ENALAPRIL MALEATE

(e-nal'a-pril)

Vasotec
ENALAPRILAT
Vasotec I.V.
Classifications: angiotensin-converting enzyme (ace) inhibitor; antihypertensive;
Therapeutic: antihypertensive; ace inhibitor
Pregnancy Category: C first trimester; D second and third trimester

Availability

2.5 mg, 5 mg, 10 mg, 20 mg tablets; 1.25 mg/mL injection; 1 mg/mL suspension

Action

Angiotensin-converting enzyme (ACE) inhibitor that catalyzes the conversion of angiotensin I to angiotensin II, a vasoconstrictor substance. Therefore, inhibition of ACE decreases angiotensin II levels, thus decreasing vasopressor activity and aldosterone secretion. Both actions achieve an antihypertensive effect by suppression of the renin–angiotensin–aldosterone system. ACE inhibitors also reduce peripheral arterial resistance (afterload), pulmonary capillary wedge pressure (PCWP), a measure of preload, pulmonary vascular resistance, and improve cardiac output as well as exercise tolerance.

Therapeutic Effect

Antihypertensive effect related to suppression of the renin-angiotensin-aldosterone system causes vasodilation and, therefore, lower blood pressure. Improvement in cardiac output results in increased exercise tolerance.

Uses

Management of mild to moderate hypertension as monotherapy or with a diuretic. Malignant, refractory, accelerated, and renovascular hypertension (except in bilateral renal artery stenosis or renal artery stenosis in a solitary kidney), CHF.

Unlabeled Uses

Hypertension or renal crisis in scleroderma.

Contraindications

Hypersensitivity to enalapril or captopril; hypotension. There has been evidence of fetotoxicity and kidney damage in newborns exposed to ACE inhibitors during pregnancy (category C in first trimester, and category D in second and third trimester); infants and children with Cl_cr <30 mL/min/1.73 m².

Cautious Use

Renal impairment, renal artery stenosis; patients with hypovolemia, receiving diuretics; undergoing dialysis; hepatic disease; bone marrow suppression; patients in whom excessive hypotension would present a hazard (e.g., cerebrovascular insufficiency); CHF; aortic stenosis, cardiomyopathy hepatic impairment; diabetes mellitus, lactation.

Route & Dosage

Hypertension
Adult: PO 5 mg/d, may increase to 10–40 mg/d in 1–2 divided doses IV 0.625–1.25 mg q6h, may give up to 5 mg q6h in hypertensive emergencies
Neonate: PO 0.1 mg/kg q24h
Child: PO 0.08 mg/kg/d in 1–2 divided doses, may increase (max: 5 mg/kg/d) IV 5–10 mcg/kg/dose q8–24h

Congestive Heart Failure
Adult: PO 2.5 mg 1–2 times/d, may increase up to 5–20 mg/d in 1–2 divided doses (max: 40 mg/d)

Renal Impairment
Enalapril: Cl_cr <30 mL/min, start with 2.5 mg dose then titrate
Enalaprilat: Cl_cr <30 mL/min, start with dose of 0.625 mg q6h then titrate
Hemodialysis: Administer post-dialysis or give 20–25% supplemental dose

Administration

Oral

Discontinue diuretics, if possible, for 2–3 d prior to initial oral dose to reduce incidence of hypotension. If the diuretic cannot be discontinued, give an initial dose of 2.5 mg. Keep patient under medical supervision for at least 2 h and until BP has stabilized for at least an additional hour.
Give with food or drink of patient's choice.
Protect from heat and light. Expiration date: 30 mo following date of manufacture if stored at <30° C.
Conversion from IV to oral therapy: Recommended initial dose is 5 mg once a day with a Cl_cr >30 mL/min, and 2.5 mg once daily with a Cl_cr <30 mL/min.
Store tablets at 30° C (86° F); protect from heat and light.

Intravenous

Note: Verify correct IV concentration and rate of infusion/injection with physician for neonates, infants, children.

PREPARE: Direct: Give undiluted. Intermittent: Dilute in 50 mL of D5W, NS, D5/NS, D5/LR.

ADMINISTER: Direct/Intermittent: Give direct IV slowly over at least 5 min through a port of a free flowing infusion of D5W or NS or as an infusion over 5 min.

INCOMPATIBILITIES Y-site: Amphotericin B, amphotericin B cholesteryl, cefepime, lansoprazole, phenytoin.

Adverse Effects (≥1%)

CNS: Headache, dizziness, fatigue, nervousness, paresthesias, asthenia, insomnia, somnolence. CV: Hypotension including postural hypotension; syncope, palpitations, chest pain. GI: Diarrhea, nausea, abdominal pain, loss of taste, dyspepsia. Hematologic: Decreased Hgb and Hct. Urogenital: Acute kidney failure, deterioration in kidney function. Skin: Pruritus with and without rash, angioedema, erythema. Metabolic: Hyperkalemia. Respiratory: Cough.

Interactions

Drug: Indomethacin and other nsaids may decrease antihypertensive activity; potassium supplements, potassium-sparing diuretics may cause hyperkalemia; may increase lithium levels and toxicity.

Pharmacokinetics

Absorption: 70% absorbed from GI tract. Onset: 1 h PO; 15 min IV. Peak: 4–8 h PO; 4 h IV. Duration: 12–24 h PO; 6 h IV. Distribution: Limited amount crosses blood–brain barrier; crosses placenta. Metabolism: PO dose undergoes first-pass metabolism in liver to active form, enalaprilat. Elimination: 60% in urine, 33% in feces within 24 h. Half-Life: 2 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness. Peak effects after the first IV dose may not occur for up to 4 h; peak effects of subsequent doses may exceed those of the first.
Maintain bedrest and monitor BP for the first 3 h after the initial IV dose. First-dose phenomenon (i.e., a sudden exaggerated hypotensive response) may occur within 1–3 h of first IV dose, especially in the patient with very high blood pressure or one on a diuretic and controlled salt intake regimen. An IV infusion of normal saline for volume expansion may be ordered to counteract the hypotensive response. This initial response is not an indicator to stop therapy.
Monitor BP for first several days of therapy. If antihypertensive effect is diminished before 24 h, the total dose may be given as 2 divided doses.
Report transient hypotension with lightheadedness. Older adults are particularly sensitive to drug-induced hypotension. Supervise ambulation until BP has stabilized.
Lab tests: Monitor serum potassium and be alert to symptoms of hyperkalemia (K⁺ >5.7 mEq/L). Patients who have diabetes, impaired kidney function, or CHF are at risk of developing hyperkalemia during enalapril treatment. Monitor kidney function closely during first few weeks of therapy.

Patient & Family Education

Full antihypertensive effect may not be experienced until several weeks after enalapril therapy starts.
When drug is discontinued due to severe hypotension, the hypotensive effect may persist a week or longer after termination because of long duration of drug action.
Do not follow a low-sodium diet (e.g., low-sodium foods or low-sodium milk) without approval from physician.
Avoid use of salt substitute (principal ingredient: potassium salt) and potassium supplements because of the potential for hyperkalemia.
Notify physician of a persistent nonproductive cough, especially at night, accompanied by nasal congestion.
Report to physician promptly if swelling of face, eyelids, tongue, lips, or extremities occurs. Angioedema is a rare adverse effect and, if accompanied by laryngeal edema, may be fatal.
Do not drive or engage in other potentially hazardous activities until response to drug is known.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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