril side effect.
Check with your doctor if you get an attack of severe diarrhea, nausea and vomiting, or sweat a lot. The loss of body fluid can make it dangerous to take enalapril.
You may get dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how enalapril affects you. To avoid dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older person. Alcohol can make you more dizzy. Avoid alcoholic drinks.
If you are going to have surgery, tell your doctor or dentist that you are taking enalapril.
Avoid salt substitutes or other foods or substances high in potassium salts.
Do not treat yourself for coughs, colds, or pain while you are taking enalapril without asking your doctor or pharmacist for advice.
If you are diabetic enalapril may affect your blood sugar, and cause hypoglycemia (low blood sugar). Check with your doctor before changing the dose of your diabetic medicine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature below 30C (86F). Protect from moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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