Full Prescribing Info
Enalapril maleate.
Each tablets contains enalapril maleate.
Enalapril maleate (Hypace) is the maleate salt of enalapril, the ethyl ester of a long-acting angiotensin converting enzyme inhibitor, enalaprilat. It is a white to off-white, crystalline powder with a molecular weight of 492.53. It is sparingly soluble in water, soluble in ethanol, and freely soluble in methanol.
Pharmacotherapeutic Group: Angiotensin-converting enzyme (ACE) inhibitor.
Pharmacology: Pharmacodynamics/Pharmacokinetics: Enalapril acts as a prodrug of the diacid enalaprilat, its active form, which is poorly absorbed orally. About 60% of an oral dose of enalapril is absorbed from the gastrointestinal tract and peak plasma concentrations are achieved within about 1 hour. Enalapril is extensively hydrolyzed in the liver to enalaprilat; peak plasma concentrations of enalaprilat are achieved 3 to 4 hours after an oral dose of enalapril. Enalaprilat is 50 to 60% bound to plasma proteins. After an oral dose, enalapril is excreted in the urine and in feces as enalaprilat and unchanged drug mainly through the urinary route. The elimination of enalaprilat is multiphasic but the effective half-life for accumulation after multiple doses of enalapril is reported to be about 11 hours in patients with normal renal function. Enalaprilat is removed by hemodialysis and peritoneal dialysis.
Treatment of hypertension and heart failure. May also be given prophylactically to patients with asymptomatic left ventricular dysfunction to delay the onset of symptomatic heart failure and to those with left ventricular dysfunction to reduce the incidence of coronary ischemic events, including myocardial infarction.
Dosage/Direction for Use
Hypertension: Initial Dose: 5 mg daily. Usual dosage range: 10 to 40 mg per day as a single dose or two divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, consider increasing dose or administering twice daily.
Dosage Adjustment in Hypertensive Patients with Renal Impairment: The usual dose of enalapril maleate (Hypace) is recommended for patients with a creatinine clearance >30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≤30mL/min (serum creatinine ≥3 mg/dL), the first dose is 2.5 mg once daily. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
Heart Failure: Initial Dose: 2.5 mg daily. Maintenance Dose: 20 mg daily as a single dose or in 2 divided doses. Recommended dosing range: 2.5 to 20 mg given twice a day. Maximum daily dose: 40 mg in divided doses.
Asymptomatic Left Ventricular Dysfunction: Initially, 2.5 mg twice daily. Titrate as tolerated to the targeted daily dose of 20 mg (in divided doses).
Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia: In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical supervision. The dose may be increased to 2.5 twice a day, then 5 mg twice a day and higher as needed, usually at intervals of four days or more if at time of dosage adjustment there is not excessive hypotension or significant deterioration of renal function. Maximum daily dose: 40 mg.
Pediatric Hypertensive Patients: Antihypertensive effects of enalapril maleate (Hypace) have been established in hypertensive pediatric patient’s age 1 month to 16 years. Recommended starting dose: 0.08 mg/kg (up to 5 mg) once daily. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients.
Administration: It should be taken with food or immediately after meals.
Most likely symptom is hypotension with stupor beginning within six hours after tablet ingestion. This can be treated by IV infusion of normal saline solution. Gastric lavage and use of activated charcoal should be considered. Enalaprilat may be removed by hemodialysis.
Hypersensitivity to any component of Hypace and history of angioneurotic edema relating to previous treatment with an angiotensin-converting enzyme inhibitor.
Special Precautions
Hypotension [systolic blood pressure (SBP) <90 mmHg]: More likely to occur if a patient has been volume-depleted eg, by diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. Patients with severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatremia or functional renal impairment should be closely supervised so that the doses of diuretic and/or enalapril maleate be adjusted. If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive IV infusion of normal saline.
Impaired Renal Function: Acute renal failure, usually reversible after discontinuation of use. Patients with renal insufficiency may require reduced and/or less frequent doses.
Hypersensitivity/Angioneurotic Edema: Rarely reported, but in such cases, Hypace-therapy should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to discharging the patient. In instances where swelling has been confined in the lips and the face, the conditions generally resolved without treatment, although antihistamines are useful in relieving the symptoms.
Angioneurotic edema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx, appropriate therapy eg, SC epinephrine solution 1:1000 (0.3-0.5 mL) should be administered promptly.
Anaphylactoid Reactions During Hymenoptera Desensitization: Rarely reported, but in such case can be avoided by temporarily withholding ACE inhibitor therapy prior to each desensitization.
Hemodialysis Patients: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with ACE inhibitor. Consideration should be given to these patients to use a different type of dialysis membrane or a different class of antihypertensive agent.
Cough: Characteristically, it is nonproductive, persistent and resolves after discontinuation of therapy.
Surgery/Anesthesia: If hypotension occurs and is considered to be due to enalapril's blockade of angiotensin II formation secondary to compensatory renin release, it can be corrected by volume expansion.
Use In Pregnancy & Lactation
Use in lactation: Following administration of a single dose of enalapril 20 mg to 5 lactating women, enalaprilat was detected in breast milk in concentrations of 1-2.3 ng/mL (mean peak 1.72 ng/mL). This was compared with peak serum values of 39-112 ng/mL for enalaprilat and 92-151 ng/mL for enalapril. Although enalapril and its metabolite are present in small amounts in breast milk, it was calculated that the average total daily dose to the neonate would only be about 2 mcg of enalaprilat.
Adverse Reactions
Cardiovascular: Myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients, syncope, orthostatic hypotension, palpitations, chest pain, rhythm disturbances, angina pectoris, Raynaud's phenomenon.
Endocrine: Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Gastrointestinal system: Ileus, pancreatitis, hepatic failure, hepatitis either hepatocellular or cholestatic, jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis.
Metabolic: Cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin have been reported.
Nervous system/Psychiatric: Depression, confusion, somnolence, insomnia, nervousness, paresthesia, vertigo, dream abnormality.
Renal: Renal failure, oliguria, renal dysfunction.
Respiratory: Pulmonary infiltrates, bronchospasm/asthma, dyspnea, rhinorrhea, sore throat and hoarseness.
Skin: Diaphoresis, erythema multiform, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, alopecia.
Others: Angioedema, vasculitis, muscle cramps, hyperhidrosis, impotence, asthenia, photosensitivity, flushing, taste alteration, tinnitus, glossitis, blurred vision.
Drug Interactions
Agents Causing Renin Release: The antihypertensive effect of enalapril maleate (Hypace) is augmented by antihypertensive agents that cause renin release (e.g., diuretics).
Other Cardiovascular Agents: Concomitant use with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine and prazosin shows no evidence of clinically significant adverse interactions.
Agents Increasing Serum Potassium: Enalapril maleate (Hypace) may attenuate potassium loss caused by thiazide-type diuretics. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g., trimethoprim-containing products).
Antidiabetics: Concomitant administration of ACEI and antidiabetic agents may cause an increased risk of hypoglycemia more likely to occur during the first weeks of combined treatment and in patients with renal impairment.
Serum Lithium: As with other drugs which eliminate sodium, lithium clearance may be reduced. Therefore, the serum lithium levels should be monitored carefully if lithium salts are to be administered.
Non-Steroidal Anti-Inflammatory Drugs including Selective Cyclooxygenase-2 Inhibitors: NSAIDs including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive drugs. Administer with caution in patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy).
Combination Use of ACE Inhibitors or Angiotensin Receptor Antagonists, Anti-inflammatory drugs and Thiazide Diuretics: The use of ACEI or ARB, NSAID or COX-2 inhibitor, and a thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed-dose combination products containing more than one class of drug.
Dual Blockade of the Renin-Angiotensin-Aldosterone System: Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARB, ACEI, or direct renin inhibitors (such as aliskiren) is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Do not co-administer aliskiren with enalapril maleate (Hypace) in patients with diabetes. Avoid use of aliskiren with enalapril maleate (Hypace) in patients with renal impairment (GFR <60 mL/min).
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 ACEI therapy.
Mammalian Target of Rapamycin (mTOR) Inhibitors: Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
Neprilysin Inhibitors: Patients taking a concomitant neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.
Store at a temperature not exceeding 30°C.
Shelf-Life: 48 months.
ATC Classification
C09AA02 - enalapril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.
Tab 5 mg x 28's. 10 mg x 28's. 20 mg x 28's.
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