Enam^® (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

C09AA02 (Enalapril)

Active Substance

Enalapril (Rec.INN WHO registered)

Dosage Forms

	Enam®	Tablets 2.5 mg: 20 pcs.
		Tablets 5 mg: 20 pcs.
		Tablets 10 mg: 20 pcs.
		Tablets 20 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, with beveled edges, marked “EMT” on one side and the number “2.5” and a score line on the other.

Excipients: maleic acid, lactose anhydrous, zinc stearate.

10 pcs. – aluminum strips (2) – cardboard boxes.

Tablets white or almost white, round, with beveled edges, marked “EMT” on one side and the number “5” and a score line on the other.

Excipients: maleic acid, lactose anhydrous, zinc stearate.

10 pcs. – aluminum strips (2) – cardboard boxes.

Tablets white or almost white, round, with beveled edges, marked “EMT” on one side and the number “10” and a score line on the other.

Excipients: maleic acid, lactose anhydrous, zinc stearate.

10 pcs. – aluminum strips (2) – cardboard boxes.

Tablets white or almost white, round, with beveled edges, marked “EMT” on one side and the number “20” and a score line on the other.

Excipients: maleic acid, lactose anhydrous, zinc stearate.

10 pcs. – aluminum strips (2) – cardboard boxes.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

Antihypertensive drug, ACE inhibitor. The mechanism of action is associated with the inhibition of ACE activity, which leads to a decrease in the formation of angiotensin II. Enalapril is a prodrug: after its hydrolysis in the body, enalaprilat is formed, which inhibits the specified enzyme. Enalapril also has some diuretic effect.

Along with lowering blood pressure, the drug reduces pre- and afterload on the myocardium in heart failure, improves pulmonary circulation and respiratory function, and reduces resistance in the renal vessels, which contributes to the normalization of blood circulation in them.

The duration of action is 12-24 hours.

Pharmacokinetics

Absorption

After oral administration, Enalapril is rapidly and sufficiently completely absorbed from the gastrointestinal tract. C_max in blood plasma is reached after 3-4 hours. The bioavailability of the drug is 53-74%.

Distribution

Plasma protein binding – 50%.

Metabolism

Enalapril is metabolized in the liver, partially hydrolyzed to enalaprilat, so in patients with impaired liver function, the time to maximum effect may increase.

Excretion

Excreted by the kidneys. T_1/2 is about 11 hours.

Indications

• Arterial hypertension (including renovascular hypertension).
• Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

Enam^® is administered orally regardless of meal time.

For patients not receiving diuretics, the recommended initial dose is 5 mg/day. Then the dose is selected individually.

The usual required dose is from 10-40 mg/day in 1 or 2 doses.

For patients receiving diuretics, in order to prevent arterial hypotension, the diuretic should be discontinued 1-2 days before starting therapy. If it is impossible to cancel the diuretic, the initial dose of Enam^® is recommended to be 2.5 mg.

In chronic heart failure, it is preferable to start treatment with a dose of 2.5 mg once a day. Constant monitoring of blood pressure is necessary. Then it is recommended to take 2.5 mg 2 times a day for 3-4 days.

Starting from the second week, the dose is increased to 10 mg once a day if necessary. On the 3-4th week, the dose is increased to 20 mg in 1 or 2 doses, if the systolic pressure is not lower than 100 mm Hg.

Dose selection and further treatment can be carried out on an outpatient basis, while it is necessary to assess the patient’s condition at least once a month (only during dose selection, examination and doctor’s control is required every 10 days), monitor the content of creatinine and electrolytes in the blood. The presence of arterial hypotension up to 80/60 mm Hg during maintenance therapy in the absence of patient complaints is not a reason to discontinue the drug. Use with caution simultaneously with diuretics (especially “loop” and potassium-sparing ones), as well as with potassium preparations. If arterial hypotension develops, the patient should be placed on bed rest for several days; if this does not help, then the patient should be given an intravenous infusion of 400-800 ml of saline.

For arterial hypertension caused by nephropathy in patients with diabetes mellitus, the dose of the drug depends on whether diabetic nephropathy is accompanied by arterial hypertension or not. If diabetic nephropathy occurs against the background of normal blood pressure, then Enam^® is prescribed in small doses – 2.5 or 5 mg/day. If nephropathy is accompanied by arterial hypertension, then the doses are selected in the same way as for arterial hypertension (maximum up to 40 mg/day).

In renal failure with CC more than 30 ml/min (serum creatinine content not more than 3 mg/dl) the drug is recommended to be prescribed at the usual dose. With CC less than 30 ml/min the initial dose is not more than 2.5 mg/day. Further dose selection is carried out individually under the control of creatinine and blood electrolyte levels. For patients on hemodialysis, the initial dose and the dose on dialysis days should not exceed 2.5 mg/day.

Adverse Reactions

From the central nervous system 2-3% – headache, dizziness, increased fatigue; very rarely when used in high doses – insomnia, increased nervous excitability, depression, imbalance, paresthesia, tinnitus.

From the respiratory system 2-3% – dry cough, shortness of breath.

From the digestive system: less than 2% – nausea, diarrhea; rarely – pancreatitis, liver failure, dyspeptic symptoms, dry mouth, abdominal pain.

From the cardiovascular system: arterial hypotension, fainting; very rarely – cardiac arrhythmia, angina pectoris.

Changes in laboratory parameters: proteinuria, hyperkalemia, increased activity of hepatic transaminases, increased concentration of bilirubin in the blood, neutropenia, decrease in hemoglobin, hematocrit and/or leukocytes.

Allergic reactions: skin rashes; in some cases – angioedema of the face, larynx.

Other: very rarely when used in high doses – hair loss, hot flashes, glossitis, impotence; in patients with autoimmune diseases – agranulocytosis.

Enam^® is generally well tolerated and in most cases does not cause side effects requiring drug withdrawal.

Contraindications

• History of angioedema associated with ACE inhibitor treatment;
• Aortic stenosis;
• Mitral stenosis;
• Pregnancy;
• Lactation period;
• Childhood;
• Hypersensitivity to enalapril and other ACE inhibitors.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation.

Use in Renal Impairment

In renal failure with CC more than 30 ml/min (serum creatinine content not more than 3 mg/dl) the drug is recommended to be prescribed at the usual dose. With CC less than 30 ml/min the initial dose is not more than 2.5 mg/day. Further dose selection is carried out individually under the control of creatinine and blood electrolyte levels. For patients on hemodialysis, the initial dose and the dose on dialysis days should not exceed 2.5 mg/day.

Pediatric Use

The drug is contraindicated in children.

Special Precautions

After prescribing Enam^®, an increase in the level of urea nitrogen and serum creatinine is possible due to developed arterial hypotension and secondary renal hypoperfusion.

When prescribing Enam^®, previous therapy with diuretics and potassium preparations should be reviewed. Two weeks after prescribing Enam^®, it is necessary to monitor laboratory parameters: urea nitrogen, creatinine and plasma electrolytes, as well as a general urine test.

The drug should be used with particular caution and under medical supervision in case of a combination of chronic heart failure or arterial hypertension with bilateral renal artery stenosis or stenosis of the artery of a single kidney.

The development of arterial hypotension is not a reason to discontinue the drug, but requires preventive measures (control of blood electrolytes, blood pressure control, drug dose adjustment).

Enam^® prevents potassium loss, so when prescribing it, there is no need to use potassium-sparing diuretics and potassium preparations. Otherwise, hyperkalemia may develop, especially in patients with renal failure and diabetes mellitus.

Before examining the function of the parathyroid glands, Enam^® should be discontinued.

During treatment, alcohol consumption is prohibited.

Overdose

Symptoms: arterial hypotension.

Treatment: the patient should be laid down, legs raised. In mild cases of overdose, the patient is prescribed a saline solution orally. In more serious cases, in a hospital setting, measures are taken to stabilize blood pressure, intravenous saline or plasma substitutes are administered. Hemodialysis is possible.

Drug Interactions

With the simultaneous appointment of Enam^® with NSAIDs, a decrease in the antihypertensive effect of enalapril is possible; with potassium-sparing diuretics (spironolactone, triamterene, amiloride) – hyperkalemia may develop; with lithium salts – slowing down the excretion of lithium (monitoring of plasma lithium concentration is indicated).

Ethanol enhances the hypotensive effect of the drug.

With simultaneous use with antipyretic and analgesic drugs, a decrease in the effectiveness of Enam^® is possible.

Enalapril weakens the effect of drugs containing theophylline.

Cimetidine prolongs the action of enalapril.

Simultaneous use with diuretics, beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin enhances the hypotensive effect of enalapril.

The use of Enam^® together with anesthetics that have an antihypertensive effect can cause arterial hypotension.

Storage Conditions

The drug should be stored out of the reach of children at a temperature up to 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.