Enalapril

Enalapril is indicated for the treatment of hypertension, and for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis.

In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction less than 35 percent), enalapril maleate decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure.

Enalapril is available under the following different brand names: enalaprilat, Epaned, Vasotec, and Vasotec IV.

Injectable solution

• 1.25mg/mL

Tablet

• 2.5mg
• 5mg
• 10mg
• 20mg

Powder for oral solution (Epaned)

• 150 mg bottle (1mg/mL after reconstitution)

Dosage Considerations – Should be Given as Follows:

Hypertension

Adult:

Oral

• Initial: 2.5-5 mg orally once/day
• Maintenance: 10-40 mg/day orally once/day or divided every 12 hours

Intravenous (IV)

• 1.25 mg/dose IV over 5 minutes every 6 hours; doses up to 5 mg/dose IV every 6 hours have been administered

Pediatric:

1 month to 16 years (Oral)

• Initial: 0.08 mg/kg/day orally or divided every 12 hours; not to exceed 5 mg/day
• May increase as needed every 2 weeks according to blood pressure not to exceed 0.58 mg/kg/day (or 40 mg/day)

1 month to 16 years Intravenous (IV)

• 0.01-0.02 mg/kg/day divided every 12 hours by intravenous (IV) infusion

Left Ventricular Dysfunction

Initial: 2.5 mg orally every 12 hours

May titrate up to 20 mg/day

Congestive Heart Failure

Initial: 2.5 mg orally once/day or every 12 hours

Maintenance: 5-40 mg/day orally divided every 12 hours; titrate slowly every 2 weeks

Intravenous (IV): 1.25-5 mg every 6 hours; avoid IV administration in unstable heart failure or acute myocardial infarction

Hypertensive Crisis, Pediatric

0.05-0.1 mg/kg by direct intravenous (IV) injection

Renal Impairment, Pediatric

GFR less than 30 mL/min/1.73m2: Not recommended

Conversion from intravenous (IV) to oral dosage form

If not concurrently receiving diuretics, initiate enalapril 5 mg orally once/day; if concurrently receiving diuretics and responding to 0.625 mg IV every 6 hours, initiate at 2.5 mg orally once/day; titrate upwards as necessary

Dosing Modifications

Hepatic impairment: No dosage adjustment required

Renal impairment

• CrCl less than 30 mL/minute: (oral) Initiate 2.5 mg; titrate to response; not to exceed 40 mg
• Dialysis: 2.5 mg orally on day of dialysis; adjust dose on non-dialysis days according to blood pressure
• CrCl less than 30 mL/minute: (IV) Initiate 0.625 mg every 6 hours; titrate based on response
• CrCl 30 mL/minute or greater: (oral) Initiate 5 mg/day; titrate to maximum of 40 mg
• CrCl 30 mL/minute or greater: (IV) 1.25 mg every 6 hours; titrate based on response

Dosing Considerations

Beneficial for many patients at risk for heart disease

Reduces risk of heart attack (myocardial infarction [MI]), stroke, diabetic nephropathy, microalbuminuria, new-onset diabetes mellitus (DM)

Consider starting an ACE inhibitor in high-risk patients, even if no hypertension or congestive heart failure (CHF)

May prolong survival in congestive heart failure (CHF)

May preserve renal function in diabetes mellitus (DM)

May help to prevent migraine headache

Good choice in hyperlipidemia patients

Requires weeks for full effect; to start, use low dose and titrate every 1-2 weeks

Abrupt discontinuation not associated with rapid increase in blood pressure

Common side effects of Enalapril include:

• Dizziness
• Lightheadedness
• Low blood pressure (hypotension)
• Headache
• Chest pain
• Dry cough
• Rash

Other side effects of enalapril include:

• Weakness
• Nausea
• Vomiting
• High blood potassium (hyperkalemia)
• Loss of taste sensation
• Loss of appetite
• Drowsiness
• Sleep problems (insomnia)
• Dry mouth
• Diarrhea
• Skin itching

Serious side effects of enalapril include:

• Fainting
• Symptoms of high potassium blood level (such as muscle weakness, slow/irregular heartbeat)
• Signs of infection (such as fever, chills, persistent sore throat)
• Changes in the amount of urine

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe Interactions of enalapril include:
  • aliskiren
  • protein A column
• Enalapril has serious interactions with at least 38 different drugs.
• Enalapril has moderate interactions with at least 110 different drugs.
• Enalapril has mild interactions with at least 31 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death.

This medication contains enalapril. Do not take enalaprilat, Epaned, Vasotec, or Vasotec IV if you are allergic to enalapril or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Hypersensitivity to enalapril/other ACE inhibitors

History of ACE inhibitor-induced angioedema, hereditary or idiopathic angioedema

Pregnancy (2nd and 3rd trimesters): Significant risk of fetal and neonatal morbidity and mortality

Do not co-administer with aliskiren in patients with diabetes mellitus or with renal impairment (i.e., GFR less than 60 mL/min/1.73 m²)

Bilateral renal artery stenosis

Effects of Drug Abuse

• No information available

Short-Term Effects

Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation.

See "What Are Side Effects Associated with Using Enalapril?”

Long-Term Effects

Taking Enalapril in large amounts for a long period of time may be unsafe. Enalapril contains chemicals that are considered cancer-causing (carcinogens).

See "What Are Side Effects Associated with Using Enalapril?”

Cautions

Apheresis (LDL) with dextran sulfate, hypertrophic cardiomyopathy, collagen vascular disease, hemodialysis with high flux membrane, renal or aortic stenosis.

For hypertension patients on diuretics, if possible discontinue diuretics 2-3 days before starting enalapril.

Excessive hypotension if concomitant diuretics, hypovolemia, or hyponatremia.

Risk of high blood potassium (hyperkalemia), especially in patients with renal impairment or diabetes mellitus or in those taking concomitant potassium-elevating drugs.

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy.

Injection contains benzyl alcohol preservative (linked to potentially fatal "gasping syndrome" in preemies).

ACE inhibition also causes an increase in bradykinin levels, which putatively mediates angioedema.

Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors.

If laryngeal stridor or angioedema of the face, tongue, or glottis occurs discontinue therapy and institute appropriate therapy immediately.

Patients receiving co-administration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors.

Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation.

Agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia reported with other ACE inhibitor; patients with renal impairment are at high risk; monitor CBC with differential in these patients.

Discontinue immediately if patient becomes pregnant.

Less effective in people of African ethnicity.

Renal impairment.

Pregnancy and Lactation

Use enalapril with caution during the first trimester of pregnancy if benefits outweigh risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done.

UDuring the second and third trimesters of pregnancy, use enalapril only in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk. Enalapril and similar drugs have been associated with fetal injury that includes low blood pressure (hypotension), neonatal skull hypoplasia, anuria, reversible and irreversible renal failure, and death.

UEnalapril enters breast milk. It is not recommended for use while breastfeeding. The American Academy of Pediatrics (AAP) Committee states enalapril is "compatible with nursing". Consult your doctor.