enalapril (Rx)

1-10%

Dizziness (4-8%)

Hypotension (0.9-6.7%)

Headache (2-5%)

Chest pain (2%)

Cough (1-2%)

Rash (1.5%)

Frequency Not Defined

Asthenia

Nausea

Vomiting

Hyperkalemia

Contraindications

Hypersensitivity to enalapril/other ACE inhibitors

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

Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)

Bilateral renal artery stenosis

Cautions

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

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

Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia

Risk of hyperkalemia, especially in patients with renal impairment or DM or in those taking concomitant K+-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 coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor 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 STAT if patient becomes pregnant

Less effective in blacks

Renal impairment

Pregnancy

May cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death; when pregnancy is detected, discontinue therapy as soon as possible

Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

Lactation

Enalapril and enalaprilat have been detected in human breast milk; because of potential for serious adverse reactions in breastfed infant, including hypotension, hyperkalemia, and renal impairment, advise women not to breastfeed during therapy

Mechanism of Action

Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart

ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed

ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles

ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction

Absorption

Bioavailability: 60%

Onset: 1 hr

Duration: 6 hr (IV), 12-24 hr (PO)

Peak plasma time: 15 min (IV), 1 hr (PO)

Distribution

Protein bound: 50-60%

Metabolism

Liver (70%); enalapril undergoes hepatic biotransformation to enalaprilat within 4 hr following oral administration

Metabolites: Enalaprilat (active)

Initial response for HTN: 15 min (IV), 1 hr (PO)

Peak response for HTN: 1-4 hr (IV), 4-6 hr (PO)

Elimination

Half-life elimination: 2 hr (parent drug), 35-38 hr (active metabolite [enalaprilat])

Dialyzable: Yes (hemodialysis)

Excretion: Urine (61%); feces (6% as enalapril, 27% as enalaprilat)

IV Incompatibilities

Y-site: Ampho B, ampho B chol SO4, cefepime, phenytoin

IV Compatibilities

Solution: D5W, Normosol R

Additive: Dobutamine, dopamine, heparin, meropenem, nitroglycerin, KCl, sodium nitroprusside

Y-site (partial list): Allopurinol, ampicillin, ampicillin-sulbactam, cefazolin, clindamycin, dobutamine, dopamine, esmolol, fentanyl, heparin, labetalol, linezolid, MgSO4, metronidazole, morphine SO4, nicardipine, KCl, propofol, tobramycin, TMP-SMX, vancomycin

IV Administration

Slow IVP over at least 5 minutes if undiluted, OR

Infused in up to 50 mL of compatible IV infusion solution

Storage

Clear, colorless solution

Store below 30°C