Epaned

Enalapril is a prescription medication used to treat high blood pressure, heart failure, and a heart condition called left ventricular dysfunction. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take:

• diuretics, or "water pills"
• spironolactone (Aldactone)
• non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin (Ecotrin) and ibuprofen (Advil)
• methyldopa
• nitrates, such as nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate
• calcium channel blocking drugs, such as amlodipine (Norvasc) and verapamil (Calan)
• hydralazine
• prazosin (Minipress)
• digoxin (Lanoxin)
• lithium
• potassium supplements
• injectable gold (sodium aurothiomalate)

This is not a complete list of enalapril drug interactions. Ask your doctor or pharmacist for more information.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of enalapril to treat hypertension in children 1 month to 16 years of age. However, use is not recommended in children younger than 1 month of age and in children with severe kidney disease.

Geriatric

No information is available on the relationship of age to the effects of enalapril in geriatric patients. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving enalapril.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Aliskiren
• Sacubitril

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Allopurinol
• Alteplase, Recombinant
• Amiloride
• Azathioprine
• Azilsartan
• Azilsartan Medoxomil
• Candesartan Cilexetil
• Canrenoate
• Eplerenone
• Eprosartan
• Everolimus
• Interferon Alfa-2a
• Irbesartan
• Lithium
• Losartan
• Mercaptopurine
• Olmesartan Medoxomil
• Oxypurinol
• Potassium
• Sirolimus
• Spironolactone
• Telmisartan
• Triamterene
• Trimethoprim
• Valsartan

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Amtolmetin Guacil
• Aspirin
• Azosemide
• Bromfenac
• Bufexamac
• Bumetanide
• Bupivacaine
• Bupivacaine Liposome
• Capsaicin
• Celecoxib
• Choline Salicylate
• Clomipramine
• Clonixin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyrone
• Droxicam
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Furosemide
• Gold Sodium Thiomalate
• Ibuprofen
• Indomethacin
• Ketoprofen
• Ketorolac
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Nesiritide
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piretanide
• Piroxicam
• Proglumetacin
• Propionic Acid
• Propyphenazone
• Proquazone
• Rifampin
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Valdecoxib

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Angioedema (swelling of the face, lips, tongue, throat, arms, or legs), history of—May increase risk of this condition occurring again.

• Collagen vascular disease (an autoimmune disease) together with kidney disease—Increased risk of blood problems.

• Diabetes or
• Kidney problems—Increased risk of potassium levels in the body becoming too high.

• Diabetic patients who are also taking aliskiren (Tekturna®) or
• Hereditary or idiopathic angioedema—Should not be used in patients with these conditions.

• Electrolyte imbalance (eg, low sodium in the blood) or
• Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
• Heart or blood vessel problems (eg, aortic stenosis, hypertrophic cardiomyopathy) or
• Kidney disease or
• Liver disease—Use with caution. May make these conditions worse.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take Epaned at the same time of day.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Measure liquid doses carefully. Use the measuring device that comes with Epaned (enalapril oral solution). If there is none, ask the pharmacist for a device to measure this medicine.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Hypertension

Epaned is indicated for the treatment of hypertension, to lower blood pressure in adults and children older than one month [see Pediatric Use (8.4) and Clinical Studies (14)].

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.

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 (12.3)].

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

Generally, 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 (2.1)].

Preparation of Epaned (for 150 mL, 1 mg/mL enalapril solution)

Epaned Powder for Oral Solution is a kit containing 1 bottle of enalapril powder and 1 bottle of Ora-Sweet SF diluent to be added to the enalapril powder prior to dispensing to the patient.

Firmly tap the Epaned Powder for Oral Solution bottle on a hard surface 5 times. Add approximately one-half (75 mL) of the Ora-Sweet SF diluent to the 150 mL Epaned Powder for Oral Solution bottle. Replace the child-resistant cap. Shake well for 30 seconds. Reopen. Add the remainder of the Ora-Sweet SF diluent to the Epaned Powder for Oral Solution bottle, replace the child-resistant cap and shake well for an additional 30 seconds. Calculate 60 days from the date of reconstitution. Write this date as the discard date on the front of the label. Affix a “Do Not Use After” or a “Discard After” label with the calculated date added to the reconstituted Epaned bottle.

Epaned Powder for Oral Solution is a kit that contains 150 mg of enalapril maleate in a 150-mL bottle and Ora-Sweet SF diluent. Reconstitution with 150 mL of the provided Ora-Sweet SF diluent results in a 1 mg/mL Epaned oral solution.

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 (8.1)].

Angioedema and Anaphylactoid Reactions

Angioedema

Head and Neck Angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including Epaned, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Epaned should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor [see Contraindications (4)]. ACE inhibitors have been associated with a higher rate of angioedema in black than in non-black patients.

Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk of angioedema [see Drug Interactions (7.6, 7.7)].

Intestinal Angioedema

Intestinal angioedema has occurred in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.

Anaphylactoid Reactions

Anaphylactoid Reactions during Desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.

Anaphylactoid Reactions during Dialysis

Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Hypotension

Epaned can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.

In these patients, Epaned should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of Epaned and/or diuretic is increased.

Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.

Surgery/Anesthesia

In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Epaned may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be through this mechanism, it can be corrected by volume expansion.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis, and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Impaired Renal Function

Monitor renal function in patients treated with Epaned. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on Epaned. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Epaned [see Adverse Reactions (6.2), Drug Interactions (7.2, 7.3)].

Hyperkalemia

Serum potassium should be monitored in patients receiving Epaned. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes [see Drug Interactions (7.3)].

Heart Failure, Mortality Trials

In a multicenter, placebo-controlled clinical trial, 2,569 patients with all degrees of symptomatic heart failure and ejection fraction ≤35 percent were randomized to placebo or enalapril and followed for up to 55 months (SOLVD-Treatment). Use of enalapril was associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure. Diseases that excluded patients from enrollment in the study included severe stable angina (>2 attacks/day), hemodynamically significant valvular or outflow tract obstruction, renal failure (creatinine >2.5 mg/dL), cerebral vascular disease (e.g., significant carotid artery disease), advanced pulmonary disease, malignancies, active myocarditis and constrictive pericarditis. The mortality benefit associated with enalapril does not appear to depend upon digitalis being present.

A second multicenter trial used the SOLVD protocol for study of asymptomatic or minimally symptomatic patients. SOLVD-Prevention patients, who had left ventricular ejection fraction ≤35% and no history of symptomatic heart failure, were randomized to placebo (n=2117) or enalapril (n=2111) and followed for up to 5 years. The majority of patients in the SOLVD-Prevention trial had a history of ischemic heart disease. A history of myocardial infarction was present in 80 percent of patients, current angina pectoris in 34 percent, and a history of hypertension in 37 percent. No statistically significant mortality effect was demonstrated in this population. Enalapril-treated subjects had 32% fewer first hospitalizations for heart failure, and 32% fewer total heart failure hospitalizations. Compared to placebo, 32 percent fewer patients receiving enalapril developed symptoms of overt heart failure. Hospitalizations for cardiovascular reasons were also reduced. There was an insignificant reduction in hospitalizations for any cause in the enalapril treatment group (for enalapril vs. placebo, respectively, 1166 vs. 1201 first hospitalizations, 2649 vs. 2840 total hospitalizations), although the study was not powered to look for such an effect.

The SOLVD-Prevention trial was not designed to determine whether treatment of asymptomatic patients with low ejection fraction would be superior, with respect to preventing hospitalization, to closer follow-up and use of enalapril at the earliest sign of heart failure. However, under the conditions of follow-up in the SOLVD-Prevention trial (every 4 months at the study clinic; personal physician as needed), 68% of patients on placebo who were hospitalized for heart failure had no prior symptoms recorded which would have signaled initiation of treatment.

The SOLVD-Prevention trial was also not designed to show whether enalapril modified the progression of underlying heart disease.

In another multicenter, placebo-controlled trial (CONSENSUS) limited to patients with NYHA Class IV congestive heart failure and radiographic evidence of cardiomegaly, use of enalapril was associated with improved survival. The results are shown in the following table.

In both CONSENSUS and SOLVD-Treatment trials, patients were also usually receiving digitalis, diuretics or both.

Carton

NDC 52652-1001-1

Kit for Preparation of

Epaned®
(Enalapril Maleate
Powder for Oral Solution)
1 mg/mL

When reconstituted, each mL contains:
Enalapril maleate 1 mg
150 mL (when reconstituted)

CONTAINS:

i. 1 bottle containing 150 mg Enalapril Maleate Powder
for Oral Solution

ii. 1 bottle containing 150 mL Ora-Sweet® SF provided as
a diluent for reconstitution

Store at controlled room temperature, 15-30°C (59-86°F).
[See USP Controlled Room Temperature] Do not freeze.

DISCARD 60 DAYS AFTER RECONSTITUTION.

Rx Only

Epaned® Powder for Oral Solution Kit

Directions for mixing: Firmly tap the Epaned Powder for Oral Solution bottle on a hard
surface 5 times. Add approximately one-half (75 mL) of the Ora-Sweet® SF diluent to the
Epaned Powder for Oral Solution bottle. Shake well for 30 seconds. Reopen. Add the
remainder of the Ora-Sweet SF diluent to the Epaned Powder for Oral Solution bottle
and shake well for an additional 30 seconds. Calculate 60 days from the date of
reconstitution. Write this date as the discard date on the front label. Affix a “Do Not Use
After” or a “Discard After” label with the calculated date added to the reconstituted
Epaned bottle. Reconstitution results in 150 mL of a 1 mg/mL Epaned Oral Solution.

Usual Dosage: See Package Insert for dosing information.

NDC 52652-1001-1

Epaned®
(Enalapril Maleate
Powder for Oral Solution)
1 mg/mL

When reconstituted, each mL contains:
Enalapril maleate 1 mg
150 mL (when reconstituted)

Manufactured for:
Silvergate Pharmaceuticals, Inc.
6251 Greenwood Plaza Blvd, Suite 101
Greenwood Village, CO 80111

Country of Origin (API): Spain

Silvergate, the Silvergate logo, and Epaned are trademarks
of Silvergate Pharmaceuticals, Inc. All other registered
trademarks are the property of their respective owners.
(08/14)

Silvergate Pharmaceuticals, Inc.

Rx Only

Epaned® Powder for Oral Solution Kit contains:

i. 1 bottle containing 150 mg Enalapril Maleate Powder for
Oral Solution

ii. 1 bottle containing 150 mL Ora-Sweet® SF provided as a diluent
for reconstitution

Usual Dosage: See Package Insert for dosing information.