Enarenal^® (Tablets) Instructions for Use

Marketing Authorization Holder

Polpharma Pharmaceutical Works, Sa (Poland)

ATC Code

C09AA02 (Enalapril)

Active Substance

Enalapril

Dosage Forms

	Enarenal®	Tablets 5 mg: 20 or 60 pcs.
		Tablets 10 mg: 20 or 60 pcs.
		Tablets 20 mg: 20 or 60 pcs.

Dosage Form, Packaging, and Composition

Tablets round, biconvex, white or almost white, with a dividing score.

Excipients: sodium bicarbonate, croscarmellose sodium, lactose monohydrate, pregelatinized starch, magnesium stearate.

20 pcs. – blister packs (1) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.

Tablets round, biconvex, white or almost white with a dividing score on both sides.

Excipients: sodium bicarbonate, croscarmellose sodium, lactose monohydrate, pregelatinized starch, magnesium stearate.

20 pcs. – blister packs (1) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.

Tablets round, biconvex, white or almost white.

Excipients: sodium bicarbonate, croscarmellose sodium, lactose monohydrate, pregelatinized starch, magnesium stearate.

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

Antihypertensive drug, ACE inhibitor.

The active metabolite of enalapril – enalaprilat is a highly specific long-acting ACE inhibitor. Enalaprilat blocks the conversion of angiotensin I to angiotensin II, which leads to suppression of the activity of the renin-angiotensin-aldosterone system.

The decrease in the concentration of angiotensin II causes an increase in renin activity, as well as a decrease in aldosterone secretion, which ultimately leads to sodium loss, an increase in potassium concentration and a decrease in the volume of extracellular fluid. The drug reduces total peripheral vascular resistance, reduces preload, reduces pressure in the right atrium and in the pulmonary circulation.

The antihypertensive effect begins 2 hours after administration and lasts 24 hours.

Pharmacokinetics

Absorption and metabolism

After oral administration of Enarenal^®, absorption is 60%. C_max of enalapril (the inactive form of the drug) in blood plasma is usually reached after 1 hour. After absorption, Enalapril undergoes hydrolysis to form the active metabolite – enalaprilat. C_max of enalaprilat in blood plasma is reached after 4 hours and is approximately 33 ng/ml, AUC – about 450 h x ng/ml

The bioavailability of enalaprilat from Enarenal^® is 98.74%. The absolute bioavailability of enalaprilat is about 40%.

Food intake does not affect the absorption of the drug.

Distribution

Enalapril is distributed in body tissues and fluids. Penetrates the placental barrier, excreted in breast milk. Enalaprilat does not penetrate into the cerebrospinal fluid, and Enalapril – only to a small extent.

About 50-60% of enalaprilat is bound to plasma proteins.

Excretion

T_1/2 is 11 hours. The drug is excreted mainly by the kidneys, partially – with feces. After oral administration of Enarenal^® at a dose of 10 mg, an average of 60-78% is excreted within 24-48 hours (including 43-56% – in the form of enalaprilat, the rest – unchanged).

Indications

• Arterial hypertension, including renovascular (as monotherapy or as part of combination therapy with other antihypertensive drugs, especially with thiazide diuretics);
• Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

The dose of the drug is selected individually, depending on the patient’s condition.

Enarenal^® is taken orally regardless of food intake.

For arterial hypertension, the initial dose for adults is 5 mg once a day. If the hypotensive effect is insufficient, the dose can be increased to 10-20 mg/day in 2 doses. The maintenance dose is 10-20 mg/day.

For severe arterial hypertension, the dose can be increased to a maximum of 40 mg/day.

For elderly patients (over 65 years old), the initial dose is 2.5 mg/day, which can be increased if necessary.

For arterial hypertension in patients with renal insufficiency with a creatinine clearance of more than 30 ml/min, a dose change is usually not required. For creatinine clearance less than 30 ml/min, the initial dose is 2.5 mg/day. If necessary, the dose of the drug can be increased until a therapeutic effect is achieved, but not more than 40 mg/day.

For chronic heart failure, Enarenal^® should be used in combination with diuretics or digitalis glycosides. The initial dose of Enarenal^® is 2.5 mg/day, if necessary, the dose is gradually increased to a maintenance dose of 20 mg/day in 1-2 doses.

The dose of the drug should be increased at intervals of 2-4 weeks; if symptoms of circulatory failure persist, these intervals can be shortened.

For chronic heart failure in patients with concomitant renal insufficiency or hyponatremia with a serum sodium concentration of less than 130 mEq/L or a creatinine concentration of more than 1.6 mg/ml, treatment should be started with a dose of 2.5 mg twice a day, and then – 5 mg twice a day or more. Longer intervals should be observed between doses of the drug.

Adverse Reactions

From the cardiovascular system often – arterial hypotension; rarely – orthostatic hypotension; about 0.5-1% – myocardial infarction, cerebral ischemia, associated with a pronounced decrease in blood pressure in the group of high-risk patients, chest pain, palpitations, arrhythmias, angina pectoris.

From the digestive system rarely – nausea, diarrhea; 0.5-1% – intestinal obstruction, pancreatitis, hepatitis, jaundice, abdominal pain, vomiting, dyspepsia, constipation, lack of appetite, inflammation of the tongue, taste disturbance.

From the central and peripheral nervous system often – dizziness and headache; rarely – feeling of fatigue, fainting; about 0.5-1% – depression, confusion, drowsiness, insomnia, paresthesia, dizziness, headache, tinnitus, blurred vision, photophobia.

From the respiratory system rarely – dry cough; 0.5-1% – rhinitis, sore throat, hoarseness, suffocation.

From the musculoskeletal system rarely – muscle cramps; 0.5-1% – muscle and joint pain.

From the urinary system rarely – impaired renal function, renal failure and oliguria.

Dermatological reactions 0.5-1% – increased sweating, polymorphic erythema, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the hematopoietic system 0.5-1% – neutropenia, thrombocytopenia, positive test for antinuclear antibodies, increased ESR, eosinophilia and leukocytosis.

Allergic reactions 0.5-1% – skin rash, itching, urticaria, angioedema, alopecia.

Laboratory tests 0.5-1% – increased levels of urea and creatinine in the blood serum, hyperkalemia, hypernatremia, decreased hemoglobin and hematocrit.

Other 0.5-1% – impotence, feeling of heat, fever, inflammation of the serous membrane.

Contraindications

• Progressive azotemia in bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• History of angioedema;
• Second and third trimesters of pregnancy;
• Lactation (breastfeeding);
• Childhood;
• Hypersensitivity to enalapril or other ACE inhibitors.

Use in Pregnancy and Lactation

Enarenal^® should not be used in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the use of Enarenal^® is contraindicated.

Enalapril and its metabolite are excreted in breast milk, so if it is necessary to use Enarenal^® during lactation, the issue of stopping breastfeeding should be decided.

Use in Renal Impairment

For arterial hypertension in patients with renal insufficiency with a creatinine clearance of more than 30 ml/min, a dose change is usually not required. For creatinine clearance less than 30 ml/min, the initial dose is 2.5 mg/day. If necessary, the dose of the drug can be increased until a therapeutic effect is achieved, but not more than 40 mg/day.

Pediatric Use

The drug is contraindicated in children.

Geriatric Use

For elderly patients (over 65 years old), the initial dose is 2.5 mg/day, which can be increased if necessary.

Special Precautions

Enarenal^® should be used with particular caution in patients with significant circulatory failure, especially with concomitant renal impairment, because there is a risk of developing hypotension.

Enarenal^® should be used with caution in patients with coronary artery disease and cerebrovascular disorders, because with an excessive decrease in blood pressure, the development of myocardial infarction or stroke is possible.

When using Enarenal^® in patients with complicated arterial hypertension, hypotension is rarely observed. The risk of developing hypotension is increased in patients previously treated with diuretics or on a salt-restricted diet, in patients on hemodialysis, as well as with fluid deficiency in the body.

Enarenal^® should be used with caution in patients with impaired renal function. In some patients with arterial hypertension, without previously diagnosed kidney disease, an increase in the level of urea and creatinine may appear, especially with the simultaneous use of Enarenal^® and a diuretic. In such cases, the dose of Enarenal^® should be reduced or the use of the diuretic should be discontinued.

In patients on dialysis, an increased frequency of anaphylactic reactions was observed when using highly permeable membranes and simultaneous therapy with ACE inhibitors.

During surgical interventions and general anesthesia in patients receiving Enarenal^®, arterial hypotension may develop, which can be eliminated by replenishing the plasma volume.

With a history of angioedema, there is a risk of its development after the use of ACE inhibitors.

In 1% of patients who took Enarenal^®, an increase in the concentration of potassium in the blood serum (over 5.7 mEq/L) was observed. The risk of hyperkalemia increases with renal failure, diabetes mellitus, as well as during the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium-containing salt substitutes.

Simultaneous use of Enarenal^® with potassium salts and potassium-sparing diuretics (spironolactone, triamterene, amiloride) is not recommended.

In patients with chronic heart failure, it is necessary to monitor blood pressure and renal function both before and after the use of Enarenal^®.

If angioedema develops, Enarenal^® should be immediately discontinued and adrenaline in a dilution of 1:1000 (0.3-0.5 ml) should be administered.

Control of laboratory parameters

During treatment, the concentration of potassium in the blood plasma should be periodically monitored. More frequent monitoring is recommended if it is necessary to use Enarenal^® and potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-containing salt substitutes simultaneously.

Use in pediatrics

Enarenal^® should not be used in children.

Effect of the drug on the ability to drive vehicles and operate machinery

Enarenal^® can cause arterial hypotension, dizziness, drowsiness, which reduce the ability to concentrate and the speed of psychomotor reactions. In this regard, the patient should be informed about the dangers associated with driving vehicles, servicing mechanical equipment and other potentially hazardous activities.

Overdose

Symptoms arterial hypotension is possible 6 hours after taking the drug, bradycardia.

Treatment intravenous administration of isotonic sodium chloride solution. Enalaprilat can be removed from the body by hemodialysis.

Drug Interactions

Beta-blockers, methyldopa, calcium antagonists enhance the effect of Enarenal^®.

With simultaneous use of Enarenal^® with potassium salts or potassium-sparing diuretics (spironolactone, triamterene, amiloride), the risk of developing hyperkalemia increases.

Enarenal^® and other ACE inhibitors increase the concentration of lithium salts in the blood serum.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date indicated on the package.

Pharmacy supply conditions

The drug is dispensed by prescription.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.