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Active ingredients
Ramipril
Release form
Uncoated Tablets
Composition
Ramipril 5 mg adjuvants: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, a mixture of dyes pb24899 pink (contains lactoses monohydrate, dye iron red oxide (e172), iron dye yellow oxide (e172).). - blisters (3) - packs cardboard.
Pharmacological effect
ACE inhibitor long acting. ACE catalyzes the conversion of angiotensin I to angiotensin II. ACE is identical to kinase (an enzyme that catalyzes the breakdown of bradykinin). ACE blockade reduces angiotensin II concentration, increases plasma renin activity, increases the effect of bradykinin and increases aldosterone secretion, which may cause increased serum potassium. Antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of vascular expansion and hypertension. decrease in OPSS, as a result, there is a gradual decrease in blood pressure. Heart rhythm usually does not change. With long-term treatment, left ventricular hypertrophy is reduced without adversely affecting heart function. The antihypertensive effect after taking a single dose appears after 1-2 hours, reaches a maximum after 3-6 hours and lasts 24 hours. Ramipril is effective in treating chronic heart failure. In patients with signs of chronic heart failure after myocardial infarction, the drug reduces the risk of sudden death, the progression of heart failure and reduces the number of hospitalizations for heart failure. As in patients with diabetes, and without it, the drug significantly reduces the existing microalbuminuria and the risk of nephropathy. These effects are observed in patients with both elevated and normal blood pressure.
Pharmacokinetics
Absorption After ingestion ramipril is rapidly absorbed from the gastrointestinal tract, absorption is 50-60%. Meal does not slow down absorption. Cmax in the blood plasma is achieved after 1 hour. Distribution and metabolism Ramipril is metabolized in the liver to form an active metabolite, ramiprilat, which is 6 times higher than ramipril and inactive diketopiperazine, which then glucuronizes.Cmax of ramiprilat in serum is reached 2-4 hours after ingestion, Css - by 4 days of taking the drug. Ramipril binds to plasma proteins about 73%, ramiprilat - 56%. Excretion of ramipril and ramiprilat is eliminated from the body mainly by the kidneys (about 60% ) mainly in the form of metabolites, less than 2% of the accepted dose is displayed as unchanged ramipril. Ramipril is displayed in several stages. T1 / 2 after prescribing a therapeutic dose of 13-17 h for ramiprilat, 5.1 h for ramipril. Pharmacokinetics in special clinical situations. Studies conducted in healthy volunteers aged 65 to 75 years showed that the pharmacokinetics of ramipril did not differ from pharmacokinetics. in young healthy volunteers.In case of impaired renal function, the elimination of ramipril and its metabolites slows down in proportion to the decrease in CC. In patients with hepatic insufficiency, the metabolism of ramipril to ramiprilat can be slowed down, and tion of ramipril in the serum increased.
Indications
- arterial hypertension; - chronic heart failure (as part of combination therapy), incl. developed for 2-9 days after myocardial infarction - diabetic nephropathy and non-diabetic nephropathy on the background of chronic diffuse diseases of the kidneys (preclinical and clinical stages), including chronic glomerulonephritis with severe proteinuria - reducing the risk of myocardial infarction, stroke and cardiovascular mortality in patients with high cardiovascular risk, including patients with confirmed coronary artery disease (with or without a history of myocardial infarction), patients with a history of heart failure, myocardial infarction (with myocardial infarction) angioplasty, coronary artery bypass surgery, with a history of stroke and patients with occlusive lesions of peripheral arteries.
Contraindications
- angioedema edema in history (hereditary, idiopathic or associated with previous therapy with ACE inhibitors); - hemodynamically significant bilateral stenosis of the renal arteries; - single kidney artery stenosis; - condition after kidney transplantation; - hemodialysis; - renal failure (QC less than 20 ml / min); - hemodynamically significant aortic or mitral stenosis (risk of an excessive decrease in blood pressure, followed by impaired renal function); - hypertrophicobstructive cardiomyopathy; chronic heart failure in the decompensation stage; severe hypotension (BP less than 90 mm Hg); unstable hemodynamics; primary hyper aldosteronism; pregnancy; lactation (breastfeeding); age up to 18 years (efficacy and safety have not been established); - intolerance to galactose, lactase deficiency or glucose-galactose malabsorption syndrome; - nephropathy, which is treated by GCS, NSAIDs, immunomodulators and / or cytotoxic drugs; sensitivity to ramipril and any other ingredient of the drug or other ACE inhibitors. With caution: severe damage to the coronary and cerebral arteries (danger of decreased blood flow with an excessive decrease in blood pressure), malignant hypertension, unstable angina, aortic and / or mitral stenosis, severe ventricular disorders , chronic heart failure (NYHA functional class IV), decompensated pulmonary heart, renal and / or liver failure, hyperkale Ia, hyponatremia (including on the background of diuretics and dietary restriction of salt intake), conditions accompanied by a decrease in BCC (including diarrhea, vomiting), systemic connective tissue diseases, diabetes mellitus, bone marrow hemopoiescence, old age, hemodialysis using high-flow polyacrylonitrile membranes ( the risk of anaphylactoid reactions), before the procedure for the apheresis of LDL, the simultaneous desensitization therapy with allergens (eg, hymenoptera).
Precautionary measures
Application for violations of liver functionWith caution, you should prescribe the drug for violations of the liver.It is not necessary to change the dose in case of renal dysfunction. The concentration of amplodipine in the blood plasma does not depend on the degree of reduction of renal function. Use in children It is contraindicated in children and adolescents under the age of 18. Application in elderly patients With caution in elderly patients.
Use during pregnancy and lactation
The drug Amprilan is contraindicated for use during pregnancy, becauseit can have an adverse effect on the fetus (impaired renal function, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs). Therefore, before using the drug Amprilan in women of childbearing age, pregnancy should be excluded. When diagnosing pregnancy, taking the drug Amprilan should be stopped as soon as possible. If you need to use the drug Amprilan during lactation, breastfeeding should be stopped.
Dosage and administration
Tablets are taken orally, completely, without chewing, with a sufficient amount of liquid, regardless of the meal. The dose is selected depending on the therapeutic effect and tolerability of the drug by the patient. Amprilan 2.5 mg 1 time / day. Depending on the patient’s response, the dose may double at a 1-2 week interval. Usually the maintenance dose is 2.5-5 mg / day, the maximum daily dose is 10 mg. Patients taking diuretics, you must cancel or reduce their dose at least 3 days before the start of the drug Amprilan. Chronic heart failure The recommended initial dose of the drug Amprilan is 1.25 mg 1 time / day. Depending on the therapeutic effect, the dose can double at intervals of 1–2 weeks. The maximum daily dose is 10 mg. In patients receiving large doses of diuretics, before starting treatment with Amprilan, the dose of diuretics should be reduced. doses of 2.5 mg (1 tab.), one of which is taken in the morning and the second in the evening. If the patient does not tolerate the initial dose (there is an excessive decrease in blood pressure), it should be reduced to 1.25 mg 2 times / day. Then, depending on the patient's response, the dose may be doubled again (2.5 mg) at intervals of 1–3 days. Later, the daily dose, which was first divided into two, may be given once. The maximum daily dose is 10 mg.If the patient does not tolerate an increase in dose up to 2.5 mg 2 times / day, then treatment with the drug should be discontinued. Diabetic nephropathy and nephropathy in the presence of chronic diffuse kidney diseases The recommended initial dose of Amprlan is 1.25 mg 1 time / day. Depending on the patient's tolerance of ramipril, the dose may further increase: it is recommended to double the dose every 2 weeks to a maintenance dose of 5 mg 1 time / day. Reducing the risk of myocardial infarction, stroke and cardiovascular mortality. The recommended initial dose of the drug Amprlan is 2.5 mg 1 time / day, which subsequently gradually increases depending on the tolerability of the drug: it is recommended to double the dose after 1 week of therapy, and then another 2-3 weeks - until the target support is reached vayuschey dose of 10 mg 1 time / sut.Primenenie Amprilan drug in individual groups patsientovU patients with CC more than 30 ml / min the dose correction is not required. For patients with QA less than 30 ml / min - the initial daily dose is 1.25 mg and the maximum daily dose is 5 mg. In patients with impaired liver function, the initial dose is 1.25 mg 1 time / day, the maximum dose 2.5 mg 1 time / day .Elder age patients (over 65 years) taking diuretics should be carefully monitored. The dose of the drug Amprilan should be selected depending on the level of blood pressure.
Side effects
Classification of the incidence of side effects (WHO): very often (more than 1/10), often (from more than 1/100 to less than 1/10), infrequently (from more than 1/1000 to less than 1/100), rarely (from more than 10/10 000 to less / 1000), very rarely (from less than 1/10 000, including individual messages). From the side of the cardiovascular system: often - pronounced decrease in blood pressure (at the beginning of therapy, increasing the dose or joining diuretic therapy), orthostatic hypotension, syncopal states ; rarely, peripheral edema, palpitations, angina pectoris, arrhythmia; very rarely - myocardial ischemia, myocardial infarction, increased circulatory disorders on the background of stenotic vascular lesions, Raynaud's syndrome, vasculitis, tachycardia, blood flushes to the skin of the face. From the nervous system: often - headache, weakness; rarely - increased fatigue, nervousness, depression, tremor, imbalance,confusion, anxiety, dizziness, motor restlessness, sleep disorders; very rarely - paresthesia, impaired perception of odors (parosmia), transient ischemic attacks, ischemic stroke, cerebral ischemia, impaired concentration. From the urogenital system: rarely - transient impotence, decreased libido, impaired renal function up to acute renal failure, an increase excretion of urine, enhancement of pre-existing proteinuria, increasing the concentration of urea and creatinine; very rarely - gynecomastia. From the side of the respiratory system: often - dry non-productive cough, aggravated at night and lying, most often in women and non-smoking patients, sinusitis, bronchitis, shortness of breath; rarely, nasal congestion, pharyngitis, bronchospasm, including aggravation of bronchial asthma. On the side of the skin: often - maculo-papular skin rash; rarely - pruritus, excessive sweating (against the background of lowering blood pressure); very rarely - maculo-papular exanthema and erythema, pemphigus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening of the course of psoriasis, psoriasis, pemphigoid and lichenoid lesions of the skin and mucous membranes, alopecia; very seldom - urticaria, oniholysis, exfoliative dermatitis, photosensitization. On the digestive system: often - inflammation of the mucous membrane of the gastrointestinal tract, digestive disorders, discomfort in the abdomen, dyspepsia, nausea, diarrhea, vomiting; rarely - increased liver enzymes, increased bilirubin concentration, cholestatic jaundice, acute liver failure, cholestatic hepatitis, hepatocellular lesions, dryness of the oral mucosa, pain in the abdomen, gastritis, constipation, pancreatitis, incl. and fatal (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), intestinal angioedema, loss of appetite, anorexia; very rarely - glossitis, aphthous stomatitis. For the musculoskeletal system: often - myalgia, muscle cramps; rarely, arthralgia. For the sense organs: rarely, visual disturbances, including blurred vision, conjunctivitis, hearing impairment,disorders of smell and taste (for example, metallic taste, partial or temporary loss of taste). Allergic reactions: very rarely - angioedema involving the mucous membrane of the lips, eyes, tongue, larynx and pharynx, anaphylactic or anaphylactoid reactions (insects), increase concentrations of antinuclear tel. Laboratory indices: rarely - hyperkalemia, moderate (sometimes severe) hypohemoglobinemia or neutropenia, erythropenia and thrombocytopenia, increased activity of pancreatic enzymes glands; very rarely - hyponatremia, proteinuria (although usually ACE inhibitors reduce previous proteinuria) or an increase in diuresis (in combination with deterioration of the heart), agranulocytosis, pancytopenia, bone marrow depression, hemolytic anemia. Other: rarely - hyperthermia; very rarely - fever.
Overdose
Symptoms: marked reduction in blood pressure, bradycardia, shock, impaired water and electrolyte balance, acute renal failure, stupor. Treatment: in mild cases, gastric lavage, the introduction of adsorbents and sodium sulfate (preferably within 30 minutes after ingestion). With a marked decrease in blood pressure, the patient should be laid on his back with a low head, IV administration of catecholamines, alpha1-adrenomimetics (norepinephrine, dopamine), angiotensin II (angiotensinamide) is indicated, and if necessary, BCC can be replenished by infusion of 0.9% sodium chloride solution; in bradycardia, a temporary artificial pacemaker is possible. It is necessary to carefully monitor blood pressure, kidney function and the content of potassium in the serum. The effectiveness of hemodialysis has not been established.
Interaction with other drugs
Vasopressor sympathomimetics (epinephrine, norepinephrine) can reduce the hypotensive effect of ramipril. With the simultaneous use of these drugs, blood pressure levels should be carefully monitored. ACE inhibitors increase the inhibitory effect of ethanol on the CNS. With simultaneous use of lithium preparations and ACE inhibitors, there have been cases of a reversible increase in the concentration of lithium in the blood serum. Simultaneous use with thiazide diuretics may increase the concentration of lithium and the risk of its toxic effect against the background of taking an ACE inhibitor. The combination of ACE inhibitors with NSAIDs (non-selective COX inhibitors, for example, acetisalicylic acid in doses that have an anti-inflammatory effect) reduces the hypotensive effect of ACE inhibitors,increases the risk of impaired renal function, up to the development of acute renal failure, increases serum potassium in patients with existing renal dysfunction. Tricyclic antidepressants, antipsychotics (neuroleptics) increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect). GCS, tetrakozaktid reduce the hypotensive effect (fluid retention). The combined use of ramipril and potassium-saving diuretics, as well as potassium drugs and potassium-containing salt substitutes are not recommended. Care should be taken to regularly monitor the content of potassium in the blood plasma and ECG parameters. The use of ACE inhibitors may enhance the hypoglycemic effect of hypoglycemic agents for ingestion and insulin in patients with diabetes mellitus; with their combined use, it is possible to increase glucose tolerance, which may require the correction of doses of hypoglycemic agents for oral administration and insulin. ACE may enhance the hypotensive effect of certain agents for general anesthesia. When prescribing ACE inhibitors, incl. ramipril, patients receiving gold medication (sodium aurothiomalate) IV were found to have nitrate-like reactions (nausea, vomiting, a pronounced decrease in blood pressure, and flushing of the skin of the face).
special instructions
At the beginning of treatment it is necessary to evaluate the function of the kidneys. It is necessary to carefully monitor renal function in patients with impaired renal function, with heart failure, bilateral renal artery stenosis or arterial stenosis of a single kidney, as well as in patients after kidney transplantation. fulminant necrosis of the liver develops, sometimes with a fatal outcome. When jaundice or a significant increase in liver transaminases occurs while taking ACE inhibitors, use of Amprilan should be discontinued. In patients with uncomplicated arterial hypertension, after taking the first dose of the drug, symptomatic hypotension rarely develops.The risk of arterial hypotension is increased in the following patients: - patients with severe chronic heart failure: treatment begins with the lowest possible dose of Amprilan (1.25 mg); - patients taking diuretics: if possible, you should cancel the diuretic beforehand or reduce its dose; treatment begins with a minimum dose of Amprilan (1.25 mg); - patients who may develop hypovolemia due to insufficient fluid intake, diarrhea, vomiting, or excessive sweating in conditions of insufficient compensation for salt and fluid loss. It is usually recommended to adjust the BCC before treatment, but if the indicated conditions become clinically significant, treatment with Amprilan can be started and / or continued with a minimum dose (1.25 mg) and under medical supervision. Aortic stenosis / Mitral stenosis / Hypertrophic cardiomyopathyAFC inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract and with aortic and / or mitral stenosis. Neutropenia / Agranulocytosis in patients taking ACE inhibitors is possible with developmental rays of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and passes on its own after discontinuation of ACE inhibitors. Ramipril should be used with great caution in patients with connective tissue diseases and at the same time receiving immunosuppressive therapy, allopurinol or procainamide, especially in existing disorders of renal function. Such patients may develop severe infections that are not susceptible to intensive antibiotic therapy. In the case of ramipril, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in the event of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor. Hyperkalemia Can develop during treatment with ACE inhibitors, including and ramipril. Risk factors for hyperkalemia are renal failure, advanced age, diabetes mellitus, some concomitant conditions (decreased BCC,acute heart failure at the stage of decompensation, metabolic acidosis), simultaneous administration of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium or potassium-containing salt substitutes and the use of other drugs that increase the content of potassium in the blood plasma (for example , heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. Calicon-saving diuretics and potassium drugsCompatible use of Amprilan and potassium-sparing diuretics, as well as potassium and potassium-containing substitutes for food salt is not recommended. intervention with general anesthesia may result in a marked decrease in blood pressure, especially when using bschey anesthesia providers hypotensive deystvie.Rekomenduetsya stop taking ACE inhibitors, including ramipril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors. CoughDuring the treatment with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs of this group. When a dry cough appears, one should be aware of the possible connection of this symptom with the use of an ACE inhibitor. Anaphylactoid reactions during desensitization procedures . ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of an ACE inhibitor in patients receiving immunotherapy with hymenoptera poison should be avoided. However, the development of anaphylactoid reactions can be avoided by temporarily canceling the ACE inhibitor no less than 24 hours before the desensitization procedure begins. Anaphylactoid reactions during LDL apheresis are rare in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate develop life-threatening anaphylactoid reactions.To prevent an anaphylactoid reaction, the ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes. Hemodialysis Anaphylactoid reactions were noted in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (eg, AN69). Therefore, it is desirable to use a different type of membrane or use a hypotensive drug of another pharmacotherapeutic group. Effect on the ability to drive vehicles and control mechanisms. During the period of treatment, care must be taken during occupations of potentially hazardous activities that require increased concentration and psychomotor speed, because dizziness, drowsiness, confusion and other side effects are possible.