Description
Release form
Tablets.
Packing
50 pcs.
Pharmacological action of
ATX code: C09AA02
Pharmacological properties of
Pharmacodynamics
Enalapril is an angiotensin converting enzyme (ACE) inhibitor used to treat arterial hypertension, heart failure, and diabetes. The clinical effect of enalapril is due to the suppression of ACE activity and, as a consequence, a decrease in the formation of angiotensin II from angiotensin I in tissues and circulating blood. A decrease in the concentration of angiotensin II, in turn, leads to vasodilation, a decrease in the secretion of aldosterone, an increase in the potassium content and the concentration of renin in blood plasma.
The hemodynamic consequences of these changes are a decrease in total peripheral vascular resistance (OPSS), systolic and diastolic blood pressure, increased cardiac output, decreased post-and preload on the myocardium. Enalapril dilates the arteries more than the veins, with no reflex increase in heart rate (HR). Reduces the degradation of bradykinin, increases the synthesis of prostaglandins. The antihypertensive effect is more pronounced with a high concentration of renin than with a normal or reduced level. The time of onset of the antihypertensive effect when taken orally is 1 hour, which reaches a maximum after 4-6 hours and lasts up to 24 hours.
Some patients require therapy for several weeks to achieve optimal blood pressure (BP). In chronic heart failure, a noticeable clinical effect is observed with prolonged treatment – 6 months or more. The duration of the therapeutic effect is dose-dependent.
The vasodilating and some diuretic effects of enalapril are also provided by the blockade of the destruction of bradykinin, which, in turn, stimulates the synthesis of vasodilating and renal prostaglandins. Increased levels of bradykinin as in blood plasma, and locally in the organs and tissues of the body, it blocks the pathological processes that occur in chronic heart failure in the myocardium, kidneys, and smooth muscles of blood vessels. At the same time, there is an increase in coronary and renal blood flow, with prolonged use (from 3-4 weeks of treatment), left ventricular hypertrophy and myofibrils of the arterial wall walls decrease in resistance, dilatation of the left ventricle slows down and blood supply to the ischemic myocardium improves, metabolism improves and the incidence of arrhythmias noted after restoration of blood supply to the heart muscle.
Due to the moderate diuretic effect of the drug, intracranial hypertension decreases, the development of glomerulosclerosis slows down and the risk of chronic renal failure decreases.
A decrease in blood pressure within the therapeutic range (not lower than 110/60 mm Hg) does not affect cerebral circulation: blood flow to the brain is maintained at a good level and against a background of low blood pressure.
Sudden cancellation of treatment does not lead to a “withdrawal” syndrome (a sharp increase in blood pressure).
Enalapril does not cause metabolic disorders, does not affect glucose metabolism, does not increase the concentration of uric acid, does not change the profile of blood lipoproteins. Enalapril may reduce the hypokalemic effect of thiazide diuretics.
Pharmacokinetics
Absorption
When taken orally, enalapril is rapidly absorbed, the maximum plasma concentration is reached within 1 h.
enalapril is well absorbed from the gastrointestinal tract (GIT), within 1 hour (maximum 4-8 hours) after oral administration, a therapeutic effect is achieved. Eating does not affect the absorption of the drug.
Distribution of
In patients with normal renal function, the equilibrium concentration of enalapril in blood plasma is reached 2-3 days after the start of administration. Does not cumulate. Communication with blood plasma proteins is about 50%.
Excretion of
It undergoes biotransformation in the liver with the formation of an active metabolite – enalaprilat, the maximum concentration of which is determined 4 hours after administration. Enalapril is excreted mainly through the kidneys – 60% (20% – as enalapril and 40% – as enalaprilat), through the intestines – 33% (6% – as enalapril and 27% – as enalaprilat). The half-life (T1 / 2) is 11 hours.
In patients with creatinine clearance (CC) of less than 30 ml / min, T1 / 2 of enalapril is increased. Decreased renal secretion of enalapril may increase hydrolysis to enalaprilat and increase extrarenal excretion of the drug.
Enalapril hydrolysis rate may decrease in patients with impaired liver function without reducing the therapeutic effect.
Crosses the placental barrier. Excreted in breast milk. Almost does not penetrate the blood-brain barrier. It does not accumulate in any tissues and organs.
Contraindications
² Ñ hypersensitivity to enalapril and other ACE inhibitors, as well as to any other component of the
preparation ² Ñ lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome
, angioneurotic syncrosis, previous hereditary angioedema or idiopathic angioedema
² Ñ simultaneous use of enalapril and aliskiren in patients with diabetes mellitus or renal failure (CC less than 60 ml / min)
² Ñ age under 18 (efficacy and safety not established)
² Ñ pregnancy.
² Ñ period of breastfeeding.
Enalapril Geksal should be used with caution in patients with bilateral renal artery stenosis or stenosis of a single kidney artery, primary hyperaldosteronism, hyperkalemia, cerebrovascular disease (including cerebrovascular insufficiency), coronary heart disease (CHD) after kidney transplantation myocardial infarction (up to 3 months) of chronic heart failure, aortic and / or mitral stenosis (with impaired hemodynamic parameters), hypertrophic obstructive cardiomyopathy of a hypovolemic state (associated with prolonged intake of diuretics, the presence of a diet with salt restriction, diarrhea or vomiting, hemodialysis, after surgical intervention) of severe autoimmune systemic diseases of connective tissue (in t including scleroderma, systemic lupus erythematosus) with inhibition of bone marrow hematopoiesis in liver failure in old age (over 65) SG diabetes with kidney failure (proteinuria – more than 1 g / day) while the use of immunosuppressive agents and diuretics in patients dialysis using high-flow membranes (such as AN69 ®) during desensitization in patients of the Negroid race with apheresis of low density lipoproteins.
Special instructions
Use with extreme caution in patients with autoimmune diseases, diabetes mellitus, impaired liver function, severe aortic stenosis, subaortic muscle stenosis of unknown origin, hypertrophic cardiomyopathy, with loss of fluid and salts. In the case of previous treatment with saluretics, in particular in patients with chronic heart failure, the risk of developing orthostatic hypotension is increased, therefore, before starting treatment with enalapril, it is necessary to compensate for the loss of fluid and salts.
With prolonged treatment with enalapril, it is necessary to periodically monitor the picture of peripheral blood. The sudden cessation of enalapril does not cause a sharp increase in blood pressure.
During surgical interventions during the treatment with enalapril, the development of arterial hypotension is possible, which should be corrected by the introduction of a sufficient amount of fluid.
Dosage and administration
When administered orally, the initial dose is 2.5-5 mg 1 time / Average dose is 10-20 mg / in 2 doses.
For iv administration, 1.25 mg every 6 hours. To detect excessive hypotension in patients with sodium deficiency and dehydration due to previous diuretic therapy, patients receiving diuretics, as well as in renal failure, are given an initial dose of 625 mg. With an inadequate clinical response, this dose can be repeated after 1 hour and treatment continued at a dose of 1.25 mg every 6 hours.
The maximum daily dose for oral administration is 80 mg.
Side effects
According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (? 1/10), often (? 1/100 to <1/10), infrequently ( from? 1 / 1,000 to <1/100), rarely (from? 1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000) the frequency is unknown - according to the available data, it was not possible to establish the frequency of occurrence. From the cardiovascular system very often: dizziness often: marked decrease in blood pressure (including orthostatic), syncope, chest pain, arrhythmia, tachycardia, angina pectoris infrequently: palpitations, myocardial infarction, myocardial infarction including secondary after the development of severe hypotension rarely: thromboembolism of a branch of the pulmonary artery, Raynaud’s syndrome. From the central nervous system often: headache, depression infrequently: dizziness, drowsiness, insomnia, irritability, confusion, paresthesia, vertigo rarely: unusual dreams, sleep disturbance. From the respiratory system very often: cough often: shortness of breath infrequently: rhinorrhea, sore throat, hoarseness, bronchospasm (bronchial asthma) rarely: infiltration in the lungs, rhinitis, allergic alveolitis, (eosinophilic). From the digestive system very often: nausea often: diarrhea, abdominal pain, taste disturbance infrequently: intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, peptic ulcer, dry oral mucosa, irritable bowel syndrome rare: stomatitis / aphthous ulcers, glossitis, liver failure, hepatitis (including liver necrosis), cholestasis, jaundice, increased activity of hepatic transaminases and bilirubin in blood plasma very rarely: intestinal angioneurotic edema. From the genitourinary system infrequently: impaired renal function, renal failure, proteinuria, impotence, an increase in the concentration of urea in the blood plasma rarely: oliguria, gynecomastia. On the part of the organ of vision very often: visual impairment. From the hematopoietic system and lymphatic system infrequently: anemia (including aplastic, hemolytic) rare: neutropenia, thrombocytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, pancytopenia, decreased hemoglobin, decreased hematocrit, lymphadenopathy, autoimmune diseases. From the endocrine system , frequency is unknown: syndrome of inadequate secretion of antidiuretic hormone. Allergic reactions often: urticaria, skin rash, exanthema, hypersensitivity reactions / angioedema (angioedema of the face, limbs, lips, tongue, pharynx and / or larynx is described) infrequently: increased sweating, sore skin, itching, rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, pemphigus, erythroderma. A symptom complex is described that may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, positive test for antinuclear antibodies. A symptom complex is also described, which includes hyperemia of the skin of the face, nausea, vomiting, and arterial hypotension and can develop with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously. Other very common: asthenia often: fatigue, hyperkalemia, increased creatinine in the blood increased blood urea concentration. Drug Interactions The simultaneous use of ACE inhibitors with other agents acting on the renin-angiotensin-aldosterone system (RAAS) increases the risk of hypotension, hyperkalemia and impaired renal function (including acute renal failure). As with other ACE inhibitors and angiotensin II receptor antagonists, the combined use of enalapril and aliskiren is contraindicated in patients with diabetes mellitus or renal failure (CC less than 60 ml / min). Mutual enhancement of action while the use of enalapril with other antihypertensives. Concomitant use with nitroglycerin or other nitrates, or other vasodilators, tricyclic antidepressants, antipsychotics, general anesthetics, narcotic drugs leads to an increase in the antihypertensive effect. With the simultaneous use of enalapril with diuretics (thiazide or “loop” diuretics), an increase in the antihypertensive effect is possible. The simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamteren, amiloride), potassium preparations or potassium-containing substitutes for edible salt, as well as the use of other drugs that increase the potassium content in blood plasma (for example, heparin) are not recommended. The simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors (COX-2)) can weaken the antihypertensive effect of antihypertensive drugs, due to an increase in potassium in the blood plasma, which leads to reversible impairment of renal function, delay liquids. Thus, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors can be attenuated by NSAIDs, including COX-2 inhibitors. NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible. Joint use should be carried out with caution in patients with impaired renal function. The simultaneous use of enalapril and lithium preparations is not recommended, since the concentration of lithium in the blood plasma increases and, accordingly, there is an increase in its toxic effects. With the simultaneous use of enalapril and lithium preparations, it is necessary to control the concentration of lithium in the blood plasma. Concomitant use with thiazide diuretics leads to an increase in the concentration of lithium salts in blood plasma. With the simultaneous use of enalapril with gold preparations for parenteral administration (sodium aurothiomalate), a symptom complex may occur, including facial flushing, nausea, vomiting, arterial hypotension. Reduces the effects of theophylline-containing drugs. Concomitant use with insulin and hypoglycemic agents for oral administration increases the risk of hypoglycemia. Immunosuppressants, allopurinol, cytostatics enhance hematotoxicity. Medications that inhibit bone marrow function increase the risk of neutropenia and / or agranulocytosis. Ethanol enhances the antihypertensive effect of enalapril. Enalapril can be used simultaneously with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and -adrenoblockers. Concomitant use with other ACE inhibitors may increase the risk of hyperkalemia. Antacids may decrease the bioavailability of ACE inhibitors. Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. Overdose Symptoms: marked decrease in blood pressure, up to the development of collapse, myocardial infarction, acute disturbance of cerebral circulation or thromboembolic complications, convulsions, stupor. Treatment: the patient is transferred to a horizontal position with a low head. In mild cases, gastric lavage and intake in saline solution are shown, in more severe cases – measures aimed at stabilizing blood pressure: in / in the introduction of saline solution, plasma substitutes, if necessary – the introduction of angiotensin II, hemodialysis (the rate of excretion of enalaprilat is on average 62 ml / min). Storage Conditions List B. Store in a dry place out of the reach of children at 15 to 25 ° C. Shelf life 3 years. Deystvuyushtee substance nalapril Terms and conditions prescription dosage form tablets Possible product names enalapril hexal tablets 20 mg 50 pcs. Salyutas Pharma GmbH, Switzerland
