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Active ingredients
Ramipril
Release form
Pills
Composition
Active ingredient: Ramipril (Ramipril) Active ingredient concentration (mg): 5
Pharmacological effect
Antihypertensive drug, ACE inhibitor. As a result of the suppression of ACE activity (regardless of plasma renin activity), the hypotensive effect develops (in the position of the patient lying and standing) without a compensatory increase in heart rate. Suppressing the activity of ACE reduces the level of angiotensin II, which in turn leads to a decrease in aldosterone secretion. As a result of a decrease in the concentration of angiotensin II, due to the elimination of negative feedback, there is an increase in plasma renin activity. Ramipril acts on an ACE circulating in the blood and located in the tissues, including vascular wall. Reduces OPSS (afterload), pressure in the pulmonary capillaries (preload); increases cardiac output and increases tolerance to stress. With long-term use, ramipril contributes to the return development of myocardial hypertrophy in patients with arterial hypertension. Ramipril reduces the incidence of arrhythmia during myocardial reperfusion; improves blood supply to the ischemic myocardium. Ramipril prevents the breakdown of bradykinin and stimulates the formation of nitric oxide (NO) in the endothelium. The antihypertensive effect begins 1-2 hours after ingestion, the maximum effect develops within 3-6 hours. daily use of antihypertensive effect increases for 3-4 weeks and persists with long-term treatment (1-2 years). Antihypertensive efficacy does not depend on the sex, age and body weight of the patient. In patients with acute myocardial infarction, ramipril limits the area of necrosis, improves the prognosis of life; reduces mortality in the early and late period of myocardial infarction, the incidence of recurrent heart attacks; reduces the severity of manifestations of heart failure, slows its progression. With prolonged use (at least 6 months) reduces the degree of pulmonary hypertension in patients with congenital and acquired heart defects. Ramipril reduces the pressure in the portal vein with portal hypertension; inhibits microalbuminuria (in the initial stages) and deterioration of renal function in patients with severe diabetic nephropathy.When non-diabetic nephropathy, accompanied by proteinuria (more than 3 g / day) and renal failure, slows down further deterioration of renal function, reduces proteinuria, reduces the risk of increased creatinine or the development of terminal renal failure.
Pharmacokinetics
Ramipril has a multiphase pharmacokinetic profile. Absorption After ingestion, ramipril is rapidly absorbed from the gastrointestinal tract. The degree of absorption is at least 50-60% of the administered dose. Cmax in plasma is achieved within 1 hour. Distribution and metabolism Almost completely metabolized (mainly in the liver) with the formation of active and inactive metabolites. Its active metabolite - ramiprilat inhibits ACE activity about 6 times stronger than ramipril. Cmax of ramiprilat in blood plasma is reached in 2-4 hours. Among the known inactive metabolites are diketopiperazine ester, diketopiperazinic acid, and ramipril and ramiprilat glucuronides. The binding of ramipril and ramiprilat to plasma proteins is approximately 73% and 56%, respectively. usual doses of 1 time / day Css ramipril in plasma is achieved by 4 days of taking the drug. Excretion of T1 / 2 ramipril - 5.1 h, T1 / 2 of ramiprilat 13-17 h. After ingestion 60% of the dose is excreted in the urine (mainly in the form of metabolites ) and about 40% - with feces. About 2% of the administered dose is excreted in the urine unchanged. Pharmacokinetics in special clinical situations. Excretion of ramipril, ramiprilat and inactive metabolites decreases with urine in renal failure (which leads to an increase in the concentration of ramiprilat). Decreased enzymatic activity in the liver causes impaired function to slow conversion of ramipril to ramiprilat, which may cause an increase in the concentration of ramipril in the blood plasma.
Indications
- Arterial hypertension. - Chronic heart failure. - Chronic heart failure after acute myocardial infarction in patients with stable hemodynamics. - Diabetic nephropathy and chronic diffuse kidney disease (non-diabetic nephropathy). - To reduce the risk of myocardial infarction, stroke or coronary death in high-risk cardiovascular patients with coronary artery disease, including patients who have had a myocardial infarction, percutaneous transluminal coronary angioplasty, aorto-coronary shunting.
Contraindications
- Angioedema in history, including associated with prior therapy with ACE inhibitors.- Hemodynamically significant bilateral renal artery stenosis or arterial stenosis of a single kidney. - Arterial hypotension or unstable hemodynamics. - Pregnancy. - Lactation period (breastfeeding). - Primary hyper aldosteronism. - Renal failure (CC) - Hypersensitivity to ramipril or any other component of the drug. It is used with caution in: - Hemodynamically significant aortic or mitral stenosis (risk of excessive reduction in blood pressure and subsequent renal impairment) - Severe primary malignant arterial hypertension - Severe lesions coronary and cerebral arteries (danger of reducing blood flow with an excessive decrease in blood pressure). - Unstable angina. - Severe ventricular arrhythmias. - Terminal stage and CHF. - Decompensated pulmonary heart. - In diseases requiring GCS and immunosuppressants (no clinical experience) - including in systemic connective tissue diseases. - Severe renal and / or liver failure. - Hyperkalemia. - Hyponatremia ( including on the background of diuretic intake and diet with restriction of sodium intake.) - Initial or pronounced manifestations of fluid and electrolyte deficiency, conditions accompanied by a decrease in BCC (including diarrhea, vomiting), diabetes. - Inhibition of bone marrow hematopoiesis. - Condition after kidney transplantation. - In elderly patients. - In children and adolescents under the age of 18 years (efficacy and safety have not been established). There is only limited experience with ramipril in patients on dialysis.
Precautionary measures
It is used with caution in hemodynamically significant aortic or mitral stenosis (risk of excessive blood pressure reduction with subsequent renal dysfunction), severe primary malignant arterial hypertension, severe lesions of the coronary and cerebral arteries (risk of blood flow with an excessive decrease in blood pressure), unstable angina, severe gastric arteries rhythm; terminal stage of chronic heart failure; decompensated pulmonary heart; for diseases requiring the use of corticosteroids and immunosuppressants (lack of clinical experience) - incl.in case of systemic diseases of the connective tissue, severe renal and / or liver failure, hyperkalemia, hyponatremia (including while taking diuretics and a sodium restricted diet); in case of initial or pronounced manifestations of fluid and electrolyte deficiency, conditions accompanied by a decrease in the BCC (including diarrhea, vomiting); diabetes; oppression of bone marrow hematopoiesis; condition after kidney transplantation; in elderly patients, in children and adolescents under the age of 18 years (efficacy and safety have not been established). There is only limited experience with the use of ramipril in patients on dialysis.
Use during pregnancy and lactation
Use during pregnancy and lactation is contraindicated. The drug causes impaired fetal kidney development, decreased fetal and newborn blood pressure, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnios, contracture of the extremities, cranial deformity, pulmonary hypoplasia.
Dosage and administration
Tablets should be taken orally, swallowing them whole, without chewing, washing down with a large amount of liquid (approximately 1 glass). Tablets can be taken regardless of meal times. Dose set individually with regard to therapeutic effect and tolerability. For hypertension, the recommended initial dose is 2.5 mg 1 time per day. (1 tablet 2.5 mg daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. The standard maintenance dose is 2.5-5 mg / day. (1 tablet 2.5 mg or 1 tablet 5 mg). The maximum daily dose should not exceed 10 mg. In chronic heart failure, the recommended initial dose is 1.25 mg 1 time per day. (daily 1 tablet Hartila 1.25 mg). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If you need to receive more than 2.5 mg of the drug, this dose can be taken immediately or divided into 2 doses. The maximum daily dose should not exceed 10 mg. For treatment after myocardial infarction, taking the drug is recommended to start at 2-9 days after acute myocardial infarction. The recommended initial dose, depending on the condition of the patient and the time elapsed after an acute myocardial infarction, is 2.5 mg 2 times / day. (2 pills of 1.25 mg or 1 tablet 2.5 mg 2 times / day.).Depending on the therapeutic effect, the initial dose can be doubled to 5 mg (2 pills of 2.5 mg or 1 tablet of 5 mg) 2 times / day. The maximum daily dose should not exceed 10 mg. In case of intolerance of the drug should reduce the dose. For non-diabetic or diabetic nephropathy, the recommended initial dose is 1.25 mg (1 tablet 1.25 mg) 1 time / day. daily. Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If necessary, receiving more than 2.5 mg of the drug, this dose can be taken immediately or divided into 2 doses. The recommended maximum daily dose is 5 mg. In order to prevent myocardial infarction, stroke or death from cardiovascular disorders, the recommended initial dose is 2.5 mg 1 time / day. Depending on the tolerability of the drug, after 1 week of intake, the dose should be doubled compared with the initial dose. This dose should be doubled again after 3 weeks of administration. The recommended maintenance dose is 10 mg 1 time / day. Use in elderly patients taking diuretics and / or heart failure, as well as in violation of the function of the liver or kidneys: the dose should be set by individual selection depending on the patient's response to treatment. Patients with renal insufficiency require correction dosing regimen. With moderate renal dysfunction (CC from 20 to 50 ml / min per 1.73 m2 of body surface), the initial dose is usually 1.25 mg 1 time / day. (1 tablet 1.25 mg / day.). The maximum daily dose should not exceed 5 mg. If CC is not measured, it can be calculated from the serum creatinine level using the Cockroft formula. For men: QC (ml / min) = (140 - age) x body weight (kg) / 72 x serum creatinine (mg / dL). For women: the result of the calculation should be multiplied by 0.85. In case of abnormal liver function, the reduced or increased effect of the drug Hartil can equally be observed, therefore, in the early stages of treatment of this category of patients, careful medical observation is required. The maximum daily dose in such cases should not exceed 2.5 mg. Use in patients receiving diuretic therapy: due to the risk of a significant reduction in blood pressure, the possibility of temporary discontinuation or at least reducing the dose of diuretics should be considered for at least 2-3 days (or longer, depending on the duration of the action of diuretics) before starting to receive Hartile . For patients who have previously received diuretics, the initial dose is usually 1.25 mg.
Side effects
Since the cardiovascular system: lower blood pressure, orthostatic hypotension, tachycardia; rarely - arrhythmia, increased circulatory disorders of organs caused by narrowing of the blood vessels. With an excessive decrease in blood pressure, mainly in patients with coronary artery disease and clinically significant narrowing of the brain vessels, myocardial ischemia (angina or myocardial infarction) and cerebral ischemia (possibly with a dynamic impairment of cerebral circulation or stroke) can develop. On the side of the urogenital system: development or increased renal failure, increased existing proteinuria, decrease in urine volume (at the beginning of the drug). For the central nervous system: dizziness, headache, weakness, drowsiness, paresthesia, nervous excite spine, anxiety, tremors, muscle spasms, mood disorders; when used in high doses - insomnia, anxiety, depression, confusion, fainting. On the part of the sense organs: vestibular disorders, taste disturbances (for example, metallic taste), smell, hearing and sight, tinnitus. On the digestive system: nausea, vomiting, diarrhea or constipation, pain in the epigastric region, dry mouth, thirst, loss of appetite, stomatitis, hypersensitivity or inflammation of the buccal mucosa, pancreatitis; rarely - hepatitis, cholestatic jaundice, impaired liver function with the development of acute liver failure. On the part of the respiratory system: "dry" cough, bronchospasm (in patients with an elevated cough reflex), shortness of breath, rhinorrhea, rhinitis, sinusitis, bronchitis. Allergic reactions: skin rash, itching, urticaria, conjunctivitis, photosensitization; rarely - angioedema of the face, extremities, lips, tongue, pharynx or larynx, exfoliative dermatitis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus (pemphigus), serositis, syrosis, serositis, serositis, serositis, erythrocytosis; , vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia. From the side of hematopoietic organs: anemia, decreased hemoglobin and hematocrit, thrombocytopenia, leukocytopenia, neutropenia, agranulocytosis, pancytopenia, hemolytic anemia; may decrease the number of red blood cells, bone marrow depression.
Overdose
Symptoms: pronounced decrease in blood pressure, bradycardia, shock, impaired water and electrolyte balance, acute renal failure. Treatment: in the case of an easy overdose - gastric lavage, the introduction of adsorbents and sodium sulfate (preferably within 30 minutes after administration). In case of acute overdose: control and support of vital functions in ICT conditions; with a decrease in blood pressure - the introduction of catecholamines and angiotensin II. The patient should be laid on his back with an elevated position of the legs, to introduce additional amounts of fluid and sodium. It is not known whether forced diuresis, hemofiltration and urine pH correction accelerate the excretion of ramipril. This should be considered when considering the possibility of hemodialysis and hemofiltration.
Interaction with other drugs
With the simultaneous use of Hartil with allopurinol, corticosteroids, procainamide, cytostatics and other substances that cause changes in the blood, the risk of disturbances from the hematopoietic system increases. With simultaneous use of Hartil with hypoglycemic drugs (insulin or sulfonylurea derivatives), an excessive decrease in blood glucose levels is possible. This phenomenon may be due to the fact that ACE inhibitors can increase tissue sensitivity to insulin. When used simultaneously with other antihypertensive drugs (including diuretics) or other drugs that have hypotensive effects (for example, nitrates, tricyclic antidepressants and anesthetics ), it is possible to enhance the antihypertensive effect. Simultaneous intake of potassium salts and potassium-sparing diuretics, heparin with ramipril is not recommended due to the risk of hyperkalemia. When used simultaneously with lithium preparations, an increase in the concentration of lithium in the blood serum is observed, which leads to an increased risk of cardio and nephrotoxicity. NSA and sodium salts reduce the effectiveness of ACE inhibitors. Ramipril can enhance the effect of ethanol.
special instructions
During treatment with Chartil, regular medical monitoring is necessary. After taking the first dose, as well as increasing the dose of diuretic and / or Hartil, patients should be under the supervision of a physician for 8 hours to avoid an uncontrolled anti-hypertensive reaction; multiple measurement of blood pressure is recommended. If possible, dehydration, hypovolemia, reduction of the number of erythrocytes should be adjusted before taking the drug.If these disorders are severe, ramipril should not be started or continued until measures are taken to prevent an excessive fall in blood pressure and renal dysfunction. Careful observation is required for patients with renal vascular damage (eg, clinically insignificant stenosis of the renal artery or hemodynamically significant stenosis of a single kidney artery) ), impaired renal function, with a marked decrease in blood pressure, mainly in patients with heart failure, as well as after kidney transplantation. Disruption of kidney function can but to detect elevated levels of urea and serum creatinine, especially if the patient is taking diuretics. Reducing sodium levels and increasing potassium levels may result from decreased synthesis of angiotensin II and serum aldosterone secretion. Hyperkalemia is more common when kidney function is impaired (for example, in diabetic nephropathy) or when taken simultaneously with potassium-sparing diuretics. If the patient's blood pressure is too low, he should lay down, lift his legs; fluid and other measures may also be required. Blood changes are more likely in patients with impaired renal function and concomitant connective tissue disease (for example, SLE and scleroderma), as well as in the case of other means that affect the hematopoietic and immune systems. serum should also be regularly monitored in patients taking diuretics simultaneously with the drug Hartil. You should also regularly check the number of leukocytes in order to avoid the development of leukopenia. Control should be more frequent at the beginning of therapy and in patients belonging to any risk group. There are reports of life-threatening anaphylactoid reactions, sometimes turning into shock, in patients on hemodialysis using membranes with high hydraulic permeability (for example, from polyacrylonitrile) while the introduction of ACE inhibitors. Anaphylactoid reactions have also been reported in patients undergoing apheresis of LDL with dextran sulphate absorption. When desensitizing therapy is used to reduce the allergic reaction to insect bites (for example, bees and wasps), anaphylactoid reaction that can be severe and life-threatening can occur during the administration of ACE inhibitors. AD, respiratory failure, vomiting, skin reactions).Therefore, ACE inhibitors should not be given to patients receiving desensitization therapy. In case of lactase deficiency, galactosemia or glucose / lactose absorption disorder syndrome, it should be noted that each tablet of Hartil contains the following amounts of lactose: 5 mg pills - 96.47 mg, 10 mg pills - 193.2 mg. Use in pediatrics Experience of using ramipril in children with severe renal insufficiency (CC <20 ml / min / 1.73 m2 of body surface) and during dialysis is limited. Effect on the ability to drive motor vehicles and the management and treatment of mehanizmamiV early blood pressure reduction may affect the ability to concentrate. In this case, patients are advised to refrain from driving vehicles and practicing potentially hazardous activities that require increased concentration and psychomotor speed. In the future, the degree of limitation is determined for each patient individually.