Enalapril Maleate (8 brand names, 4 dosage forms, 1 route)
Available dosage forms: TABLET, SOLUTION, FOR SOLUTION, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- ENALAPRIL MALEATE
- ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE
- EPANED
- EPANED KIT
- LEXXEL
- TECZEM
- VASERETIC
- VASOTEC
Boxed Warning
See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue enalapril maleate tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (See WARNINGS, Fetal Toxicity.)
Contraindications
Enalapril maleate tablets are contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Do not coadminister aliskiren with enalapril maleate tablets in patients with diabetes (see PRECAUTIONS, Drug Interactions ). Enalapril maleate tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer enalapril maleate tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS, Head and Neck Angioedema ).
Adverse Reactions
Enalapril maleate tablets have been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. Enalapril maleate tablets have been found to be generally well tolerated in controlled clinical trials involving 2987 patients. For the most part, adverse experiences were mild and transient in nature. In clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 3.3 percent of patients with hypertension and in 5.7 percent of patients with heart failure. The frequency of adverse experiences was not related to total daily dosage within the usual dosage ranges. In patients with hypertension the overall percentage of patients treated with enalapril maleate tablets reporting adverse experiences was comparable to placebo.
Drug Interactions
Neprilysin Inhibitors Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema (see WARNINGS ). 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. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on enalapril maleate tablets and other agents that affect the RAS. Do not coadminister aliskiren with enalapril maleate tablets in patients with diabetes. Avoid use of aliskiren with enalapril maleate tablets in patients with renal impairment (GFR <60 mL/min). Hypotension — Patients on Diuretic Therapy Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS, Hypotension and DOSAGE AND ADMINISTRATION ). Agents Causing Renin Release The antihypertensive effect of enalapril maleate tablets is augmented by antihypertensive agents that cause renin release (e.g., diuretics). Nonsteroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compr
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 PRECAUTIONS ). 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 enalapril maleate tablets remains to be elucidated. While the mechanism through which enalapril maleate tablets lower blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, enalapril maleate tablets are 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.
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 (see WARNINGS, Anaphylactoid Reactions during Membrane Exposure ).