Expiration date: 04/2025

Dosage form: tablets

Composition: 1 tablet contains: active substance: ramipril 2.5 mg, 5 mg, and 10 mg excipients: lactose monohydrate (ektapress) (milk sugar) – 96,5 mg, 143,5 mg, 188,0 mg, magnesium stearate – 1.0 mg, 1.5 mg, 2.0 mg

Description 

Tablets at a dosage of 2.5 mg is a white or almost white, round, valium, with a facet and valium. Tablets with a dosage of 5 mg and 10 mg white, or almost white, round, ploskotsylindriceskie, with facet. Pharmacotherapeutic group of the medicinal product: angiotensin-converting enzyme Inhibitor (ACE). Code ATX: [C09AA05]

PHARMACOLOGICAL PROPERTIES 

Pharmacodynamics

Formed under the influence of "liver" enzymes active metabolite of ramipril – ramiprilat is a long-acting ACE inhibitor, representing peptidyldipeptide. ACE in plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II and breakdown of bradykinin. Therefore, when the reception ramiprila inside decreasing the formation of angiotensin II and accumulation of bradykinin, which causes vasodilation and decrease blood pressure (BP). Increased activity of the kallikrein-kinin system in the blood and tissues and causes the cardioprotective endotheliopathy action of ramipril due to the activation of prostaglandin system and, consequently, increasing the synthesis of prostaglandins, stimulating the formation of nitric oxide (NO) in endothelial cells. Angiotensin II stimulates secretion of aldosterone, so the reception ramiprila leads to reduced secretion of aldosterone and increased serum concentration of potassium ions. By reducing the concentration of angiotensin II in the blood eliminates its inhibitory effect on renin secretion by the type of negative feedback, which leads to an increase in renin activity of blood plasma. It is assumed that the development of some adverse reactions (particularly dry cough) is also associated with increased activity of bradykinin. 

In patients with arterial hypertension reception ramiprila leads to a decrease in blood pressure in the lying position and standing, without a compensatory increase in heart rate (HR). Ramipril significantly reduces the total peripheral vascular resistance (OPSS), virtually without causing changes in renal blood flow and glomerular filtration rate. Hypotensive effect begins to manifest after 1-2 hours after ingestion of a single dose of the drug, reaching the highest values after 3 to 9 hours and lasts for 24 hours. If you take hypotensive effect may gradually increase, stabilizing typically 3 - 4 weeks of regular intake of the drug and then persisting for a long time. The sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (absence of the syndrome of "lifting"). In patients with hypertension ramipril slows the development and progression of myocardial hypertrophy and vascular wall. 

In patients with chronic heart failure ramipril reduces peripheral vascular resistance (decrease postnagruzki on the heart), increases venous capacity and decreases the filling pressure of the left ventricle, which, respectively, leads to a reduction of preload on the heart. In these patients, while taking ramipril, an increase in cardiac output, ejection fraction and improvement in endurance exercise. 

In diabetic and non-diabetic nephropathy receiving ramipril slows the rate of progression of renal failure and time of occurrence of end-stage renal failure and thereby reduces the need for dialysis treatments or kidney transplantation. In the early stages of diabetic or non-diabetic nephropathy ramipril reduces the severity of albuminuria. 

In patients with a high risk of developing cardiovascular diseases due to vascular lesions (diagnosed coronary heart disease, occlusive peripheral arterial disease history of stroke history), or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increased concentrations of total cholesterol (UH), lower concentrations of cholesterol high density lipoproteins (HDL-C), non-Smoking) the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and mortality from cardiovascular causes. In addition, ramipril reduces total mortality and the need for revascularization procedures, and slows the occurrence or progression of chronic heart failure. 

In patients with heart failure, which developed in the first days of acute myocardial infarction (2-9 day), while taking ramipril, ranging from 3 to 10 days of acute myocardial infarction, reduced risk of mortality (27 %), the risk of sudden death (30 %), the risk of progression of chronic heart failure to severe (III-IV functional class NYHA classification)/resistant to therapy (27 %), the likelihood of subsequent hospitalization due to heart failure (26 %). 

In the General population of patients, and in patients with diabetes, as with hypertension and normal blood pressure parameters ramipril significantly reduces the risk of development of nephropathy and the occurrence of microalbuminuria. 

Pharmacokinetics 

After oral ramipril is rapidly absorbed from the gastrointestinal tract (50-60 %). Food intake slows the absorption but does not affect the completeness of absorption. Ramipril undergoes extensive first-pass metabolism/activation (mainly in the liver by hydrolysis) to form its only active metabolite, ramiprilat, whose activity in respect of inhibition of ACE is approximately 6 times higher than the activity of ramipril. In addition, as a result of metabolism of ramipril is formed not possess pharmacological activity diketopiperazine, which then undergoes conjugation with glucuronic acid, ramiprilat also glukuronidiruetsa and metabolized to diketopiperazine acid. The bioavailability of ramipril after ingestion ranges from 15 % (dose 2.5 mg) to 28 % (dose 5 mg). The bioavailability of the active metabolite - ramiprilat after ingestion of 2.5 mg and 5 mg of ramipril is about 45 % (compared to its bioavailability after intravenous administration at the same doses). After taking the inside ramipril maximum plasma concentrations of ramipril and ramiprilat are reached in 1 and 2 - 4 hours, respectively. The decrease in the plasma concentrations of ramiprilat occurs in several stages: phase distribution and excretion with a half-life (T1/2) of ramiprilat approximately 3 hours, and then the intermediate phase with a T1/2 of ramiprilat approximately 15 hours, and final phase with a very low concentration of ramiprilat in plasma and T1/2 of ramiprilat approximately 4-5 days. This final phase due to the slow release of ramiprilat from strong ties with the receptors of the enzyme. Despite the long terminal phase with a single during the day the reception of ramipril oral dose of 2.5 mg or more equilibrium plasma concentration of ramiprilat achieved after approximately 4 days of treatment. In exchange the appointment of a drug "effective" T1/2 in a dose dependent is 13-17 hours. Relationship with blood plasma proteins is approximately equivalent to ramipril 73 % and of ramiprilat is 56 %. After intake of labeled radioactive isotope of ramipril (10 mg) 39 % of the radioactivity excreted via the bowel and about 60 % in the kidneys. After ingestion of 5 mg of ramipril in patients with drainage of the bile ducts is almost the same amount of ramipril and its metabolites excreted by the kidneys and through the intestine during the first 24 hours after ingestion. Approximately 80 - 90% of metabolites in urine and bile was identificira intended as ramiprilat and the ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazine approximately 10 – 20 % of the total number, and concentration in urine nematerializiranih ramiprila is approximately 2 %. In animal studies it was shown that ramipril is secreted in breast milk. If impaired renal function with creatinine clearance (CC) less than 60 ml/min excretion of ramiprilat and its metabolites by the kidneys slows down. This leads to increased plasma concentrations of ramiprilat, which decreases more slowly than in patients with normal renal function. When receiving ramipril high dose (10 mg) impaired liver function leads to slower first-pass metabolism of ramipril to ramiprilat active and slower excretion of ramiprilat. In healthy volunteers and in patients with arterial hypertension after two weeks of treatment with ramipril in a daily dose of 5 mg not observed clinically significant accumulation of ramipril and ramiprilat. In patients with chronic heart failure after two weeks of treatment with ramipril in a daily dose 5 mg notes 1,5 - 1,8 fold increase in plasma concentrations of ramiprilat and the area under pharmacokinetic curve "concentration-time" (AIS). In healthy volunteers elderly (65-76 years), the pharmacokinetics of ramipril and ramiprilat did not significantly differ from that in young healthy volunteers.

INDICATIONS FOR USE 

• Essential hypertension. 
  
• Chronic heart failure (in combination therapy, particularly in combination with diuretics). 
  
• Diabetic or non-diabetic nephropathy preclinical and symptomatic stages, including with severe proteinuria, especially when combined with hypertension. 
  
• Reduction in the risk of myocardial infarction, stroke or cardiovascular mortality in patients with high cardiovascular risk: 
  
• in patients with confirmed coronary heart disease, with myocardial infarction in the anamnesis or without it, including patients undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, 
  
• patients with stroke in anamnesis, 
  
• in patients with occlusive lesions of the peripheral arteries, 
  
• in patients with diabetes with at least one additional risk factor (microalbuminuria, hypertension, increased plasma OH concentrations, reduced plasma concentrations of HDL - C, Smoking). 
  
• Heart failure, which developed during the first few days (from 2 to 9 days) after acute myocardial infarction (see section "Pharmacodynamics").
  

CONTRAINDICATIONS 

• Hypersensitivity to ramipril, other ACE inhibitors or to any component of the drug (see "Composition"). 
  
• Angioedema (hereditary or idiopathic, and after taking ACE inhibitors) in history 
  
• the risk of rapid development of angioedema (see section "Side effects"). 
  
• Hemodynamically significant renal artery stenosis (bilateral or unilateral in the case of a solitary kidney). 
  
• Hypotension (systolic BP less than 90 mm Hg. Hg), or condition with unstable hemodynamics. 
  
• Hemodynamically significant stenosis of the aortic or mitral valve, or hypertrophic obstructive cardiomyopathy (HACMP).
• Primary hyperaldosteronism. 
  
• Severe renal insufficiency (KK less 20 ml/min at the surface of the body 1.73 m2) (clinical experience is insufficient). 
  
• Pregnancy. 
  
• Lactation. 
  
•  Nephropathy, treatment which is a corticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulator-Rami and/or other cytotoxic drugs (clinical experience is insufficient, see section "Interaction with other medicinal products"). 
  
• Chronic cardiac insufficiency of the decompensation (clinical experience is insufficient). 
  
• The age 18 years (clinical experience is insufficient). 
  
• Hemodialysis (clinical experience is insufficient). Hemodialysis or hemofiltration with the use of some membranes with negatively charged surface, such as high-flow membranes from polyacrylnitrile (risk of development of hypersensitivity reactions) (see "Interaction with other medicinal products", "Special instructions"). 
  
• Apheresis low density lipoproteins using dextran sulfate (risk of development of hypersensitivity reactions) (see Special instructions). 
  
• Desensitizing therapy in the reactions increased sensitive-ness to poisons insects such as bees, wasps (see "Special instructions"). 
  

Additional contraindications to use of the drug Ramipril in the acute phase of myocardial infarction: 

• severe heart failure (functional class IV of NYHA classification), 
  
• unstable angina, 
  
• life-threatening ventricular arrhythmias, 
  
• "pulmonary" heart. 
  

With caution 
- A condition in which excessive reduction of blood pressure is especially dangerous (in atherosclerotic lesions of coronary and cerebral arteries). 
- The state, accompanied by increased activity of the renin-angiotensin-aldosterone system (RAAS) in which the inhibition IF there is a risk of sharp decline AD with deterioration of renal function: 

• severe hypertension, especially malignant hypertension, 

• chronic heart failure, especially severe or about which to take other medicines with hypotensive action 

• hemodynamically significant unilateral renal artery stenosis (in the presence of both kidneys), 

• before taking diuretics, 

• violations of water-electrolyte balance as a result of insufficient fluid intake and salt, diarrhea, vomiting, sweating. 

- Infringements of function of a liver (lack of experience in the application: might as strengthening and weakening effects of ramipril, the presence in patients of liver cirrhosis with ascites and edema may be a significant activation of the RAAS, see the above State, accompanied by increased activity of the RAAS). 

- Renal dysfunction (CC 20 ml/min at the surface of the body 1.73 m2) because of the risk of hyperkalemia, and leukopenia). 

- The condition after kidney transplantation. 

- Systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the peripheral blood (possible inhibition of bone marrow hematopoiesis, the development of neutropenia or agranulocytosis, see Interaction with other medicines). 

- Diabetes mellitus (risk of hyperkalemia). 

- Old age (the risk of increasing the hypotensive effect). 

- Hyperkalemia. Use during pregnancy and breastfeeding Ramipril-Sz contraindicated in pregnancy, as it can have adverse effects on the fetus: impaired development of the kidneys of the fetus, reducing AD the fetus and newborn, violation of the kidney, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the limbs, deformation of the skull bones, hypoplasia of the lungs. Therefore, before taking the drug in women of childbearing age should exclude pregnancy. If a woman is planning pregnancy, treatment with ACE inhibitors should be discontinued. In the case of diagnosis of pregnancy during treatment with the drug Ramipril-Sz, you should ASAP stop taking it and put the patient on other medications, the application of which the risk to the child is the least. If treatment with Ramipril-Sz is needed in the lactation period, breastfeeding must be discontinued.

METHOD OF APPLICATION AND DOSES 

Tablets should be swallowed whole (not chewed) and drink plenty (1/2 Cup) of water, regardless of meals (i.e., tablets can be taken both before and during or after eating). The dose is adjusted depending on therapeutic effect and tolerability of the patient. Treatment with Ramipril-Sz is usually long, and its duration in each particular case is determined by the doctor. If not assigned otherwise, normal renal function and liver recommended the following dosage regimen. 

In case of essential hypertension 

The usual starting dose is 2.5 mg 1 times per day in the morning. If when taking the drug at this dose for 3 weeks and more fails to normalize the AD, the dose may be increased to 5 mg of ramipril per day. The lack of effectiveness of a dose of 5 mg after 2-3 weeks she could still be doubled to the maximum recommended daily dose of 10 mg per day. As an alternative to increasing the dose to 10 mg per day in case of insufficient antihypertensive effectiveness of a daily dose of 5 mg, may be added to the treatment of other antihypertensive agents, particularly diuretics or blockers "slow" calcium channels. 

In chronic heart failure 

Recommended initial dose: 1.25 mg 1 times / day (1/2 tablet of 2.5 mg). Depending on the patient's response to ongoing therapy, the dose may be increased. It is recommended to double the dose every 1-2 weeks. If you want receiving a daily dose of 2.5 mg and above it can be given as once a day, and is divided into 2 admission. Maximum recommended daily dose is 10 mg. 

In diabetic or non-diabetic nephropathy 

Recommended initial dose: 1.25 mg 1 times / day (1/2 tablet of 2.5 mg). The dose may be increased to 5 mg once a day. Under these conditions doses above 5 mg once daily in controlled clinical trials has not been studied. 

To reduce the risk of myocardial infarction, stroke or cardiovascular mortality in patients with high cardiovascular risk

Recommended initial dose: 2.5 mg 1 time per day. Depending on tolerability by the patient, the dose can be gradually increased. It is recommended to double the dose after 1 week of treatment, and for the next 3 weeks - to increase it to the usual maintenance dose 10 mg 1 time per day. Doses greater than 10 mg in controlled clinical trials has not been studied. The use of the drug in patients with CC less than 0.6 ml/sec has not been studied. 

In heart failure, which developed during the first few days (from 2nd to 9th day) after acute myocardial infarction 

The recommended starting dose is 5 mg per day, divided into two doses of 2.5 mg, taken one in the morning and the second in the evening. If the patient does not tolerate this initial dosage (there is no excessive decrease in blood pressure), he recommended for two days to give 1.25 mg 2 times a day (1/2 tablet of 2.5 mg). Then, depending on patient response, the dose may be increased. It is recommended that the dose increase has doubled with an interval of 1-3 days. Later, the total daily dose, initially divided into two doses, may be given once. The maximum recommended dose is 10 mg. At present experience in the treatment of patients with severe heart failure (III-IV functional class NYHA classification), arising directly following acute myocardial infarction, is insufficient. If in such patients the decision on the treatment of drug Ramipril-Sz, it is recommended that treatment is started with the lowest possible dose is 1.25 mg once daily (1/2 tablet of 2.5 mg) and special caution should be observed at each increasing dose. 

The use of the drug is Ramipril-Sz in individual groups of patients 

- Patients with the human kidney When QC from 50 to 20 ml/min per 1.73 m2 of body surface, the initial daily dose is usually 1.25 mg (1/2 tablet of 2.5 mg). The maximum allowable daily dose of 5 mg. 

- Patients with not fully adjusted for the loss of fluid and electrolytes, patients with severe hypertension, and patients for whom excessive BP reduction is a risk (eg, severe atherosclerotic lesions of the coronary and cerebral arteries), the Initial dose is reduced to 1.25 mg/day (1/2 tablet of 2.5 mg). 

- Patients with previous therapy, diuretic Should, if possible, to cancel diuretics for 2-3 days (depending on the duration of action of the diuretic) before starting treatment with the drug Ramipril-Sz, or at least to reduce the dose of diuretics taken. The treatment of such patients should start with the lowest dose of 1,25 mg ramipril (1/2 tablet of 2.5 mg) taken once a day, in the morning. After the first dose and every time after increasing the dose of ramipril and (or) "loop" diuretics patients should be under medical observation for at least 8 hours in order to avoid uncontrolled hypotensive reaction. 

- Elderly patients (over 65 years) the Initial dose is reduced to 1.25 mg per day (1/2 tablet of 2.5 mg). 

- Patients with impaired liver function Reaction AD on the drug Ramipril-Sz may increase (due to slow excretion of ramiprilat) or fall (by slowing down the conversion of inactive to active ramipril ramiprilat). Therefore, at the beginning of treatment requires careful medical supervision. Maximum daily dose of 2.5 mg.

SIDE EFFECTS 

Classification of frequency of side effects (who): 

very common: (? 10 %), 

often: (? 1 % - <, 10="" br="">,uncommon: (?0,1 % - <,1 br="">,rare (0,01 % - 0,1 %), 

very rare: (<,0,01 br="">,the frequency is unknown: according to the available data set the frequency of occurrence is not possible. 

Disorders of the heart

Infrequent: myocardial ischemia, including the development of angina or myocardial infarction, tachycardia, arrhythmia (new or increasing), palpitations, peripheral edema. 

Violations by vessels 

Often excessive reduction of blood pressure, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncope, 

Uncommon: "tides" of blood to the skin. 

Rarely the emergence or strengthening of circulatory disorders on the background of stenotic vascular lesions, vasculitis. 

Frequency unknown: Raynaud's syndrome. 

Violations of the Central nervous system 

Often: headache, a feeling of "lightness" in the head. 

Uncommon: dizziness, ageusia (loss of taste sensitivity), dysgeusia (violation of taste sensitivity). 

Rare: tremor, balance disorder. 

Frequency is unknown cerebral ischemia including ischemic stroke and transient disorders of cerebral circulation, disturbance of psychomotor reactions, paresthesia (burning sensation), parosmia (impaired perception of odors). 

Violations of the organ of vision 

Uncommon: visual disturbances including blurred vision. 

Rare: conjunctivitis. 

Violations of the organ of hearing 

Rare: hearing impairment, ringing in the ears. 

Violations of the psyche 

Uncommon: depressed mood, anxiety, nervousness, restlessness, sleep disturbance, including drowsiness. 

Rare: confusion. 

Frequency not known: impaired attention. 

Violations of the respiratory system 

Frequent: dry cough (increasing at night and in the supine position), bronchitis, sinusitis, shortness of breath. 

Uncommon: bronchospasm, including exacerbation of asthma, nasal congestion. 

Disorders from the digestive tract 

Often inflammatory reactions in the stomach and intestines, indigestion, a feeling of discomfort in the abdomen, indigestion, diarrhea, nausea, vomiting. 

Uncommon: pancreatitis, including fatal (cases of pancreatitis with a fatal outcome while taking the ACE inhibitors were observed very rarely), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dry mucous membranes of the oral cavity 

Rare: glossitis 

Frequency unknown: aphthous stomatitis (inflammatory reactions of the mucous membrane of the oral cavity).

Violations of the hepatobiliary system 

Infrequent: increased activity of "liver" enzymes and the concentration of conjugated bilirubin in plasma. 

Rare: cholestatic jaundice, hepatocellular injury. 

Frequency unknown: acute hepatic failure, cholestatic or cytolytic hepatitis (fatal outcome has been observed very rarely). 

Violations of the kidneys and urinary tract 

Infrequent: impaired renal function, including acute renal failure, increase the excretion of urine, increased pre-existing proteinuria, increase of urea and creatinine in the blood. 

Violations of the reproductive system and mammary glands 

Infrequent: erectile dysfunction with transient impotence, decreased libido. 

Frequency unknown: gynaecomastia. 

Violations by the blood and lymphatic system 

Uncommon: eosinophilia. 

Rare: leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, decrease in hemoglobin concentration, thrombocytopenia. 

Frequency unknown: oppression kostnomozgovy blood, demoliti-cal anemia. 

Violations of the skin and mucous membranes 

Frequent: skin rash, in particular makelessnoise. 

Uncommon: angioedema, including fatal (edema of the larynx may cause airway obstruction, leading to death), pruritus, hyperhidrosis (excessive sweating). 

Rare: exfoliative dermatitis, urticaria, onycholysis. 

Very rare: reactions of photosensitivity. 

Frequency not known: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriasiform dermatitis, lichenoid or pemphigoid (michaelina) rash or enanthema, alopecia. 

Violations by musculoskeletal and connective tissue 

Frequent: muscle cramps, myalgia. 

Uncommon: arthralgia. 

Violations of metabolism, nutrition and laboratory values 

Frequent: increased content of potassium in the blood. 

Infrequent: anorexia, decreased appetite. 

Unknown frequency: a decrease in the content of sodium in the blood. 

Violations by the immune system 

Frequency unknown: anaphylactic or anaphylactoid reactions (the inhibition of ACE increases the number of anaphylactic or anaphylactoid reactions to insect venoms), increase in titer of antinuclear antibodies. 

General disorders 

Frequent: chest pain, fatigue. 

Uncommon: fever. 

Rare: asthenia (weakness). While the use of ACE inhibitors and gold preparations (sodium aurothiomalate) for intravenous injection is described a complex of symptoms, including redness of the skin, nausea, vomiting and hypotension. When using ACE inhibitors may develop symptoms, including fever, myalgia, arthralgia, serozit, vasculitis, increased erythrocyte sedimentation rate, leukocytosis, eosinophilia, skin rash, positive test for antinuclear antibodies. When using ACE inhibitors may develop syndrome of inadequate secretion of antidiuretic hormone.

OVERDOSE 

Symptoms: excessive peripheral vasodilation with the development of expressed lower AD, shock, bradycardia, fluid and electrolyte disorders, acute renal failure, stupor. 

Treatment: gastric lavage, appointment of adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of Express reduce AD therapy for replenishment of circulating blood volume and restore electrolyte balance may be added the introduction of alpha1-adrenergic agonists (norepinephrine, dopamine). In the case of refractory to medical treatment bradycardia may require temporary artificial pacemaker. In case of overdose should be monitored serum concentrations of creatinine and electrolytes.

INTERACTION WITH OTHER DRUGS 

Contraindicated in combination 

- The use of some high-flow membranes with negatively charged surface (e.g., polyacrylnitrile membranes) during hemodialysis or hemofiltration, the use of dextran sulfate in apherese low density lipoproteins the Risk of severe anaphylactic reactions. 

Not recommended combinations 

- Salts of potassium, kalisberegatmi dioretikami (for example, amiloride, triamterene, spironolactone) Perhaps a more pronounced increase in the content of potassium in the blood serum (in case of simultaneous use requires careful control of the content of potassium in the blood serum). 

Combinations that should be used with caution 

- Antihypertensives (especially diuretics) and other drugs that reduce blood pressure (nitrates, tricyclic antidepressants) Potentiation of hypotensive effect in combination with diuretics should monitor the sodium content in the blood serum. 

- With hypnotics, narcotic and non-narcotic analgesics May be more pronounced decrease in blood pressure, 

- Simpatomimetikami of vasopressor (epinephrine) Decrease the hypotensive effect of ramipril, requires careful control of AD. 

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic corticosteroids and other drugs, which may affect the hematological parameters combined use increases the risk of leukopenia. 

- With lithium salts Increase serum concentrations of lithium and increased cardio and neurotoxic effect of lithium. 

With hypoglycemic agents for oral administration (sulfonylureas, biguanide) with insulin In connection with a decrease in insulin resistance under the influence of ramipril may increase hypoglycemic effect of these drugs until the development of hypoglycemia. Combinations to be taken into account 

- Non-steroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid) May weaken the effect of ramipril, increase the risk of renal dysfunction and improve the potassium content in the blood serum. 

- Heparin May increase the amount of potassium in the blood serum. 

With sodium chloride the Weakening of the hypotensive effect of ramipril and less effective treatment of the symptoms of chronic heart failure. 

- With ethanol Increased vasodilation. Ramipril may potentiate the adverse effects of ethanol on the body. 

- With estrogen, the Weakening of the hypotensive effect of ramipril (fluid retention). 

- Desensitizing therapy if you are sensitive to insect poisons ACE Inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to the venoms of insects. While the use of ACE inhibitors and gold preparations (sodium aurothiomalate) for intravenous injection is described a complex of symptoms, including redness of the skin, nausea, vomiting and hypotension.