Medication Guide App

Enalapril Maleate

Pronunciation

Pronunciation: en-AL-a-pril MAL-ee-ate
Class: ACE inhibitor

Trade Names

Vasotec
- Tablets, oral 2.5 mg
- Tablets, oral 5 mg
- Tablets, oral 10 mg
- Tablets, oral 20 mg

Enalaprilat
- Injection, solution 1.25 mg/mL

Vasotec IV (Canada)

Pharmacology

Competitively inhibits angiotensin I–converting enzyme, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates release of aldosterone. Results in decreased BP, reduced sodium absorption, and potassium retention.

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Pharmacokinetics

Absorption

Bioavailability is approximately 60%. T max is within 1 h (enalapril); 3 to 4 h (enalaprilat).

Distribution

Enalapril crosses the blood-brain barrier poorly, if at all. Enalaprilat does not cross the blood-brain barrier.

Metabolism

Enalapril is a prodrug and is hydrolyzed to enalaprilat (more potent than enalapril).

Elimination

Intact enalapril and approximately 40% of the dose as enalaprilat is excreted in the urine. Approximately 94% is recovered in the urine and feces. The half-life is 1.3 h (enalapril). Enalaprilat is dialyzable.

Onset

1 h.

Peak

4 to 6 h.

Duration

At least 24 h.

Special Populations

Renal Function Impairment

In those with glomerular filtration rate (GFR) 30 mL/min or less, the peak and trough enalaprilat levels increase, T max increases, and time to steady state may be delayed. Dosage adjustment is recommended.

Children

Pharmacokinetics are consistent with those seen in adults.

Indications and Usage

PO

Treatment of hypertension; symptomatic CHF in combination with diuretics and digitalis; asymptomatic left ventricular dysfunction.

IV

Treatment of hypertension.

Unlabeled Uses

Diabetic nephropathy; Raynaud phenomenon.

Contraindications

History of angioedema related to previous treatment with an ACE inhibitor; hereditary or idiopathic angioedema; hypersensitivity to any component of the product.

Dosage and Administration

Heart Failure
Adults

PO Initial dosage is 2.5 mg twice daily. Usual dosage is 2.5 to 20 mg/day in 2 divided doses (max, 40 mg/day). Titrate doses upward as tolerated over a period of a few days or weeks. The max daily dose is 40 mg in divided doses.

Hypertension
Adults

PO Initial dosage is 2.5 mg (patients on diuretics) to 5 mg (patients not on diuretics) per day. Titrate to desired BP control. Usual maintenance dosage is 10 to 40 mg/day in a single dose or 2 divided doses.

IV 1.25 mg over a 5-min period every 6 h. For patients at high risk of excessive hypotension, the starting dose should be 0.625 mg or less administered IV over a period of 5 min or more and preferably longer (up to 1 h).

Children 1 mo to 16 y of age

PO Initial dosage is 0.08 mg/kg (up to 5 mg) once daily. Adjust dose according to BP response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients.

Left Ventricular Dysfunction
Adults

PO Initial dosage is 2.5 mg twice daily. Titrate to targeted daily dose of 20 mg in divided doses.

Renal Function Impairment
Adults

PO Titrate dosage upward until BP is controlled or until a max dosage of 40 mg/day is reached. Use an initial dosage of 5 mg/day in normal renal function and mild impairment (CrCl more than 30 mL/min); 2.5 mg/day in moderate to severe renal impairment (CrCl 30 mL/min or less); and 2.5 mg on the day of dialysis in dialysis patients (adjust dosage on nondialysis days based on BP response). For patients with heart failure and a serum creatinine more than 1.6 g/dL, initial dosage is 2.5 mg once daily. Increase to 2.5 mg twice daily, then 5 mg twice daily, and higher as needed, usually at intervals of 4 d or more if there is not excessive hypotension or significant deterioration of renal function.

IV For patients with CrCl of 30 mL/min or less, the dose is 0.625 mg. Dose may be repeated if after 1 h the clinical response is inadequate. Additional doses of 1.25 mg may be administered at 6-h intervals. For dialysis patients, the initial dose is 0.625 mg or less given over 5 min or preferably longer (up to 1 h).

General Advice

  • PO
  • Give without regard to meals. Administer with food if GI upset occurs.
  • Tablets may be mixed with Bicitra and Ora-Sweet SF , following manufacturer's guidelines, to form a suspension.
  • Shake well before measuring dose.
  • Administer prescribed dose using a cup, spoon, or syringe.
  • Injection
  • For IV administration only when oral therapy is not practical.
  • May be administered undiluted or mixed with up to 50 mL of dextrose 5% in water, normal saline, dextrose 5% in water in normal saline, or dextrose 5% in water in Ringer's lactate injection. Dilution is stable for up to 24 h at room temperature.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • Administer as a slow IV infusion over 5 min.

Storage/Stability

Store tablets and injection at 59° to 89°F. Protect tablets from moisture. Store suspension in refrigerator (36° to 46°F). Discard any unused suspension after 30 days.

Drug Interactions

Aldosterone blockers (eg, eplerenone)

Serious hyperkalemia, possibly with cardiac arrhythmias or arrest, may result from additive potassium-sparing effects. Periodic monitoring of serum potassium concentration is recommended until the effect of the aldosterone blocker is established. Dose reduction of the aldosterone blocker may be necessary to decrease potassium concentrations.

Aliskiren, potassium-containing salt substitutes, potassium preparations, potassium-sparing diuretics, trimethoprim

May increase serum potassium levels. Coadminister with caution and frequent monitoring of serum potassium. In general, avoid potassium-sparing agents in heart failure patients receiving enalapril.

Angiotensin II receptor antagonists (eg, candesartan, telmisartan)

Risk of hyperkalemia and renal dysfunction may be increased as a result of additive renal toxicity. If coadministration cannot be avoided, close monitoring of renal function and potassium plasma concentrations are warranted.

Capsaicin

Cough may be exacerbated. If cough is severe, discontinue one or both drugs.

Gold salts (eg, sodium aurothiomalate)

Risk of gold-induced nitritoid reactions may be increased. Close monitoring of patients for signs and symptoms of nitritoid reactions (facial flushing, nausea, hypotension, syncope) is warranted.

Lithium

Increased lithium levels and symptoms of lithium toxicity may occur. Frequent monitoring of lithium concentrations is warranted.

mTOR inhibitors (eg, everolimus, sirolimus)

Risk of angioedema may be increased. If an interaction is suspected, stop one or both drugs.

NSAIDs (eg, indomethacin)

Antihypertensive effects of enalapril may be decreased. Also, nephrotoxicity associated with enalapril or NSAIDs may be increased. If BP control deteriorates, consider stopping the NSAID. Periodic measurement of renal function is warranted.

Salicylates (eg, aspirin)

By inhibiting synthesis of prostaglandins, aspirin may decrease antihypertensive effects of enalapril. It may be necessary to increase the enalapril dose or decrease the aspirin dose.

Sulfonylureas (eg, glyburide)

Risk of hypoglycemia may be increased. Close clinical and laboratory monitoring is warranted.

Thiazide diuretics (eg, chlorothiazide)

Additive BP-lowering effects. In addition, the risk of acute renal dysfunction may be increased. Monitor BP and renal function, especially in elderly patients and patients with impaired renal function. If an adverse interaction is suspected, stop one or both agents.

Tizanidine

Risk of severe hypotension may be increased. Coadminister with caution and closely monitor BP.

Adverse Reactions

Cardiovascular

Hypotension (7%); angina, chest pain, orthostatic hypotension, syncope (2%); MI (1%).

CNS

Dizziness (8%); headache (5%); fatigue (3%); asthenia, vertigo (2%).

Dermatologic

Rash (1%).

GI

Abdominal pain, diarrhea (2%); nausea, vomiting (1%).

Genitourinary

UTI (1%).

Hematologic

Bone marrow depression, neutropenia, and thrombocytopenia (rare).

Lab Tests

Increases in BUN and serum creatinine (11%).

Metabolic

Hyperkalemia (4%).

Respiratory

Bronchitis, cough, dyspnea, pneumonia (1%).

Precautions

Warnings

Fetal toxicity

When pregnancy is detected, discontinue enalapril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Monitor

Evaluation of patients with hypertension or heart failure should always include assessment of renal function. In patients with unilateral or bilateral renal artery stenosis, monitor renal function during the first few weeks of therapy. Periodically monitor WBC in patients with collagen vascular disease and renal disease.


Pregnancy

Category D . Discontinue drug as soon as pregnancy is detected. Closely observe infants with history of in utero exposure.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in neonates younger than 1 mo of age or in pediatric patients with GFR less than 30 mL/min/1.73 m 2 (oral). Safety and efficacy not established (IV).

Hypersensitivity

Anaphylactoid reactions have occurred in patients taking ACE inhibitors undergoing desensitization, and in patients being dialyzed with high-flux membranes or undergoing LDL apheresis with dextran sulfate absorption.

Renal Function

Dosage reduction is recommended in patients with moderate to severe renal impairment or in patients on dialysis. In patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN may occur.

Angioedema

Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis, or larynx may occur. Intestinal angioedema has also been reported. Use with caution in patients with a history of angioedema unrelated to ACE inhibitor therapy.

Aortic stenosis/Hypertrophic cardiomyopathy

As with other vasodilators, use enalapril with caution in patients with obstruction in the outflow tract of the left ventricle.

Cough

Persistent nonproductive cough may occur and should resolve with discontinuation of treatment.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hyperkalemia

May occur; risk factors include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes.

Hypotension/First-dose effect

Significant decreases in BP may occur after first dose, especially in severely salt- or volume-depleted patients or in those with heart failure. Monitor closely for 2 h or more after initial dose and during first 2 wk of therapy. Minimize risk by discontinuing diuretics, decreasing dose, or increasing salt intake approximately 1 wk prior to initiating enalapril.

Neutropenia and agranulocytosis

Have occurred; risk appears greater with renal dysfunction, especially if the patient also has a collagen vascular disease.

Renal effects

In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors may be associated with oliguria or progressive azotemia, and rarely with acute renal failure and death.

Surgery/Anesthesia

Risk of hypotension may be increased; if hypotension occurs, it can be corrected by volume expansion.

Overdosage

Symptoms

Hypotension.

Patient Information

  • Injection
  • Advise patients that medication will be prepared and administered by a health care provider in a medical setting.
  • Tablets and Suspension
  • Advise patients to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
  • Advise patients to try to take each dose at about the same time each day.
  • Advise patients or caregivers to shake suspension well before measuring each dose.
  • Inform hypertensive patients that the drug controls, but does not cure, hypertension and to continue taking the drug as prescribed, even when BP is not elevated.
  • Caution patients not to change the dose or stop taking the drug unless advised by their health care provider.
  • Instruct patients to continue taking other medications for the condition as prescribed by their health care provider.
  • Instruct patients in BP and pulse measurement skills.
  • Advise patients to monitor and record BP and pulse at home and to inform their health care provider if abnormal measurements are noted. Also advise patients to bring record of BP and pulse to each follow-up visit.
  • Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patients to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Emphasize to hypertensive patients the importance of other modalities on BP control: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Emphasize to heart failure patients the importance of other modalities that can help control heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
  • Advise heart failure patients to weigh daily, keep a record of daily weights, and notify their health care provider if rapid weight gain (eg, 5 lb in 1 wk) is noted or if edema or shortness of breath are getting worse.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Advise patients that medication may cause dizziness or light-headedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patients to avoid unnecessary exposure to UV light (sunlight, tanning booths), and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reactions.
  • Instruct patients to stop taking the drug and immediately report any of these symptoms to health care provider: sore throat, fever, swelling of the hands or feet, irregular heartbeat, chest pains, fainting, swelling of the face, lips, eyelids, or tongue, difficulty breathing.
  • Instruct patients to inform their health care provider if a persistent cough develops while taking this medication.
  • Caution patients not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by their health care provider.
  • Inform women of childbearing age about the consequences of exposure to enalapril during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their health care providers as soon as possible.

Copyright © 2009 Wolters Kluwer Health.

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