Epaned

• •
  When pregnancy is detected, discontinue EPANED^® as soon as possible.

  [See Warnings and Precautions (

  5.1 Fetal Toxicity

  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. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue EPANED as soon as possible

  [see Use

  in Specific Populations ]

  .

  )]
• •
  Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

  [See Warnings and Precautions (

  5.1 Fetal Toxicity

  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. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue EPANED as soon as possible

  [see Use

  in Specific Populations ]

  .

  )]

EPANED is an angiotensin-converting enzyme inhibitor indicated for:

• •treatment of hypertension in adults and children older than one month, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (
  1.1 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.
  ).
• •treatment of symptomatic heart failure (
  1.2 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.
  ).
• •treatment of asymptomatic left ventricular dysfunction, to decrease the rate of development of overt heart failure and reduce hospitalization for heart failure (
  1.3 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

• •Adult: recommended initial dose is 5 mg once daily. Maximum dose is 40 mg daily (
  2.1 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.

  Renal Status	Creatinine-Clearance mL/min	Initial Dose mg/day
  Normal or Mild Impairment of Renal Function	>30 mL/min	5 mg
  Moderate to Severe Impairment	≤30 mL/min	2.5 mg
  Dialysis Patients [See Warnings and Precautions ] .Should be taken after hemodialysis on dialysis days [see Clinical Pharmacology ] . Calculated using ideal body weight.	–	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.
  ).
• •Pediatrics: recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily (
  2.1 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.

  Renal Status	Creatinine-Clearance mL/min	Initial Dose mg/day
  Normal or Mild Impairment of Renal Function	>30 mL/min	5 mg
  Moderate to Severe Impairment	≤30 mL/min	2.5 mg
  Dialysis Patients [See Warnings and Precautions ] .Should be taken after hemodialysis on dialysis days [see Clinical Pharmacology ] . Calculated using ideal body weight.	–	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: 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.

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.

• •EPANED is not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m² (
  8.4 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.
  ).
• •Lactation: Advise not to breastfeed (
  8.2 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.
  ).