Enzix Duo, tablets set 2.5mg+10 mg 45 pcs

ENZIX DUO contains two separate drugs in one package: the angiotensin-converting enzyme (ACE) inhibitor ENALAPRIL and the diuretic INDAPAMID.

Enalapril

Antihypertensive drug, its mechanism of action is related to the reduction of angiotensin I angiotensin II, the reduction of which leads to a direct reduction of aldosterone release.

This decreases total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preload on myocardium.

It dilates arteries more than veins and there is no reflexive increase of heart rate.

Hypotensive effect is more expressed at high level of plasma renin than at normal or reduced level.

Decrease in BP within therapeutic limits does not affect cerebral blood flow, blood flow in the brain vessels is maintained at a sufficient level even at reduced blood pressure.

It increases coronary and renal blood flow. Long-term use reduces left ventricular myocardial hypertrophy and myocyte walls of resistant arteries, prevents the progression of heart failure and slows the development of left ventricular dilatation.

Improves blood supply to ischemic myocardium.

Reduces platelet aggregation. It has some diuretic effect. Enalapril is a “prodrug”: as a result of its hydrolysis enalaprilat is formed which inhibits angiotensin-converting enzyme (ACE).

Time of onset of hypotensive effect when taken orally is 1 hour, it reaches a maximum after 4-6 hours and lasts up to 24 hours.

Indapamide

Hypotensive agent, thiazide-like diuretic of moderate potency and long duration of action, benzamide derivative.

Reduces arterial smooth muscle tone, reduces total peripheral vascular resistance.

It has moderate saluretic and diuretic effects associated with blockade of reabsorption of sodium, chloride, hydrogen and, to a lesser extent, potassium ions in proximal tubules and the cortical segment of the distal tubule of the nephron.

Vasodilator effects and reduction of total peripheral vascular resistance are based on the following mechanisms: reduction of reactivity of the vascular wall to noradrenaline and angiotensin II;

increased synthesis of prostaglandins, having vasodilator activity; inhibition of calcium current in vascular smooth muscle cells. Contributes to the reduction of left ventricular hypertrophy.

In therapeutic doses has no effect on lipid and carbohydrate metabolism (including in patients with concomitant diabetes).

Antihypertensive effect is developed at the end of the first/beginning of the second week if the drug is constantly used and maintained for 24 hours after single use.

Simultaneous use of Enalapril and Indapamide leads to enhancement of antihypertensive effect of Enalapril.

Pharmacokinetics

Enalapril

After oral administration about 60% is absorbed from the gastrointestinal tract. Simultaneous intake of food does not affect the absorption of enalapril. The plasma protein binding of enalaprilat is 50-60%.

Enalapril is rapidly and completely hydrolyzed in the liver to form the active metabolite – enalaprilat, which is a more active ACE inhibitor than enalapril. The bioavailability of the drug is 40%.

Maximum concentration of enalapril in blood plasma is reached after 1-2 hours, enalaprilat – after 3-4 hours.

Enalaprilat easily passes through the histohematic barriers, excluding the blood-brain barrier, a small amount passes through the placenta and into the breast milk.

The elimination half-life of enalaprilat is about 11 hours. Enalapril is mainly excreted through the kidneys 60% (20% as enalapril and 40% as enalaprilate), through the intestine 33% (6% as enalapril and 27% as enalaprilate).

Elimination by hemodialysis (rate 62 ml/min.) and peritoneal dialysis.

Indapamide

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Food intake slightly slows down the absorption rate, but does not affect the completeness of absorption.

Maximal concentration in plasma is reached 1-2 hours after oral administration. The equilibrium concentration is reached after 7 days of regular use.

Half-life period is on the average 14-18 hours, the blood plasma protein binding is 79%. It also binds with elastin of vascular smooth muscle.

It has high volume of distribution, passes through histohematic barriers (including placental), penetrates into breast milk.

Metabolized in liver. The kidneys excrete 60 – 80% as metabolites (about 5% is excreted unchanged), through the intestines – 20%.

In patients with renal insufficiency pharmacokinetics is not changed. It does not cumulate.

Indications

Arterial hypertension.

Active ingredient

Composition

How to take, the dosage

Interaction

Enalapril

The concomitant use of enalapril and indapamide leads to enhancement of the antihypertensive effect of enalapril.

Concomitant use of enalapril with NSAIDs, including selective COX-2 inhibitors, analgesics-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 impairment of renal function. These changes are reversible.

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

The use of enalapril together with potassium-saving 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 hematotoxicity of enalapril. Drugs that cause bone marrow suppression increase the risk of neutropenia and/or agranulocytosis.

Enalapril promotes delayed excretion of lithium (when concomitant use of enalapril with lithium salts, monitoring of plasma lithium concentrations is indicated).

The co-administration of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may increase the hypoglycemic effect of the latter with the risk of hypoglycemia.

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

In diabetic patients receiving oral hypoglycemic agents and insulin, monitoring of blood glucose levels is necessary, especially during the first month of coadministration with ACE inhibitors.

A symptom complex including facial redness, nausea, vomiting and arterial hypotension have been described in rare cases when parenteral gold drugs (sodium aurothiomalate) and ACE inhibitors (enalapril) are used together.

Ethanol enhances the hypotensive effect of enalapril.

Indapamide

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

In concomitant administration of indapamide with cardiac glycosides increases the risk of glycoside intoxication; with calcium preparations – hypercalcemia; with metformin – possible aggravation of lactic acidosis.

Indapamide helps to slow excretion of lithium and thus increases its concentration in plasma.

Astemizole, erythromycin (intravenous), pentamidine, sultopride, terfenadine, vincamine, antiarrhythmic drugs of class I A (quinidine, disopyramide) and class III (amiodarone, brettilium, sotalol) when taken with indapamide may lead to development of “pirouette” type arrhythmia.

NSAIDs, GCS, tetracosactide, sympathomimetics decrease the hypotensive effect of indapamide; baclofen increases it.

The combination of indapamide with potassium-saving diuretics may be effective in some patients; however, this does not completely exclude the possibility of hypo- or hyperkalemia, especially in diabetic patients and patients with renal failure.

The ACE inhibitors, when used simultaneously with indapamide, increase the risk of arterial hypotension and/or acute renal failure (especially if there is renal artery stenosis).

Indapamide increases the risk of renal dysfunction when combined with iodine-containing contrast agents in high doses (dehydration).

In patients taking indapamide, fluid loss must be restored before using iodine-containing contrast agents.

Tricyclic antidepressants and antipsychotics increase the hypotensive effect of indapamide and increase the risk of orthostatic hypotension.

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

Indapamide decreases the effect of indirect anticoagulants (coumarin or indandion derivatives) due to increased concentration of clotting factors as a result of decrease of BOD and increased production by liver (dose adjustment may be required).

Indapamide increases the effect of nondepolarizing myorelaxants.

Special Instructions

Enalapril

Patients should be monitored for 2 hours after the initial dose and an additional 1 hour before BP stabilizes.

In patients with decreased RBC (as a result of diuretic therapy, restriction of table salt intake, hemodialysis, diarrhea, vomiting), even at the initial dose, enalapril (as well as other ACE inhibitors) increases the risk of a sudden and significant BP drop.

Transient arterial hypertension is not a contraindication to continue treatment with the drug after BP stabilization. In case of repeated pronounced BP decrease, 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 of dialysis, the dosing regimen should be adjusted according to the BP level.

Patients with severe heart failure, CHD and cerebrovascular disease should be closely monitored.

In these patients, a sharp decrease in BP can lead to myocardial infarction, stroke, or impaired renal function.

The abrupt withdrawal of the drug does not result in a dramatic increase in BP.

Enalapril should be discontinued before parathyroid function study.

If side effects or Quincke’s edema develop, the drug should be stopped and appropriate treatment administered.

The patient should warn the surgeon/anesthesiologist about the use of ACE inhibitors before surgical procedures (including dentistry).

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

Indapamide

Patients who are taking cardiac glycosides, laxatives, hyperaldosteronism, and elderly patients should have their potassium and creatinine monitored regularly when indapamide is prescribed.

Periodic administration of indapamide requires systematic monitoring of plasma potassium, sodium, magnesium, pH, glucose, uric acid, and residual nitrogen concentrations.

The most careful control is indicated in liver cirrhosis (especially with edema or ascites – the risk of metabolic alkalosis intensifying manifestations of hepatic encephalopathy), CHD, heart failure, and in elderly patients.

The increased risk group also includes patients with prolonged QT interval on ECG (congenital or developed against a background of some pathological process).

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

Hypercalcemia on indapamide administration may be due to previously undiagnosed hyperparathyroidism.

In diabetic patients it is extremely important to monitor blood glucose levels, especially if hypokalemia is present.

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

Indapamide may give a positive result in doping control.

Patients with arterial hypertension and hyponatremia (due to diuretics) should discontinue diuretics 3 days before starting ACE inhibitors (if necessary, diuretics may be resumed somewhat later), or initial low-dose ACE inhibitors are prescribed in these cases.

When prescribing indapamide, it should be noted that sulfonamide derivatives may exacerbate SLE.

Pediatric use

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

Impact on driving and operating machinery

At the beginning of treatment, until the dose adjustment period is complete, the patient should refrain from driving and engaging in potentially hazardous activities requiring increased concentration and quick psychomotor reactions, because dizziness and dizziness may occur.dizziness is possible, especially after the initial dose of the drug.

Contraindications

Side effects

Enalapril

CNS and peripheral nervous system disorders: headache, dizziness, weakness, insomnia, anxiety, confusion, fatigue, somnolence (2-3%); in some cases when used in high doses – nervousness, depression, paresthesias.

Respiratory system: non-productive dry cough, interstitial pneumonitis, bronchospasm/bronchial asthma, dyspnea, rhinorrhea, pharyngitis.

Sensory organs: vestibular disorders, hearing and vision disorders, tinnitus.

Digestive system disorders: Dry mouth, anorexia, dyspeptic symptoms (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, disorders of liver function and

biliary excretion, hepatitis (hepatocellular or cholestatic), jaundice, increased activity of liver transaminases, hyperbilirubinemia.

Cardiovascular system disorders: excessive decrease in BP, orthostatic collapse; rarely – chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in BP),

arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitation, pulmonary artery branch thromboembolism, heart pain, syncope.

Metabolism disorders: hyperkalemia, hyponatremia, hypoglycemia (in patients with diabetes).

Hematopoietic system disorders: rarely – decrease of hematocrit and hemoglobin concentration, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia, increased sedimentation rate.

Urinary system disorders: impaired renal function, proteinuria, hypercreatininemia, increased urea.

Anxiety of the sexual system: decreased libido, hot flashes, decreased potency.

Dermatological reactions: alopecia, photosensitization.

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

Toxic epidermal necrolysis, pemphigus, pruritus, urticaria, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis; very rare – intestinal angioedema.

Indapamide

CNS and peripheral nervous system disorders: asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression, paresthesias; rarely – increased fatigue, general weakness, malaise, muscle spasm, tension, irritability, anxiety.

Digestive system disorders: nausea, anorexia, dry mouth, gastralgia, vomiting, diarrhea or constipation, abdominal discomfort, pancreatitis are possible.

Sensory organs: conjunctivitis, visual impairment.

Respiratory system: cough, pharyngitis, sinusitis, rhinorrhea; rarely – rhinitis.

Cardiovascular system disorders: orthostatic hypotension, ECG changes characteristic of hypokalemia, arrhythmias, palpitations.

Since the urinary system: increased incidence of infections, nycturia, polyuria, increased plasma urea nitrogen, hypercreatininemia.

Metabolism disorders: hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, glucosuria, sweating, weight loss.

The sexual system: decreased potency, decreased libido.

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

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

Overdose

Enalapril

Symptoms:

The pronounced decrease in BP up to the development of collapse, myocardial infarction, acute cerebral circulation disorder or thromboembolic complications, seizures, stupor.

Treatment:

The patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and oral administration of saline laxatives are indicated.

In more severe cases, measures aimed at blood pressure stabilization are performed: intravenous administration of saline solution, plasma substitutes, angiotensin II, hemodialysis may be performed.

Indapamide

Symptoms: nausea, vomiting, weakness, GI dysfunction, water-electrolyte disorders; in some cases – excessive BP reduction, dizziness, somnolence, confusion, respiratory depression. In patients with cirrhosis liver may develop hepatic coma.

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

Pregnancy use

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

In newborns and infants who have had intrauterine exposure to ACE inhibitors should be closely monitored for early detection of marked BP decrease, oliguria,

Hyperkalemia and neurologic disorders that may develop due to decreased renal and cerebral blood flow with ACE inhibitor-induced BP decrease.

In oliguria, BP and renal perfusion should be maintained by administration of appropriate fluids and vasoconstrictors.

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