Enam N - instructions for use, doses, side effects, contraindications

Enalapril inhibits ACE that promotes the conversion of angiotensin I into angiotensin II, reduces the concentration of aldosterone in the blood, increases the release of renin, improves the functioning of the callikrene-kininase vasodepressive system, stimulates the release of prostaglandin and endothelial relaxing factor of veins, depresses the sympathetic nervous system. Together, these effects eliminate spasm and dilate the peripheral arteries, reduce the overall peripheral resistance of blood vessels, systolic and diastolic blood pressure (BP), post- and preload on the myocardium. Expands arteries to a greater extent than veins, with a reflex increase in heart rate (heart rate) is not noted.The hypotensive effect is more pronounced with a high concentration of renin in the blood plasma than with normal or decreased. Decrease in blood pressure within the therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level and against a background of reduced blood pressure. Strengthens coronary and renal blood flow. With prolonged use, hypertrophy of the left ventricle of the myocardium and myofibrils of the walls of the arteries of the resistive type decreases, prevents the progression of chronic heart failure and slows the development of dilatation of the left ventricle (LV). Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets. Increases the life expectancy in patients with chronic heart failure, slows the progression of LV dysfunction in patients who underwent myocardial infarction, without clinical manifestations of heart failure. Increases renal blood flow, the rate of glomerular filtration remains unchanged. In patients with initially reduced glomerular filtration, its rate usually increases.

Hydrochlorothiazide - Thiazide diuretic with moderate strength of action.Reduces the reabsorption of sodium ions at the level of the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of convoluted tubules, increases the excretion of potassium ions, hydrocarbonates and phosphates by the kidneys. Virtually does not affect the acid-base state. Increases the excretion of magnesium ions. Delays in the body calcium ions. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min. In patients with type 2 diabetes mellitus has an antidiuretic effect (reduces the volume of urine and increases its concentration). Reduces blood pressure by reducing the volume of circulating blood, changing the reactivity of the vascular wall and increasing the depressor effect on the ganglion.

Using a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure in comparison with the monotherapy of each of the drugs alone and allows to maintain the antihypertensive effect of the ENAM-H preparation for at least 24 hours.Hydrochlorothiazide - Thiazide diuretic with moderate strength of action. Reduces the reabsorption of sodium ions at the level of the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of convoluted tubules, increases the excretion of potassium ions, hydrocarbonates and phosphates by the kidneys. Virtually does not affect the acid-base state. Increases the excretion of magnesium ions. Delays in the body calcium ions. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min. In patients with type 2 diabetes mellitus has an antidiuretic effect (reduces the volume of urine and increases its concentration). Reduces blood pressure by reducing the volume of circulating blood, changing the reactivity of the vascular wall and increasing the depressor effect on the ganglion.

Pharmacokinetics:

Enalapril. After ingestion, absorption is 60%.Eating does not affect absorption. In the liver is metabolized to form an active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. The connection with the proteins of the blood plasma enalaprilata - 50-60%. Time to reach peak concentration (Tcmax) enalapril -1h, enalaprilat - 3-4h. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates through the placenta and into breast milk. The half-life of Enalaprilat (T1 / 2) is 11 hours. It is mainly excreted by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilate), 33% through the intestine (6% in the form of enalapril and 27% in the form of enalaprilate). It is removed during hemodialysis (rate 62 ml / min) and peritoneal dialysis.

Hydrochlorothiazide. Absorption - 80%, fast. Connection with blood plasma proteins - 60-80%. Bioavailability is 70%, Tmax is 2-5 hours. In the therapeutic range of doses, the average area under the pharmacokinetic curve (AUC) increases in direct proportion to the increase in dose, with the appointment of 1 time a day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. T1 / 2 - 6-15 hours. It is not metabolized in the liver.It is excreted by the kidneys: 95% unchanged and about 4% as hydrolyzate-2-amino-4-chloro-m-benzene disulfonamide (reduced in alkaline urine) by glomerular filtration and active tubular secretion in the proximal nephron.

Indications:Arterial hypertension (patients who are shown combined therapy).

Contraindications:Hypersensitivity to the components of the drug (including other derivatives of sulfonamide); angioedema in history, associated with the administration of ACE inhibitors; hereditary or idiopathic angioedema; severe renal dysfunction (creatinine clearance less than 30 ml / min or serum creatinine concentration greater than 265 μmol / l); anuria; pregnancy; lactation period (breastfeeding); age under 18 years (effectiveness and safety not established); hereditary intolerance to galactose, a deficiency in the body of lactase or a syndrome of malabsorption of glucose and galactose.

Carefully:Renal or hepatic insufficiency, severe systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma),bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, condition after kidney transplantation, aortic stenosis, chronic heart failure, ischemic heart disease oppression of bone marrow hematopoiesis, cerebrovascular diseases (including cerebral circulatory insufficiency), diabetes mellitus, hyperkalemia, sodium restricted diet, conditions, accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), advanced age, oppression of bone marrow hematopoiesis.

Dosing and Administration:

Inside, regardless of food intake, 1 tablet 1 time per day.

At the beginning of therapy with ENAM-H, symptomatic hypotension may develop, which often occurs in patients with water-electrolyte balance disorders, as a result of previous therapy with diuretics. The intake of diuretics should be discontinued 2-3 days before the onset with the drug ENAM-N.

In patients with creatinine clearance greater than 30 ml / min, the drug should be used only after preliminary selection of the doses of each component. With mild renal insufficiency, the recommended initial dose of enalapril,when administered in monotherapy, is 5 to 10 mg.

Side effects:

From the hematopoiesis: eosinophilia, neutropenia.

On the part of the digestive system: change in taste, nausea, vomiting, indigestion, diarrhea or constipation, hepatitis, pancreatitis, flatulence, dry mouth, abdominal pain.

From the central nervous system: increased fatigue, dizziness, fainting, headache, asthenia, insomnia or drowsiness, increased excitability, depression, confusion, paresthesia.

From the respiratory system: unproductive "dry" cough, bronchospasm, dyspnea, rhinorrhea, pharyngitis, interstitial pneumonitis.

From the cardiovascular system: excessive depression of blood pressure (including orthostatic hypotension), tachycardia, cardialgia, angina pectoris, arrhythmias, fainting, palpitations.

From the sense organs: noise in the ears, violations of the vestibular apparatus, hearing and vision impairment.

From the urinary system: impaired renal function, proteinuria, renal failure.

Allergic reactions: angioedema (tongue, lips, vocal cords, larynx, extremities,intestine), exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), photosensitivity, fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, positive antinuclear antibody test, increased ESR, eosinophilia, leukocytosis), skin rash, itching .

From the skin: skin rash, itching, sweating.

Laboratory indicators: hyperglycemia, increased ESR, hypercreatininaemia, hyperuricemia, increased activity of "hepatic" transaminases, hyperbilirubinemia, decreased hemoglobin and hematocrit concentration, hyperkalemia, hypokalemia, increased urea concentration in blood serum.

Other: alopecia, tinnitus, arthralgia, decreased potency and / or libido, blood flushes to the face, gout, lupus-like syndrome (fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, positive test for antinuclear antibodies, increased ESR, eosinophilia, leukocytosis, skin rash, photosensitivity).

Overdose:Symptoms: excessive reduction in blood pressure, up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications; convulsions,stupor; symptoms caused by loss of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration caused by excessive diuresis. Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage, ingestion of saline solution are shown, in more serious cases, measures aimed at stabilizing blood pressure: intravenous administration of plasma substitutes, physiological sodium chloride solution, if necessary, intravenous administration of angiotensin II, hemodialysis (enalaprilate removal rate - 62 ml / min), correction of electrolyte balance disturbances.

Interaction:

The hypotensive effect reduces non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 inhibitors, estrogens, ethanol; increase -diuretics, drugs for general anesthesia, antihypertensive drugs, hemodialysis.

In patients with impaired renal function taking NSAIDs, including cyclooxygenase-2 inhibitors, concomitant administration of ACE inhibitors may lead to further impairment of renal function.

Immunosuppressants, allopurinol, cytostatics increase the risk of hematotoxicity.

Strengthens the action of ethanol and slows the elimination of lithium ions.

Simultaneous appointment with beta-adrenoblockers, blockers of "slow" calcium channels increases the risk of developing arterial hypotension. Thiazide diuretics can enhance the effect of tubocurarine.

Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of lithium intoxication.

The loss of potassium on the background of taking thiazide diuretics, as a rule, decreases under the action of enalapril. The concentration of potassium in the serum usually remains within normal limits. The use of potassium supplements, potassium-sparing agents or - potassium-containing salts, especially in patients with renal insufficiency, can lead to a significant increase in potassium in the serum.

Special instructions:

Thiazide diuretics can cause impaired glucose tolerance. You may need to adjust the dosage of hypoglycemic agents, including insulin. Thiazide diuretics can reduce the excretion of calcium by the kidneys, and also cause a slight and transient increase in the concentration of calcium in the serum. Expressed hypercalcemia may be a sign of latent hyperparathyroidism.Therapy with thiazide diuretics should be discontinued before the study of parathyroid function.

Before and during treatment, it is necessary to monitor blood pressure, kidney function, and potassium ion concentrations in the plasma.

Caution should be exercised in appointing patients with reduced circulating blood volume (as a result of diuretic therapy, limiting intake of table salt, hemodialysis, diarrhea and vomiting) because of the increased risk of sudden hypotension after applying even the initial dose. Transient arterial hypotension is not a contraindication for continuing treatment with the drug after stabilizing blood pressure. In the case of repeated occurrence of severe arterial hypotension, the dose should be reduced or the drug should be withdrawn.

In case of excessive reduction in blood pressure, the patient is transferred to a horizontal position with a low headboard, if necessary, 0.9% sodium chloride solution is injected (to increase the volume of blood plasma). It is necessary to observe patients with chronic heart failure, ischemic heart disease and cerebrovascular diseases,in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke, impaired renal function.

The use of dialysis membranes AN69 in combination with ACE inhibitors is not recommended.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Tablets 10 mg + 25 mg.

Packaging:For 10 tablets in an aluminum strip. For 2, 3, 10 strips in a cardboard pack together with instructions for use.

Storage conditions:

List B. In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008486/08

Date of registration:24.10.2008

Date of cancellation:2017-09-26

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp26.09.2017

Illustrated instructions

Instructions

Enam® H (Enam® H)