Enalapril Maleate
FDA Drug Information • Also known as: Enalapril Maleate, Enalapril Maleate Oral Solution, Epaned, Vasotec
- Brand Names
- Enalapril Maleate, Enalapril Maleate Oral Solution, Epaned, Vasotec
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue enalapril maleate oral solution as soon as possible. [See Warnings and Precautions ( 5.1 )] Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. [See Warnings and Precautions ( 5.1 )] WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue enalapril maleate oral solution 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 )
Description
11 DESCRIPTION Enalapril maleate oral solution is the maleate salt of enalapril, the ethyl ester prodrug of a long-acting angiotensin-converting enzyme inhibitor, enalaprilat. Enalapril maleate is chemically described as (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, (Z)-2-butenedioate salt (1:1). Its empirical formula is C 20 H 28 N 2 O 5
What Is Enalapril Maleate Used For?
1 INDICATIONS AND USAGE Enalapril is an angiotensin-converting enzyme inhibitor indicated for: treatment of symptomatic heart failure. ( 1.2 ) treatment of asymptomatic left ventricular dysfunction, to decrease the rate of development of overt heart failure and reduce hospitalization for heart failure. ( 1.3 ) 1.2 Heart Failure Enalapril maleate oral solution is indicated for the treatment of symptomatic heart failure, usually in combination with diuretics and digitalis. In these patients, enalapril maleate oral solution increases survival and decreases the frequency of hospitalization. 1.3 Asymptomatic Left Ventricular Dysfunction In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35 percent), enalapril maleate oral solution decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Heart Failure: Initiate at 2.5 mg twice daily. Titrate up to 20 mg twice daily as tolerated. ( 2.2 ) Asymptomatic Left Ventricular Dysfunction: Initiate at 2.5 mg twice daily. Titrate up to 10 mg twice daily. ( 2.3 ) Enalapril maleate oral solution is a ready-to-use solution intended for oral use only. 2.2 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 enalapril maleate oral solution does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension. 2.3 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.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere: Angioedema [see Warnings and Precautions ( 5.2 )] Hypotension [see Warnings and Precautions ( 5.3 )] Hepatic failure [see Warnings and Precautions ( 5.4 )] Renal impairment [see Warnings and Precautions ( 5.5 )] Hyperkalemia [see Warnings and Precautions ( 5.6 )] The most common adverse reactions for patients treated for heart failure (>6%) were hypotension and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bionpharma Inc. at 1-888-235-BION or 1-888-235-2466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Enalapril has been evaluated for safety in more than 10,000 patients, including over 1,000 patients treated for one year or more. In clinical trials, discontinuation of therapy for clinical adverse experiences was required in 5.7% of patients with heart failure. Heart Failure In patients treated for heart failure, there was an increased incidence of hypotension 6.7 percent versus 0.6 percent in placebo and dizziness 7.9 percent versus 0.6 percent in placebo. 6.2 Other Adverse Reactions from Clinical Studies or Postmarketing Experience The following adverse reactions have been reported in clinical studies or postmarketing experience with enalapril. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Other serious clinical adverse experiences occurring since the drug was marketed or adverse experiences occurring in 0.5 to 1.0% of patients with hypertension or heart failure in clinical trials are listed below and, within each category, are in order of decreasing severity. Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients [see Warnings and Precautions ( 5.3 )] ; pulmonary embolism and infarction; pulmonary edema; rhythm disturbances, including atrial tachycardia and bradycardia; atrial fibrillation; palpitation; Raynaud's phenomenon. Digestive: Ileus, pancreatitis, melena, anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth. Hematologic: Rare cases of neutropenia, thrombocytopenia, and bone marrow depression. Musculoskeletal: Muscle cramps. Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality. Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection, pulmonary infiltrates, eosinophilic pneumonitis. Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity. Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing. Urogenital: Flank pain, gynecomastia, impotence. Miscellaneous: A symptom complex has been reported which may include some or all of the following: a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, dermatologic manifestations.
Drug Interactions
7 DRUG INTERACTIONS In patients who are elderly, volume-depleted (as on diuretic therapy), or with compromised renal function, use with NSAIDs, including selective COX-2 inhibitors, may result in deterioration of renal function, including renal failure. Monitor renal function periodically. ( 7.1 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia. ( 7.2 ) Avoid potassium sparing agents in patients with heart failure. ( 7.3 ) Monitor serum lithium levels frequently. ( 7.4 ) 7.1 Non-Steroidal Anti-Inflammatory Agents (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving enalapril and NSAID therapy. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate. In this study, there was no evidence of a blunting of the antihypertensive action of enalapril maleate. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. 7.2 Dual Blockade 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. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on enalapril and other agents that affect the RAS. Do not co-administer aliskiren with enalapril in patients with diabetes. Avoid use of aliskiren with enalapril in patients with renal impairment (GFR <60 mL/min). 7.3 Agents Increasing Serum Potassium Enalapril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. 7.4 Lithium Lithium toxicity has been reported in patients receiving enalapril and lithium concomitantly which was generally reversible. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium. 7.5 Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril. 7.6 mTOR...
Contraindications
4 CONTRAINDICATIONS Enalapril is contraindicated in patients with: a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme (ACE) inhibitor. [see Warnings and Precautions ( 5.2 )] hereditary or idiopathic angioedema. [see Warnings and Precautions ( 5.2 )] Do not co-administer aliskiren with enalapril in patients with diabetes [see Drug Interactions ( 7.2 )] . Enalapril is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer enalapril within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions ( 5.2 )] . Hypersensitivity related to previous treatment with an ACEI. ( 4 ) Hereditary or idiopathic angioedema. ( 4 ) Do not co-administer aliskiren in patients with diabetes. ( 4 ) In combination with a neprilysin inhibitor. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Enalapril 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 enalapril 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 to 4% and 15 to 20%, respectively. Clinical Considerations 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 enalapril for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs in neonates with a history of in utero...
Overdosage
10 OVERDOSAGE Limited data are available in regard to overdosage in humans. Single oral doses of enalapril above 1,000 mg/kg and ≥1,775 mg/kg were associated with lethality in mice and rats, respectively. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Enalaprilat may be removed from general circulation by hemodialysis and has been removed from neonatal circulation by peritoneal dialysis.
How Supplied
16 HOW SUPPLIED/ STORAGE AND HANDLING Enalapril maleate oral solution is a ready-to-use solution that contains 1 mg/mL of enalapril maleate, USP. It is a clear, colorless oral 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 placed in a carton with tamper-evident seal. Each bottle contains 150 mL. NDC 69452-237-46 Store refrigerated (2° to 8°C/36° to 46°F) in a tightly closed container. Protect from freezing and excessive heat. Patients may store enalapril maleate oral solution at room temperature (20° to 25°C/68° to 77°F) for up to 60 days.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.