playing with [30:<0.1) 2.6 Orthostatic Effects 1.2 (> <0.1) 0.0 Asthenia 1.1 (0.1) 0.9 Respiratory Cough 1.3 (0.1) 0.9 Skin Rash 1.4 (0.4) 0.4 Heart Failure Adverse reactions seen 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 6.7 percent versus 0.6 percent in placebo and dizziness 7.9 percent versus 0.6 percent in placebo. 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 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. 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 Epaned and other agents that affect the RAS. Do not co-administer aliskiren with Epaned in patients with diabetes. Avoid use of aliskiren with Epaned in patients with renal impairment (GFR> <60 mL/min). Agents Increasing Serum Potassium Epaned 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. 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. 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. mTOR Inhibitors Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema [see Warnings and Precautions ( 5.2 )]. Neprilysin Inhibitor Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema [see Warnings and Precautions ( 5.2 )] . USE IN SPECIFIC POPULATIONS 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 m 2 [see Nonclinical Toxicology ( 13.2 )]. 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 ( 12.3 ) and Dosage and Administration ( 2.1 )] . 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 ( 12.3 )] . 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 ( 13.2 )]. 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 ( 2.1 ) and Clinical Pharmacology ( 12.3 )]. 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 . Epaned Description Epaned (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 •C 4 H 4 O 4 , and its structural formula is: Enalapril maleate is a white to off-white, crystalline powder with a molecular weight of 492.52. It is sparingly soluble in water, soluble in ethanol, and freely soluble in methanol. Epaned Oral Solution is a ready-to-use oral solution. Each 1 mL contains 1 mg of enalapril maleate, USP equivalent to 0.764 mg of enalapril. Inactive ingredients include citric acid, mixed berry flavor, purified water, sodium benzoate, sodium citrate, and sucralose. It may also contain hydrochloric acid or sodium hydroxide for pH adjustment. Epaned Oral Solution is clear and colorless. Epaned - Clinical Pharmacology Mechanism of Action Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Although the latter decrease is small, it results in small increases of serum potassium. In hypertensive patients treated with enalapril maleate tablets alone for up to 48 weeks, mean increases in serum potassium of approximately 0.2 mEq/L were observed. In patients treated with enalapril maleate tablets plus a thiazide diuretic, there was essentially no change in serum potassium [see Warnings and Precautions ( 5.6 )] . Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Epaned remains to be elucidated. While the mechanism through which Epaned lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, enalapril is antihypertensive even in patients with low-renin hypertension. Although enalapril maleate tablets were antihypertensive in all races studied, Black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to enalapril monotherapy than non-Black patients. Pharmacodynamics Hypertension Adults Administration of enalapril maleate tablets to patients with hypertension of severity ranging from mild to severe results in a reduction of both supine and standing blood pressure, usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients [see Warnings and Precautions ( 5.3 )] . In most patients studied, after oral administration of a single dose of enalapril, onset of antihypertensive activity was seen at one hour with peak reduction of blood pressure achieved by four to six hours. At recommended doses, antihypertensive effects have been maintained for at least 24 hours. In some patients the effects may diminish toward the end of the dosing interval [see Dosage and Administration ( 2.1 )] . In some patients achievement of optimal blood pressure reduction may require several weeks of therapy. The antihypertensive effects of enalapril have continued during long-term therapy. Abrupt withdrawal of enalapril has not been associated with a rapid increase in blood pressure. In hemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little or no change in heart rate. Following administration of enalapril, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension. When given together with thiazide-type diuretics, the blood pressure lowering effects of enalapril maleate are approximately additive. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate tablets. In this study, there was no evidence of a blunting of the antihypertensive action of enalapril [see Drug Interactions ( 7.1 )] . Pediatric Patients In a clinical study involving 110 hypertensive pediatric patients 6 to 16 years of age, patients who weighed> <50 kg received either 0.625, 2.5, or 20 mg of enalapril daily and patients who weighed ≥50 kg received either 1.25, 5, or 40 mg of enalapril daily. Enalapril administration once daily lowered trough blood pressure in a dose-dependent manner. The dose-dependent antihypertensive efficacy of enalapril was consistent across all subgroups (age, Tanner stage, gender, race). However, the lowest doses studied, 0.625 mg and 1.25 mg, corresponding to an average of 0.02 mg/kg once daily, did not appear to offer consistent antihypertensive efficacy. In this study, enalapril maleate was generally well tolerated. Limited information exists on the blood pressure lowering effects in pediatric patients less than 6 years of age. Heart Failure In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increased cardiac output and exercise tolerance. Heart rate was unchanged or slightly reduced, and mean ejection fraction was unchanged or increased. There was a beneficial effect on severity of heart failure as measured by the New York Heart Association (NYHA) classification and on symptoms of dyspnea and fatigue. Hemodynamic effects were observed after the first dose, and appeared to be maintained in uncontrolled studies lasting as long as four months. Effects on exercise tolerance, heart size, and severity and symptoms of heart failure were observed in placebo-controlled studies lasting from eight weeks to over one year. Pharmacokinetics The pharmacokinetics of ready-to-use Epaned Oral Solution was shown to be bioequivalent to that of reconstituted Epaned Powder for Oral Solution under fasted conditions. Reconstituted Epaned Powder for Oral Solution was shown to be bioequivalent to Vasotec tablets. Reconstituted Epaned Powder for Oral Solution was also evaluated under fed and fasted conditions. A high-fat meal reduced the C max of enalapril and enalaprilat by 46% and 36%, respectively. The exposure, as measured by AUC, to enalaprilat was reduced by 23%. The time to peak concentrations (C max ) was delayed by 20 minutes for enalapril and 62 minutes for enalaprilat. The trough plasma concentrations of enalapril (from 6 to 12 hours) and enalaprilat (from 16 to 36 hours) are similar between fasted and fed administrations. Adults Following oral administration of enalapril maleate tablets, peak serum concentrations of enalapril occur within about one hour. Based on urinary recovery, the extent of absorption of enalapril is approximately 60%. Enalapril absorption is not influenced by the presence of food in the gastrointestinal tract. Following absorption, enalapril is hydrolyzed to enalaprilat, which is a more potent angiotensin-converting enzyme inhibitor than enalapril; enalaprilat is poorly absorbed when administered orally. Peak serum concentrations of enalaprilat occur three to four hours after an oral dose of enalapril maleate. Excretion of enalapril is primarily renal. Approximately 94% of the dose is recovered in the urine and feces as enalaprilat or enalapril. The principal components in urine are enalaprilat, accounting for about 40% of the dose, and intact enalapril. There is no evidence of metabolites of enalapril, other than enalaprilat. The serum concentration profile of enalaprilat exhibits a prolonged terminal phase, apparently representing a small fraction of the administered dose that has been bound to ACE. The amount bound does not increase with dose, indicating a saturable site of binding. The effective half-life for accumulation of enalaprilat following multiple doses of enalapril maleate is 11 hours. The disposition of enalapril and enalaprilat in patients with renal insufficiency is similar to that in patients with normal renal function until the glomerular filtration rate is 30 mL/min or less. With glomerular filtration rate 30 mL/min, peak and trough enalaprilat levels increase, time to peak concentration increases, and time to steady state may be delayed. The effective half-life of enalaprilat following multiple doses of enalapril maleate is prolonged at this level of renal insufficiency [see Dosage and Administration ( 2.1 )] . Enalaprilat is dialyzable at the rate of 62 mL/min. Administering enalapril 1 h after hemodialysis led to a reduction of approximately 50% in the enalaprilat AUC 0-6 h compared to off dialysis days. Pediatric Patients A multiple dose pharmacokinetics study was conducted in 40 hypertensive male and female pediatric patients aged 2 months to 16 years following daily oral administration of 0.07 to 0.14 mg/kg enalapril maleate. At steady state, the mean effective half-life for accumulation of enalaprilat was 14 hours and the mean urinary recovery of total enalapril and enalaprilat in 24 hours was 68% of the administered dose. Conversion of enalapril to enalaprilat was in the range of 63-76%. The overall results of this study indicate that the pharmacokinetics of enalapril in hypertensive children aged 6 to 16 years are consistent across the studied age groups and consistent with pharmacokinetic historical data in healthy adults. Hypertensive children aged 2 months to 6 years required higher weight-based doses (0.13 mg/kg and 0.11 mg/kg) compared to the older age groups (0.11 mg/kg and 0.07 mg/kg), to achieve similar steady-state AUC. In the above pediatric study, enalapril maleate was given as tablets and for those children and infants who were unable to swallow tablets or who required a lower dose than is available in tablet form, enalapril was administered in a suspension formulation. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of a tumorigenic effect when enalapril was administered for 106 weeks to male and female rats at doses up to 90 mg/kg/day or for 94 weeks to male and female mice at doses up to 90 and 180 mg/kg/day, respectively. These doses are 26 times (in rats and female mice) and 13 times (in male mice) the maximum recommended human daily dose (MRHDD) when compared on a body surface area basis. Neither enalapril maleate nor the active diacid was mutagenic in the Ames microbial mutagen test with or without metabolic activation. Enalapril was also negative in the following genotoxicity studies: rec-assay, reverse mutation assay with E. coli , sister chromatid exchange with cultured mammalian cells, and the micronucleus test with mice, as well as in an in vivo cytogenic study using mouse bone marrow. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril (26 times the MRHDD when compared on a body surface area basis). Animal Toxicology and/or Pharmacology In several experimental published studies, rat pups exposed to daily enalapril from birth to post natal Day 13 (the period of nephrogenesis in this species) developed irreversible renal toxicity. In contrast, treatment after post-natal Day 14 was not toxic to the more mature kidney. Rat kidney development at birth and at 14 days is similar to the human at mid-trimester and in infancy, respectively. The toxic dosages in these studies were about 10X, on a mg/m 2 basis, the highest recommended oral (0.58 mg/kg/day) pediatric dosages to treat hypertension. Lower dosages were not studied. Clinical Studies 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. CONSENSUS Survival Rates SURVIVAL (%) Six Months One Year VASOTEC (n = 127) 74 64 Placebo (n = 126) 56 48 In both CONSENSUS and SOLVD-Treatment trials, patients were also usually receiving digitalis, diuretics or both. How Supplied/Storage and Handling Epaned is a ready-to-use solution that contains 1 mg/mL of enalapril maleate. 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 tamper-evident seal. Each bottle contains 150 mL. NDC 52652-4001-1 Store refrigerated (2 -8 C/36 -46 F) in a tightly closed container. Patients may store Epaned either refrigerated (2 -8 C/36 -46 F) or at room temperature (20 -25 C/68 -77 F). If stored at room temperature, discard after 60 days. Avoid freezing and excessive heat. Patient Counseling Information • Pregnancy Tell female patients of childbearing age about the consequences of exposure to Epaned during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible. • Angioedema Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme inhibitors, including enalapril. Advise patients to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, or tongue, or difficulty in swallowing or breathing) and to consult with the prescribing physician before taking more drug. • Hypotension Caution patients to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, tell patients to discontinue the drug until they have consulted with the prescribing physician. Tell patients that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; advise patients to consult with their physician. • Hyperkalemia Tell patients to consult their physician prior to using salt substitutes containing potassium. Epaned is a registered trademark of Silvergate Pharmaceuticals, Inc. Vasotec is a registered trademark of Valeant International Bermuda. Manufactured For: Silvergate Pharmaceuticals, Inc. 6251 Greenwood Plaza Blvd., Suite 101 Greenwood Village, CO 80111 U. S. Patents 9669008, 9808442 EOS-1711 PRINCIPAL DISPLAY PANEL - BOTTLE LABEL Bottle Label NDC 52652-4001-1 Epaned (enalapril maleate) Oral Solution 1 mg/mL For Oral Use Only READY TO USE 150 mL Silvergate Pharmaceuticals, Inc. Rx Only Each 1 mL contains 1 mg enalapril maleate equivalent to 0.764 mg enalapril. Usual Dose: See prescribing information. Store refrigerated 2 - 8 C (36 - 46 F) After dispensing, may be stored at room temperature 20 - 25 C (68 - 77 F) for up to 60 days. Avoid freezing and excessive heat. Keep container tightly closed. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN P/N 140538 Manufactured for: Silvergate Pharmaceuticals, Inc. Greenwood Village, CO 80111 Lot: Exp: Epaned enalapril maleate solution Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52652-4001 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ENALAPRIL MALEATE (ENALAPRILAT ANHYDROUS) ENALAPRIL MALEATE 1 mg in 1 mL Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE WATER SODIUM BENZOATE SODIUM CITRATE, UNSPECIFIED FORM SUCRALOSE HYDROCHLORIC ACID SODIUM HYDROXIDE Product Characteristics Color Score Shape Size Flavor BERRY (Mixed Berry) Imprint Code Contains Packaging # Item Code Package Description 1 NDC:52652-4001-1 150 mL in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA208686 10/03/2016 Labeler - Silvergate Pharmaceuticals, Inc. (011248265) Establishment Name Address ID/FEI Operations Zhejiang Huahai Pharmaceutical Co., Ltd. 530732460 API MANUFACTURE(52652-4001) Establishment Name Address ID/FEI Operations Medichem Sa 464043381 API MANUFACTURE(52652-4001) Establishment Name Address ID/FEI Operations Dpt Laboratories, Ltd. 832224526 MANUFACTURE(52652-4001), ANALYSIS(52652-4001), PACK(52652-4001) Revised: 11/2017 Silvergate Pharmaceuticals, Inc. Next Interactions Print this page Add to My Med List More about Epaned (enalapril) Side Effects During Pregnancy or Breastfeeding Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Consumer resources Epaned Epaned (Advanced Reading) Professional resources Enalaprilat/Enalapril Maleate (AHFS Monograph) Enalapril Tablets Soluble (FDA) Other brands: Vasotec> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Silvergate Pharmaceuticals, Inc. Recently Approved Lonhala Magnair Lonhala Magnair (glycopy to utilize
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