Dosage & Administration
Hypertension
Heart Failure: Initiate at 2.5 mg twice daily. Titrate up to 20 mg twice daily as tolerated .
Asymptomatic Left Ventricular Dysfunction: Initiate at 2.5 mg twice daily. Titrate up to 10 mg twice daily .
EPANED Oral Solution is a ready-to-use solution intended for oral use only.
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Epaned Prescribing Information
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- When pregnancy is detected, discontinue EPANED® as soon as possible. [See Warnings and Precautions ]
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- Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. [See Warnings and Precautions ]
Hypertension
EPANED is indicated for the treatment of hypertension, to lower blood pressure in adults and children older than one month [see Pediatric Use and Clinical Studies ].
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in Black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
EPANED is effective alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of EPANED and thiazides are approximately additive.
Heart Failure
EPANED is indicated for the treatment of symptomatic heart failure, usually in combination with diuretics and digitalis. In these patients, EPANED increases survival and decreases the frequency of hospitalization.
Asymptomatic Left Ventricular Dysfunction
In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35 percent), EPANED decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure.
Hypertension
Adults: The recommended initial dose in adults is 5 mg taken orally once a day. Titrate upward to maximum of 40 mg daily as needed to help achieve blood pressure goals. The dose may be divided and administered twice daily if the antihypertensive effect diminishes at the end of the dosing interval.
Use with diuretics: If additional blood pressure reduction is needed, EPANED may be administered with a low dose of diuretic. The recommended initial dose in patients taking diuretics is 2.5 mg daily.
Dosage Adjustment for Renal Impairment: See table below. The dosage may be titrated upward as needed to a maximum of 40 mg daily.
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Renal Status | Creatinine-Clearance | Initial Dose |
Normal or Mild Impairment of Renal Function | >30 mL/min | 5 mg |
Moderate to Severe Impairment | ≤30 mL/min | 2.5 mg |
Dialysis Patients * † | – | 2.5 mg |
Children greater than 1 month of age: The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Adjust dose based on blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology ].
EPANED is not recommended in neonates (i.e., infants 1 month of age or less), preterm infants who have not reached a corrected post-conceptual age of 44 weeks, and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2.
Heart Failure
The recommended initial dose is 2.5 mg twice a day titrated up to a maximum of 20 mg twice a day, as tolerated. Doses are usually given in combination with diuretics and digitalis.
In patients with hyponatremia (serum sodium less than 130 mEq/L) or serum creatinine greater than 1.6 mg/dL, the recommended initial dose is 2.5 mg once daily.
Diuretic dose may need to be adjusted to minimize hypovolemia and hypotension. The appearance of hypotension after the initial dose of EPANED does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.
Asymptomatic Left Ventricular Dysfunction
The recommended initial dose is 2.5 mg twice a day titrated up to a maximum of 10 mg twice a day, as tolerated. Diuretic dose may need to be adjusted [see Dosage and Administration ].
EPANED is a ready-to-use oral solution that contains 1 mg/mL of enalapril maleate. It is a clear, colorless solution with a mixed berry flavor packaged in a 150 mL white, round, high-density polyethylene bottle with a white, polypropylene, child-resistant cap and tamper-evident seal. Each bottle contains 150 mL.
Pregnancy
Risk Summary
EPANED can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue EPANED as soon as possible.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.
Adverse reactions in the fetus or in neonates with a history of in utero exposure to enalapril maleate.
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydraminos may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to EPANED for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs in neonates with a history of in utero exposure to EPANED, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.
Lactation
Risk Summary
Enalapril and enalaprilat have been detected in human breast milk. Because of the potential for severe adverse reactions in the breastfed infant, including hypotension, hyperkalemia and renal impairment, advise women not to breastfeed during treatment with EPANED.
Pediatric Use
Neonates with a history of in utero exposure to enalapril maleate
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Enalapril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.
Pediatric patients with hypertension
EPANED is not recommended in neonates (i.e., infants 1 month of age or less), preterm infants who have not reached a corrected post-conceptual age of 44 weeks, and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2[see Nonclinical Toxicology ].
Enalapril lowers blood pressure in hypertensive pediatric patients age 6 years to 16 years. Use of enalapril in these age groups is supported by evidence from adequate and well-controlled studies of enalapril in pediatric and adult patients as well as by published literature in pediatric patients [see Clinical Pharmacology and Dosage and Administration ]. Clinical efficacy studies of enalapril in pediatric patients with hypertension did not enroll patients less than 6 years of age. In a previous clinical study in pediatric patients between 2 months and 6 years of age, a higher weight-based dose was required to match exposure in children aged 6 to 16 years [see Clinical Pharmacology ].
It is unknown whether post-natal use of ACE inhibitors such as enalapril before maturation of renal function is complete has long-term deleterious effects on the kidney. In humans, nephrogenesis is thought to be complete around birth; however maturation of other aspects of kidney function (such as glomerular filtration and tubular function) may continue until approximately 2 years of age [see Nonclinical Toxicology ].
Pediatric patients with heart failure or asymptomatic left ventricular dysfunction
Safety and effectiveness of enalapril have not been established in pediatric patients with heart failure or asymptomatic left ventricular dysfunction.
Geriatric Use
This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Race
ACE inhibitors, including EPANED, as monotherapy have an effect on blood pressure that is less in Black patients than in non-Blacks.
Renal Impairment
Use a lower initial dose of EPANED in patients undergoing hemodialysis and in patients whose eGFR is ≤ 30 mL/min [see Dosage and Administration and Clinical Pharmacology ].
EPANED is contraindicated in patients with:
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- a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme (ACE) inhibitor [see Warnings and Precautions ].
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- hereditary or idiopathic angioedema [see Warnings and Precautions ].
Do not co-administer aliskiren with EPANED in patients with diabetes [see Drug Interactions ].
EPANED is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer EPANED within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions ].