Expiration date: 05/2026

Tablets, 1 tablet contains ramipril 1.25, 2.5, 5 or 10 mg

auxiliary substances for the table. 1,25 2,5 5 or 10 mg: sodium hydrogen carbonate lactose monohydrate croscarmellose sodium starch pregelatinization sodium fumarate 

for dosage 2.5 mg: a mixture of dyes "RV 22886 yellow" (lactose monohydrate, dye iron oxide yellow (E172) 

for dosage 5 mg: a mixture of dyes "RV 24899 pink" (lactose monohydrate, colorant iron oxide red (E172), dye iron oxide yellow (E172) 

blister of 7 or 10 PCs per cartons 2, 4, 8, 12, 14 blisters (7 pieces) or 3, 6, 9 blisters (for 10 PCs).

Description pharmaceutical form:

Tablets 1.25 and 10 mg: oval, flat, white or nearly white, with beveled.

Pills 2.5 mg: oval, flat, light yellow color, with facet.

Tablets 5 mg: oval, flat, pink in color, with beveled and visible inclusions.

Feature:

Ramipril — ACE inhibitor long-acting.

Pharmacokinetics:

After intake of 50-60% of the ramipril is rapidly absorbed from the gastrointestinal tract, food intake does not slow down the absorption. Cmax in plasma is reached in 1 HR.

Metabolized in the liver, with the formation of the active metabolite — ramiprilat, the activity of which is 6 times higher than ramipril and inactive diketopiperazine, which is then glukuronidiruetsa. Cmax of ramiprilat in plasma is reached within 2-4 h after ingestion, CSS to the 4th day of treatment.

About 73% for ramipril and 56% of ramiprilat bind to proteins of blood plasma.

Ramipril and ramiprilat is excreted primarily by the kidneys (about 60%) mainly as metabolites, less than 2% of the dose is excreted in unchanged ramipril.

Ramipril is excreted in several stages. T1/2 after application of a therapeutic dose is 13 to 17 hours for ramiprilat, 5.1 CH — ramipril.

Studies conducted in healthy volunteers aged 65 to 76 years, showed that the pharmacokinetics of ramipril in them did not differ from the pharmacokinetics in young healthy volunteers.

When violation of the kidney excretion ramiprila and its metabolites is slowed in proportion to the reduction in creatinine clearance. In patients with hepatic insufficiency the metabolism of ramipril to ramiprilat may be slowed, and the concentration of ramipril in the blood serum increased.

Description pharmacological action:

ACE catalyzes the conversion of angiotensin I to angiotensin II. ACE is identical to kininase, the enzyme catalyzing the decay of bradykinin. The blockade of ACE leads to reduced concentrations of angiotensin II, increase of renin activity in blood plasma, enhancing the effect of bradykinin and increased secretion of aldosterone, which can cause an increase in the content of potassium in the blood serum. Antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of vasodilation and reducing peripheral vascular resistance, which in turn gradually reduces AD. Heart rhythm is usually not affected. With long-term therapy decreases left ventricular hypertrophy with no negative effect on heart function. Antigipertenzivny effect after a single dose of the drug inside is manifested through 1-2 h after administration of ramipril to the inside, reaches its maximum after 3-6 hours and lasts for 24 hours

Ramipril is effective in the treatment of chronic heart failure (CHF). In patients with signs of heart failure after myocardial infarction ramipril reduces the risk of sudden death, progression of heart failure and reduces the number of hospitalizations for exacerbation of CHF currents. As patients with diabetes, and without it, the drug significantly reduces existing microalbuminuria and the risk of developing nephropathy. These effects have been reported in patients with elevated and normal blood pressure.

Indications:

• hypertension
  
• CHF (in combination therapy), including developed 2 to 9 days after myocardial infarction
  
• diabetic nephropathy and nephropathy with chronic diffuse renal disease (preclinical and clinical stages), including chronic glomerulonephritis with severe proteinuria
  
• reduction in the risk of myocardial infarction, stroke and cardiovascular mortality in patients with high cardiovascular risk, including patients with confirmed coronary artery disease (myocardial infarction in the anamnesis or without it), patients undergoing percutaneous transluminal coronary angioplasty, coronary bypass surgery, stroke in anamnesis and patients with occlusive lesions of the peripheral arteries.
  

Contraindications:

• hypersensitivity to ramipril or any other component of the drug or other ACE inhibitors
  
• a history of angioedema (hereditary or idiopathic angioedema as a result of taking ACE inhibitors
  
• hemodynamically significant bilateral renal artery stenosis
  
• stenosis of artery only kidneys
  
• condition after kidney transplantation
  
• hemodialysis
  
• renal failure (Cl creatinine <20 ml/min)
  
• hemodynamically significant aortic and/or mitral stenosis (the risk of excessive decline in blood pressure with subsequent impairment of renal function)
  
• hypertrophic obstructive cardiomyopathy (GECMC)
  
• CHF decompensation
  
• severe hypotension (BP less than 90 mm Hg. Hg), or unstable hemodynamics
  
• primary hyperaldosteronism
  
• pregnancy
  
• lactation
  
• the age of 18 years (efficacy and safety not established)
  
• galactose intolerance, lactase insufficiency, or syndrome of glucose-galactose malabsorption
  
• nephropathy, the treatment of which is corticosteroids, NSAIDs, immunomodulators and/or cytotoxic agents.
  

With caution:

• severe lesions of coronary and cerebral arteries (risk of reduced blood flow with excessive decline in AD)
  
• malignant hypertension
  
• unstable angina
  
• aortic and/or mitral stenosis
  
• severe ventricular arrhythmias
  
• CHF (IV functional class NYHA classification)
  
• decompensated pulmonary heart
  
• renal and/or hepatic insufficiency
  
• hyperkalemia
  
• hyponatremia (including dioretikov and diet with restriction of consumption of table salt)
  
• state, accompanied by a decrease in BCC, including diarrhea, vomiting
  
• systemic diseases of connective tissue
  
• diabetes
  
• inhibition of bone marrow hematopoiesis
  
• old age
  
• hemodialysis using a high-flow polyacrylnitrile membranes — risk of anaphylactoid reactions
  
• before the procedure LDL apheresis
  
• simultaneous desensitizing treatment with allergen (e.g. Hymenoptera venom).
  

Application of pregnancy and breast-feeding:

Drug Amprilan contraindicated during pregnancy, because it can have adverse effects on the fetus (impaired renal function, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs, etc.). Therefore, before the drug Amprilan in women of childbearing age should exclude pregnancy. When the diagnosis of pregnancy the drug Amprilan should be discontinued as soon as possible. If necessary, the drug Amprilan during lactation breastfeeding should be discontinued.

Side effects:

Classification of frequency of side effects (who): very often — >often 1/10 — >1/100 to <1/10 uncommon — >1/1000 to <1/100 rare >1/10000 to <1/1000 very rare <1/10000, including individual messages.

From the CCC: often — expressed lower AD (at the beginning of therapy, when increasing doses or adherence to therapy diuretics), orthostatic hypotension, syncope rarely — peripheral edema, palpitations, angina, arrhythmias very rare — myocardial ischemia, myocardial infarction, increased circulatory disorders on the background of stenotic vascular lesions, Raynaud's syndrome, vasculitis, tachycardia, a rush of blood to the skin.

From the nervous system: often — headache, weakness rarely — fatigue, nervousness, depression, tremor, impaired balance, confusion, anxiety, dizziness, restlessness, sleep disorder very rarely — paresthesia, impaired sense of smell (parosmia), transient ischemic attack, ischemic stroke, cerebral ischemia, impaired concentration of attention.

From the urogenital system: rarely — transient impotence, reduced libido, impaired renal function, up to acute renal failure, increase the excretion of urine, increased pre-existing proteinuria, increase of urea and creatinine very rarely — gynecomastia.

The respiratory system: often — dry non-productive cough, worse at night and in the supine position, often occurs in women and non-Smoking patients, sinusitis, bronchitis, shortness of breath rarely nasal congestion, pharyngitis, bronchospasm, including exacerbation of bronchial asthma.

With the skin: often — skin rash makulopapuleznaya rarely — itching, increased sweating (due to a decline in AD) very rare — maculopapular exanthema and erythema, pemphigus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening of psoriasis, psoriasiform, pemphigoid and lichenoid lesions of the skin and mucous membranes, alopecia very rare — urticaria, onycholysis, exfoliative dermatitis, photosensitivity.

From the digestive system: often — inflammation of the mucous membrane of the gastrointestinal tract, indigestion, discomfort in the abdomen, indigestion, nausea, diarrhea, vomiting rarely — increased liver enzymes, increased concentration of bilirubin, cholestatic jaundice, acute liver failure, cholestatic hepatitis, hepatocellular injury, dryness of the mucous membrane of the mouth, abdominal pain, gastritis, constipation, pancreatitis, including and fatalities (cases of pancreatitis with a fatal outcome while taking the ACE inhibitors were observed very rarely), intestinal angioedema, decreased appetite, anorexia rarely — glossitis aphthous stomatitis.

From the side of musculoskeletal system: often — myalgia, muscle cramps rare — arthralgia.

From the sensory organs: rare — visual disturbances, including blurred vision, conjunctivitis, hearing disorders, disturbances of smell and taste (e.g., metallic taste, partial or temporary loss of taste).

Allergic reactions: very rarely — angioneurotic syndrome with involvement of the mucous membrane of the lips, eyes, tongue, larynx and pharynx, anaphylactic or anaphylactoid reactions (insect poisons), increased concentration of antinuclear bodies.

Laboratory parameters: rare — hyperkalemia, moderate (sometimes severe) gipogemoglobinemia or neutropenia, erythropenia and thrombocytopenia, increased activity of pancreatic enzymes very rarely — hyponatremia, proteinuria (usually ACE inhibitors reduce proteinuria precedes) or increase in urine output (in combination with the deterioration of the heart), agranulocytosis, pancytopenia, bone marrow depression, haemolytic anaemia.

Other: rarely — hyperthermia very rare — fever.

Drug interactions:

Vasopressor sympathomimetics (epinephrine, norepinephrine) can reduce gipotenzivny effect ramiprila. While the use of these drugs should carefully monitor the blood pressure. ACE inhibitors enhance the inhibitory effect of ethanol on the Central nervous system.

Lithium drugs: with simultaneous use of drugs lithium and ACE inhibitors were registered cases of reversible increase in the concentration of lithium in the blood serum. Concurrent use with thiazide diuretics may increase the concentration of lithium and the risk of its toxic effect in patients receiving the ACE inhibitor.

NSAIDs: the combination of ACE inhibitors with NSAIDs (non-selective inhibitors of COX-1 and COX-2 group of NSAIDs, for example azetilsalicilovaya acid in doses providing anti-inflammatory effect): reduced hypotensive effect of ACE inhibitors increases the risk of renal dysfunction, until the development of acute renal failure increased potassium in the blood serum in patients with existing impaired renal function.

Tricyclic antidepressants, antipsychotic means (neuroleptics): enhance hypotensive effect and increase risk of orthostatic hypotension (additive effect).

GKS, tetracosactide: reduction in antihypertensive effect (water retention).

Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and a potassium supplements: concomitant use of ramipril and potassium-sparing diuretics and potassium supplements and potassium-containing substitutes table salt is not recommended.

Use caution and conduct regular monitoring of potassium in the blood plasma and ECG parameters.

Hypoglycemic drugs for oral administration (sulfonylureas) and insulin: use of ACE inhibitors may increase hypoglycemic effect of hypoglycemic agents for oral administration and insulin in patients with diabetes in their combined use may increase glucose tolerance, which may require correction doses of hypoglycemic agents for oral administration and insulin.

Allopurinol, cytostatic drugs, immunosuppressants, corticosteroids (when administered systemically) and procainamide: concomitant use of these drugs with ACE inhibitors can increase the risk of leukopenia.

Funds for General anaesthesia: ACE inhibitors may increase the hypotensive effect of some funds for General anesthesia.

Gold drugs: the appointment of ACE inhibitors, including ramipril, patients receiving the drug gold (aurothiomalate sodium) in/in was observed narutopedia reactions (nausea, vomiting, marked reduction in blood pressure, redness of the skin).

Method of application and dose:

Inside, alone with liquid, regardless of meals, squeezed enough liquid.

The dose is adjusted depending on therapeutic effect and tolerability of the patient.

Treatment with Amprilan long, its duration in each particular case is determined by the doctor.

Hypertension: the recommended initial dose of the drug Amprilan 2.5 mg 1 time per day. Depending on patient response, the dose can be doubled with a 1-2 week interval. Usually supporting dose is 2.5–5 mg/essence, the maximum daily dose is 10 mg. Patients taking diuretics, you need to cancel or reduce their dose for at least 3 days before you start taking the drug Amprilan.

CHF: the recommended initial dose of the drug Amprilan is 1.25 mg 1 times per day. Depending on the therapeutic effect, the dose may be doubled at intervals of 1-2 weeks.

The maximum dose is 10 mg.

In patients receiving large doses of diuretics before starting drug therapy Amprilan, the dose of diuretics should be reduced.

Heart failure developed in a few days (from 2nd to 9th day) after acute myocardial infarction: the recommended starting dose is 5 mg/day, divided into 2 single doses of 2.5 mg (1 table.), one of which is taken in the morning and second evening. If the patient does not tolerate the initial dose (there is no excessive decline in AD), it shall be reduced to 1.25 mg 2 times a day. Then, depending on patient response, the dose may be doubled (2.5 mg) with an interval of 1-3 days. Later daily dose, which was divided into two, may be given once. The maximum daily dose is 10 mg. if the patient does not tolerate a dose increase to 2.5 mg 2 times a day, the drug treatment should be discontinued.

Diabetic nephropathy and nephropathy with chronic diffuse diseases of the kidneys: the recommended initial dose of the drug Amprilan is 1.25 mg 1 times per day. Depending on patient tolerability of ramipril, the dosage of the drug in the future, may increase: it is recommended to double the dose every 2 weeks to a maintenance dose of 5 mg 1 time per day.

Reduction in the risk of myocardial infarction, stroke, and cardiovascular death: the recommended initial dose of the drug Amprilan is 2.5 mg 1 times a day, which is then gradually increased based on tolerability: it is recommended to double the dose after 1 week of treatment and then another 2-3 weeks to achieve the target maintenance dose of 10 mg 1 time per day. The use of the drug Amprilan in certain group of patients.

Violations of kidney function

Patients with Cl creatinine more than 30 ml/min dose adjustment is not required.

For patients with Cl creatinine less than 30 ml/min the initial daily dose 1.25 mg, maximum daily dose of 5 mg.

The liver

The initial dose is 1.25 mg 1 times per day. Maximum dose of 2.5 mg 1 time per day.

Careful monitoring of elderly patients (over 65 years) receiving diuretics. The dose of the drug Amprilan should be chosen depending on the level of AD.

Overdose:

Symptoms: expressed lower AD, aetiology, shock, violation vodno-elektrolitnogo balance, acute renal failure, stupor.

Treatment: in mild cases of overdose — gastric lavage, appointment of adsorbents and sodium picosulfate (preferably within 30 min after ingestion). When expressed lower AD — /with the introduction of catecholamines, alpha-1-adrenergic agonists (norepinephrine, dopamine), angiotensin II (angiotensinamide), the patient should be laid on his back on the surface with a low headboard, if necessary, BCC can be replenished by infusion of 0.9% sodium chloride solution with bradycardia the possibility of setting a temporary artificial pacemaker. Closely monitor blood pressure, renal function and potassium in blood serum. The effectiveness of hemodialysis is not established.

Precautions:

At the beginning of treatment it is necessary to assess renal function. You must carefully monitor renal function in patients with impaired renal function, heart failure, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, and in patients after kidney transplantation.

Special instructions:

Liver failure

In rare cases, on a background of ACE inhibitors occurs cholestatic jaundice, with the progression which develops fulminant liver necrosis, sometimes fatal. When the jaundice or a significant increase in liver transaminases in patients receiving ACE inhibitors the drug Amprilan should be discontinued.

In patients with uncomplicated arterial hypertension after taking the first dose symptomatic hypotension is rare. The risk of hypotension is increased in the following patients:

- with severe CHF: start treatment with the lowest possible dose of the drug Amprilan (1.25 mg)

- receiving diuretics: if possible in advance to cancel or reduce the diuretic dose start treatment with minimum dose of the drug Amprilan (1.25 mg)

- with the risk of hypovolemia due to inadequate fluid intake, diarrhea, vomiting or excessive sweating when in conditions of inadequate compensation for loss of salt and fluids. It is generally recommended before starting treatment to correct BCC, but if the condition becomes clinically significant, treatment with Amprilan may be initiated and/or continued minimum dose (1.25 mg) and under medical supervision.

Aortic stenosis/mitral stenosis/HACMP

ACE inhibitors should be used with caution used in patients with obstruction of the output tract of the left ventricle and in the aortic and/or mitral stenosis.

Neutropenia/agranulocytosis

In patients taking ACE inhibitors, possible cases of neutropenia/agranulocytosis, thrombocytopenia and anaemia. In patients with normal renal function in the absence of other complications of neutropenia is rare and resolves on its own after the abolition of ACE inhibitors.

Ramipril must with great caution in patients with connective tissue diseases and at the same time receiving immunosuppressive therapy, allopurinol or procainamide, especially when the existing renal dysfunction. These patients can develop serious infections that can not be intensive antibiotic treatment. In the case of the use of ramipril is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in case of any signs of infection (sore throat, fever), you should immediately consult a doctor.

Hyperkalemia

May develop during treatment with ACE inhibitors, including ramipril. Risk factors for hyperkalemia are renal failure, advanced age, diabetes, and some related condition (a decrease in the BCC, cardiac decompensation, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride) and potassium supplements or potassium-containing substitutes of salt and the use of other drugs that increase potassium levels in the blood plasma (e.g. heparin). Hyperkalemia can cause serious cardiac arrhythmias, sometimes fatal.

Potassium-sparing diuretics and potassium supplements

The combined use of the drug Amprilan and potassium-sparing diuretics and potassium supplements and potassium-containing substitutes table salt is not recommended.

Surgical intervention/General anesthesia

The use of ACE inhibitors in patients undergoing surgery with the use of General anesthesia, may lead to a marked decrease in blood pressure, especially when using the funds for General anesthesia, providing gipotenzivne effect.

It is recommended to stop taking ACE inhibitors, including ramipril, for 12 h before a surgical intervention, warning anesthesiologists about application of ACE inhibitors.

Cough

The therapy of enzyme inhibitor may experience a dry cough, which disappears after discontinuation of the drugs in this group. The appearance of dry cough should be aware of the possible Association of this symptom with the administration of the ACE inhibitor.

Anaphylactoid reactions during the procedures of desensitization

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions patients receiving ACE inhibitors during desensitizing treatment with Hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients, prone to allergic reactions, undergoing desensitization. Should avoid prescribing ACE inhibitor patients receiving immunotherapy with Hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by suspending ACE inhibitor at least 24 hours before the beginning of the desensitization procedure.

Anaphylactoid reaction during apheresis LDL

In rare cases, patients receiving ACE inhibitors, when performing LDL apheresis using dextran sulfate may develop life-threatening anaphylactoid reactions. To prevent anaphylactoid reactions should discontinue treatment with ACE inhibitor prior to each apheresis procedure in LDL using high-flow membranes.

Hemodialysis

Patients receiving ACE inhibitors during hemodialysis using a high-flow membranes (e.g. AN69) was recorded anafilaktoidnye reaction. It is therefore desirable to use a membrane of another type or use of antihypertensive drug other pharmacological groups.

The impact on the ability to control vehicles and other complex mechanisms. During treatment care must be taken during classes potentially hazardous activities, require high concentration and psychomotor speed reactions, because. possible dizziness, drowsiness, confusion and other side effects.