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Active ingredients
Lisinopril
Release form
Pills
Composition
Lisinopril dihydrate 10.89 mg, which corresponds to the content of Lisinopril 10 mg. Excipients: 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. 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 a myocardial infarction without clinical manifestations of heart failure. The onset of action of the drug - after 1 h, reaches a maximum after 6-7 hours and lasts for 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. Diroton 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 inside 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 Lisinopril is weakly bound to plasma proteins. Permeability through the BBB and placental barrier is low.Metabolism Lisinopril is not metabolized. Withdrawal Excreted exclusively by the kidneys in unchanged form. After repeated administration, the effective T1 / 2 is 12 hours. Pharmacokinetics in special clinical situations In patients with chronic heart failure, absorption and clearance of lisinopril are reduced. Impaired renal function leads to an increase in AUC and T1 / 2 of lisinopril, but these changes become clinically significant only when the glomerular filtration rate is less than 30 ml / min. In elderly patients, the concentration of the drug in blood plasma and AUC is 2 times higher than in young patients. Lisinopril is excreted by hemodialysis.
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 (in the first 24 hours with stable hemodynamic parameters to maintain these indicators and prevent left ventricular dysfunction and heart failure); - diabetic nephropathy (to reduce albuminuria in patients with insulin-dependent diabetes mellitus with normal blood pressure and in patients with insulin-dependent diabetes mellitus with arterial hypertension).
Contraindications
- idiopathic angioedema in the history of history (including when using ACE inhibitors); - hereditary angioedema; - children's and teenage age up to 18 years (efficiency and safety are not established); - Hypersensitivity to lisinopril or other ACE inhibitors. The drug should be prescribed with caution in bilateral renal artery stenosis or arterial stenosis of a single kidney, a condition after kidney transplantation, renal failure (CC less than 30 ml / min), aortic osteoarthritis, hypertrophic obstructive cardiomyopathy, primary hyper aldosteronism, arterial hypotension, cerebral circulation including cerebrovascular insufficiency), ischemic heart disease, severe diabetes, severe chronic heart failure, systemic diseases noy tissue (including scleroderma, systemic lupus erythematosus), inhibition of bone marrow hematopoiesis, hypovolemic states (includingas 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).
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 to timely detect a pronounced decrease in blood pressure, oliguria, hyperkalemia. Data on the penetration of lisinopril into breast milk is not. 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. In essential hypertension, patients who do not receive other antihypertensive drugs are prescribed 10 mg 1 time per 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 has received prior treatment with diuretics, then they should be discontinued 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 concentration). 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 accordance with the reaction under conditions of frequent monitoring of renal function, serum potassium and sodium concentrations. In chronic heart failure, the initial dose is 2.5 mg 1 time / day, which can be gradually increased in 3-5 days to the usual, 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 the associated renal dysfunction. In acute myocardial infarction (as part of a combination therapy), 5 mg is prescribed on the first day, 5 mg again on the second day, 10 mg on the third day, 10 mg a maintenance dose 1 time / 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 the case of a prolonged pronounced decrease in blood pressure (systolic blood pressure below 90 mmHg. More than 1 hour), it is necessary to discontinue the drug treatment. In diabetic nephropathy in patients with insulin-dependent diabetes mellitus, diroton is used in 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%). The frequency of other adverse reactions is less than 1%.Since the cardiovascular system: marked reduction in blood pressure, chest pain; rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, impaired AV conduction, myocardial infarction. On the part of the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, a violation of taste, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice (hepatocellular or cholestatic), hyperbilirubinemia, increased liver disease (hepatocellular or cholestatic), hyperbilirubinemia, increased liver disease (hepatocellular or cholestatic), hyperbilirubinemia, increased hepatic cell pain, hepatic cell disease or cholestatic, hyperbilirubinemia, increased hepatic cell disease, cholestatic, cholestatic On the part of the skin: urticaria, increased sweating, photosensitivity, pruritus, hair loss. From the side of the central nervous system: mood lability, impaired concentration, paresthesia, fatigue, drowsiness, jerky muscles of the limbs and lips; rarely - asthenic syndrome, confusion. Respiratory system disorders: dyspnea, dry cough, bronchospasm, apnea. On the part of the hematopoietic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (a decrease in the concentration of hemoglobin, hematocrit, erythrocytopenia). Allergic reactions: angioedema 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 transudate exit into the lumen of the alveoli). From the genitourinary system: uremia, oliguria, anuria, impaired renal function, acute renal failure, reduced potency. Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, increased concentration of urea and creatinine in the blood plasma, hypercholesterolemia, hypertriglyceridemia, reduced glucose tolerance. Other: arthralgia, arthritis, myalgia, fever, exacerbation of gout.
Overdose
Symptoms: marked reduction in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability. Treatment: gastric lavage, taking activated carbon, giving the patient a horizontal position with raised legs, replenishing the BCC (iv injection of plasma-substituting solutions), symptomatic therapy, monitoring the functions of the cardiovascular and respiratory systems, BCC, urea, creatinine and electrolytes in the blood serum , as well as 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, a joint appointment is possible only on the basis of an individual decision of a doctor with regular monitoring of the content of potassium in the blood serum and kidney function. With simultaneous use with beta-blockers, blockers of slow calcium channels, diuretics and other antihypertensive drugs, there is an increase in the hypotensive effect of the drug. With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate), a symptom complex is described in / in, including facial flushing, nausea, vomiting, and hypotension. With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol, the hypotensive effect of the drug is enhanced. With simultaneous use with NSAIDs (including selective COX-2 inhibitors), estrogens, and adrenergic mimetic drugs, the antihypertensive effect of lisinopril is reduced. With simultaneous use with lithium preparations, the excretion of lithium from the body is slowed down (enhancement of the cardiotoxic and neurotoxic action of lithium). With simultaneous use with antacids and Kolestiramin decreases absorption in the gastrointestinal tract. The drug 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) of cardiac glycosides, the effect of peripheral muscle relaxants, reduces the excretion of quinidine. Reduces the effect of oral contraceptives. At the same time taking methyldopa increases the risk of hemolysis.
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). Similar rules should be followed when appointing Dyroton to patients with coronary artery disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke. Transient hypotensive reaction is not a contraindication for the next dose of the drug. Before starting treatment with Diroton, if possible, normalize the concentration of sodium and / or fill up the lost volume of fluid, carefully monitor the effect of the initial dose of Diroton on the patient's blood pressure. Treatment of symptomatic hypotension consists of providing bed rest and, if necessary, intravenous fluids (infusion of saline). Transient 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 BP does not exceed 100 mm Hg. st. 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 the drug Dyroton. If kidney failure develops during lisinopril treatment (creatinine concentration in the blood plasma is more than 265 µmol / L, or twice the initial level), the doctor must decide whether to stop treatment. With bilateral renal artery stenosis and renal artery stenosis of a single kidney, as well as with hyponatremia and / or reduction of BCC or circulatory failure, arterial hypotension caused by taking Dyroton, and subsequent development of reversible (after drug withdrawal) 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 renal function (CC less than 30 ml / min), caution and control of renal function is required. Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely observed in patients treated with ACE inhibitors, including Dyroton, which can 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. In patients who already had angioedema in history, which was not associated with the previous treatment with ACE inhibitors, the risk of its development during treatment with an ACE inhibitor may be increased. Anaphylactic reaction has also been observed in patients taking Diroton and simultaneously on hemodialysis using high-flow dialysis 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. In 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), an anesthesiologist should be warned about the use of the drug Dyroton. The use of the drug in recommended doses by elderly patients may be accompanied by an increase in the concentration of lisinopril in the blood, so the dose selection requires special attention and is carried out depending on the kidney function and the patient's blood pressure. At the same time, in elderly and young patients, the antihypertensive effect of the drug Diroton is equally pronounced. When using ACE inhibitors, cough was noted (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 must also be taken into account. In some cases, hyperkalemia was observed. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, taking potassium drugs or drugs that cause an increase in blood potassium levels (for example, heparin), especially in patients with impaired kidney function. During the period of drug treatment requires regular monitoring in the blood plasma of potassium ions, glucose, urea, lipids. During the period of treatment is not recommended to drink alcohol, because ethanol enhances the hypotensive effect of the drug. Caution must be exercised when performing physical exercises, in hot weather (the risk of dehydration and an excessive decrease in blood pressure due to a decrease in the BCC). Since the potential risk of agranulocytosis cannot be excluded, periodic monitoring of the blood picture is required. Impact on the ability to drive vehicles and control mechanisms When side reactions from the central nervous system appear, driving control is not recommended, as well as performance of work associated with increased risk.