Dosing and uses of Enalaprilat, Vasotec (enalapril)
Adult dosage forms and strengths
injectable solution
- 1.25mg/mL
tablet
- 2.5mg
- 5mg
- 10mg
- 20mg
powder for oral solution (Epaned)
- 150 mg bottle (1mg/mL after reconstitution)
Hypertension
OraL
- Initial: 2.5-5 mg PO qDay
- Maintenance: 10-40 mg/day PO qDay or divided q12hr
IV
- 1.25 mg/dose IV over 5 minutes q6hr; doses up to 5 mg/dose IV q6hr have been administered
Left Ventricular Dysfunction
Initial: 2.5 mg PO q12hr
May titrate up to 20 mg/day
Congestive Heart Failure
Initial: 2.5 mg PO qDay or q12hr
Maintenance: 5-40 mg/Day PO divided q12hr; titrate slowly q2Weeks
IV: 1.25-5 mg q6hr; avoid IV administration in unstable heart failure or acute myocardial infarction
Dosing Modifications
Hepatic impairment: No dosage adjustment required
Renal impairment
- CrCl <30 mL/min: (PO) Initiate 2.5 mg; titrate to response; not to exceed 40 mg
- Dialysis: 2.5 mg PO on day of dialysis; adjust dose on nondialysis days according to BP
- CrCl <30 mL/min: (IV) Initiate 0.625 mg q6hr; titrate based on response
- CrCl ≥30 mL/min: (PO) Initiate 5 mg/day; titrate to maximum of 40 mg
- CrCl ≥30 mL/min: (IV) 1.25 mg q6hr; titrate based on response
Dosing Considerations
Beneficial for many patients at risk for heart disease
Reduces risk of MI, stroke, diabetic nephropathy, microalbuminuria, new-onset Dm
Consider starting an ACE inhibitor in high-risk patients, even if no HTN or CHF
May prolong survival in CHF
May preserve renal function in Dm
May help to prevent migraine headache
Good choice in hyperlipidemia patients
Requires weeks for full effect; to start, use low dose and titrate q1-2Weeks
Abrupt discontinuation not associated with rapid increase in Bp
Pediatric dosage forms and strengths
injectable solution
- 1.25mg/mL
tablet
- 2.5mg
- 5mg
- 10mg
- 20mg
powder for oral solution (Epaned)
- 150 mg bottle (1mg/mL after reconstitution)
Hypertension
1 month to 16 years (oral)
- Initial: 0.08 mg/kg/day PO or divided q12hr; not to exceed 5 mg/day
- May increase PRN q2Weeks according to blood pressure not to exceed 0.58 mg/kg/day (or 40 mg/day)
1 month to 16 years (IV)
- 0.01-0.02 mg/kg/day divided q12hr by IV infusion
Hypertensive Crisis
0.05-0.1 mg/kg by direct IV injection
Renal Impairment
GFR <30 mL/min/1.73 m⊃: Not recommended
Enalaprilat, Vasotec (enalapril) adverse (side) effects
1-10%
Dizziness (4-8%)
Hypotension (0.9-6.7%)
Headache (2-5%)
Chest pain (2%)
Cough (1-2%)
Rash (1.5%)
Frequency not defined
Asthenia
Nausea
Vomiting
Hyperkalemia
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to enalapril/other ACE inhibitors
History of ACE inhibitor-induced angioedema, hereditary or idiopathic angioedema
Pregnancy (2nd and 3rd trimesters): Significant risk of fetal and neonatal morbidity and mortality
Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Bilateral renal artery stenosis
Cautions
Apheresis (LDL) with dextran sulfate, hypertrophic cardiomyopathy, collagen vascular disease, hemodialysis with high flux membrane, renal or aortic stenosis
For HTN patients on diuretics, if possible discontinue diuretics 2-3 days before starting enalapriL
Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia
Risk of hyperkalemia, especially in patients with renal impairment or DM or in those taking concomitant K+-elevating drugs
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
Injection contains benzyl alcohol preservative (linked to potentially fatal "gasping syndrome" in preemies)
ACE inhibition also causes an increase in bradykinin levels, which putatively mediates angioedema
Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors
If laryngeal stridor or angioedema of the face, tongue, or glottis occurs discontinue therapy and institute appropriate therapy immediately
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors
Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation
Agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia reported with other ACE inhibitor; patients with renal impairment are at high risk; monitor CBC with differential in these patients
Discontinue STAT if patient becomes pregnant
Less effective in blacks
Renal impairment
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd and 3rd trimesters). During the second and third trimesters of pregnancy, these drugs have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure, and death
Lactation: Enters breast milk, not recommended (AAP Committee states "compatible with nursing")
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Enalaprilat, Vasotec (enalapril)
Mechanism of action
Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart
ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed
ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles
ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction
Absorption
Bioavailability: 60%
Onset: 1 hr
Duration: 6 hr (IV), 12-24 hr (PO)
Peak plasma time: 15 min (IV), 1 hr (PO)
Distribution
Protein bound: 50-60%
Metabolism
Liver (70%); enalapril undergoes hepatic biotransformation to enalaprilat within 4 hr following oral administration
Metabolites: Enalaprilat (active)
Initial response for HTN: 15 min (IV), 1 hr (PO)
Peak response for HTN: 1-4 hr (IV), 4-6 hr (PO)
Elimination
Half-life elimination: 2 hr (parent drug), 35-38 hr (active metabolite [enalaprilat])
Dialyzable: Yes (hemodialysis)
Excretion: Urine (61%); feces (6% as enalapril, 27% as enalaprilat)
Administration
IV Incompatibilities
Y-site: Ampho B, ampho B chol SO4, cefepime, phenytoin
IV Compatibilities
Solution: D5W, Normosol r
Additive: Dobutamine, dopamine, heparin, meropenem, nitroglycerin, KCl, sodium nitroprusside
Y-site (partial list): Allopurinol, ampicillin, ampicillin-sulbactam, cefazolin, clindamycin, dobutamine, dopamine, esmolol, fentanyl, heparin, labetalol, linezolid, MgSO4, metronidazole, morphine SO4, nicardipine, KCl, propofol, tobramycin, TMP-SMX, vancomycin
IV Administration
Slow IVP over at least 5 minutes if undiluted, Or
Infused in up to 50 mL of compatible IV infusion solution
Storage
Clear, colorless solution
Store below 30°C
