enalaprilat
Vasotec I.V.

enalapril maleate
Vasotec

Available forms
Available by prescription only
Injection: 1.25 mg/ml in 2-ml vials
Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg

Indications and dosages
 Hypertension. Adults: If patient doesn’t take a diuretic, 5 mg P.O. once daily initially, adjusted according to response. Usual dosage range is 10 to 40 mg daily as a single dose or two divided doses. Or, 1.25-mg I.V. infusion q 6 hours over 5 minutes. If patient takes a diuretic, 2.5 mg P.O. once daily initially. Or, 0.625 mg I.V. over 5 minutes; repeat in 1 hour, if needed, and then follow with 1.25 mg I.V. q 6 hours.
 To convert from I.V. to P.O. therapy. Adults: If patient didn’t receive diuretics and did receive 1.25 mg I.V. q 6 hours, then give 5 mg P.O. once daily initially. If patient did receive diuretics and received 0.625 mg I.V. q 6 hours, then give 2.5 mg P.O. once daily. Adjust dosage according to response.
 To convert from P.O. to I.V. therapy. Adults: 1.25 mg I.V. over 5 minutes q 6 hours.
≡ Dosage adjustment. For hypertensive patients with renal impairment and a creatinine clearance less than 30 ml/minute, begin therapy at 2.5 mg P.O. daily. Gradually adjust dosage according to response. If oral therapy isn’t feasible, give 0.625 mg I.V. If blood pressure is adequate after 1 hour, may give another dose of 0.625 mg I.V. Additional doses of 1.25 mg I.V. may be given q 6 hours. Patients undergoing hemodialysis should receive a supplemental dose of 2.5 mg P.O. after each dialysis session. The initial I.V. dosage for patients undergoing dialysis is 0.625 mg q 6 hours.
 Heart failure. Adults: Initially, 2.5 mg P.O. once or twice daily. Usual maintenance dose is 5 to 20 mg P.O. daily, given in two divided doses. Maximum daily dose is 40 mg P.O. in two divided doses.
 Asymptomatic left ventricular dysfunction. Adults: Initially, 2.5 mg P.O. b.i.d.; adjust to targeted daily dose of 20 mg (in divided doses) as tolerated.
≡ Dosage adjustment. For patients with heart failure and renal impairment or hyponatremia (serum sodium below 130 mEq/L or serum creatinine level above 1.6 mg/dl), start with 2.5 mg P.O. daily. Increase to 2.5 mg b.i.d. and then 5 mg b.i.d. and higher as indicated, usually at intervals of 4 days or more.

Pharmacodynamics
Antihypertensive action: Enalapril inhibits ACE, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Reduced angiotensin II levels decrease peripheral arterial resistance, thus lowering blood pressure, and decrease aldosterone secretion, thus reducing sodium and water retention.

Pharmacokinetics
Absorption: About 60% of dose is absorbed from the GI tract.
Distribution: Full distribution pattern is unknown; drug doesn’t appear to cross the blood-brain barrier.
Metabolism: Metabolized extensively to the active metabolite enalaprilat.
Excretion: About 94% is excreted in urine and feces as enalaprilat and enalapril.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with a history of angioedema related to previous treatment with an ACE inhibitor. Use cautiously in patients with impaired renal function. Avoid use in patients at high risk for cardiogenic shock.

Interactions
Drug-drug. Antihypertensives, diuretics, phenothiazines: Increases antihypertensive effects. Use together cautiously.
Aspirin, NSAIDs: Decreases antihypertensive effect. Use together cautiously.
Insulin, oral antidiabetics: Increases risk of hypoglycemia, especially at the start of enalapril therapy. Monitor glucose level closely.
Lithium: Decreases lithium clearance. Monitor lithium level.
Potassium-sparing diuretics, potassium supplements: Enhances diuretic effects and possible hyperkalemia. Use together cautiously.
Rifampin: Decreases rifampin effects. Monitor patient closely.
Drug-herb. Capsaicin: Increases risk of cough. Discourage use together.
Drug-food. Salt substitutes: May enhance effects, thereby causing hyperkalemia. Tell patient to use together cautiously.

Adverse reactions
CNS: headache, dizziness, fatigue, vertigo, asthenia, syncope.
CV: hypotension, chest pain, bradycardia.
GI: diarrhea, nausea, abdominal pain, vomiting.
GU: decreased renal function in patients with bilateral renal artery stenosis or heart failure.
Hematologic: neutropenia, thrombocytopenia, agranulocytosis.
Respiratory: dry, persistent, tickling, nonproductive cough; dyspnea.
Skin: rash.
Other: angioedema.

Effects on lab test results
• May increase BUN, creatinine, potassium, liver enzyme and bilirubin levels. May decrease sodium level.
• May decrease hemoglobin, hematocrit, and neutrophil and platelet counts.

Overdose and treatment
The most likely effect is hypotension.
 After acute ingestion, empty stomach by induced emesis or gastric lavage. Follow with activated charcoal to reduce absorption. Consider hemodialysis in severe cases. Subsequent treatment is usually symptomatic and supportive.

Special considerations
• Stop diuretic therapy 2 to 3 days before starting enalapril therapy to reduce risk of hypotension; if drug doesn’t control blood pressure adequately, reinstate diuretic.
• Give drug without regard to meals; food doesn’t appear to affect absorption.
• Proteinuria and nephrotic syndrome may occur in patients receiving enalapril.
• Obtain WBC and differential counts before treatment, every 2 weeks for 3 months, and periodically thereafter.
Pregnant patients
• Neonatal and fetal death may occur when drug is given during second and third trimesters.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk; an alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safety and efficacy of enalapril in children haven’t been established; use only if potential benefit outweighs risk.
Geriatric patients
• Elderly patients may need lower doses because of impaired drug clearance.

Patient education
• Tell patient to report light-headedness, especially in first few days, so dosage can be adjusted; signs of infection, such as sore throat and fever, because drug may decrease WBC count; facial swelling or difficulty breathing, because drug may cause angioedema; and loss of taste, which may necessitate discontinuing drug.
• Advise patient to avoid sudden position changes to minimize orthostatic hypotension.
• Warn patient to seek medical approval before taking herbal or OTC cold preparations, particularly cough medications.and symptoms of digoxin toxicity occur, obtain serum digoxin levels and adjust digoxin doses accordingly.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use