enalaprilat


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Related to enalaprilat: Fenoldopam, Pivampicillin

enalaprilat

 [ĕ-nal´-ah-pril-at″]
an angiotensin-converting enzyme inhibitor, the active metabolite of enalapril, administered intravenously in the treatment of hypertensive crisis or when oral administration of enalapril maleate is impractical.

enalapril maleate

Apo-Enalapril (CA), CO Enalapril (CA), Gen-Enalapril (CA), Innovace (UK), Novo-Enalapril (CA), PMS-Enalapril (CA), Ratio-Enalapril (CA), Riva-Enalapril (CA), Sandoz-Enalapril (CA), Taro-Enalapril (CA), Vasotec

enalaprilat

Vasotec IV

Pharmacologic class: Angiotensin-converting enzyme (ACE) inhibitor

Therapeutic class: Antihypertensive

Pregnancy risk category C (first trimester), D (second and third trimesters)

FDA Box Warning

• When used during second or third trimester of pregnancy, drug can cause fetal injury and even death. Discontinue as soon as pregnancy is detected.

Action

Inhibits conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; inactivates bradykinin and prostaglandins. Also increases plasma renin and potassium levels and reduces aldosterone levels, resulting in systemic vasodilation.

Availability

Injection: 1.25 mg/ml

Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg

Indications and dosages

Hypertension

Adults: For patients not taking concomitant diuretics-initially, 5 mg P.O. once daily, increased after 1 to 2 weeks as needed to a maintenance dosage of 10 to 40 mg P.O. daily given as a single dose or in two divided doses; or 1.25 mg I.V. q 6 hours. For patients taking diuretics-initially, 2.5 mg P.O. or 0.625 mg I.V.

Children: 0.08 mg/kg P.O. once daily; may be increased based on blood pressure response up to 5 mg daily. Maximum dosage is 0.58 mg/kg/dose.

Heart failure

Adults: Initially, 2.5 mg P.O. once or twice daily, increased after 1 to 2 weeks as needed to maintenance dosage of 5 to 40 mg P.O. daily given as a single dose or in two divided doses

Asymptomatic left ventricular dysfunction

Adults: Initially, 2.5 mg P.O. once or twice daily, increased after 1 to 2 weeks as needed to a maximum of 20 mg/day in divided doses

Dosage adjustment

• Renal impairment

Off-label uses

• Diabetic nephropathy

• Hypertensive emergency

Contraindications

• Hypersensitivity to drug or other ACE inhibitors

• Angioedema

• Pregnancy

Precautions

Use cautiously in:

• renal or hepatic impairment, hypovolemia, hyponatremia, aortic stenosis, hypertrophic cardiomyopathy, cerebrovascular or cardiac insufficiency

• concurrent diuretic use

• elderly patients

• breastfeeding patients

• children.

Administration

• Give oral doses with food or beverage.

• Discontinue diuretics for 2 to 3 days before starting drug, if possible.

• Know that I.V. administration is usually reserved for patients who cannot take P.O. form.

• Be aware that I.V. administration isn't recommended for pediatric patients.

• Administer I.V. dose either undiluted or diluted in 50 ml of dextrose 5% in water, normal saline solution, dextrose 5% in normal saline solution, or dextrose 5% in lactated Ringer's solution.

• Give single I.V. dose by push or piggyback over 5 minutes. If patient is at risk for hypotension, infusion may be given over 1 hour.

• Be aware that black patients have a higher risk of angioedema.

Adverse reactions

CNS: dizziness, fatigue, headache, insomnia, drowsiness, vertigo, asthenia, paresthesia, ataxia, confusion, depression, nervousness,cerebrovascular accident

CV: orthostatic hypotension, palpitations, angina pectoris, tachycardia, peripheral edema,arrhythmias, cardiac arrest

EENT: sinusitis

GI: nausea, vomiting, constipation, dyspepsia, abdominal pain, dry mouth, pancreatitis

GU: proteinuria, urinary tract infection, erectile dysfunction, decreased libido,oliguria

Hematologic: agranulocytosis, bone marrow depression

Hepatic: hepatitis

Metabolic: hyponatremia,hyperkalemia Respiratory: cough, upper respiratory tract infection, asthma, bronchitis, dyspnea,eosinophilic pneumonitis

Skin: rash, alopecia, photosensitivity, diaphoresis, exfoliative dermatitis, angioedema,erythema multiforme

Other: altered taste, fever, increased appetite, anaphylactoid reactions

Interactions

Drug-drug. Allopurinol: increased risk of hypersensitivity reaction

Antacids: decreased enalapril absorption Cyclosporine, indomethacin, potassiumsparing diuretics, potassium supplements: hyperkalemia

Digoxin, lithium: increased blood levels of these drugs, possible toxicity

Diuretics, nitrates, other antihypertensives, phenothiazines: additive hypotension

Nonsteroidal anti-inflammatory drugs: decreased antihypertensive response

Rifampin: decreased enalapril efficacy

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen (BUN), creatinine, potassium: increased levels Antinuclear antibodies: positive titer Sodium: decreased level

Drug-food. Salt substitutes containing potassium: hyperkalemia

Drug-herbs. Capsaicin: increased incidence of cough

Drug-behaviors. Acute alcohol ingestion: additive hypotension

Sun exposure: photosensitivity reaction

Patient monitoring

Assess for rapid blood pressure drop leading to cardiovascular collapse, especially when giving with diuretics.

In patient with renal insufficiency or renal artery stenosis, monitor for worsening renal function.

• After initial dose, observe patient closely for at least 2 hours until blood pressure has stabilized. Then continue to observe for additional hour.

• Monitor vital signs, fluid intake and output, and daily weight.

• Supervise patient during ambulation until effects of drug are known.

• Monitor liver function tests, BUN, and creatinine and electrolyte levels.

Patient teaching

• Inform patient that drug's full effect may not occur for several weeks.

• Advise patient to report persistent dry cough with nasal congestion.

Tell patient to immediately report swelling of face, eye area, tongue, lips, hands, or feet; rash, hives, or severe itching; unexplained fever; unusual tiredness; yellowing of skin or eyes; abdominal pain; or easy bruising.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness or light-headedness from sudden blood pressure decrease.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.

References in periodicals archive ?
This study aimed to develop and validate a method using LC-MS/MS to measure enalapril and enalaprilat in plasma samples and to determine the bioequivalence of a new tablet formulation of enalapril (20 mg tablets).
The MS parameters were improved for enalapril and enalaprilat analysis in ESI negative mode as follows: nitrogen gas 1 flow = 55 units, gas 2 = 70 units, curtain gas = 30 units, ion spray voltage = 5000 V, drying temperature = 550[degrees]C, and collision energy of 20 V.
The enalapril and enalaprilat assay standards were prepared by dissolving 1 mg of each in 1 mL of d[H.sub.2]O and then diluted in drug-free pooled heparinized human plasma to prepare a stock solution of 200 [micro]g/mL.
Enalapril, enalaprilat levels in plasma, and the internal standard sitagliptin were measured by API 4000 LC-MS/MS.
Specificity was defined as lacking of interference of enalapril and enalaprilat at retention times from the plasma components and lack of cross-interference between analytes and IS using extraction method and LC-MS/MS.
The recovery study of enalapril and enalaprilat from protein precipitation procedure was assessed by using the low, medium, and high QC levels and comparing their peak areas with peak area in unprocessed samples (spiked blank with true corresponding amount).
Three freeze-thaw cycles were applied to evaluate the freeze-thaw cycles stability for enalapril and enalaprilat in plasma by thawing from frozen state at room temperature for 1 hr and refreezing again for 24 hrs.
The LOD in plasma was found to be 0.907 and 0.910 ng/ml for both enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml in plasma.
The within-day and between-days accuracy range for both enalapril and enalaprilat were from 94 to 101% and 95 to 99%, respectively, for individual measurements in both while precision values (CV%) for enalapril and enalaprilat were less than 5%.
The peak area ratios for enalapril and enalaprilat to IS in human plasma were linear over the calibration range from 1.0 to 200 ng/ml during the validation and the routine analysis for both enalapril (Figure 3) and enalaprilat (Figure 4) LC-MS/MS.
The extraction procedures for enalapril and enalaprilat were highly efficient from plasma matrix and the recovery values for low OC, mid QC, and high QC for enalapril were 94.220%, 103.62%, and 101.96%, respectively, and those for enalaprilat were 98.17% for low QC, 108.40% for mid QC, and 101.83% for high QC (Table 3).
"The launch of enalaprilat injection is a good example of the strength of our internal development and regulatory ability with Faulding receiving tentative approval from the FDA in less than 12 months when the average approval time is 20 months.