Pyramil Extra capsules 10mg/5mg №7×4

Name:
Pyramil Extra caps. 10mg5mg in bl. in pack. No. 7×4 Storage conditions The drug should be stored out of the reach of children, dry, dark place at a temperature not exceeding 25°C. Expiration date from the date of manufacture2 years Product
Description:
Tablets are white or almost white, oblong, biconvex, with a rough surface and a notch on one side. Pharmacological action ACE inhibitor. Ramipril is rapidly absorbed from the gastrointestinal tract and hydrolyzed in the liver to form the active metabolite ramiprilat. Ramiprilat is a long-acting ACE inhibitor, an enzyme that catalyzes the conversion of angiotensin I to angiotensin II. Ramipril causes a decrease in the level of angiotensin II in the blood plasma, an increase in renin activity and a decrease in the release of aldosterone. Suppresses the level of kinase II, prevents the breakdown of bradykinin, enhances the synthesis of prostaglandins. Under the action of ramipril, peripheral vessels expand and peripheral vascular resistance decreases. Arterial hypertension Has a hypotensive effect in the position of the patient lying and standing. Reduces OPSS (afterload), wedge pressure in the pulmonary capillaries without a compensatory increase in heart rate. Enhances coronary and renal blood flow without affecting the glomerular filtration rate. The beginning of the hypotensive action is 1-2 hours after ingestion, the maximum effect develops 3-6 hours after ingestion. The action persists for at least 24 hours. Chronic heart failure and heart failure due to acute myocardial infarction Ramipril reduces OPSS and, ultimately, blood pressure. Increases cardiac output and exercise tolerance. With prolonged use, it contributes to the regression of myocardial hypertrophy in patients with heart failure I and II FC according to the NYHA classification; improves blood supply to ischemic myocardium. Ramipril improves the survival of patients with symptoms of transient or chronic heart failure after myocardial infarction. It has a cardioprotective effect, prevents coronary ischemic episodes, reduces the likelihood of myocardial infarction and reduces the duration of hospitalization. Diabetic and non-diabetic nephropathy In patients with diabetic and non-diabetic nephropathy, ramipril slows down the rate of progression of renal failure and the time to onset of end-stage renal disease, and thereby reduces the need for hemodialysis procedures or kidney transplantation. In the initial stages of diabetic or non-diabetic nephropathy, ramipril reduces the severity of albuminuria. Patients at high risk of cardiovascular disease Patients at high risk of cardiovascular disease due to vascular disease (diagnosed coronary artery disease, obliterating diseases of peripheral arteries or stroke in anamnesis), diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increase in plasma concentrations of total cholesterol, decrease in plasma concentrations of high-density lipoprotein cholesterol (HDL-C), smoking), the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and mortality from cardiovascular causes. Pharmacokinetics Absorption Ramipril is rapidly absorbed from the gastrointestinal tract after oral administration. Absorption does not depend on food intake. After absorption, ramipril is rapidly and almost completely converted to the active metabolite ramiprilat by the action of the liver esterase enzyme. Ramiprilat is approximately 6 times more ACE inhibitor than ramipril. Other pharmacologically inactive metabolites have also been found. Cmax of ramipril in plasma is achieved within 1 hour after administration, Cmax of ramiprilat – within 2-4 hours after taking the drug. The bioavailability of ramipril is 60%. Distribution Plasma protein binding reaches 73% for ramipril and 56% for ramiprilat. Withdrawal T1 / 2 of ramiprilat with prolonged use at a dose of 5-10 mg 1 time / day is 13-17 hours. After taking 5 mg, the renal clearance of ramipril is 10-55 ml / min, extrarenal clearance reaches 750 ml / min. For ramiprilat, these figures are 70-120 ml / min and about 140 ml / min, respectively. Ramipril and ramiprilat are mainly excreted by the kidneys (40-60%). Pharmacokinetics in special clinical situations In patients with impaired renal function, the transformation of ramipril to ramiprilat slows down due to the relatively short period of esterase action, so the plasma level of ramipril in these patients is increased. With impaired renal function, the excretion of ramipril and ramiprilat slows down. Indications for use arterial hypertension; chronic heart failure (as part of combination therapy); diabetic or non-diabetic nephropathy, preclinical and clinically pronounced stages, incl. with severe proteinuria, especially when combined with arterial hypertension and the presence of microalbuminuria; reduced risk of myocardial infarction, stroke or cardiovascular death in patients with a high risk of cardiovascular disease: in patients with confirmed coronary artery disease, myocardial infarction with or without a history of myocardial infarction , including patients who underwent percutaneous transluminal coronary angioplasty, coronary artery bypass grafting; – in patients with a history of stroke; in patients with occlusive lesions of peripheral arteries; in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of total cholesterol, a decrease in plasma concentrations of HDL-C, smoking); heart failure that developed during the first few days (from 2 to 9 days) after acute myocardial infarction. Use during pregnancy and lactation Use of Piramil® during pregnancy and breastfeeding is contraindicated, tk. the use of ramipril can have an adverse effect on the fetus: a violation of the development of the kidneys of the fetus, a decrease in blood pressure of the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs. Piramil® is not recommended for women planning pregnancy. In the event of pregnancy during therapy with Piramil®, the drug should be discontinued as soon as possible and fetal development should be monitored. Women of reproductive age receiving therapy with ACE inhibitors should use effective contraception. If women of childbearing age with arterial hypertension are taking ACE inhibitors, then it should be remembered that, in case of pregnancy, the patient should be transferred to an antihypertensive drug from another group. In all cases, close medical supervision is necessary. There is no information on whether ramipril is excreted in breast milk. Animal studies have shown that ramipril is excreted in the milk of lactating rats. The use of the drug Piramil® during breastfeeding is contraindicated. If it is necessary to prescribe Piramil® to a nursing mother, the issue of stopping breastfeeding should be resolved. Special instructions Before starting treatment with Piramil®, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to cancel them or reduce their dose 2-3 days before taking Piramil®. In this case, the condition of patients with chronic heart failure should be carefully monitored due to the possibility of developing decompensation in them against the background of an increase in BCC. After taking the first dose, as well as with an increase in the dose of a diuretic and / or the drug Piramil®, patients should be under medical supervision for 8 hours due to the possibility of developing orthostatic hypotension. Transient arterial hypotension is not a contraindication for continuing treatment with Piramil®, because when restoring BCC and normalizing blood pressure, taking the following doses of the drug usually does not cause symptomatic arterial hypotension. In case of recurrence of severe arterial hypotension, the dose should be reduced or the drug should be discontinued. Patients with malignant arterial hypertension or concomitant heart failure, especially in the acute stage of myocardial infarction, should begin treatment only in a hospital setting. In patients with chronic heart failure, taking Piramil® can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and, rarely, the development of acute renal failure. In patients with increased activity of the RAAS, taking the drug for the first time or at a high dose, blood pressure and kidney function should be regularly monitored, especially at the beginning of treatment, because. these patients have an increased risk of excessive BP lowering and renal dysfunction due to ACE suppression. Care should be taken when treating elderly patients, because. they may be particularly sensitive to ACE inhibitors. Caution should also be exercised during physical exertion and / or hot weather due to the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in BCC and a decrease in sodium in the blood. Before and during treatment with Piramil®, it is necessary to regularly monitor kidney function (creatinine, urea), plasma potassium, complete blood count, hemoglobin, liver function tests. With the development of cholestatic jaundice or a pronounced increase in the activity of hepatic transaminases, ACE inhibitors should be discontinued. The risk group for hyperkalemia is made up of patients with renal insufficiency, diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium preparations or potassium-containing table salt substitutes, and drugs that increase the content of potassium in the blood serum (for example, heparin). In patients with an increased risk of developing neutropenia (in case of impaired renal function, systemic connective tissue diseases), when prescribing Piramil®, it is necessary to control the complete blood count once a month during the first 3-6 months of therapy, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000/µl), ACE inhibitor therapy should be discontinued. In rare cases, during treatment with ACE inhibitors, incl. ramipril, angioedema of the face, extremities, lips, tongue, larynx and / or pharynx is noted. If edema occurs, which can develop suddenly at any time during treatment, you should immediately stop taking the drug, take emergency medical care and ensure careful monitoring of the patient until the symptoms disappear completely and permanently. In patients treated with ACE inhibitors, cases of angioedema of the intestine were observed, which was manifested by abdominal pain with or without nausea and vomiting, in some cases, angioedema of the face was simultaneously observed. If a patient develops the above symptoms during treatment with ACE inhibitors, the possibility of developing angioedema of the intestine should also be considered during the differential diagnosis. The use of ACE inhibitors, incl. ramipril, in patients undergoing surgery with general anesthesia, may lead to the development of arterial hypotension. It is recommended to stop taking Piramil® 1 day before surgery. Some high-strength membranes with a negatively charged surface (eg, polyacrylonitrile membranes) should be avoided, for example, for urgent hemodialysis or hemofiltration in combination with ACE inhibitors (due to the possibility of anaphylactoid reactions in patients). In rare cases, LDL apheresis with dextran sulfate and the simultaneous use of ACE inhibitors may develop anaphylactoid reactions. Therefore, this method should not be used in patients receiving ACE inhibitors. Antihypertensive drugs that inhibit the RAAS are usually ineffective in the treatment of patients with primary hyperaldosteronism, so the use of ramipril in such cases is not recommended. As with other ACE inhibitors, the concomitant use of ramipril with aliskiren and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or moderate or severe renal insufficiency. (CC less than 60 ml / min / 1.73 m2). Simultaneous use with drugs containing aliskiren or with angiotensin II receptor antagonists, leading to a double blockade of the RAAS, is not recommended due to the risk of excessive reduction in blood pressure, the development of hyperkalemia and deterioration of renal function compared with monotherapy. Simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy is contraindicated. There is no need for special precautions when destroying unused product. Influence on the ability to drive vehicles and control mechanisms There are no data on the negative effect of the drug Piramil® in recommended doses on the ability to drive vehicles or work with mechanisms. However, due to the likelihood of side effects, such as lowering blood pressure and drowsiness, it is recommended to refrain from engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, including driving, especially after taking the initial dose, switching to another drug, concomitant use of diuretics and alcohol. With caution (Precautions) The use of the drug in severe hepatic insufficiency is contraindicated (no clinical experience). With caution, the drug should be prescribed for liver failure. The use of the drug is contraindicated in severe renal failure (CC less than 20 ml / min / 1.73 m2), nephropathy, which is treated with corticosteroids, NSAIDs, immunomodulators and / or other cytotoxic drugs (clinical experience is insufficient). With caution, the drug should be prescribed in the condition after kidney transplantation, hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys). Contraindicated in children and adolescents under 18 years of age (efficacy and safety of use has not been studied). With caution, the drug should be prescribed to elderly patients (over 65 years of age) (increased risk of concomitant liver and / or kidney dysfunction and heart failure). Contraindications hereditary or idiopathic angioedema angioedema (including when taking ACE inhibitors in history); hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney); cardiogenic shock; primary hyperaldosteronism; severe arterial hypotension (systolic blood pressure less than 90 mm Hg) or conditions with unstable hemodynamic parameters; severe renal failure (CC less than 20 ml / min / 1.73 m2); severe liver failure (no clinical experience); hemodialysis or hemofiltration using some membranes with a negatively charged surface (high-flow polyacrylonitrile membranes (danger of developing hypersensitivity reactions); LDL apheresis using dextran sulfate (danger of developing hypersensitivity reactions); use in the acute stage of myocardial infarction: severe chronic heart failure (CHF) IV FC according to NYHA classification), unstable nocardia, life-threatening ventricular arrhythmias, cor pulmonale; the combined use of ramipril and drugs containing aliskiren in patients with diabetes mellitus or moderate or severe renal insufficiency (CC less than 60 ml / min / 1.73 m2); simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy; nephropathy treated with corticosteroids, NSAIDs, immunomodulators and / or other cytotoxic drugs (clinical experience is insufficient); hemodynamically significant aortic or mitral stenosis (risk of excessive decrease in blood pressure with subsequent impaired renal function ( CC more than 20 ml / min / 1.73 m2)); hypertrophic obstructive cardiomyopathy; pregnancy; breastfeeding period; age up to 18 years (efficacy and safety of use has not been studied); hypersensitivity to ramipril, other ACE inhibitors or auxiliary components of the drug. With caution drug should be prescribed for the simultaneous use of drugs containing aliskiren, or angiotensin II receptor antagonists, leading to a double blockade of the RAAS; hyperkalemia, hyponatremia (including against the background of the use of diuretics and diet with restriction of salt intake); diabetes mellitus (risk of developing hyperkalemia); chronic heart failure, especially severe or for which other drugs with antihypertensive action are taken; severe lesions of the coronary and cerebral arteries (danger of reducing blood flow with an excessive decrease in blood pressure); hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys); conditions accompanied by a decrease in BCC (including diarrhea, vomiting), the simultaneous use of lithium preparations, immunosuppressants and saluretics; connective tissue diseases (including systemic lupus erythematosus, scleroderma – an increased risk of developing neutropenia or agranulocytosis); conducting desensitizing therapy; elderly patients (over 65 years of age) (increased risk of concomitant liver and / or kidney dysfunction and heart failure); condition after kidney transplantation; liver failure. Dosage and administration The drug is taken orally, regardless of the meal, without chewing, drinking a sufficient amount (1/2 cup) of water. Arterial hypertension The recommended initial dose of Piramil® for patients without heart failure who are not taking diuretics is 2.5 mg / day. The dose can be gradually increased every 2-3 weeks depending on the effect and tolerability. The maximum dose is 10 mg 1 time / day. Usually the maintenance dose is 2.5-5 mg 1 time / day. In the absence of a satisfactory therapeutic effect when taking Piramil® at a dose of 10 mg / day, it is recommended to prescribe a combined drug treatment. If the patient is taking diuretics, they should stop taking them or reduce their dose 2-3 days before starting treatment with Piramil®. For such patients, the recommended initial dose of the drug is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day. Chronic heart failure The recommended initial dose of Piramil® is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day. The dose can be gradually increased depending on the effect and tolerability, doubling it every 1-2 weeks. Doses of 2.5 mg / day and above can be taken in 1-2 doses. The maximum dose is 10 mg 1 time / day. For patients taking high doses of diuretics, their doses should be reduced before starting treatment with Piramil® to minimize the risk of developing symptomatic arterial hypotension. To reduce the risk of myocardial infarction, stroke or cardiovascular mortality in patients with high cardiovascular risk The recommended initial dose is 2.5 mg 1 time / day. Depending on tolerance, the dose can be doubled after 1 week of treatment, and during the next 3 weeks of treatment, increase it to the usual maintenance dose of 10 mg 1 time / day. Heart failure due to acute myocardial infarction Treatment begins 3-10 days after acute myocardial infarction. The initial dose of Piramil® is 5 mg / day (2.5 mg 2 times – in the morning and evening), after two days the dose is increased to 5 mg 2 times / day. If the initial dose of 2.5 mg 2 times / day is poorly tolerated, a dose of 1.25 mg (1/2 tab. 2.5 mg) 2 times / day should be prescribed for 2 days, then increasing the dose to 2.5 mg and 5 mg 2 times / day. The maintenance dose of Piramil® is 2.5-5 mg 2 times / day. The maximum daily dose is 10 mg. Diabetic and non-diabetic nephropathy The recommended initial dose of Piramil® is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day. Depending on tolerance, the dose can be doubled at intervals of 2-3 weeks up to a maximum dose of 5 mg/day. If the patient is taking diuretics, they should stop taking them or reduce the dose 2-3 days before starting treatment with Piramil®; in this case, the recommended initial dose of Piramil® is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day. Special groups of patients For patients with impaired renal function (CC 20-50 ml / min / 1.73 m2), the recommended initial dose of Piramil® is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day, and the maximum dose should not exceed 5 mg/day. In severe renal failure (CC below 20 ml / min / 1.73 m2), the recommended initial dose of Piramil® is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day, if necessary, the dose can be increased to 2.5 mg / day . In patients with impaired liver function, both an increase and a decrease in the therapeutic effect of the drug Piramil® can be observed. Treatment should begin under the supervision of a physician with a dose of 1.25 mg (1/2 tab. 2.5 mg). The maximum dose should not exceed 2.5 mg / day. Caution should be exercised when prescribing Piramil® to elderly patients (over 65 years of age) if they have renal or hepatic insufficiency, as well as heart failure and / or concurrent use of diuretics. The dose should be selected individually depending on the target level of blood pressure. The initial dose is reduced to 1.25 mg / day. Overdose Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, impaired water and electrolyte balance, shock, acute renal failure, stupor. Treatment: in mild cases of overdose – gastric lavage, the introduction of adsorbents, sodium sulfate (preferably within the first 30 minutes after ingestion). The function of vital organs should be monitored. In more severe cases, measures aimed at stabilizing blood pressure: intravenous administration of a 0.9% sodium chloride solution, plasma substitutes, installation of a temporary artificial pacemaker in case of drug-resistant bradycardia, hemodialysis. With a pronounced decrease in blood pressure, the administration of alpha-adrenergic agonists (norepinephrine, dopamine) can be added to therapy to replenish bcc and restore water and electrolyte balance. In the case of bradycardia, the appointment of atropine or the installation of a temporary artificial pacemaker is recommended. It is necessary to carefully monitor blood pressure, kidney function and electrolytes in the blood serum. There is no experience with the use of forced diuresis, changes in urine pH, hemofiltration or dialysis to accelerate the elimination of ramipril from the body. Hemodialysis is indicated in cases of renal failure. Side effectAccording to WHO, undesirable effects are classified according to their frequency of development as follows: very often (?1/10), often (?1/100, <1/10), infrequently (?1/1000, <1/100) , rarely (?1/10,000, <1/1000) and very rarely (<1/10,000), the frequency is unknown (the frequency of occurrence of events cannot be determined based on the available data). From the side of the cardiovascular system: often - a pronounced decrease in blood pressure, a violation of the orthostatic regulation of vascular tone (orthostatic hypotension), syncope; infrequently - orthostatic collapse, myocardial ischemia, including the development of an attack of angina pectoris or myocardial infarction, cerebrovascular accident (due to a sharp decrease in blood pressure in patients at risk), tachycardia, arrhythmia, peripheral edema, palpitation, "tides" of blood to the skin of the face; rarely - the occurrence or intensification of circulatory disorders against the background of stenosing vascular lesions, vasculitis; frequency unknown - Raynaud's syndrome. From the hemopoietic system: often - eosinophilia; rarely - leukopenia, including neutropenia and agranulocytosis (neutropenia and agranulocytosis are reversible and disappear when ACE inhibitors are discontinued), anemia, thrombocytopenia, lymphadenopathy, decreased hemoglobin; frequency is unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia. From the nervous system: often - weakness, headache; infrequently - mood lability, anxiety, nervousness, paresthesia, dizziness, sleep disturbances, insomnia, restlessness; rarely - tremor, imbalance, confusion; the frequency is unknown - cerebral ischemia, including stroke and transient cerebrovascular accident, parosmia, impaired psychomotor reactions, impaired concentration. From the senses: infrequently - visual disturbances, including blurred images, impaired taste sensations; rarely - conjunctivitis, hearing loss, tinnitus. From the respiratory system: often - dry cough, bronchitis, sinusitis, shortness of breath; infrequently - bronchospasm, including worsening of the course of bronchial asthma, nasal congestion. From the digestive system: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; infrequently - anorexia, loss of appetite, pancreatitis, increased activity of hepatic transaminases and concentration of conjugated bilirubin in blood plasma, increased activity of pancreatic enzymes, angioedema of the intestine, abdominal pain, gastritis, constipation, dryness of the oral mucosa; rarely - glossitis, cholestatic jaundice, hepatocellular lesions; the frequency is unknown - aphthous stomatitis, acute liver failure, cholestatic or cytolytic hepatitis, incl. with a lethal outcome. From the urinary system: rarely - a violation of kidney function, including the development of acute renal failure, an increase in the amount of urine, an increase in pre-existing proteinuria, an increase in the concentration of urea and creatinine in the blood. On the part of the skin and mucous membranes: often - skin rash, in particular maculo-papular; infrequently - angioedema, incl. fatal (laryngeal edema can cause airway obstruction leading to death), pruritus, hyperhidrosis; rarely - exfoliative dermatitis, urticaria, onycholysis; very rarely - photosensitivity reactions; frequency unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid exanthema or enanthema, alopecia. From the musculoskeletal system: often - muscle cramps, myalgia; infrequently - arthralgia. From the side of metabolism: often - an increase in the content of potassium in the blood; the frequency is unknown - a decrease in the content of sodium in the blood. From the immune system: the frequency is unknown - anaphylactic or anaphylactoid reactions, increased titer of antinuclear antibodies. From the endocrine system: the frequency is unknown - the syndrome of inadequate ADH secretion. From the reproductive system: infrequently - transient impotence due to erectile dysfunction, decreased libido; frequency unknown - gynecomastia. General disorders and disorders at the injection site: often - chest pain, fatigue; infrequently - fever; rarely - asthenia. Composition of ramipril 10 mg Excipients: microcrystalline cellulose - 289 mg, pregelatinized starch - 18 mg, precipitated silicon dioxide - 32 mg, glycine hydrochloride - 3 mg, glyceryl dibehenate - 8 mg. Interaction with other drugs Contraindicated combinations The use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration, the use of dextran sulfate during LDL apheresis may lead to the risk of severe anaphylactic reactions; if the patient needs these procedures, other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be transferred to other antihypertensive drugs. As with other ACE inhibitors, the combined use of ramipril with aliskiren and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or moderate or severe renal insufficiency (CC less than 60 ml / min / 1.73 m2). Simultaneous use with other ACE inhibitors increases the risk of developing renal failure (including acute renal failure), hyperkalemia. The simultaneous use of the drug and angiotensin II receptor antagonists in patients with diabetic nephropathy is contraindicated and is not recommended in other patients. Combinations to be used with caution Concurrent use with potassium salts, potassium-sparing diuretics (eg, amiloride, triamterene, spironolactone), and drugs that increase serum potassium levels (including trimethoprim, tacrolimus, cyclosporine, angiotensin II receptor antagonists) may lead to an increase in the content of potassium in the blood serum (regular monitoring of the content of potassium in the blood serum is required). Antihypertensive drugs (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin), baclofen, diuretics, nitrates, tricyclic antidepressants, neuroleptics, hypnotics, narcotic analgesics, agents for general and local anesthesia increase the antihypertensive effect of ramipril. Vasopressor sympathomimetics and other drugs that cause antihypertensive effects (for example, isoproterenol, dobutamine, dopamine, epinephrine) reduce the antihypertensive effect of ramipril, and regular monitoring of blood pressure is required. Simultaneous use with allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticoids and mineralocorticoids) and other agents that can affect hematological parameters increases the risk of leukopenia. Co-administration of ramipril with corticosteroids is not recommended. Lithium salts lead to an increase in the concentration of lithium in the blood serum and an increase in the cardio- and neurotoxic effects of lithium. Ramipril enhances the hypoglycemic effect of hypoglycemic agents (insulin, oral hypoglycemic agents (sulfonylurea derivatives)) up to the development of hypoglycemia. It is necessary to control the concentration of glucose. Vildagliptin leads to an increase in the incidence of angioedema. Simultaneous use of ramipril with mTOR (mammalian Target of Rapamycin - the target of rapamycin in mammalian cells), for example, with temsirolimus, may lead to an increase in the incidence of angioedema. Combinations that should be taken into account NSAIDs (eg, acetylsalicylic acid (more than 3 g / day), COX2 inhibitors) can weaken the antihypertensive effect of ramipril, and also cause impaired renal function, sometimes leading to the development of renal failure. Heparin can increase the content of potassium in the blood serum. Sodium chloride may weaken the effect of ramipril. Ethanol should not be consumed during treatment with ramipril (the inhibitory effect of ethanol on the central nervous system is enhanced). Estrogens weaken the antihypertensive effect (fluid retention). Desensitizing therapy for hypersensitivity to insect venoms. ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms. Release form Tablets are white or almost white, oblong, biconvex, with a rough surface and a score line on one side. 1 tab. ramipril 10 mg Excipients: microcrystalline cellulose - 289 mg, pregelatinized starch - 18 mg, precipitated silicon dioxide - 32 mg, glycine hydrochloride - 3 mg, glyceryl dibehenate - 8 mg. 7 pcs. - blisters (4) - cardboard packs. Buy Pyramil Extra capsules 10mg/5mg No. 7x4