enalapril, enalaprilat

Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin levels and ↓ aldosterone levels. Net result is systemic vasodilation.

Therapeutic effects:

Lowering of BP in patients with hypertension.
Increased survival and reduction of symptoms in patients with symptomatic heart failure.
Decreased development of overt heart failure.

Pharmacokinetics ⬆ ⬇

Absorption: Enalapril: 55–75% absorbed following oral administration. Enalaprilat: IV administration results in complete bioavailability.

Distribution: Crosses the placenta; small amounts enter breast milk.

Metabolism/Excretion: Converted by the liver to enalaprilat, the active metabolite; primarily eliminated by kidneys.

Half-Life: Enalapril: Adults: 2 hr; Adults with HF: 3.4–5.8 hr; Children and infants with HF: 2.7 hr; Neonates with HF: 10.3 hr; Enalaprilat:Adults: 35–38 hr; Children and infants with HF: 11.1 hr; Infants 6 wks–8 mo: 6–10 hr; Neonates with HF: 11.9 hr.

Time/Action Profile ⬆ ⬇

(effect on BP—single dose‡)

ROUTE	ONSET	PEAK	DURATION
Enalapril PO	1 hr	4–8 hr	12–24 hr
Enalaprilat IV	15 min	1–4 hr	4–6 hr

‡Full effects may not be noted for several weeks.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
History of angioedema (either idiopathic or with previous use of ACE inhibitors);
Concurrent use with aliskiren in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min)
Concurrent use with sacubitril/valsartan; must be a 36–hr washout period after switching to/from sacubitril/valsartan;
OB: Pregnancy (may cause fetal harm).;
Lactation: Lactation.

Use Cautiously in:

Patients with renal impairment, hypovolemia, hyponatremia, and concurrent diuretic therapy;
Black patients (monotherapy of hypertension less effective, may require additional therapy; higher risk of angioedema);
Surgery/anesthesia (hypotension may be exaggerated);
Rep: Women of reproductive potential;
Pedi: Injectable product contains benzyl alcohol which is associated with gasping syndrome in neonates; oral solution not recommended in pediatric patients with GFR 30 mL/min/1.73 m2;
Geri: Initial dose recommended.

Family history of angioedema.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, chest pain

Derm: rash

F and E: hyperkalemia

GI: abdominal pain, diarrhea, nausea, vomiting

GU: proteinuria, impaired renal function

Neuro: dizziness, fatigue, headache, vertigo, weakness

Resp: cough, dyspnea

Misc: ANGIOEDEMA

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with sacubitril↑ risk of angioedema; concurrent use contraindicated; do not administer within 36 hr of switching to/from sacubitril/valsartan.
Excessive hypotension may occur with concurrent use of diuretics.
Additive hypotension with other antihypertensives.
↑risk of hyperkalemia with concurrent use of potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes.
↑risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of angiotensin II receptor blockers or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min; avoid concurrent use with angiotensin II receptor blockers
NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.
↑levels and may ↑ the risk of lithium toxicity.
↑risk of angioedema with temsirolimus, sirolimus, or everolimus.

Drug-Natural Products:

Avoid natural licorice; causes sodium and water retention and ↑ potassium loss.

Route/Dosage ⬆ ⬇

Hypertension

PO (Adults ): 2.5–5 mg once daily, ↑ as required up to 40 mg/day in 1–2 divided doses (initiate therapy at 2.5 mg once daily in patients receiving diuretics).
PO (Children >1 mo): 0.08 mg/kg once daily; may be slowly titrated up to a maximum of 0.58 mg/kg/day.
IV (Adults ): 0.625–1.25 mg (0.625 mg if receiving diuretics) every 6 hr; can be titrated up to 5 mg every 6 hr.
IV (Children >1 mo): 5–10 mcg/kg/dose given every 8–24 hr.

Renal Impairment

PO IV (Adults ): CCr 10–50 mL/min: 75% of dose; CCr <10 mL/min: 50% of dose.

Renal Impairment

PO IV (Children >1 mo): CCr <30 mL/min: Contraindicated.

Heart Failure

PO (Adults ): 2.5 mg 1–2 times daily, titrated up to target dose of 10 mg twice daily; initiate therapy at 2.5 mg once daily in patients with hyponatremia (serum sodium <130 mEq/L).

Asymptomatic Left Ventricular Dysfunction

PO (Adults ): 2.5 mg twice daily, titrated upward to a target dose of 10 mg twice daily.

Availability ⬆ ⬇

(Generic available)

Enalapril

Oral solutionmixed berry flavor: 1 mg/mL
Tablets: 2.5 mg; 5 mg; 10 mg; 20 mg
In combination with: hydrochlorothiazide (Vaseretic). See Appendix [not included in this PDA edition].

Enalaprilat

Solution for injection: 1.25 mg/mL

Assessment ⬆ ⬇

Hypertension: Monitor BP and pulse frequently during initial dose adjustment and periodically during therapy. Notify health care professional of significant changes.
- Monitor frequency of prescription refills to determine compliance.
- Assess patient for signs of angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing); may occur at any time during therapy. Discontinue medication and provide supportive care.
Heart Failure: Monitor weight and assess patient routinely for resolution of fluid overload (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).

Lab Test Considerations:

Monitor renal function. May cause ↑ in BUN and serum creatinine.
- May cause hyperkalemia.
- Monitor CBC periodically during therapy in patients with collagen vascular disease and/or renal disease. May rarely cause slight ↓ hemoglobin and hematocrit and agranulocytosis.
- May cause ↑ AST, ALT, alkaline phosphatase, and serum bilirubin.

Implementation ⬆ ⬇

Correct volume depletion, if possible, before initiation of therapy due to possible precipitous drop in BP during first 1–3 hr following first dose. Risk of hypotension may be decreased by discontinuing diuretics or cautiously increasing salt intake 2–3 days prior to beginning enalapril. Monitor BP closely. Resume diuretics if BP is not controlled.
PO: Administer once daily. For patients with difficulty swallowing tablets, oral solution is available. Shake solution before each use. Solution is stable at controlled room temperature for 60 days.

IV Administration:

Diluent: May be administered undiluted.
Rate: Administer over at least 5 min.
Intermittent Infusion: Diluent: Dilute in D5W, 0.9% NaCl, D5/0.9% NaCl, or D5/LR. Diluted solution is stable for 24 hr at room temperature.Concentration: 25 mcg/mL.
Rate: Administer as a slow infusion over at least 5 min.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of continuing to take medication as directed at the same time each day, even if feeling well. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses. Warn patient not to discontinue enalapril unless directed by health care professional.
- Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care professional. See Food Sources for Specific Nutrients.
- Caution patient to change positions slowly to minimize orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs and cough, cold, or allergy remedies.
- May cause dizziness, especially during first few days of therapy. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
- Advise patient to inform health care professional of medication regimen before treatment or surgery.
- Instruct patient to notify health care professional immediately if rash; mouth sores; sore throat; fever; swelling of hands or feet; irregular heart beat; chest pain; dry cough; hoarseness; swelling of face, eyes, lips, or tongue; or if difficulty swallowing or breathing occurs. Persistent dry cough may occur and may not subside until medication is discontinued. Consult health care professional if cough becomes bothersome. Also notify health care professional if nausea, vomiting, or diarrhea occurs and continues.
- Advise diabetic patients to monitor blood glucose closely, especially during first mo of therapy; may cause hypoglycemia.
- Advise females of reproductive potential to use effective contraception and notify health care professional of pregnancy is planned or suspected and to avoid breastfeeding during therapy. If pregnancy is detected, discontinue medication as soon as possible.
- Emphasize the importance of follow-up examinations to evaluate effectiveness of medication.
Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
- Instruct patient and family on correct technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care professional.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇