IMPORTANT SAFETY INFORMATION
EPANED® (enalapril maleate) Oral Solution, 1 mg/mL
WARNING: FETAL TOXICITY
See Full Prescribing Information for complete boxed warning.
- When pregnancy is detected, discontinue EPANED as soon as possible (5.1).
- Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1).
EPANED is an angiotensin-converting enzyme (ACE) inhibitor indicated for:
- Treatment of hypertension in adults and children older than 1 month, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
- Treatment of symptomatic heart failure.
- Treatment of asymptomatic left ventricular dysfunction, to decrease the rate of development of overt heart failure and reduce hospitalization for heart failure.
FDA-APPROVED MEDICATIONS DIFFER FROM EXTEMPORANEOUSLY COMPOUNDED DRUGS
The FDA is reinforcing the importance of prescribing an FDA-approved product such as Epaned. According to the FDA:
“When a drug is FDA-approved, patients are assured that the FDA has reviewed the safety and efficacy of the drug and the adequacy of the manufacturing process to produce a quality product….compounded drugs do not provide such assurance and, therefore, should only be used when an FDA-approved product is not available to meet the medical needs of an individual patient.” *
* Hamburg MA. Department of Health and Human Services. Letter to: Colleague. January 8, 2014.
The FDA approval process helps ensure safety and effectiveness for your patients over 1 month of age.
FDA-Approved Medications Differ From Extemporaneously Compounded Drugs
|EPANED Oral Solution||Extemporaneously compounded enalapril suspension|
|Meets FDA standards for potency and purity*||Variable1,2|
|Required compliance with FDA’s CGMPs*||Variable2|
|Sourcing of active ingredient approved by FDA**||Variable1|
|Shelf life/stability*||Well established; Routinely monitored3||Variable1|
|Available at retail pharmacies||YES||Unknown|
|Covered by Medicaid||YES3||Unknown|
* Not all compounders are registered with the FDA; therefore, compounding is dependent on whether the product is compounded at a facility that meets the conditions of sections 503A of the FD&C Act or an outsourcing facility. (CGMP = Current Good Manufacturing Practices)
** In a 2004 published analysis sponsored by STD Pharmaceuticals found that compounding samples purchased from three compounding pharmacies contained significant concentrations of a contaminant that suggested possible use of non-pharmaceutical grade chemicals.
1. Sellers S, Utian WH. Pharmacy Compounding Primer for Physicians. Drugs. 2012;72:2043-2050.
2. FDA/CDER. Guidance for Industry: Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act. January 2018.
3. Data on file, Azurity Pharmaceuticals, Inc.
4. Formulations: Enalapril Maleate 1-mg/ml in SyrSpend SF PH4 Oral Suspension. Int. J Pharm Comp. Vol 22. No. 6, November/December 2018:494
5. Epaned (enalapril maleate) Oral Solution Full Prescribing Information.
Ensured efficacy delivered with consistent potency
The efficacy of enalapril is well established for pediatric patients with hypertension who are older than one month.5 Epaned is also indicated for symptomatic heart failure and asymptomatic left ventricular dysfunction† in adults.5
Epaned Oral Solution provides weight-based dosing (mg/kg) for the treatment of hypertension in children over 1 month of age.
When you choose to prescribe or dispense Epaned, it provides consistent potency from first to last dose in every prescription, and helps ensure consistency from hospital to home.
†To decrease the rate of development of overt heart failure and reduce hospitalization for heart failure.5
ADDITIONAL IMPORTANT SAFETY INFORMATION
EPANED is contraindicated in patients with a history of hypersensitivity related to previous treatment with an ACE inhibitor.
EPANED is contraindicated in patients with hereditary or idiopathic angioedema.
Do not co-administer aliskiren with EPANED in patients with diabetes.
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.
Warnings and Precautions:
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx, including some fatal reactions, have been reported in patients treated with ACE inhibitors, including EPANED, at any time during treatment. EPANED should be promptly discontinued and appropriate therapy and monitoring provided until complete and sustained resolution of signs and symptoms of angioedema has occurred. Patients with a history of angioedema may be at increased risk of angioedema while receiving an ACE inhibitor. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.
Intestinal Angioedema has been reported in patients treated with ACE inhibitors.
Anaphylactoid Reactions: Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. 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. Life-threatening anaphylactoid reactions have been reported with concomitant ACE inhibitor and desensitizing treatment with hymenoptera venom.
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. These patients should be started under close medical supervision and closely followed for the first 2 weeks of treatment with EPANED and whenever the dose of EPANED and/or a 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.
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. Patients 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. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on EPANED.
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 Full Prescribing Information for other Adverse Reactions (6).
Adverse Reactions (where rate on enalapril exceeds the rate on placebo by at least 0.2%) occurring in greater than 1% of patients with hypertension treated with enalapril in controlled trials include: fatigue, orthostatic effects, asthenia, cough, and rash. Adverse reactions reported in clinical trials of heart failure were similar to those seen in clinical trials for hypertension. In patients treated for heart failure, there was an increased incidence of hypotension and dizziness.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, use of non-steroidal anti-inflammatory agents (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure. Monitor renal function periodically in patients receiving enalapril and NSAID therapy.
Dual Inhibition of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function, (including acute renal failure) compared to monotherapy. Closely monitor BP, renal function and electrolytes.
Avoid use of aliskiren with EPANED in patients with renal impairment.
EPANED attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.
Lithium toxicity has been reported in patients receiving enalapril and lithium concomitantly. Monitor serum lithium levels frequently if lithium is concomitantly administered with EPANED.
Nitritoid reactions have been reported rarely in patients with injectable gold (sodium aurothiomalate) and concomitant enalapril therapy.
mTOR or neprilysin inhibitors: Patients receiving coadministration of an ACE inhibitor and a mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.
Use in Specific Populations: See Full Prescribing Information for Additional Information (8).
EPANED can cause fetal harm. See Full Prescribing Information for Additional Information (5.1, 8.1).
Women should not breastfeed during treatment with EPANED.
EPANED is not recommended in neonates (i.e., infants 1 month of age or less), preterm infants who have not reached a post-conceptual age of 44 weeks, and in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2.
This Important Safety Information does not include all the information needed to use EPANED safely and effectively. Visit EPANED.com for Full Prescribing Information
To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-855-379-0383, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.