Enap-nl pills 10mg 12.5mg N20
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Active ingredients
Enalapril + Hydrochlorothiazide
Release form
Pills
Composition
enalapril maleate 10 mg hydrochlorothiazide 12.5 mg Auxiliary substances: sodium bicarbonate, lactose monohydrate, anhydrous calcium hydrogen phosphate, corn starch, talc, magnesium stearate.
Pharmacological effect
Enalapril, an ACE inhibitor, is a prodrug: as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE. Hydrochlorothiazide is a thiazide diuretic. Acts at the level of the distal renal tubules, increasing the excretion of sodium ions and chlorine. At the beginning of hydrochlorothiazide treatment, the volume of fluid in the vessels decreases as a result of increased sodium excretion and fluid, which leads to a decrease in blood pressure and a decrease in cardiac output. activated by the raaS. A reactive increase in the concentration of angiotensin II partially limits the decrease in blood pressure. With continued therapy, the hypotensive effect of hydrochlorothiazide is based on a decrease in OPSS. The activation of the renin-angiotensin-aldosterone system results in metabolic effects on blood electrolyte balance, uric acid, glucose and lipids, which partially neutralizes the effectiveness of antihypertensive treatment. Despite effective blood pressure reduction, thiazide diuretics do not reduce structural changes in the heart and blood vessels. Enalapril enhances the antihypertensive effect: inhibits the RAAS, i.e. angiotensin II production and its effects. Additionally reduces the production of aldosterone and enhances the effect of bradykinin and the release of prostaglandins. Since it often has its own diuretic effect, it can increase the effect of hydrochlorothiazide. Enalapril reduces pre- and afterload, which unloads the left ventricle, reduces hypertrophy regression and collagen growth, prevents damage to myocardial cells. As a result, the heart rhythm slows down and reduces the load on the heart (in chronic heart failure), improves coronary blood flow and decreases oxygen consumption by cardiomyocytes.Thus, the sensitivity of the heart to ischemia decreases, and the number of dangerous ventricular arrhythmias also decreases. It has a beneficial effect on cerebral blood flow in patients with arterial hypertension and chronic cardiovascular diseases. It prevents the development of glomerulosclerosis, supports and improves kidney function and slows down the course of chronic kidney disease even in those patients who have not yet developed arterial hypertension. The antihypertensive effect of ACE inhibitors is known to be higher in patients with hyponatremia, hypovolemia and elevated renin levels in serum, whereas the effect of hydrochlorothiazide does not depend on the level of renin in the serum. Therefore, the simultaneous appointment of enalapril and hydrochlorothiazide has an additional antihypertensive effect. In addition, enalapril prevents or reduces the metabolic effects of diuretic therapy and has a beneficial effect on structural changes in the heart and vessels. Simultaneous administration of an ACE inhibitor and hydrochlorothiazide is used when each drug alone is not effective enough or monotherapy is performed using maximum doses of the drug, which increases frequency of undesirable effects. This combination allows you to get a better therapeutic effect with lower doses of enalapril and hydrochlorothiazide and reduce the development of undesirable effects. The antihypertensive effect of the combination usually lasts for 24 hours.
Pharmacokinetics
Enalapril Absorption Enalapril is rapidly absorbed from the gastrointestinal tract. The suction volume is 60%. Food does not affect the absorption of enalapril. Tmax is 1 h. Tmax enalaprilat in the serum is 3-6 hours. DistributionEnalaprilat penetrates into most tissues of the body, mainly in the lungs, kidneys and blood vessels. Plasma protein binding of 50-60%. Enalapril and enalaprilat penetrate the placental barrier, are excreted in breast milk. Metabolism Enalapril in the liver is hydrolyzed to the active metabolite - enalaprilat, which is the carrier of the pharmacological effect and is not subjected to further metabolism. tubular secretion.Renal clearance of enalapril and enalaprilat are 0.005 ml / s (18 l / h) and 0.00225-0.00264 ml / s (8.1-9.5 l / h), respectively. It is displayed in several stages. With the appointment of multiple doses of enalapril T1 / 2 enalaprilat from the serum is approximately 11 hours. Enalapril is eliminated in the urine - 60% and feces - 33% mainly in the form of enalaprilat. Enalaprilat is 100% excreted in the urine. Enalaprilat is removed from the bloodstream during hemodialysis or peritoneal dialysis. Hemodialysis clearance of enalaprilat 0.63-1.03 ml / s (38-62 ml / min). The serum enalaprilat concentration after 4 hours of hemodialysis is reduced by 45-57%. Pharmacokinetics in special clinical situations In patients with reduced renal function, the elimination slows down, which requires a change in dosage in accordance with kidney function, especially in patients with severe renal failure. with hepatic insufficiency, the metabolism of enalapril can be slowed down without damaging its pharmacodynamic effect. In patients with heart failure, absorption and metabolism of enalap Relate slows, Vd also decreases. Since these patients may have kidney failure, they may slow the removal of enalapril. In elderly patients, the pharmacokinetics of enalapril may be altered to a greater extent due to concomitant diseases than the elderly. Absorption is 70% and increases by 10% when taken with food. Tmax is 1.5-5 hours. The distribution of Vd is about 3 l / kg. Binding to plasma proteins - 40%. The drug accumulates in the erythrocytes, the accumulation mechanism is unknown. It penetrates the placental barrier and accumulates in the amniotic fluid. Serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in maternal blood. The concentration in the amniotic fluid is 19 times higher than that in the serum from the umbilical vein. The level of hydrochlorothiazide in breast milk is very low. Hydrochlorothiazide was not detected in the serum of infants, whose mothers took hydrochlorothiazide during breastfeeding. MetabolismHydrochlorothiazide is not metabolized toliver. ExcretionHydrochlorothiazide is excreted mainly in the urine - 95% unchanged and about 4% in the form of 2-amino-4-chloro-m-bensedisulfonamide hydrolyzate. Hydrochlorothiazide renal clearance in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s 335 ml / min). Hydrochlorothiazide has a biphasic elimination profile. T1 / 2 in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours. Pharmacokinetics in special clinical situations In elderly patients, hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilat is higher In patients with heart failure with hydrochlorothiazide, it has been established that its absorption decreases in proportion to the degree of the disease by 20-70%. T1 / 2 hydrochlorothiazide is increased to 28.9 h. Renal clearance is 0.17–3.12 ml / s (10-187 ml / min), average values 1.28 ml / s (77 ml / min). In patients undergoing intestinal bypass surgery for obesity , hydrochlorothiazide absorption can be reduced by 30%, and serum concentration by 50% than in healthy volunteers. Simultaneous use of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.
Indications
- arterial hypertension (to patients for whom combination therapy is indicated).
Contraindications
- anuria; - pronounced renal dysfunction (KK less than 30 ml / min); - hereditary or idiopathic angioedema; - angioedema associated with the use of ACE inhibitors (in history); - primary hyperaldosteronism; - Addison's disease; - porphyria; - children and adolescence to 18 years of age (efficacy and safety have not been established); - hypersensitivity to the components of the drug; - hypersensitivity to sulfonamides. With caution, use the drug for bilateral renal artery stenosis, st single kidney arteries of the kidney, impaired renal function (CC 30-75 ml / min), marked stenosis of the aortic mouth, idiopathic hypertrophic subaortic stenosis, coronary artery disease, cerebrovascular diseases (including with cerebrovascular insufficiency), chronic heart failure, severe autoimmune Systemic diseases of the connective tissue (includingSLE, scleroderma), inhibition of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, condition after kidney transplantation, severe impaired liver function and / or kidney, conditions accompanied by a decrease in BCC (as a result of diuretic therapy, while limiting the consumption of salt, diarrhea, gout, in elderly patients.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
The drug is contraindicated in pregnancy. When pregnancy occurs, the drug should be immediately discontinued. If necessary, use of the drug during lactation should decide on the termination of breastfeeding.
Dosage and administration
Treatment of hypertension should not begin with a combination of drugs. Initially, adequate doses of the individual components should be determined. The dose should always be chosen individually for each patient. The drug should be taken regularly at the same time (preferably in the morning). The pills are swallowed whole during or after a meal with a small amount of liquid. The usual dose is 1 tablet / day. If you miss the next dose, you need to take it as soon as possible, if enough time remains before the next dose. If a few hours are left before taking the next dose, you should wait and take it only.Do not double the dose. If a satisfactory therapeutic effect is not achieved, it is recommended to add another drug or change therapy. In patients on diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment with Enap-NL to prevent development of symptomatic hypotension. Before starting treatment, renal function should be investigated. The duration of treatment is not limited. For patients with QC greater than 30 ml / min or serum creatinine less than 265 µmol / L (3 mg / dL), the usual dose of Enap-NL can be prescribed.
Side effects
Since the cardiovascular system: palpitations, various cardiac arrhythmias, marked reduction in blood pressure, orthostatic hypotension, cardiac arrest, myocardial infarction, cerebrovascular stroke, angina pectoris, Raynaud’s syndrome, necrotizing angiitis. On the digestive system: dry mouth, glossitis, stomatitis, inflammation of the salivary glands, anorexia, nausea, vomiting, diarrhea, constipation, flatulence, epigastric pain, intestinal colic, ileus, pancreatitis, hepatic failure, hepatitis, jaundice, melena. From the respiratory side Systems: rhinitis, sinusitis, pharyngitis, hoarseness, bronchospasm, asthma, pneumonia, pulmonary infiltrates, eosinophilic pneumonia, pulmonary embolism, pulmonary infarction, respiratory distress (including pneumonitis and pulmonary edema). From the side of the CNS and peripheral nervous system: depression, attacks , drowsiness, insomnia, anxiety, nervousness, peripheral neuropathy (paresthesias, dysesthesia). From the urinary system: oliguria, renal failure, impaired renal function, interstitial nephritis. From the reproductive side Noah system: gynecomastia, reduced potency. For the sense organs: visual impairment, taste damage, olfactory impairment, tinnitus, conjunctivitis, conjunctivitis dryness, watery eyes. For the hematopoietic system: leukocytosis, eosinophilia, neutropenia, leukopenia, agranulocytosis, anemia hypohemoglobinemia, pancytopenia. On the side of metabolism: hypokalemia, hyperkalemia, hypomagneemia, hypercalcemia, hyponatremia, hypochloraemic alkalosis, hyperglycemia, glycosuria, hyperuricemia,hypercholesterolitis, hypertrigal hypersensitivity reactions (angioedema, thrombocytopenic purpura), anaphylactic reactions. Others: weakness, fever, lupus-like syn rum, described in the literature (fever, myalgia and arthralgia, serositis, vasculitis, cutaneous eruption, increase of ESR, leucocytosis, eosinophilia, positive test for antinuclear antibody).
Overdose
When a patient takes too many pills at once, you should immediately call a doctor. Symptoms: increased diuresis, marked reduction in blood pressure with bradycardia or other heart rhythm disorders, convulsions, paresis, paralytic ileus, impairment of consciousness (including coma), renal failure, impaired CRP, violation of the electrolyte balance of the blood. Treatment: the patient is transferred to a horizontal position with a low head. In mild cases, gastric lavage and ingestion of saline is indicated. In more serious cases, measures aimed at stabilizing blood pressure are shown: iv injection of saline, plasma substitutes. It is necessary to control the level of blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and patient's diuresis. If necessary, in / in the introduction of angiotensin II, hemodialysis (the rate of removal of enalaprilat - 62 ml / min).
Interaction with other drugs
The simultaneous use of Enapa-NL with other antihypertensive drugs, barbiturates, tricyclic antidepressants, phenothiazine and narcotic drugs, as well as with ethanol, enhances the anti-hypertensive effect of Enap-NL. Enapa-NL. If possible, the simultaneous use of Enapa-NL and lithium preparations should be avoided, since lithium intoxication may develop as a result of decreased elimination of l ment.It is necessary to control the concentration of lithium in the blood serum; its dose is corrected accordingly. Simultaneous use of Enapa-NL and NSAIDs, analgesics (due to inhibition of prostaglandin synthesis) may reduce the effectiveness of enalapril and increase the risk of deterioration of renal function and / or heart failure. In some patients, the antihypertensive effect of enalapril may also be reduced with simultaneous treatment, so patients should be carefully monitored. Using Enapa-NL at the same time with potassium-sparing diuretics (including spironolactone, amiloride, triamterene) or adding potassium can lead to hyperkalemia. Simultaneous use of Enapa -NL with allopurinol, cytostatics, immunosuppressants, or systemic corticosteroids can cause leukopenia, anemia, or pancytopenia, therefore, periodic monitoring of hemogram is required. In two patients after kidney transplantation, both enalapril and cyclosporine were treated for acute renal failure. It is assumed that acute renal failure was the result of a decrease in renal blood flow caused by cyclosporine and a decrease in glomerular filtration caused by enalapril. Therefore, caution is necessary when using simultaneous enalapril and cyclosporine. Simultaneous use of Enapa-NL with sulfonamides and oral hypoglycemic agents from the sulfonylurea group may cause hypersensitivity reactions (cross-hypersensitivity is possible). Care should be taken when using simultaneous use of Enapa-NL with glycoside glycidol). Possible hydrochlorothiazide-induced hypovolemia, hypokalemia, and hypomagnesemia can increase the toxicity of glycosides. Simultaneous use of Enapa-NL with GCS increases the risk of hypokalemia. With simultaneous use of Enapa-NL and theophylline, enapapril can reduce T1 / 2 theophiline tissue and can be reduced by using T1 / 2 -phiropylamine by a tissue, a tissue will be reduced by a T1 / 2 -phiropylamine by a glyphide, tefillina can reduce T1 / 2, and you will need to put deo-lyophiline. cimetidine, enalapril T1 / 2 may increase. The risk of hypotension increases during general anesthesia or the use of non-depolarizing muscle relaxants (for example, tubocurarine).
special instructions
Hypotension with all clinical consequences can be observed after the first dose of Enap-NL pills in patients with severe heart failure and hyponatremia, severe renal failure, arterial hypertension or left ventricular dysfunction and, in particular, in patients who are in the state of hilovolemia, as a result of therapy diuretics, salt-free diets, diarrhea, vomiting, or hemodialysis. Arterial hypotension after taking the first dose and its more serious consequences is rare and transient. . In order to avoid arterial hypotension, diuretics should be discontinued before treatment with Enap-NL. In case of arterial hypotension, place the patient on the back with a low head and, if necessary, adjust the plasma volume by infusion of saline. Transient hypotension is not a contraindication to continue treatment. After normalization of blood pressure and replenishment of BCC, patients usually tolerate subsequent doses well. Care must be taken when using the drug in patients with impaired renal function (CC 0.5–1.3 ml / s), as there may be signs of accumulation of the drug. If necessary, a combination of enalapril with a lower amount of hydrochlorothiazide may be used or combination therapy with enalapril and hydrochlorothiazide should be discontinued. In patients taking hydrochlorothiazide, azotemia may develop. Patients with bilateral renal artery stenosis or stenosis should be avoided. kidneys, as this can lead to deterioration of renal function or even acute renal failure (enalapril effect). It is necessary to monitor kidney function before and during drug treatment. Caution is required when using the drug in patients with coronary artery disease, severe cerebrovascular disease, aortic stenosis or other stenosis that prevents the outflow of blood from the left ventricle, severe atherosclerosis, in elderly patients as a result of the risk of arterial hypotension and deterioration of the perfusion of the heart, brain, and kidneys. Regularly monitor the serum concentration of electrolytes during the treatment period to identify possible of the imbalance and the timely adoption of the necessary measures.Determining the serum electrolyte concentration is mandatory for patients with prolonged diarrhea, vomiting and receiving intravenous infusion. In patients taking Enap-NL, it is necessary to actively detect signs of electrolyte imbalance: dry mouth, thirst, weakness, drowsiness, lethargy, agitation, muscle pain and convulsions (predominantly calf muscles), lowering blood pressure, tachycardia, oliguria, and gastrointestinal disturbances (nausea, vomiting). Enap-NL should be used with caution in patients with hepatic insufficiency or progression diseases of the liver, since hydrochlorothiazide can cause hepatic coma even with minimal electrolyte disturbances. During treatment with Enap-NL, hypomagnemia and sometimes hypercalcemia can occur, resulting from an increase in magnesium excretion and a slower calcium excretion in the urine under the influence of hydrochlorothiazide. may be a sign of latent hyperparathyroidism. In some patients, hyperuricemia may occur as a result of hydrochlorothiazide me or worsening of the flow of gout. If a rise in serum uric acid concentration is noted, treatment should be discontinued. It can be resumed after normalization of laboratory parameters and subsequently carried out under their control. Caution in the use of the drug is necessary in all patients receiving treatment with oral hypoglycemic agents or insulin, since hydrochlorothiazide can weaken and enalapril enhance their action. Patients with diabetes mellitus should be observed more frequently, and some dosage of hypoglycemic agents may be required. If you experience angioedema of the face or neck, it is usually enough to cancel therapy and prescribe antihistamines to the patient. In more severe cases (swelling of the tongue, pharynx and larynx), angioedema is treated with epinephrine, the airway is maintained by intubation or laryngotomy. hemodialysis using polyacrylonitrile membranes,who undergo apheresis with dextran sulfate and immediately before the desensitization procedure to aspen or bee venom. During treatment with Enap-NL, hypersensitivity reactions can be observed in patients without prior allergies or bronchial asthma. acute liver failure with cholestatic jaundice, liver necrosis and death (rarely) during treatment with ACE inhibitors. The cause of these syndromes is unknown. If jaundice occurs and liver enzymes increase, treatment should be stopped, the patient should be monitored. Caution is also needed in patients taking sulfonamides or oral hypoglycemic agents from the sulfonylurea group due to possible cross-sensitivity. During treatment, periodic monitoring of the number of leukocytes is required especially in patients with connective tissue or kidney disease. In patients who received during general anesthesia and or after major surgery drugs cause hypotension, enalapril can block the formation of angiotensin II, secondary to compensatory renin release. If the doctor suggests this mechanism of arterial hypotension, treatment may be performed by increasing the BCC. During treatment, periodic monitoring of the serum concentration of electrolytes, glucose, urea, creatinine and liver enzyme activity, as well as urine protein, is necessary. Enapom-NL treatment should be stopped before the parathyroid function is studied. Influence on the ability to drive vehicles and control mechanismsEnap-NL does not affect driving or working with mechanisms, however, some patients (mainly at the beginning of treatment) may experience hypotension and dizziness, which reduce the ability to drive and work with mechanisms. Therefore, at the beginning of treatment it is recommended to avoid driving, working with mechanisms and doing other work that requires concentration, until the answer to treatment is established.