enalapril, enalaprilat

(e-nal-a-pril, e-nal-a-pril-at) enalapril,

Epaned

(trade name),

Vasotec

(trade name),

Vasotec IV

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: ace inhibitors
Pregnancy Category: D

Indications

Alone or with other agents in the management of hypertension.Management of symptomatic heart failure.Slowed progression of asymptomatic left ventricular dysfunction to overt heart failure.Treatment of proteinuria in steroid-resistant nephrotic syndrome patients.

Action

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 and 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

Contraindications/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) Obstetric: Can cause injury or death of fetus – if pregnancy occurs, discontinue immediately.; Lactation: Discontinue drug or use formula.Use Cautiously in: Patients with renal impairment, hypovolemia, hyponatremia, and concurrent diuretic therapy; genetic implication Black patients (monotherapy of hypertension less effective, may require additional therapy; higher risk of angioedema); Surgery/anesthesia (hypotension may be exaggerated); Women of childbearing potential; Pediatric: Injectable product contains benzyl alcohol which is associated with gasping syndrome in neonates ; Geriatric: Initial dose ↓ recommended.Exercise Extreme Caution in: Family history of angioedema.

Adverse Reactions/Side Effects

Central nervous system

dizziness
fatigue
headache
vertigo
weakness

Respiratory

cough (most frequent)

Cardiovascular

hypotension (most frequent)
chest pain

Gastrointestinal

abdominal pain
diarrhea
nausea
vomiting

Genitourinary

proteinuria (most frequent)
impaired renal function

Dermatologic

rashes

Fluid and Electrolyte

hyperkalemia

Respiratory

dyspnea

Miscellaneous

angioedema (life-threatening)

Interactions

Drug-Drug interaction

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 antagonists or aliskiren ; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/minNSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.↑ levels and may ↑ the risk of lithium toxicity.Avoid natural licorice; causes sodium and water retention and ↑ potassium loss.

Route/Dosage

Hypertension

Oral (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).Oral (Children and Neonates) 0.1 mg/kg/day q 12–24 hr (once a day in neonates); may be slowly titrated up to a maximum of 0.5 mg/kg/day.Intravenous (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.Intravenous (Children and Neonates) 5–10 mcg/kg/dose given q 8–24 hr.

Renal Impairment

Oral Intravenous (Adults) CCr 10–50 mL/min—75% of dose; CCr <10 mL/min—50% of dose.

Renal Impairment

Oral Intravenous (Children and Neonates) CCr <30 mL/min—Contraindicated.

Heart Failure

Oral (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

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

Availability (generic available)

Enalapril

Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg Powder for oral solution (requires reconstitution): 1 mg/mL In combination with: hydrochlorothiazide (Vaseretic). See combination drugs.

Enalaprilat

Injection: 1.25 mg/mL

Nursing implications

Nursing 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, or tongue, or difficulty in swallowing or breathing).
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.

Potential Nursing Diagnoses

Decreased cardiac output (Indications, Side Effects)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)
Noncompliance (Patient/Family Teaching)

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.
Oral: For patients with difficulty swallowing tablets. Shake suspension before each use.
Intravenous 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.
Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, allopurinol, amifostine, amikacin, aminophylline, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, ascorbic acid, atracurium, atropine, azathioprine, azithromycin, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftaroline, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, cisatracurium, cisplatin, cladribine, clindamycin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doripenem, doxacurium, doxorubicin hydrochloride, doxorubicin liposome, doxycycline, ephedrine, epinephrine, epirubicin, epoetin, eptifibatide, ertapenem, erythromycin lactobionate, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, fluorouracil, folic acid, foscarnet, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hetastarch, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, indomethacin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, metaraminol, methotrexate, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, miconazole, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, multiple vitamin infusion, mycophenolate, nafcillin, nalbuphine, naloxone, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, papaverine, pemetrexed, penicillin G, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, phytonadione, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propofol, propranolol, protamine, pyridoxime, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sodium acetate, sodium bicarbonate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, tetracycline, theophylline, thiamine, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trastuzumab, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconazole, zoledronic acid
Y-Site Incompatibility: amphotericin B cholesteryl, amphotericin B colloidal, caspofungin, cefepime, dantrolene, diazepam, diazoxide, phenytoin

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 ACE inhibitor therapy 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.
- 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 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 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 women of childbearing age to use contraception and notify health care professional of pregnancy is planned or suspected. 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.

Evaluation/Desired Outcomes

Decrease in BP without appearance of excessive side effects.
Improvement in survival and reduction of symptoms in heart failure.
Decrease in development of overt heart failure.

enalapril, enalaprilat