Enzix Duo pills Set 2.5mg+10mg, 45pcs

Composition

1 tablet of enalapril contains: Active ingredient: Enalapril maleate-10,000 mg; Excipients: Lactose monohydrate — 125,000 mg, Magnesium Carbonate-84,600 mg, Gelatin-9,200 mg, Crospovidone-9,200 mg, Magnesium stearate-2,000 mg. : Active ingredient: Indapamide 2,5000 mg; Excipients: Lactose monohydrate-76.9600 mg, Povidone-K 30-2.8200 mg, Crospovidone-0.8800 mg, Magnesium stearate-0.8800 mg, Sodium lauryl sulfate-0.4400 mg, Talc — 3.5200 mg; Shell composition: Hypromellose — 1,7222 mg, Macrogol 6000-0,3445 mg, Talc-1,9030 mg, Titanium dioxide E 171-0,4303 mg

Pharmacological action

ENZIX DUO contains two separate drugs in one package: angiotensin converting enzyme (ACE) inhibitor ENALAPRIL and diuretic agent INDAPAMIDE. enalaprilantithypertensive drug, its mechanism of action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the content of which leads to a direct decrease in the release of aldosterone. This reduces the total peripheral vascular resistance, systolic and diastolic blood pressure( BP), post-and preload on the myocardium. Dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate. Reduces the degradation of bradykinin, increases the synthesis of prostaglandin. The hypotensive effect is more pronounced with high plasma renin levels than with normal or reduced renin levels. Lowering blood pressure within therapeutic limits does not affect cerebral circulation, blood flow in the brain vessels is maintained at a sufficient level and against the background of reduced blood pressure. Increases coronary and renal blood flow. With prolonged use, hypertrophy of the left ventricle of the myocardium and myocytes of the walls of resistant arteries decreases, prevents the progression of heart failure and slows down the development of left ventricular dilation. Improves blood supply to the ischemic myocardium. Reduces platelet aggregation. It has some diuretic effect. Enalapril is a “prodrug”: as a result of its hydrolysis, enalaprilate is formed, which inhibits the angiotensin-converting enzyme (ACE). The time of onset of the hypotensive effect when taken orally is 1 hour, it reaches a maximum in 4-6 hours and persists for up to 24 hours. Indapamide is a hypotensive agent, a thiazide-like diuretic with moderate and long-lasting effects, a benzamide derivative. Reduces the smooth muscle tone of the arteries, reduces the total peripheral vascular resistance. It has moderate saluretic and diuretic effects, which are associated with the blockade of reabsorption of sodium, chlorine, hydrogen ions, and to a lesser extent potassium ions in the proximal tubules and cortical segment of the distal nephron tubule. Vasodilating effects and a decrease in total peripheral vascular resistance are based on the following mechanisms: reduced reactivity of the vascular wall to norepinephrine and angiotensin II; increased synthesis of prostaglandins with vasodilating activity; inhibition of calcium flow to vascular smooth muscle cells. Helps to reduce hypertrophy of the left ventricle of the heart. In therapeutic doses, it does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus). The antihypertensive effect develops at the end of the first/beginning of the second week with constant use of the drug and persists for 24 hours against the background of a single dose. Concomitant use of Enalapril and Indapamide increases the antihypertensive effect of Enalapril. Pharmacokinetics of enalapril After oral use, about 60% is absorbed from the gastrointestinal tract. Simultaneous food intake does not affect the absorption of enalapril. The binding to plasma proteins for enalaprilat is 50-60%. Enalapril is rapidly and completely hydrolyzed in the liver to form the active metabolite enalaprilate, which is a more active ACE inhibitor than enalapril. Bioavailability of the drug is 40%. The maximum concentration of enalapril in blood plasma is reached in 1-2 hours, enalaprilat – in 3-4 hours. Enalaprilat easily passes through the histohematic barriers, excluding the blood-brain barrier, and a small amount passes through the placenta and into breast milk. The elimination half-life of enalaprilat is approximately 11 hours. Enalapril is mainly excreted through the kidneys 60% (20% – in the form of enalapril and 40% – in the form of enalaprilat), through the intestines — 33% (6% — in the form of enalapril and 27% — in the form of enalaprilat). It is removed during hemodialysis (rate 62 ml / min) and peritoneal dialysis. Indapamide is rapidly and completely absorbed from the gastrointestinal tract after oral use; bioavailability is high (93%). Food intake slightly slows down the rate of absorption, but does not affect the completeness of absorption. The maximum concentration in blood plasma is reached 1-2 hours after oral use. The equilibrium concentration is established after 7 days of regular use. The average elimination half-life is 14-18 hours, and the binding to plasma proteins is 79%. It also binds to the smooth muscle elastin of the vascular wall. It has a high volume of distribution, passes through histohematic barriers (including placental), penetrates into breast milk. It is metabolized in the liver. 60-80% is excreted by the kidneys in the form of metabolites (about 5% is excreted unchanged), and 20% is excreted through the intestines. In patients with renal insufficiency, the pharmacokinetics do not change. It doesn’t accumulate.

Indications

Arterial hypertension.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation. If it is necessary to use Enzix during lactation, breastfeeding should be discontinued.

Newborns and children who have been exposed to ACE inhibitors in utero are recommended to be carefully monitored for timely detection of a pronounced decrease in blood pressure, oliguria,

hyperkalemia, and neurological disorders that may develop due to a decrease in renal and cerebral blood flow with a decrease in blood pressure caused by ACE inhibitors.

With oliguria, it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictors.

Contraindications

The composition of the drug Enzix Duo includes lactose monohydrate. Do not use the drug in patients with lactose intolerance, lactase deficiency, glucose-galactose malabsorption. Enalapril hypersensitivity to enalapril and other ACE inhibitors, a history of angioedema associated with treatment with ACE inhibitors, hereditary or idiopathic angioedema, concomitant use with aliskiren and / or aliskiren-containing drugs in patients with diabetes mellitus and / or moderate to severe renal impairment (glomerular filtration rate (GFR)less than 60 ml / min/1.73 m2), pregnancy, breast-feeding period, age up to 18 years (efficacy and safety have not been established). Use with caution in primary hyperaldosteronism, bilateral renal artery stenosis, conditions accompanied by a decrease in the volume of circulating blood (BCC) (including vomiting, diarrhea), stenosis of the artery of a single kidney, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with impaired hemodynamic parameters), hypertrophic obstructive cardiomyopathy, renovascular hypertension, systemic diseases connective tissue disorders (systemic lupus erythematosus, scleroderma, etc. ), coronary heart disease, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria of more than 1 g/day), liver failure, a history of allergic diseases or angioedema in patients who follow a diet with the addition of table salt or are on hemodialysis; when taken simultaneously with immunosuppressants, saluretics, potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and lithium preparations, during low-density lipoprotein apheresis (LDL apheresis) procedures using dextran sulfate, during desensitization of hymenopteran insect venom; in patients of the black race; in patients after major surgical interventions or during general anesthesia; in patients undergoing dialysis with the use of high-flow membranes (such as AN 69®); in elderly patients (older than 65 years). Indapamide hypersensitivity to the drug, other sulfonamide derivatives or other components of the drug, anuria, refractory hypokalemia, severe hepatic insufficiency (including with encephalopathy)and/or severe renal insufficiency (creatinine clearance less than 30 ml/min), pregnancy, breast-feeding, age up to 18 years (efficacy and safety have not been established). With caution, it is prescribed for diabetes mellitus in the decompensation stage, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), impaired liver and kidney function, impaired water-electrolyte balance, hyperparathyroidism;in weakened patients or in patients receiving concomitant therapy with other antiarrhythmic drugs, while taking drugs that prolong the QT interval.

Side effects

Enalapril

From the central nervous system and peripheral nervous system: headache, dizziness, weakness, insomnia, anxiety, confusion, fatigue, drowsiness (2-3%); in some cases, when used in high doses – nervousness, depression, paresthesia.

From the respiratory system: unproductive dry cough, interstitial pneumonitis, bronchospasm/bronchial asthma, shortness of breath, rhinorrhea, pharyngitis.

From the sensory organs: vestibular disorders, hearing and vision disorders, tinnitus.

From the digestive system: dry mouth, anorexia, dyspeptic symptoms (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, impaired liver and

biliary function, hepatitis (hepatocellular or cholestatic), jaundice, increased activity of hepatic transaminases, hyperbilirubinemia.

From the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse; rarely-chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure),

arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitations, pulmonary embolism, pain in the heart, syncope.

From the side of metabolism: hyperkalemia, hyponatremia, hypoglycemia (in patients with diabetes mellitus).

From the hematopoietic system: rarely-decreased hematocrit and hemoglobin concentration, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia, increased ESR.

From the urinary system: impaired renal function, proteinuria, hypercreatininemia, increased urea content.

From the side of the reproductive system: decreased libido, hot flashes, decreased potency.

Dermatological reactions: alopecia, photosensitization.

Allergic reactions: skin rash, angioedema of face, extremities, lips, tongue, glottis and/or larynx, dysphonia, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome,

toxic epidermal necrolysis, pemphigus, itching, hives, Ceresit, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis; very rarely – intestinal angioedema.

Indapamide

From the central nervous system and peripheral nervous system: asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression, paresthesia; rarely – increased fatigue, general weakness, malaise, muscle spasms, tension, irritability, anxiety.

From the digestive system: nausea, anorexia, dry mouth, gastralgia, vomiting, diarrhea or constipation, abdominal discomfort, pancreatitis are possible.

From the sensory organs: conjunctivitis, visual impairment.

From the respiratory system: cough, pharyngitis, sinusitis, rhinorrhea; rarely-rhinitis.

From the cardiovascular system: orthostatic hypotension, ECG changes characteristic of hypokalemia, arrhythmias, palpitations.

From the urinary system: increased frequency of infections, nocturia, polyuria, increased urea nitrogen in blood plasma, hypercreatininemia.

From the side of metabolism: hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, glucosuria, sweating, weight loss.

From the side of the reproductive system: decreased potency, decreased libido.

Allergic reactions: skin rash, urticaria, pruritus, hemorrhagic vasculitis.

Others: flu-like syndrome, chest pain, back pain, infections, SLE exacerbation.

Interaction

Enalapril

Concomitant use of enalapril and indapamide increases the antihypertensive effect of enalapril.

Concomitant use of enalapril with NSAIDs, including selective COX-2 inhibitors, analgesics and antipyretics may reduce the hypotensive effect of enalapril.

In some cases, in patients with impaired renal function receiving NSAIDs, including selective COX-2 inhibitors, the use of ACE inhibitors may lead to further deterioration of renal function. These changes are reversible.

The antihypertensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, slow calcium channel blockers of the dihydropyridine series, hydralazine, prazosin.

The use of enalapril together with potassium-sparing diuretics (spironolactone, triamterene, amiloride), as well as with potassium-containing drugs increases the risk of hyperkalemia.

Enalapril weakens the effect of drugs containing theophylline.

Immunosuppressants, allopurinol, cytostatics increase the hematotoxicity of enalapril. Drugs that cause bone marrow suppression increase the risk of neutropenia and / or agranulocytosis.

Enalapril helps to slow the elimination of lithium (when enalapril is used simultaneously with lithium salts, monitoring of the concentration of lithium in blood plasma is indicated).

The combined use of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic drugs) may increase the hypoglycemic effect of the latter with the risk of hypoglycemia.

This is most common during the first 3 weeks of co-use, as well as in patients with renal insufficiency.

In patients with diabetes mellitus receiving oral hypoglycemic drugs and insulin, blood glucose monitoring is necessary, especially during the first month of co-use with ACE inhibitors.

A symptom complex that includes facial flushing, nausea, vomiting, and hypotension has been described in rare cases with the combined use of parenteral gold preparations (sodium aurothiomalate) and ACE inhibitors (enalapril).

Ethanol enhances the hypotensive effect of enalapril.

Indapamide

Concomitant use of indapamide with saluretics, cardiac glycosides, gluco-and mineralocorticoids, tetracosactide, amphotericin B (intravenously), and laxatives increases the risk of hypokalemia.

Concomitant use of indapamide with cardiac glycosides increases the likelihood of developing glycoside intoxication; with calcium preparations-hypercalcemia; with metformin-possible aggravation of lactic acidosis.

Indapamide helps to slow down the elimination of lithium and thereby increase its concentration in blood plasma.

Astemizole, erythromycin (intravenous), pentamidine, sultoprid, terfenadine, vincamine, antiarrhythmic drugs of class Ia (quinidine, disopyramide) and class III (amiodarone, bretilium, sotalol) when taken against the background of idapamide can lead to the development of arrhythmia of the “pirouette”type.

NSAIDs, corticosteroids, tetracosactide, sympathomimetics reduce the hypotensive effect of indapamide; baclofen increases it.

The combination of indapamide with potassium-sparing diuretics may be effective in some patients, but the possibility of hypo – or hyperkalemia is not completely excluded, especially in patients with diabetes mellitus and renal insufficiency.

ACE inhibitors, when used concomitantly with indapamide, increase the risk of hypotension and / or acute renal failure (especially with existing renal artery stenosis).

Indapamide increases the risk of developing impaired renal function when used concomitantly with high-dose iodine-containing contrast agents (dehydration of the body).

Before using iodine-containing contrast agents in patients taking indapamide, it is necessary to restore fluid loss.

Tricyclic antidepressants and antipsychotic medications enhance the hypotensive effect of indapamide and increase the risk of orthostatic hypotension.

Concomitant use of indapamide with cyclosporine increases the risk of hypercreatininemia.

Indapamide reduces the effect of indirect anticoagulants (coumarin or indandione derivatives) due to an increase in the concentration of clotting factors as a result of a decrease in BCC and an increase in their production by the liver (dose adjustment may be required).

Indapamide enhances the effect of non-depolarizing muscle relaxants.

How to take, course of use and dosage

of ENZIX DUO: 1 tablet of Enalapril (10 mg) and 1 tablet of film-coated Indapamide (2.5 mg) are taken orally, in the morning at the same time. Depending on the dynamics of blood pressure indicators, the dose of Enalapril can be increased to twice a day. The maximum daily dose of enalapril is 40 mg, and indapamide-2.5 mg. In chronic renal failure, accumulation of Enalapril occurs with a decrease in filtration of less than 10 ml/min. With a creatinine clearance of 80-30 ml/min. the dose of enalapril should be 5-10 mg / day.

Overdose

Enalapril

Symptoms: 

marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.

Treatment: 

the patient is placed in a horizontal position with a low headboard. In mild cases, gastric lavage and oral saline laxative are indicated.

In more severe cases, measures are taken to stabilize blood pressure: intravenous use of saline solution, plasma substitutes, angiotensin II, hemodialysis is possible.

Indapamide

Symptoms: nausea, vomiting, weakness, impaired gastrointestinal function, water and electrolyte disorders; in some cases – excessive decrease in blood pressure, dizziness, drowsiness, confusion, respiratory depression. Patients with cirrhosis of the liver may develop hepatic coma.

Treatment: gastric lavage and / or use of activated charcoal, correction of water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Special instructions

Enalapril

Patients should be monitored for 2 hours after the initial dose of the drug and an additional 1 hour before blood pressure stabilizes.

In patients with a decrease in BCC (due to diuretic therapy, restriction of table salt intake, hemodialysis, diarrhea, vomiting), the use of enalapril (as well as other ACE inhibitors), even at the initial dose, increases the risk of a sudden and pronounced decrease in blood pressure.

Transient arterial hypertension is not a contraindication for continuing treatment with the drug after blood pressure stabilization. In case of repeated pronounced decrease in blood pressure, the dose should be reduced or the drug should be discontinued.

The use of high-strength dialysis membranes increases the risk of anaphylactic reaction. On days free from dialysis, the dosage regimen should be adjusted depending on the blood pressure level.

Patients with severe heart failure, coronary artery disease, and cerebral vascular diseases should be carefully monitored.

In such patients, a sharp decrease in blood pressure can lead to a myocardial infarction, stroke, or impaired renal function.

Sudden withdrawal of the drug does not lead to a sharp increase in blood pressure.

Enalapril should be discontinued prior to parathyroid function testing.

In case of side effects or angioedema, the drug should be discontinued and appropriate treatment should be prescribed.

Before surgery (including dentistry), the patient should warn the surgeon / anesthesiologist about the use of ACE inhibitors.

Before and during treatment with ACE inhibitors, periodic monitoring of blood pressure, blood parameters (hemoglobin, potassium, creatinine, urea, hepatic transaminase activity), and protein in the urine is necessary.

Indapamide

When prescribing indapamide to patients taking cardiac glycosides, laxatives, against the background of hyperaldosteronism, as well as elderly patients, regular monitoring of potassium and creatinine levels is indicated.

When taking indapamide, the concentration of potassium, sodium, magnesium in blood plasma, pH, glucose, uric acid and residual nitrogen should be systematically monitored.

The most careful monitoring is indicated for cirrhosis of the liver (especially with edema or ascites – the risk of developing metabolic alkalosis, which increases the manifestations of hepatic encephalopathy), coronary heart disease, heart failure, as well as in elderly patients.

The high-risk group also includes patients with an extended QT interval on the ECG (congenital or developed against the background of some pathological process).

The first determination of the blood potassium concentration should be made during the first week of treatment.

Hypercalcemia with indapamide may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes, it is extremely important to monitor blood glucose levels, especially in the presence of hypokalemia.

Significant dehydration can lead to acute renal failure (decreased glomerular filtration rate). Patients need to compensate for water loss and carefully monitor kidney function at the beginning of treatment.

Indapamide can give a positive result during doping control.

Patients with arterial hypertension and hyponatremia (due to taking diuretics) should stop taking diuretics 3 days before the start of taking ACE inhibitors (if necessary, the diuretic can be resumed a little later), or in such cases, the initial low doses of ACE inhibitors are prescribed.

When prescribing indapamide, it should be taken into account that sulfonamide derivatives can exacerbate the course of SLE.

Use in pediatrics

The efficacy and safety of enalapril and indapamide in children and adolescents under 18 years of age have not been established.

Influence on the ability to drive motor vehicles and manage mechanisms

At the beginning of treatment, until the end of the dose selection period, the patient should refrain from driving vehicles and engaging in potentially dangerous activities that require increased

concentration of attention and speed of psychomotor reactions, since dizziness is possible, especially after taking the initial dose of the drug.

Form of production

Enalapril

Round, biconvex tablets of white color with a risk on one side.

Indapamide

Round, biconvex film-coated tablets of white color

Storage conditions

In a dry place, at a temperature of 15-25 °C

Shelf life

3 years

Active ingredient

Indapamide, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension