Enara-5/Enara-20

Enalapril maleate.

Enara-5: Each 1 tablet contains Enalapril Maleate 5 mg.
Enara-20: Each 1 tablet contains Enalapril Maleate 20 mg.

Pharmacology: Pharmacodynamics: Enalapril maleate is a prodrug of enalaprilat. Enalapril is competitive inhibitor of angiotensin converting enzyme (ACE). Renin is released into the circulation when it acts on angiotensin to produce angiotensin I. Angiotensin I is then converted by the ACE to angiotensin II. Enalapril prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of ACE. Inhibition of ACE initially results in decreased plasma angiotensin II concentration and consequently blood pressure may be reduced in part through decreased vasoconstriction. Enalapril reduces blood pressure by decreasing total peripheral resistance with a slightly increase or no change in heart rate, stroke volume, or cardiac output. The drug causes arterial and possibly venous dilation. Enalapril generally decreases systolic and diastolic blood pressures by approximately 10-15%
Pharmacokinetics: Absorption: Enalapril maleate is well absorbed following oral administration. Approximately 55-75% of an oral dose of enalapril maleate is rapidly absorbed from the GI tract. Food does not appear to substantially affect the rate or extent of absorption of enalapril maleate. Time to peak in serum of enalapril maleate and enalaprilat is 0.5-1.5 and 3-4.5 hours, respectively.
Distribution: Approximately 50-60% of enalaprilat is bound to plasma proteins. Enalapril maleate crosses the placenta. Information on distribution into the CNS is limited, but enalapril appears to cross the blood-brain barrier poorly, and enalaprilat does not appear to distribute into CNS. Enalapril and enalaprilat are distributed into milk in trace amounts.
Metabolism: About 60% of an absorbed dose of enalapril is extensively hydrolyzed to enalaprilat (active metabolite), principally in the liver via esterase. About 20% appears to be hydrolyzed on first pass through the liver. Enalaprilat is a more potent ACE inhibitor than enalapril.
Excretion: The elimination half-life of Enalapril to be less than 2 hours in healthy volunteers, 3.4-5.8 hours in congestive heart failure. Enalapril and enalaprilat are excreted in urine and feces. A mean of 60-78% (a mean of 43-56% as enalaprilat and the remainder as unchanged drug) of enalapril maleate is excreted in urine within 24-48 hour after administration and approximately 33% (about 27% as enalaprilat and 6% as unchanged drug) is excreted in feces within 24-48 hour after administration. Renal clearance of enalaprilat and enalapril are reported to be approximately 100-158 and 300 mL/minute, respectively, in adults with normal renal function. Enalaprilat is removed by hemodialysis and also appears to be removed by peritoneal dialysis.

Treatment of hypertension.
Treatment of symptomatic heart failure.

Enara-5/Enara-20: Hypertension: Adult: Initial dosage: 5 mg once daily.
In patients not on diuretics: 2.5 mg once daily.
If patient is taking diuretic that cannot be discontinued.
Usual dosage: 10 to 40 mg/day as a single dose or 2 divided doses.
Maximum dosage: 40 mg/day.
Pediatric (less than 16 years of age): Initial dosage: 0.08 mg/kg (up to 5 mg) once daily.
Enara-5: Heart Failure: Initial dosage: 2.5 mg twice daily.
Usual dosage: 5 to 20 mg/day as a single dose or 2 divided doses.
Maximum dosage: 40 mg/day.
Enara-20: Heart Failure: Initial dosage: 2.5 mg twice daily.
Usual dosage: 10 to 40 mg/day as a single dose or 2 divided doses.
Maximum dosage: 2.5 to 20 mg/day.
Mode of Administration: Enalapril maleate is administered orally. For patients unable to swallow tablets, may be administered orally as an extemporaneously prepared suspension. The drug can be given before, during, or after meals since food does not appear to substantially affect the rate or extent of absorption of enalapril.

The oral LD₅₀ of enalapril maleate ranged from 2000-3500 mg/kg in mice and male rats and 2000-3000 mg/kg in female rats. Overdosage of enalapril produces effects that are mainly extensions of the drugs pharmacologic effects as an ACE inhibitor. Plasma ACE activity was completely suppressed within 10-15 hours after acute ingestion of 300-400 mg of enalapril maleate in 2 patients. The most likely manifestation of enalapril overdosage is hypotension. Hypotension may be accompanied by stupor. Renal dysfunction, including acute renal failure, hyperkalemia and hyponatremia may occur.
Management of enalapril overdosage is mainly supportive and symptomatic. Hypotension can be corrected with fluid volume expansion (e.g. IV infusion of 0.9% Sodium chloride injection). Renal function also improves during supportive therapy with sodium chloride infusion. Treatment of acute oral overdosage may also include gastric lavage and administration of activated charcoal to prevent further GI absorption of the drug. The active metabolite enalaprilat may be removed by hemodialysis.

Patients with known hypersensitivity to ACE inhibitor or any component of the formulation.
Patients with a history of angioedema related to ACE inhibitor therapy and those with hereditary or and those with hereditary or idiopathic angioedema.
Patients with diabetes mellitus concomitant use with aliskiren.
Coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (e.g. sacubitril).

ACE inhibitors may cause a profound fall in blood pressure following the first dose. Symptomatic hypotension with or without syncope can occur with ACE inhibitors.
Hyperkalemia may occur with ACE inhibitors.
Chronic cough has occurred with the use of all ACE inhibitors. The cough is nonproductive, persistent, and resolves within 1 to 7 days (but can take as long as 2 weeks) after therapy discontinuation.
Renal function should be evaluated prior to initiation of enalapril therapy and the drug should be used with caution in patients with renal impairment.
Serum creatinine and electrolyte concentrations should be evaluated prior to and 1 week following initiation of therapy in patients with congestive heart failure.
Enalapril should be used with caution in patients with sodium depletion or hypovolemia, those receiving diuretics, and those undergoing dialysis since severe hypotension may occur.
Angioedema may occur especially following the first dose of enalapril and if associated with laryngeal edema, maybe fatal. Should be discontinued and the patient carefully observed until swelling disappears.
Enalapril is not recommended for neonates or for pediatric patients with glomerular filtration rate of less than 30 mL/minute per 1.73 m².

Pregnancy: Pregnancy category: D.
Fetal and neonatal morbidity and mortality have been reported in at least 50 pregnant women who were receiving ACE inhibitors during pregnancy. Enalapril act on the renin angiotensin system can cause injury and death to developing fetus. Enalapril crosses the placenta, teratogenic effects may occur following maternal use during pregnancy. Drug are associated with oligohydramnios, due to decreased fetal renal function may lead to fetal lung hypoplasia and skeletal malformations. The use of these drug in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia and death in the fetus/neonate. ACE inhibitors are not recommended during pregnancy to treat maternal hypertension or heart failure. Woman who are planning a pregnancy should be considered for other medication option if an ACE inhibitor is currently prescribed or the ACE inhibitor should be discontinued as soon as possible once pregnancy is detected.
Lactation: Because enalapril is distributed into human milk and potentially may cause serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or enalapril.

Cardiovascular: Chest pain, hypotension, orthostatic hypotension, syncope.
CNS: Dizziness, fatigue, headache.
Dermatologic: Skin rash.
Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dysgeusia, nausea, vomiting.
Neuromuscular & skeletal: Weakness.
Renal: Increased serum creatinine, renal insufficiency.
Respiratory: Bronchitis, cough, dyspnea.

Avoid concomitant use: Bromperidol, Sacubitril.
Increased Effect/Toxicity: Enalapril may increase the effect of: Allopurinol, Amifostine, Angiotensin II, Antipsychotic agents (second generation), Azathioprine, Bromperidol, Ciprofloxacin (systemic), Drospirenone, Duloxetine, Ferric gluconate, Ferric hydroxide polymaltose complex, Gelatin (succinylated), Gold sodium Thiomalate, Grass pollen allergen extract, Hypotension-associated agents, Iron Dextran Complex, Levodopa, Lithium, Nitroprusside, Nonsteroidal Anti-inflammatory Agents, Pholcodine, Pregabalin, Sacubitril, Sodium phosphate.
The effect of Enalapril may be increased by: Alfuzosin, Aliskiren, Angiotensin II receptor blocker, Barbiturates, Benperidol, Brigatinib, Brimonidine (topical), Canagliflozin, Dapoxetine, Diazoxide, Dipeptidyl Peptidase-IV inhibitors, Eplerenone, Everolimus, Heparin, Heparin (low molecular weight), Herbs (Hypotensive properties), Loop diuretics, Lormetazepam, Molsidomine, Naftopidil, Nicergoline, Nicorandil, Obinutuzumab, Pentoxifylline, Phosphodiesterase 5 inhibitors, Potassium salts, Potassium-sparing diuretics, Prostacyclin analogues, Quinagolide, Salicylates, Sirolimus, Temsirolimus, Thiazide and thiazide-like diuretics, Tizanidine, Tolvaptan, Trimethoprim.
Decreased Effect: The effect of Enalapril may be decreased by: Amphetamines, Aprotinin, Brigatinib, Bromperidol, Herbs (Hypotensive properties), Icatibant, Lanthanum, Methylphenidate, Nonsteroidal antiflammatory agents, Salicylates, Yohimbine.

Preserve in well closed containers and store below 30°C.

ACE Inhibitors/Direct Renin Inhibitors

C09AA02 - enalapril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.

D