More info
Active ingredients
Lisinopril
Release form
Pills
Composition
Lisinopril dihydrate 10.89 mg, which corresponds to the content of lisinopril 10 mg. Adjuvants: magnesium stearate, talc, mannitol, corn starch, calcium hydrogen phosphate dihydrate.
Pharmacological effect
An ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases prostaglandin synthesis. Reduces the OPSS, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and an increase in myocardial tolerance to stress in patients with chronic heart failure. Expands arteries to a greater extent than veins. Some effects are attributed to effects on tissue renin-angiotensin systems. With prolonged use, hypertrophy of the myocardium and the walls of resistive arteries is reduced. It improves blood supply to ischemic myocardium. ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. within 24 hours. The duration of the effect also depends on the size of the dose taken. In case of arterial hypertension, the effect is noted in the first days after the start of treatment, a stable action develops after 1-2 months. With the abrupt cancellation of the drug did not observe a pronounced increase in blood pressure. Dyroton reduces albuminuria. In patients with hyperglycemia, it helps normalize the function of the damaged glomerular endothelium. It does not affect the concentration of glucose in the blood of patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.
Pharmacokinetics
Absorption After ingestion of lisinopril into Cmax is achieved in 7 hours. The average degree of absorption of lisinopril is about 25%, with significant interindividual variability (6-60%). Food intake does not affect the absorption of lisinopril. Distribution Lysinopril is poorly bound to plasma proteins.Permeability through the BBB and placental barrier is low. Metabolism Lysinopril is not metabolized. Excretion Excreted exclusively by the kidneys in unchanged form. After repeated administration, the effective T1 / 2 is 12 hours. The pharmacokinetics in special clinical situations. Patients with chronic heart failure have reduced absorption and clearance of lisinopril. Disruption of renal function leads to an increase in AUC and T1 / 2 of lisinopril, but these changes become clinically significant only when glomerular filtration rate of less than 30 ml / min. In elderly patients, the concentration of the drug in the blood plasma and AUC is 2 times higher than in young patients. Lysinopril is excreted from the body by hemodial for.
Indications
- essential and renovascular arterial hypertension (as monotherapy or in combination with other antihypertensive drugs); - chronic heart failure (as part of combination therapy); - acute myocardial infarction (during the first 24 hours with stable hemodynamic indicators to maintain these indicators and prevent dysfunction left ventricle and heart failure) - diabetic nephropathy (to reduce albuminuria in patients with insulin-dependent diabetes mellitus in normal blood pressure and in patients with and non-insulin dependent diabetes mellitus with arterial hypertension).
Contraindications
- idiopathic angioedema in history (including with the use of ACE inhibitors); - hereditary angioedema; - children and adolescents under 18 years of age (efficacy and safety not established); - hypersensitivity to lisinopril or other ACE inhibitors.C caution should be prescribed the drug for bilateral renal artery stenosis or arterial stenosis of a single kidney, condition after kidney transplantation, renal failure (CC less than 30 ml / min), aortic stenosis, hypertrophic obstructive rdiomiopatii, primary hyperaldosteronism, hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, severe diabetes, severe chronic heart failure, systemic connective tissue diseases (includingscleroderma, systemic lupus erythematosus), inhibition of bone marrow hematopoiesis, hypovolemic conditions (including as a result of diarrhea, vomiting); hyponatremia (in patients on a low-salt or salt-free diet, an increased risk of arterial hypotension), elderly patients, with hemodialysis using high-flow dialysis membranes (AN69).
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 use of Diroton in pregnancy is contraindicated. Lisinopril penetrates the placental barrier. At establishment of pregnancy reception of a preparation should be stopped as soon as possible. Acceptance of ACE inhibitors in the II and III trimesters of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, cranial hypoplasia, fetal death are possible). Data on the negative effects of the drug on the fetus in the case of use in the first trimester is not. For newborns and infants who have undergone intrauterine effects of ACE inhibitors, it is recommended to establish careful monitoring for the timely detection of pronounced reduction in blood pressure, oliguria, hyperkalemia. If necessary, the appointment of the drug during lactation breastfeeding should be discontinued.
Dosage and administration
The drug is taken orally 1 time / day, for all indications, regardless of the meal, preferably at the same time of day. For essential hypertension, patients who do not receive other antihypertensive drugs are prescribed 10 mg 1 time / day. The usual daily maintenance dose is 20 mg.The maximum daily dose is 40 mg. The full effect usually develops after 2-4 weeks from the start of treatment, which should be considered when increasing the dose. With insufficient clinical effect, it is possible to combine the drug with other antihypertensive drugs. If the patient received prior treatment with diuretics, they should be stopped for 2-3 days before the use of Diroton. If it is impossible to cancel diuretics, then the initial dose of Diroton should not exceed 5 mg / day. In this case, after taking the first dose, medical control is recommended for several hours (the maximum effect is reached after about 6 hours), because A pronounced decrease in blood pressure may develop. In case of renovascular hypertension or other conditions with increased activity of the RAAS, it is also advisable to prescribe a lower initial dose of 2.5–5 mg / day under enhanced medical control (control of blood pressure, kidney function, serum potassium serum concentrations). The maintenance dose should be determined depending on the dynamics of blood pressure. In renal failure, due to the fact that lisinopril is excreted by the kidneys, the initial dose should be determined depending on the CC, then a maintenance dose should be established in response to frequent monitoring of renal function, potassium and sodium in serum. In chronic heart failure, the initial dose is 2.5 mg 1 time / day, which can be gradually increased in 3-5 days to a normal, supporting daily dose of 5-20 mg. The dose should not exceed the maximum daily dose of 20 mg. With simultaneous use with diuretics pre-, if possible, the dose of diuretic should be reduced. Before proceeding with treatment with Diroton and later, during treatment, blood pressure, kidney function, potassium and sodium in the blood should be regularly monitored to prevent the development of arterial hypotension and related renal dysfunction. In acute myocardial infarction (as part of combination therapy 5 mg is prescribed on the first day, 5 mg repeatedly on the second day, 10 mg on the third day, the maintenance dose is 10 mg once a day. In patients with acute myocardial infarction, the drug should be used for at least 6 weeks. With a low systolic blood pressure (less than 120 mmHg), treatment begins with a low dose (2.5 mg / day).In the case of arterial hypotension, when systolic blood pressure is less than 100 mm Hg. Art., the maintenance dose is reduced to 5 mg / day, if necessary, you can temporarily appoint 2.5 mg / day. In case of a prolonged pronounced decrease in blood pressure (systolic blood pressure below 90 mmHg. More than 1 hour), treatment with the drug should be discontinued. In diabetic nephropathy in patients with insulin-dependent diabetes mellitus, Diroton is used at a dose of 10 mg 1 time / day. If necessary, the dose can be increased to 20 mg 1 time / day in order to achieve diastolic blood pressure values below 75 mm Hg. st. in a sitting position. In patients with non-insulin dependent diabetes mellitus, the drug is prescribed in the same dose, in order to achieve diastolic blood pressure values below 90 mm Hg. in a sitting position.
Side effects
The most common side effects are dizziness, headache (5-6%), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, chest pain (1-3%). Others frequency adverse reactions - less than 1%. From the side of the cardiovascular system: marked decrease in blood pressure, chest pain; rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of heart failure symptoms, impaired AV conduction, myocardial infarction. On the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste disorder, pancreatitis hepatitis (hepatocellular and cholestatic), jaundice (hepatocellular or cholestatic), hyperbilirubinemia, increased activity of hepatic transaminases. From the side of the skin: urticaria, increased sweating, photosensitization, to zhny itching, loss volos.So CNS side: mood lability, impaired concentration, paresthesia, fatigue, somnolence, jerking of the limbs and lips; rarely - asthenic syndrome, confusion. From the respiratory system: dyspnea, dry cough, bronchospasm, apnea. swelling of the face, extremities, lips, tongue, epiglottis and / or larynx, intestinal angioedema,vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia; in very rare cases - interstitial angioedema (edema of the interstitial lung tissue without transudation into the alveoli lumen). From the urogenital system: uremia, oliguria, anuria, renal dysfunction, acute renal failure, reduced potency. Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, increased concentrations of urea and creatinine in the blood plasma, hypercholesterolemia, hypertriglyceridemia, decreased tolerance ty to glucose.Other: arthralgia, arthritis, myalgia, fever, aggravation of gout.
Overdose
Symptoms: pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability. Treatment: gastric lavage, intake of activated carbon, giving the patient a horizontal position with raised legs, replenishment of the BCC (w / in the introduction of plasma-substituting solutions) symptomatic therapy, control of the cardiovascular and respiratory systems, BCC, urea, creatinine and electrolytes in the serum, and diuresis. Lisinopril can be removed from the body through hemodialysis.
Interaction with other drugs
When applied simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, the risk of hyperkalemia increases, especially in patients with impaired renal function. Therefore, co-administration is possible only on the basis of an individual physician's decision with regular monitoring of serum potassium and kidney function. When used simultaneously with beta-blockers, slow calcium channel blockers, diuretics and other antihypertensive drugs, an increase in the hypotensive effect of the drug is observed. ACE and preparations of gold (sodium aurothiomalate) in / in the described symptom complex, including facial flushing, nausea, vomiting and arterial ipotenziyu.Pri simultaneous use of vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol Preparata.pri enhanced hypotensive effect of the simultaneous use of NSAIDs (includingselective inhibitors of COX-2), estrogen, as well as adrenergic mimetic drugs, reduces the antihypertensive effect of lisinopril. When used simultaneously with lithium, removal of lithium from the body slows down (enhancing the cardiotoxic and neurotoxic action of lithium). enhances the neurotoxicity of salicylates, weakens the effect of hypoglycemic agents for oral administration, norepinephrine, epinephrine and anti-gout agents , enhances the effects (including side effects) of cardiac glycosides, the effect of peripheral muscle relaxants, reduces the excretion of quinidine. Reduces the effect of oral contraceptives. If you simultaneously take methyldopa, the risk of hemolysis increases.
special instructions
Most often, a pronounced decrease in blood pressure occurs when a decrease in the volume of fluid caused by diuretic therapy, a decrease in salt content in food, dialysis, diarrhea or vomiting. In chronic heart failure with simultaneous renal failure or without it, a pronounced decrease in blood pressure is possible. A more pronounced decrease in blood pressure is detected in patients with severe stage of chronic heart failure, as a result of the use of high-dose diuretics, hyponatremia or impaired renal function. In such patients, treatment with Diroton should be started under the strict supervision of a physician (carefully select the dose of the drug and diuretics). These rules should be followed when prescribing Dyroton for patients with coronary artery disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke. the reaction is not a contraindication for taking the next dose of the drug. Prior to initiating treatment with Diroton, if possible, normalize the concentration of sodium and / or replenish it by lost volume of fluid, carefully controlling the effect of the initial dose of Diroton on the patient's AD. Treatment of symptomatic arterial hypotension consists of providing bed rest and, if necessary, IV fluid injection (saline infusion). Transient arterial hypotension is not a contraindication for treatment with Dyroton, however, it may require temporary cancellation,or dose reduction. Dyroton treatment is contraindicated in case of cardiogenic shock and in acute myocardial infarction, if the administration of a vasodilator can significantly worsen hemodynamic parameters, for example, when systolic blood pressure does not exceed 100 mm Hg. In patients with acute myocardial infarction, a decrease in renal function (plasma creatinine concentration of more than 177 μmol / L and / or proteinuria of more than 500 mg / 24 h) is a contraindication for the use of Dyroton. In case of development of renal failure during treatment with lisinopril (plasma creatinine concentration is more than 265 µmol / L or twice the initial level), the doctor should decide whether to stop treatment. In case of bilateral stenosis of the renal arteries and stenosis of the renal artery of the only kidney, as well as hyponatremia and / or a decrease in blood volume control or circulatory insufficiency arterial hypotension caused by taking the drug Dyroton, can lead to a decrease in renal function with subsequent development of reversible (by after discontinuation of the drug) acute renal failure. A slight temporary increase in the concentration of urea in the blood and creatinine can be observed in cases of impaired renal function, especially against the background of simultaneously treated diuretics. In cases of significant reduction in kidney function (CC less than 30 ml / min), caution and control of renal function are required. Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely observed in patients treated with ACE inhibitors, including Dyroton, which may occur during any period of treatment. In this case, treatment with Dyroton should be stopped as soon as possible and patients should be monitored until symptoms are fully regressed. In cases where there is swelling of the face and lips, the condition most often passes without treatment, but antihistamines can be prescribed. Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx is covered, airway obstruction can occur, therefore, appropriate therapy should be immediately carried out (0.3-0.5 ml of epinephrine (adrenaline) solution 1: 1000 patches, administration of GCS, antihistamines) and / or measures to ensure the respiratory ways.Patients who have already had angioedema in their history, which is not associated with previous treatment with ACE inhibitors, may have an increased risk of developing during treatment with an ACE inhibitor. membranes (AN69). In such cases, it is necessary to consider the possibility of using a different type of membrane for dialysis or another antihypertensive agent. In some cases of desensitization against arthropod allergens, treatment with ACE inhibitors was accompanied by hypersensitivity reactions. This can be avoided if you temporarily interrupt the use of ACE inhibitors. Patients with extensive surgery or during general anesthesia, ACE inhibitors (in particular, lisinopril) can block the formation of angiotensin II. The decrease in blood pressure associated with this mechanism of action is corrected by increasing the BCC. Before surgery (including dentistry), it is necessary to warn the anesthesiologist about the use of the drug Diroton. The use of the drug in recommended doses by elderly patients may be accompanied by an increase in lisinopril concentration in the blood; However, in elderly and young patients, the antihypertensive effect of the drug Diroton is equally pronounced. When using ACE inhibitors, there was a cough (dry, long-lasting, which disappears after stopping treatment with ACE inhibitors). In the differential diagnosis of cough, cough caused by the use of ACE inhibitors should also be taken into account. In some cases hyperkalemia was noted. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, taking potassium drugs or drugs that cause an increase in blood potassium (eg heparin), especially in patients with impaired renal function. , glucose, urea, lipids. During treatment, it is not recommended to drink alcoholic beverages, becauseethanol enhances the hypotensive effect of the drug. Care should be taken when exercising in hot weather (risk of dehydration and excessive blood pressure reduction due to reduced BCC). driving a car and controlling machinery; In the event of adverse reactions from the central nervous system, it is not recommended to drive a vehicle or perform work associated with increased risk.