Hypotef, pills, 50pcs

Composition

1 tablet contains vinpocetine 2.5 mg, indapamide 0.75 mg, metoprolol tartrate 25 mg, enalapril maleate 5 mg; excipients: -15 thousand hypromellose (hydroxypropyl methylcellulose 15) – 5.05 mg, stearic acid – 2 mg copovidone (kollidon VA64, kollidon BA64)- 5 mg, croscarmellose sodium (Primerose) 12 mg, silicon dioxide colloid (Aerosil) – 2 mg, lactose monohydrate (milk sugar, lactose 80) – 45 mg, microcrystalline cellulose – to the mass of the tablets of 200 mg.

Pharmacological action

Hypotef is a combination drug for the treatment of arterial hypertension in patients over 45 years of age, which has less pronounced side effects than in monotherapy, its components, due to lower doses. Vinpocetine is a semi-synthetic derivative of the devincan alkaloid found in the periwinkle plant; the Active ingredient is apovincamic acid ethyl ether. Vinpocetine improves cerebral circulation, activates metabolic processes in the central nervous system. Vinpocetine has a significant protective effect on higher brain functions, has a pronounced cerebroprotective effect. Vinpocetine intensively and selectively increases cerebral blood flow. The pharmacological effects of the drug are realized through several mechanisms. Vinpocetine significantly improves brain microcirculation, inhibits platelet aggregation, and reduces increased blood viscosity. The drug has a direct effect on brain metabolism, inhibiting cycloadenosine monophosphate (cAMP), thereby slowing down the rate of cAMP breakdown. The level of cAMP also increases as a result of the indirect effect of vinpocetine on cAMP synthesis through an increase in the level of norepinephrine and dopamine in brain tissue, which, in turn, increase the activity of adenylate cyclase, a catalyst for the last stage of cAMP synthesis. Vinpocetine improves the tolerance of hypoxia by brain cells, promoting the transport of oxygen to the tissues, due to a decrease in the affinity of red blood cells for it, increasing the absorption and metabolism of glucose. Glucose metabolism switches to an energetically more favorable, aerobic direction. Another important target of vinpocetine is calcium. The drug inhibits the entry of calcium into the intracellular space or synaptosomes induced by depolarization, and the release of intracellular calcium. Vinpocetine combines vascular and metabolic action, contributes to the normalization of venous outflow against the background of reducing the resistance of brain vessels. Vinpocetine is prescribed orally. Taking the drug for a long time, at least 2 months. Indapamide Indapamide is a drug with diuretic, vasodilating and hypotensive activity. The drug is a diuretic, a derivative of sulfonamide, which inhibits the reabsorption of sodium in the cortical segment of the nephron loop, increases the excretion of sodium, chlorine, calcium and magnesium by the kidneys. Indapamide reduces the sensitivity of the vascular wall to norepinephrine and angiotensin II; stimulates the synthesis of prostaglandin E 2, which has vasodilating and hypotensive effects; inhibits the flow of calcium into the smooth muscle cells of the vascular wall and, thus, reduces the total peripheral vascular resistance (OPSS). This mechanism leads to a decrease in vasoconstriction and normalization of blood pressure. Indapamide is used once a day (preferably in the morning). Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the frequency of side effects continues to increase with further increase in the dose of the drug. Metoprolol acts mainly on beta-1-adrenergic receptors of the heart, does not have internal sympathomimetic and membrane-stabilizing activity. Reduces the stimulating effect of sympathetic innervation on the heart, has an antianginal, antihypertensive, antiarrhythmic effect. Selectively blocks beta-adrenergic receptors. Reduces heart rate( HR), slows down antrioventricular (AV) conduction, reduces contractility and excitability of the myocardium. Blood pressure decreases due to these mechanisms, as well as by suppressing the secretion of blood renin activity. In addition, there is a decrease in pressure in the portal vein system due to a decrease in hepatic and mesenteric blood flow. The effect of metoprolol develops 1 h after oral use. Enalapril inhibits ACE, which promotes the conversion of angiotensin I to angiotensin II, reduces the concentration of aldosterone in the blood, increases the release of renin, improves the functioning of the kallikrein-kinin system, stimulates the release of prostaglandins and endothelial relaxing factor, and inhibits the sympathetic nervous system. Together, these effects eliminate spasm and dilate peripheral arteries, reduce OPSS, systolic and diatolic blood pressure, and 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. The antihypertensive effect is more pronounced at high plasma renin concentrations than at normal or reduced levels. Lowering blood pressure within therapeutic limits does not affect cerebral circulation. Improves blood supply to the ischemic myocardium. Increases renal blood flow, while the glomerular filtration rate does not change. In patients with initially reduced glomerular filtration rate, its rate usually increases. The maximum effect of enalapril develops in 6-8 hours and persists up to 24 hours after oral use. Hypotef is a combined drug, the doses of active components in which are 2-4 times lower than the therapeutic ones for each component. The antihypertensive effect is achieved by simultaneous exposure to most of the stages that cause the development of arterial hypertension, leading to vascular relaxation (enalapril, vinpocetine), a decrease in the amount of fluid in the body (indapamide) and normalization of cardiac activity (metoprolol). The drug prevents an increase in the tone of the meninges, including with ischemic brain damage – a condition characteristic of a very wide range of diseases, as well as for the elderly. The introduction of vinpocetine into the combination helps to limit the development of lipid peroxidation, maintain the partial pressure of oxygen in the brain, has an anti-edematous effect and improves mental activity in arterial hypertension in combination with cerebral ischemia. Pharmacokinetics of absorption for the drug Hypotef, it was found that when administered orally to rabbits at a dose of 18.5 mg/kg, metoprolol is absorbed fairly quickly in the gastrointestinal tract, the maximum concentration (Cmax) is reached within 1.17 hours, followed by the elimination of metoprolol from the bloodstream, the half – life (T1/2b) is 2.15 hours. For the remaining components, the pharmacokinetics in combination have not been studied, but it is known that: — vinpocetine is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 57%. The value of the therapeutic concentration of vinpocetine in blood plasma is from 10 to 20 ng / ml;- indapamide is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is high (93%). Cmax of indapamide is created 1-2 hours after oral use. In the blood plasma, it binds to blood proteins by 71-79%, and can also be sorbed by red blood cells;- enalapril-about 60% of enalapril is absorbed from the gastrointestinal tract. The suction volume is 60%. Cmax in the blood serum is reached in 3-4 hours after use, the equilibrium concentration – in 4 days. A decrease in blood pressure occurs 1 hour after use, reaches a maximum by 6 hours and continues for 1 day. Distributiondistribution in combination has not been studied. – vinpocetine easily passes through histohematic barriers (including BBB, placental), penetrates into breast milk. – indapamide has a high volume of distribution, passes through histohematic (including placental) barriers, penetrates into breast milk. – metoprolol passes through the BBB and placental barrier, penetrates into breast milk. – enalapril easily passes through histohematic barriers, excluding BBB, penetrates the placental barrier. Metabolism Metabolism in combination has not been studied. – vinpocetine is extensively metabolized in the body, the main metabolites are apovincamic acid and hydroxyvinpocetine. – indapamide is almost completely metabolized in the liver. The only pharmacologically active metabolite is formed as a result of hydrolysis of the indole ring. – metoprolol is intensively biotransformed in the liver with the formation of metabolites-o-desmethylmetoprolol and α-hydroxymethoprolol. enalapril undergoes biotransformation in the liver to form a metabolite, enalaprilate, whose Cmax is determined after 4 hours. Elimination Elimination in combination has not been studied. – vinpocetine T1 / 2 – about 5 hours. Most of vinpocetine is excreted by the kidneys in the form of metabolites. Only a few percent of the drug is excreted unchanged. – indapamide T1 / 2-about 14 hours. Up to 80% is excreted by the kidneys in the form of inactive metabolites and 20% – through the intestine. – metoprolol-T1 / 2 is 2.15 hours. It is excreted by the kidneys mainly in the form of metabolites, about 3% – in unchanged form. – enalapril-T1 / 2 is 11 hours. It is mainly excreted by the kidneys (up to 40% is excreted in the form of enalaprilat). Up to 90% of the amount entered is displayed within 24 hours.

Indications

Arterial hypertension of 1 and 2 degrees of severity in patients older than 45 years.

Contraindications

Vinpocetine: — hypersensitivity to vinpocetine; – acute phase of hemorrhagic stroke, severe CHD, severe cardiac arrhythmias— – pregnancy, breast-feeding; – age up to 18 years. Metoprolol: – hypersensitivity to metoprolol;- cardiogenic shock— – AV block of II and III degrees (without artificial pacemaker);- sinoatrial block, sinus node weakness syndrome, severe bradycardia (heart rate less than 50 beats).-hyperreactivity of the bronchi (for example, with severe bronchial asthma, patients receiving constant or intermittent therapy with inotropic drugs acting on beta-adrenergic receptors, COPD in the acute stage), severe peripheral circulatory disorders, heCombination of drugs that require special attentionpreparations that can cause arrhythmia of the “pirouette”type:- Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);- Class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide) and sotalol;- some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levopromazine, thioridazine, triftoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);- others: bepridil, cisapride, difemanil, erythromycin (iv), halofantrin, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (iv). Increased risk of ventricular arrhythmias, especially pirouette-type arrhythmias (risk factor – hypokalemia). It is necessary to monitor the content of potassium in the blood plasma and, if necessary, adjust it before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, blood plasma electrolyte content, and ECG. NSAIDs (with systemic use), including selective COX-2 inhibitors, high-dose salicylates (≥3 g / day):- it is possible to reduce the antihypertensive effect of indapamide;- with a significant loss of fluid, acute renal failure may develop (due to a decrease in the glomerular filtration rate). Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and during therapy. ACE inhibitors:The use of ACE inhibitors in patients with hyponatremia in the blood (especially in patients with renal artery stenosis) is associated with the risk of sudden hypotension and/or acute renal failure. Patients with arterial hypertension and possibly reduced, due to the use of diuretics, the content of sodium in the blood plasma should::- stop taking diuretics 3 days before starting treatment with an ACE inhibitor. In the future, if necessary, the use of diuretics can be resumed;- or start therapy with an ACE inhibitor with low doses, followed by a gradual increase in the dose if necessary. In patients with chronic heart failure, treatment with ACE inhibitors should be initiated at low doses, with possible preliminary reductions in diuretic doses. In all cases, during the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (plasma creatinine concentration). Other drugs that can cause hypokalemia: amphotericin B (IV), gluco-and mineralcorticoids (with systemic use), tetracosactide, laxatives that stimulate intestinal motility. Increased risk of hypokalemia (additive effect). It is necessary to regularly monitor the content of potassium in the blood plasma, if necessary – its correction. Special attention should be paid to patients receiving concomitant cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility. – Baclofen:There is an increase in the antihypertensive effect. Patients should be compensated for fluid loss and renal function should be carefully monitored at the beginning of treatment. – cardiac glycosides:Hypokalemia increases the toxic effect of cardiac glycosides. When indapamide and cardiac clinosides are used concomitantly, the blood plasma potassium content, ECG should be monitored, and therapy should be adjusted if necessary. A combination of drugs that requires attention— potassium-sparing diuretics (amiloride, spironolactone, triamterene):Combination therapy with indapamide and potassium-sparing diuretics is appropriate in some patients, but the possibility of hypokalemia (especially in patients with diabetes mellitus and patients with renal insufficiency) or hyperkalemia is not excluded. It is necessary to monitor the content of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy. – metformin:Functional renal failure, which may occur with diuretics, especially “loop” diuretics, with simultaneous use of metformin increases the risk of lactic acidosis. Do not take metformin if the creatinine concentration exceeds 15 mg / g (135 mmol/l) in men and 12 mg / g (100 micromol/l) for women. – iodine-containing contrast agents:Dehydration of the body while taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Patients should be compensated for fluid loss before using iodine-containing contrast agents. – tricyclic antidepressants, antipsychotics (neuroleptics):Drugs of these classes enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect). – calcium salts:With simultaneous use, hypercalcemia may develop due to a decrease in the excretion of calcium ions by the kidneys. – cyclosporine, tacrolimus:It is possible to increase the concentration of creatinine in blood plasma without changing the concentration of circulating cyclosporine, even with normal fluid and sodium ions. — corticosteroid drugs (mineral and glucocorticosteroids), tetracosactide (with systemic use):Reduced antihypertensive effect (fluid retention and sodium ions as a result of corticosteroids). Metoprolol is recommended for concomitant use with MAO inhibitors due to a significant increase in the antihypertensive effect. The treatment interval between taking MAO inhibitors and metoprolol should be at least 14 days. Beta-blockers, theophylline, cocaine, estrogens (sodium retention), Indometacin, and other NSAIDs (sodium retention and blocking of prostaglandin synthesis by the kidneys) weaken the antihypertensive effect of metoprolol. When used concomitantly with hypoglycemic agents for oral use, their effect may decrease; with insulin – an increased risk of hypoglycemia, an increase in its severity and duration, masking some symptoms of hypoglycemia (tachycardia, increased sweating, increased blood pressure). When used concomitantly with antihypertensive agents, diuretics, ACE inhibitors, nitroglycerin or slow calcium channel blockers, a sharp decrease in blood pressure may develop (special caution is necessary when combined with prazosin); the risk of bradycardia increases when combined with epinephrine; a pronounced decrease in heart rate and suppression of AV conduction up to complete blockade-when using metoprolol with verapamil, diltiazem, reserpine, methyldopa, clonidine, guanfacine and cardiac glycosides, general anesthesia agents (along with cardiodepressive and antihypertensive effects). Simultaneous intravenous use of verapamil may cause cardiac arrest. Drugs that induce or inhibit the CYP2D6 isoenzyme may affect the concentration of metoprolol in blood plasma. The concentration of metoprolol in blood plasma may increase when taken simultaneously with other drugs that are a substrate for CYP2D6, for example, antiarrhythmic drugs, antihistamines, H2-receptor antagonists, antidepressants (selective inhibitors of neuronal reuptake of serotonin, for example, paroxetine, fluoxetine, sertraline), neuroleptics and COX-2 inhibitors. Class I antiarrhythmic drugs can lead to the summation of a negative inotropic effect with the development of pronounced hemodynamic side effects in patients with impaired left ventricular function (this combination should be avoided in patients with sinus node weakness syndrome and impaired AV conduction). Quinidine inhibits the metabolism of metoprolol in patients with “fast” metabolism, leading to a significant increase in the concentration of metoprolol in blood plasma and an increase in its beta-blocking effect. Combination with amiodarone increases the risk of severe sinus bradycardia (including after a long time after the withdrawal of amiodarone, due to its long half-life). If metoprolol and clonidine are taken simultaneously, then when metoprolol is discontinued, clonidine is canceled after a few days (due to the risk of “withdrawal”syndrome). Inducers of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism and a decrease in the effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) – increase the concentration of metoprolol in blood plasma. Diphenhydramine reduces the clearance of metoprolol, increasing its effect. Concomitant use with high doses of phenylpropanolamine can lead to a paradoxical increase in blood pressure (up to a hypertensive crisis). Allergens used for immunotherapy or allergen extracts for skin tests when combined with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque substances for intravenous use increase the risk of anaphylactic reactions. Reduces the clearance of xanthines (except diphylline), especially in patients with an initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in blood plasma. Enhances and prolongs the action of antidepolarizing muscle relaxants; prolongs the anticoagulation effect of coumarins. When combined with anxiolytics and drugs with hypnotic activity, the antihypertensive effect is enhanced, with ethanol-the risk of a pronounced decrease in blood pressure increases and the depressing effect on the central nervous system increases. There is an increased risk of peripheral circulatory disorders – with ergot alkaloids. Simultaneous use of ENALAPRIL is not recommended— potassium-sparing diuretics (spironalactone, eplerenone, triamterene, amiloride) or potassium-containing salts, potassium supplements: when used simultaneously with ACE inhibitors, hyperkalemia may develop.If, due to the diagnosed hypokalemia, the simultaneous use of these drugs is still indicated, then they should be used with caution, with regular monitoring of the potassium content in the blood serum and electrocardiogram. Concomitant use with caution— thiazide or loop diuretics: previous treatment with high-dose diuretics may lead to a decrease in BCC at the beginning of enalapril therapy and contribute to the development of arterial hypotension. The antihypertensive effect can be reduced by discontinuing the diuretic, increasing the intake of fluids or salts in the body, or starting therapy with low doses of enalapril. ;- drugs for general anesthesia: when used with ACE inhibitors, they can lead to an aggravation of orthostatic hypotension;— narcotic drugs/tricyclic antidepressants/psychotropic drugs/barbiturates: orthostatic hypotension may occur— – other antihypertensive drugs (alpha-and beta-blockers, slow calcium channel blockers): the antihypertensive effect can be summed up or potentiated. Caution is required when treating with nitroglycerin in various dosage forms and other nitrates or other vasodilators;- cimetidine: increased risk of collapse;- cyclosporine: concomitant use with ACE inhibitors increases the risk of developing impaired renal function;— allopurinol, procainamide, cytostatics or immunosuppressants: when used concomitantly with ACE inhibitors, the risk of hypersensitivity reactions, leukopenia increases— – hypoglycemic agents: in rare cases, ACE inhibitors can increase the hypoglycemic effect of insulin and hypoglycemic agents for oral use (for example, sulfonylureas) in patients with diabetes mellitus. In these cases, when ACE inhibitors are used simultaneously, it may be necessary to reduce the dose of the hypoglycemic agent;— sympathomimetics may weaken the antihypertensive effect of ACE inhibitors. To confirm the antihypertensive effect, such patients should be under close medical supervision. ;- anatcids reduce the bioavailability of ACE inhibitors when used concomitantly;— when used concomitantly with the preparation of gold (sodium aurothiomalate) for intravenous use, patients were observed: “flushes” of blood to the skin of the face, nausea, vomiting, and hypotension. Arterial hypotension can be regarded as an increase in the effect of ACE inhibitors under the influence of the drug gold. Double blockade of the renin-angiotensin-aldosterone system (RAAS)It has been reported in the literature that RAAS blockade in patients with an established diagnosis of atherosclerosis, heart failure, or diabetes mellitus with target organ damage is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to the use of a single-component RAAS blockade. The use of dual blockade of the RAAS (for example, by concomitant use of an ACE inhibitor with an angiotensin II receptor antagonist) should be decided on a case-by-case basis, with careful monitoring of renal function.

How to take, course of use and dosage

Inside before meals,1 tablet 1 time a day (in the morning). With insufficient efficacy and good tolerability, the dose can be increased to 2-3 tablets. per day, with an even distribution of time between meals.

The therapeutic effect is achieved within two to three weeks of therapy.

Overdose

Vinpocetine No overdose reports. Treatment: gastric lavage, taking activated charcoal; symptomatic treatment. Indapamid Symptoms: possible violations of water-electrolyte balance (hyponatremia, hypokalemia), nausea, vomiting, marked decrease in blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hopivolemia). Treatment: urgent measures aimed at removing the drug from the body: gastric lavage and / or use of activated carbon with subsequent restoration of water and electrolyte balance, symptomatic therapy. There is no specific antidote. Metoprolol symptoms: severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole, bronchospasm, syncope, acute overdose – cardiogenic shock, loss of consciousness, coma, AV block (up to the development of complete transverse block and cardiac arrest), cardialgia, hypoglycemia, hyperkalemia, convulsions, respiratory arrest. Signs of overdose appear 20 minutes-2 hours after taking the drug. Treatment: gastric lavage and use of adsorbents; symptomatic therapy: with a pronounced decrease in blood pressure, the patient should be in the Trendelenburg position; in case of excessive decrease in blood pressure, bradycardia and heart failure – intravenously (IV), with an interval of 2-5 minutes, beta-adrenomimetics-until the desired effect is achieved or IV 0.5-2 mg of atropine. In the absence of a positive effect – dopamine, dobutamine or norepinephrine (norepinephrine). As a follow-up, it is possible to install an artificial pacemaker. In case of bronchospasm, intravenous beta-2-adrenomimetics should be administered. Metoprolol is poorly excreted by hemodialysis. Enalapril Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other cardiac arrhythmias, convulsions, impaired consciousness (including coma), acute renal failure, impaired acid-base state and water-electrolyte balance of the blood. Treatment: gastric lavage and ingestion of activated charcoal; in more serious cases – transfer the patient to a horizontal position with raised legs, then carry out measures aimed at stabilizing blood pressure – intravenous use of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient should be monitored for blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary – hemodialysis (the rate of elimination of enalaprilat-62 ml / min).

Special instructions

When used concomitantly with drugs that prolong the QT interval, periodic monitoring of the electrocardiogram is necessary. The most careful monitoring is indicated in patients with severe heart failure, CHD, and vascular diseases of the brain, in which a sharp decrease in blood pressure can lead to myocardial infarction, stroke, or impaired renal function, as well as in patients with cirrhosis of the liver. In patients taking cardiac glycosides, laxatives, on the background of hyperaldosteronism, as well as in elderly patients (over 60 years), careful monitoring of potassium and creatinine levels is indicated. Orthostatic hypotension may occur, which can be provoked by taking alcohol, barbiturates, narcotic drugs and simultaneous use of other antihypertensive agents. It can mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Hypercalcemia associated with taking the drug Hypotef may be a consequence of previously undiagnosed hyperparathyroidism. Significant dehydration can lead to acute renal failure (decreased glomerular filtration rate). Patients should be compensated for fluid loss and renal function should be carefully monitored at the beginning of treatment. The drug Hypotef can give a positive result during doping control (the drug contains indapamide). 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, diuretics can be resumed a little later), or they are prescribed initial low doses of ACE inhibitors. Sulfonamide derivatives can exacerbate the course of systemic lupus erythematosus (it is necessary to keep in mind when prescribing the drug Hypotef). Patients taking beta-blockers should not be given intravenous verapamil-type BMCC. Monitoring of the condition of patients taking beta-blockers includes regular monitoring of heart rate and blood pressure, blood glucose concentration in patients with diabetes mellitus. If necessary, for patients with diabetes mellitus, the dose of insulin or hypoglycemic agents prescribed by mouth should be selected individually. The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min. Patients with Prinzmetal angina should not be prescribed non-selective beta-blockers. In patients taking beta-blockers, anaphylactic shock occurs in a more severe form. It is possible to increase the severity of hypersensitivity reactions (against the background of a burdened allergic history) and the lack of effect from the introduction of conventional doses of epinephrine (epinephrine). It may increase the symptoms of peripheral arterial circulation disorders. Discontinuation of the drug is carried out gradually, reducing the dose over 14 days. If treatment is abruptly discontinued, a “withdrawal” syndrome may occur (increased angina attacks, increased blood pressure). Special attention should be paid to patients with angina pectoris when discontinuing the drug. Patients who use contact lenses should take into account that against the background of treatment with beta-blockers, tear fluid production may decrease. Metoprolol may mask some clinical manifestations of hyperthyroidism (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, as it can increase symptoms. In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal levels.If it is necessary to prescribe it to patients with bronchial asthma, beta-2-adrenomimetic therapy should be prescribed as concomitant therapy. The minimum effective dose of metoprolol should be prescribed, and an increase in the dose of beta-2-adrenomimetic may be required. Patients with pheochromocytoma, in parallel with metoprolol, should be prescribed an alpha-blocker. If surgical intervention is necessary, it is necessary to warn the anesthesiologist about the therapy being performed (the choice of a general anesthesia agent with minimal negative inotropic effect), the drug withdrawal is not recommended. Drugs that reduce the supply of catecholamines (for example, reserpine) can increase the effect of beta-blockers, so patients taking such combinations of drugs should be constantly monitored by a doctor for excessive lowering of blood pressure and bradycardia. In elderly patients, regular monitoring of liver function is recommended. Monitoring of renal function is recommended for patients with severe renal insufficiency. Special monitoring of the condition of patients with depressive disorders taking metoprolol should be carried out; in case of depression caused by taking beta-blockers, it is recommended to stop therapy. There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients with a burdened allergic history or a tendency to allergic reactions, undergoing desensitization procedures. Avoid prescribing an ACE inhibitor to patients receiving hymenopteran venom immunotherapy. However, an anaphylactoid reaction can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure. In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure. Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is desirable to use a different type of membrane or use a hypotensive agent of a different pharmacotherapeutic group. ACE inhibitors should be used with caution in patients with left ventricular outlet obstruction. Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, impaired renal function, advanced age (over 60 years), diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, as well as the use of other agents that increase the content of ions potassium in the blood plasma (for example, heparin). The use of potassium-sparing drugs instead of food salt can lead to a significant increase in the content of potassium ions in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal cardiac arrhythmias. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of the potassium content in the blood serum (see the section “Drug interaction”). Influence on the ability to drive motor vehicles and control mechanisms During treatment, care should be taken when driving motor vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Pills.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25°C.

Shelf

life is 2 years.

Active ingredient

Vinpocetine, Indapamide, Metoprolol, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension