Ramigamma - instructions for use, doses, side effects, contraindications

active substance: ramipril 2.5 mg Excipients: sodium hydrogen carbonate 2.5 mg, lactose monohydrate 155.0 mg, croscarmellose sodium 4.0 mg, pregelatinized starch (starch 1500) 30.0 mg, sodium stearyl fumarate 2.0 mg, dye Blend RV 22960 yellow 4.0 mg (lactose monohydrate 3.8 mg, iron dye yellow oxide 0.2 mg), ethanol 96%: water in a ratio of 1: 1- 44.0 mg (removed during production).

1 tablet 5 mg contains:

active substance: ramipril 5 mg

Excipients: sodium bicarbonate 5.0 mg, lactose monohydrate 94.0 mg, croscarmellose sodium 2.6 mg, pregelatinized starch (starch 1500) 19.5 mg, sodium stearyl fumarate 1.3 mg, dye Blend RV 24877 pink 2.6 mg (lactose monohydrate 2.47 mg, iron dye oxide red 0.09 mg, iron dye yellow oxide 0.04 mg), ethanol 96%: water in a ratio of 1: 1 to 28.0 mg ( are removed during production).

1 tablet of 10 mg contains: active substance: ramipril 10 mg Excipients: sodium hydrogen carbonate 10.0 mg, lactose monohydrate 193.2 mg, croscarmellose sodium 5.2 mg, starch pregelatinized (starch 1500) 39.0 mg, sodium stearyl fumarate 2.6 mg, ethanol 96%: water in a ratio of 1: 1 - 56.0 mg (removed in the manufacturing process).

Description:

2.5 mg tablets - oblong flat tablets from light yellow to light orange color, it is possible the presence of impregnations of a lighter or darker shade. One side of the tablet is engraved "R2", divided by risk. On both sides of the tablet is a shallow chamfer, on the side faces there are risks.

5 mg tablets - oblong flat tablets of light pink color, it is possible the presence of impregnations of a lighter or darker shade. On one side of the tablet is the engraving "Yu", divided by the risk. On both sides of the tablet is a shallow chamfer, on the side faces there are risks.

10 mg tablets - oblong flat tablets of white or almost white color. One side of the tablet is engraved "R4", divided by risk. On both sides of the tablet is a shallow chamfer, on the side faces there are risks.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE).

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I into angiotensin II and the breakdown of bradykinin. Therefore, when taking ramipril, the formation of angiotensin II decreases and the accumulation of bradykinin occurs, which leads to vasodilation and a decrease in blood pressure (BP). The increased activity of kallikrein-kinin system in blood and tissues causes cardioprotective and endothelioprotective action of ramipril due to activation of prostaglandin system and, accordingly,increase synthesis

prostaglandins, stimulating the formation of nitric oxide (N0) in endotheliocytes.

Angiotensin II stimulates the production of aldosterone, therefore, taking ramipril leads to a decrease in the secretion of aldosterone and an increase in the serum concentrations of potassium ions.

With a decrease in the concentration of angiotensin II in the blood, its inhibiting effect on renin secretion by negative feedback is eliminated, which leads to an increase in renin activity of the blood plasma.

It is assumed that the development of some unwanted reactions (in particular, "dry" cough) is also associated with an increase in bradykinin activity.

In patients with hypertension taking ramipril leads to a decrease in blood pressure in the "lying" and "standing", without compensatory increase in the heart rate (heart rate). Ramipril significantly reduces the overall peripheral vascular resistance (OPSS), virtually without causing changes in the renal blood flow and glomerular filtration rate. The hypotensive effect begins to appear 1-2 hours after ingestion of a single dose of the drug, reaching the highest value in 3-9 hours, and persists for 24 hours.With the course of treatment, the hypotensive effect can gradually increase, stabilizing usually to 3-4 weeks of regular intake of the drug and then remaining for a long time. A sudden discontinuation of the drug does not lead to the development of the "withdrawal" syndrome.

In patients with hypertension ramipril slows the development and progression of myocardial hypertrophy and vascular wall.

The drug reduces mortality in the early and distant periods of myocardial infarction, the frequency of repeated heart attacks and the incidence of heart failure. Increases the survival rate and improves the quality of life in patients with chronic heart failure.

In patients with congenital and acquired heart defects reduces the severity of arterial hypertension in the "small" circle of circulation with a duration of intake of at least 6 months.

Increases the sensitivity of tissues to insulin, the concentration of fibrinogen, stimulates the synthesis of the tissue activator of the profibrinolysin (plasminogen), promoting thrombolysis.

With portal hypertension reduces pressure. Reduces the degree of microalbuminuria (in the initial stage) andprogression of chronic renal failure in patients with severe renal damage in diabetic nephropathy.

Pharmacokinetics:

After oral administration ramipril quickly absorbed from the gastrointestinal tract, absorption is 50-60%, eating does not affect the degree of absorption, but slows absorption.

Ramipril is metabolized in the liver, with the formation of an active metabolite - ramiprilata, whose activity is 6 times higher than ramipril and inactive diketopiperazine, which is then glucuronized. The maximum concentration of ramiprilate in the blood serum is reached in 2-4 hours after administration, the equilibrium concentration - by the 4th day of taking the drug.

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

Ramipril and ramiprilate are excreted from the body by the kidneys (about 60%) and through the intestine (about 40%), predominantly in the form of metabolites, less than 2% of the accepted dose is excreted as unchanged ramipril.

The half-life for ramipril is 5.1 hours; in the phase of distribution and elimination, the drop in concentration of ramiprilata in the serum occurs with a half-life of 3 hours,followed by a transitional phase with a half-life of 15 hours and a long final phase with very low concentrations of ramipril in plasma and a half-life of 4-5 days. In chronic renal failure, the elimination half-life increases. If renal function is impaired, excretion of ramipril and its metabolites slows in proportion to a decrease in creatinine clearance (CC).

In patients with hepatic insufficiency, the metabolism of ramipril to ramiprilate can be slowed down.

In chronic heart failure, the concentration of ramiprilata increases 1.5-1.8 times.

In healthy elderly volunteers (65-76 years old), the pharmacokinetics of ramipril and ramiprilate are not significantly different from that of young healthy volunteers.

Indications:

arterial hypertension

Contraindications:

Hypersensitivity to ramipril and any other ingredient in the drug or other ACE inhibitors;
angioedema (hereditary or idiopathic, as well as in anamnesis, including those associated with previous therapy with ACE inhibitors);
hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney);
arterial hypotension (systolic blood pressure less than

90 mm Hg) or a condition with unstable hemodynamics;

hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;
primary aldosteronism;
expressed renal failure (CC less than 20 ml / min.);
liver failure;
condition after kidney transplantation;
hemodialysis;
Nephropathy, which is treated with glucocorticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressants and / or other cytotoxic agents;
chronic heart failure in the stage of decompensation;
apheresis of low-density lipoproteins using dextran sulfate;
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;
hyposensitizing therapy in reactions of hypersensitivity to poisons of insects, such as bees, wasps;
pregnancy and lactation;
age to 18 years (efficacy and safety not established).

Carefully:

conditions in which excessive reduction in blood pressure is dangerous (with atherosclerotic lesions of the coronary or cerebral arteries);
states accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS) in which, with ACE inhibition, there is a risk of a sharp decrease in blood pressure with impaired renal function: severe arterial hypertension, especially malignant hypertension; chronic heart failure, especially severe or about which other drugs with hypotensive action are taken; hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys); previous administration of diuretics; disturbance of water electrolyte balance as a result of insufficient intake of liquid and table salt, vomiting, diarrhea, excessive sweating;
impaired liver function; impaired renal function (QC more than 20 ml / min.);
systemic connective tissue diseases (including systemic

lupus erythematosus, scleroderma, concomitant drug therapy,

5 0 4 1 ?

capable of causing changes in the picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis));

diabetes;
elderly age;
hyperkalemia.

Pregnancy and lactation:

The drug Ramigamma is contraindicated in pregnancy and lactation. Before starting therapy with Ramigamma, pregnancy should be excluded. Ramigamma is not recommended for women planning a pregnancy. In case of pregnancy during treatment with Ramigamma, the drug should be stopped as soon as possible and transferred to the patient for taking other medications. If therapy with Ramigamma is needed during breastfeeding, breastfeeding should be discontinued.

Dosing and Administration:

Inside, not liquid, squeezed enough liquid, regardless of food intake.

The dose of Ramigamma should be selected depending on the therapeutic effect and the tolerance of the drug to the patient. Arterial hypertension:

the recommended initial dose of Ramigamma is 2.5 mg per day, once, in the morning or 2 times a day. Depending on the reaction of the patient, the dose can be doubled with a 2-3-week interval. Usually the maintenance dose is 2.5-5 mg per day, the maximum daily dose is 10 mg per day.

Patients taking diuretics should cancel or reduce their dose at least 3 days before the start of taking Ramigammma. The initial daily dose in patients with arterial hypertension, which diuretics were not abolished, or in patients with hypertension and heart failure or renal failure is 1.25 mg per dose. Treatment should be started under the strict supervision of a physician.

If it is not possible to completely correct the disturbance of the water electrolyte balance in the case of severe arterial hypertension, and also for patients for whom the hypotensive reaction represents a certain risk, the initial dose is 1.25 mg.

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of the frequency of their development:

Often: > 10% of appointments;

often:> 1% - <10% of prescriptions;

not often:> 0.1% - <1% of prescriptions;

Very rarely:> 0.01% - <0.1% of prescriptions;

rarely: <0.01% of appointments, including individual messages;

frequency is unknown: according to available data, set the frequency

occurrence is not possible.

Heart Disease

Infrequently: myocardial ischemia, including the development of an attack of angina or

myocardial infarction, tachycardia, arrhythmia (appearance or gain), palpitation, peripheral edema.

Vascular disorders

Often: excessive reduction in blood pressure, orthostatic hypotension,

syncope (fainting).

Infrequently: the "tides" of blood to the skin of the face.

Rarely: the occurrence or enhancement of peripheral

blood circulation against a background of stenosing vascular lesions, vasculitis.

The frequency is unknown: Raynaud's syndrome.

Disorders from the central nervous system

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

Infrequently: dizziness, agevia (loss of taste sensitivity),

dysgeusia (a violation of taste sensitivity).

Rarely: tremor, imbalance.

The frequency is unknown: cerebral ischemia, including ischemic stroke and transient impairment of cerebral circulation, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired perception of odors).

Disturbances on the part of the organ of sight

Infrequent: visual disturbances, including blurred image.

Rarely: conjunctivitis.

Hearing disorders

Rarely: hearing impairment, ringing in the ears.

Disorders from the psyche

Infrequently: depressed mood, anxiety, nervousness, impellent

anxiety, sleep disturbances, including drowsiness.

Rarely: confusion.

The frequency is unknown: attention violation.

Disturbances from the respiratory system

Often: "dry" cough (worse at night and lying down),

bronchitis, sinusitis, dyspnea.

Infrequently: bronchospasm, including weighting of the course of bronchial asthma,

nasal congestion.

Disturbances from the digestive tract

Often: inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting.

Infrequently: pancreatitis, including fatal cases (cases of pancreatitis with fatal outcome with the intake of ACE inhibitors were very rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa

Rarely: glossitis

The frequency is unknown: aphthous stomatitis (inflammatory reaction of the oral mucosa).

Disorders from the hepatobiliary system

Rarely: Cholestatic jaundice, hepatocellular lesions.

Infrequently: increased activity of "hepatic" enzymes and concentration of conjugated bilirubin in blood plasma

The frequency is unknown: acute liver failure, cholestatic or cytolytic hepatitis (lethal outcome was observed extremely rarely).

Disorders from the kidneys and urinary tract

Sometimes: renal dysfunction, including the development of acute renal failure, increased urine output, increased pre-existing proteinuria, increased urea and creatinine levels in the blood.

Disorders from the reproductive system and mammary glands

Infrequently: transient impotence due to erectile dysfunction,

decreased libido.

The frequency is unknown: gynecomastia.

Violations of the blood and lymphatic system

Infrequently: eosinophilia.

Rarely: leukopenia, including neutropenia and agranulocytosis, decrease

the number of erythrocytes in the peripheral blood, a decrease in the concentration of hemoglobin, thrombocytopenia, leukocytosis.

The frequency is unknown: oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Disturbances from the skin and mucous membranes

Often: skin rash, in particular maculopapular.

Infrequently: angioedema, including fatal outcome

(laryngeal edema can cause airway obstruction leading to death), skin itching, hyperhidrosis.

Rarely: exfoliative dermatitis, urticaria, onycholysis.

Very rarely: photosensitization reactions.

The frequency is unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (exocrine) exanthema or enanthema, alopecia.

Disorders from the musculoskeletal system and connective

fabrics

Often: muscle cramps, myalgia

Infrequently: arthralgia

Disorders from the metabolism, nutrition and laboratory indicators

Often: increased potassium levels in the blood.

Infrequent: anorexia, decreased appetite.

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

Immune system disorders

The frequency is unknown: anaphylactic or anaphylactoid reactions

inhibition of ACE increases the amount of anaphylactic or anaphylactoid reactions to insect venoms), increasing the concentration of antinuclear antibodies.

Common violations

Often: chest pain, fatigue.

Infrequent: increased body temperature.

Rarely: asthenia (weakness).

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, shock, disturbance of water electrolyte balance, acute renal failure, stupor.

Treatment: gastric lavage, intake of adsorbents.

With a marked decrease in blood pressure, the patient should be placed on the back with a low head, measures are taken to replenish the volume of circulating blood and normalize the electrolyte balance, and also the administration of alpha 1-adrenomimetics (norepinephrine, dopamine) and angiotensin II (angiotensinamide); in the case of refractory to medical treatment of bradycardia, it may be necessary to install a temporary artificial pacemaker.

It is necessary to carefully monitor blood pressure, kidney function and the concentration of electrolytes and creatinine in the blood serum.

The effectiveness of hemodialysis to eliminate intoxication is not established.

Interaction:

Symptoms: marked decrease in blood pressure, bradycardia, shock, disturbance of water electrolyte balance, acute renal failure, stupor.

Treatment: gastric lavage, intake of adsorbents.

It is necessary to carefully monitor blood pressure, kidney function and the concentration of electrolytes and creatinine in the blood serum.

The effectiveness of hemodialysis to eliminate intoxication is not established.

Special instructions:

At the beginning of treatment, it is necessary to evaluate the kidney function.Kidney function should be closely monitored during treatment with Ramigamma, especially in patients with impaired renal function, renal vascular disease (eg, clinically insignificant stenosis of the renal arteries); heart failure.

After taking the first dose, as well as increasing the dose of a diuretic and / or Ramigamma, patients should stay for 8 hours under medical supervision to avoid the development of an uncontrolled hypotensive reaction.

In patients with chronic heart failure, taking the drug may lead to the development of severe arterial hypotension, which in some cases is accompanied by oliguria or azotemia and rarely - the development of acute renal failure.

Patients with malignant hypertension should begin treatment in a hospital.

Before and during treatment with Ramigamma, it is necessary to monitor blood pressure, kidney function (creatinine, urea), the content of potassium and other electrolytes, hemoglobin, the activity of "liver" transaminases.

The risk of hypersensitivity and allergic-like (anaphylactoid) reactions increases in patients,simultaneously taking ACE inhibitors and undergoing hemodialysis procedures using dialysis membranes AN69. Similar reactions were detected in the apheresis of low density lipoproteins with dextran sulfate, therefore, when using ACE inhibitors, this method should be avoided.

During treatment with Ramigamma in patients with impaired renal function, especially with simultaneous treatment with diuretics, the concentration of urea and creatinine in serum can increase. In this case, treatment should be continued with smaller doses of Ramigammma or cancellation of the drug. In patients with impaired renal function, the risk of developing hyperkalemia increases.

In patients with impaired liver function due to a decrease in the activity of "liver" transaminases, metabolism of ramipril and the formation of an active metabolite can be slowed. In this regard, the treatment of such patients should be started only under strict medical supervision. Care should be taken when prescribing Ramigamma to patients on a low-salt or salt-free diet (the risk of developing arterial hypotension is increased).In patients with a reduced volume of circulating blood (as a result of diuretic therapy) during dialysis, with diarrhea and vomiting, and with restriction of consumption of table salt, symptomatic arterial hypotension may develop.

Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure. In the case of repeated occurrence of severe arterial hypotension, the dose of Ramigamma should be reduced or the drug should be withdrawn.

Before surgery, including dentistry, it is necessary to alert the surgeon and anesthesiologist about the use of ACE inhibitors.

In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, decreased hemoglobin or inhibition of bone marrow function are observed. At the beginning and during treatment with Ramigamma, it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More regular monitoring is recommended in patients with renal insufficiency, connective tissue diseases (for example,systemic lupus erythematosus or scleroderma), and in patients receiving both drugs that affect hematopoiesis (see. Section "Interactions with other drugs"). Counting blood cells should also be performed if there are clinical signs of neutropenia / agranulocytosis and increased bleeding.

In patients with hypertension in the treatment of drug Ramigamma rarely marked increase potassium in the blood serum. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the administration of potassium preparations.

With the use of ACE inhibitors during desensitizing therapy to a wasp or bee venom may arise anaphylactoid reactions (e.g., hypotension, dyspnea, vomiting, skin rash), which can be life threatening. Hypersensitivity reactions can occur with insect bites (eg, bees or wasps). If necessary, the procedure desensitization (bites) to cancel ACE inhibitors and continue treatment with other antihypertensive agents.

For newborns who have been exposed to intrauterine exposure to ACE inhibitors, careful monitoring is recommended to detect arterial hypotension, oliguria, and hyperkalemia. In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors. In newborns and infants, there is a risk of oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors (received by pregnant women and after childbirth). Careful observation is recommended.

Caution should be exercised when performing physical exercises and in hot weather due to the risk of dehydration and arterial hypotension due to a decrease in fluid volume

Effect on the ability to drive transp. cf. and fur:

At the beginning of treatment, it is necessary to evaluate the kidney function. Kidney function should be closely monitored during treatment with Ramigamma, especially in patients with impaired renal function, renal vascular disease (eg, clinically insignificant stenosis of the renal arteries); heart failure.

Patients with malignant hypertension should begin treatment in a hospital.

The risk of hypersensitivity and allergic-like (anaphylactoid) reactions increases in patients who simultaneously take ACE inhibitors and undergo hemodialysis procedures using dialysis membranes AN69. Similar reactions were detected in the apheresis of low density lipoproteins with dextran sulfate, therefore, when using ACE inhibitors, this method should be avoided.

In patients with impaired liver function due to a decrease in the activity of "liver" transaminases, metabolism of ramipril and the formation of an active metabolite can be slowed. In this regard, the treatment of such patients should be started only under strict medical supervision. Care should be taken when prescribing Ramigamma to patients on a low-salt or salt-free diet (the risk of developing arterial hypotension is increased). In patients with a reduced volume of circulating blood (as a result of diuretic therapy) during dialysis, with diarrhea and vomiting, and with restriction of consumption of table salt, symptomatic arterial hypotension may develop.

Before surgery, including dentistry, it is necessary to alert the surgeon and anesthesiologist about the use of ACE inhibitors.

In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, decreased hemoglobin or inhibition of bone marrow function are observed. At the beginning and during treatment with Ramigamma, it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More regular monitoring is recommended in patients with renal insufficiency, connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients taking medications that affect hemopoiesis simultaneously (see section "Interactions with Other Drugs"). Counting blood cells should also be performed if there are clinical signs of neutropenia / agranulocytosis and increased bleeding.

For newborns who have been exposed to intrauterine exposure to ACE inhibitors, careful monitoring is recommended to detect arterial hypotension, oliguria, and hyperkalemia. In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors.In newborns and infants, there is a risk of oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors (received by pregnant women and after childbirth). Careful observation is recommended.

Caution should be exercised when performing physical exercises and in hot weather due to the risk of dehydration and arterial hypotension due to a decrease in fluid volume

Form release / dosage:

Tablets of 2.5 mg, 5 mg, 10 mg.

10 tablets per blister of A1 / A1.

By 2, 3, 5, 10 blisters together with the instructions for use are placed in a cardboard bundle

Packaging:

10 tablets per blister of A1 / A1.

By 2, 3, 5, 10 blisters together with the instructions for use are placed in a cardboard bundle

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

List B

Shelf life:

Shelf life 2 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000315

Date of registration:22.02.2011

Date of cancellation:2016-02-29

The owner of the registration certificate:Wörwag Pharma GmbH & Co. KG. KGWörwag Pharma GmbH & Co. KG. KG Germany

Manufacturer: & nbsp

ARTESAN PHARMA, GmbH & Co. KG. KG Germany

Information update date: & nbsp22.02.2011

Illustrated instructions

Instructions

Ramigamma® (Ramigamma®)