2010/09/20

Amprilan

Composition, structure and packing

The tablets are oval, flat, white or nearly white, with beveled.

1 tab. Ramipril 1.25 mg.

Excipients: sodium carbonate, lactose monohydrate, croscarmellose sodium, starch prezhelatinirovanny, sodium stearyl fumarate.

The tablets are oval, flat, light yellow, with a bevel.

1 tab. Ramipril 2.5 mg.

Excipients: sodium carbonate, lactose monohydrate, croscarmellose sodium, starch prezhelatinirovanny, sodium stearyl fumarate, iron oxide yellow (E172). Tablets are oval, flat, pink, with beveled, with visible inclusions.

1 tab. Ramipril 5 mg.

Excipients: sodium carbonate, lactose monohydrate, croscarmellose sodium, starch prezhelatinirovanny, sodium stearyl fumarate, iron oxide red (E172). The tablets are oval, flat, white or nearly white, with beveled.

1 tab. ramipril 10 mg.

Excipients: sodium carbonate, lactose monohydrate, croscarmellose sodium, starch prezhelatinirovanny, sodium stearyl fumarate.

Clinical-pharmacological group: ACE inhibitor.

Pharmacological action

ACE inhibitor. Ramipril is a prodrug and after absorption is metabolized in the liver to ramiprilata. Ramipril - an ACE inhibitor long-acting. ACE catalyzes the conversion of angiotensin I to angiotensin II. ACE is identical to the kinase (an enzyme that catalyzes the decomposition of bradykinin). Blockade of ACE reduces the concentration of angiotensin II, increase the activity of renin in the blood plasma, intensification of the effect of bradykinin and increased secretion of aldosterone, which may lead to increased potassium levels in blood serum. Antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of expansion of resistive vessels and reduce TPVR, therefore there is a gradual lowering of blood pressure. The heart rate usually does not change.

With long-term treatment reduced left ventricular hypertrophy without affecting cardiac function. The hypotensive effect after administration of a single dose appears after 1-2 h, reaches a maximum after 3-6 h and lasts for 24 hours Ramipril also effective for the treatment of chronic heart failure.

In patients with chronic heart failure after myocardial infarction drug reduces the risk of sudden death, progression of heart failure in severe / resistant failure and reduces the number of hospitalizations for heart failure. It is known that ramipril significantly reduces the incidence of myocardial infarction, stroke and cardiovascular death in patients with increased cardiovascular risk due to cardiovascular disease (CHD, stroke or peripheral vascular disease) or diabetes, for which there is at least one additional risk factor (microalbuminuria , arterial hypertension, increased total cholesterol, low HDL, smoking). The drug also reduces total mortality and need for revascularization procedures, slows the emergence and progression of chronic heart failure. As patients with diabetes mellitus, and without it, the drug significantly reduces the available microalbuminuria and risk of nephropathy. These effects were observed in patients with both elevated and normal blood pressure.

Pharmacokinetics

Absorption

Following oral administration ramipril is rapidly absorbed from the gastrointestinal tract, absorption is 50-60%. Eating does not slow down absorption. Cmax plasma levels achieved after 1 h.

Distribution and metabolism

Ramipril is metabolized in the liver with the formation of an active metabolite - ramiprilata, the activity of which is 6 times higher than ramipril and inactive diketopiperazina, which then glyukuroniziruetsya. The maximum concentration ramiprilata in serum obtained 2-4 hours after admission, the equilibrium concentration - to 4 day treatment. Linking ramipril with plasma proteins is about 73%, ramiprilata - 56%.

Withdrawal

Ramipril and ramiprilat excreted primarily in urine (approximately - 60%) mainly in the form of metabolites, less than 2% of the accepted dose was excreted as unchanged ramipril.

Ramipril is displayed in several stages. T1 / 2 after the appointment of a therapeutic dose is 13-17 h for ramiprilata, 5.1 h - for ramipril.

Pharmacokinetics in special clinical situations

Studies in healthy volunteers aged from 65 to 75 years, showed that the pharmacokinetics of ramipril they did not differ from the pharmacokinetics in young healthy volunteers.

In case of violation of renal function elimination of ramipril and its metabolites is slowed down proportionally reduce spacecraft. Patients with liver failure in the metabolism of ramipril ramiprilat can be slowed, and the concentration of ramipril in the serum increased.

Statement
hypertension;
Chronic heart failure;
Chronic heart failure after acute myocardial infarction in patients with stable hemodynamics.

Dosage regimen

When hypertension Amprilana recommended initial dose is 2.5 mg 1 time / day (morning, empty stomach) or in 2 divided doses. Depending on the reaction of the patient's dose may be doubled with a 2-3 week intervals. Typically, the maintenance dose of 2.5-5 mg / day, maximum daily dose - 10 mg / day. Patients taking diuretics, you must cancel or reduce their dose of at least 3 days prior to the appointment Amprilana.

Patients with hypertension who were not removed diuretics or in patients with hypertension and congestive heart failure or renal insufficiency initial daily dose is 1.25 mg in 1 device.

Treatment should start under close medical supervision.

In chronic heart failure the initial dose Amprilana patients in stable condition, receiving treatment with diuretics, is 1.25 mg / day in 1 reception. Depending on the therapeutic response to the patient's dose can be doubled with a 1-2-week intervals. The maximum daily dose is 10 mg.

Patients receiving diuretics in high doses, before the start of therapy with a dose of diuretics should be reduced. The initial dose Amprilana for such patients is 1.25 mg.

Treatment after myocardial infarction may be initiated only in the hospital between 3 and 10 days after myocardial infarction. The initial dose is 2.5 mg 2 times / day, 2 days later the dose is increased to 5 mg 2 times / day.

Supporting dose Amprilana is 2.5-5 mg 2 times / day.

Drugs are taken in the morning and evening. The maximum daily dose - 10 mg. With the development of arterial hypotension, the initial dose is reduced to 1.25 mg 2 times / day. After 2 days the dose may be increased again to 2.5 mg 2 times / day, even after 2 days the dose may be increased to 5 mg 2 times / day (morning and evening).

If the patient is poorly tolerate higher doses of up to 2.5 mg 2 times / d, the treatment Amprilanom should be discontinued. In patients with CC more than 0.5 ml / sec (30 ml / min) change in dose is required. For patients with CC is less than 0.5 ml / sec (30 ml / min) recommended initial daily dose of 1.25 mg, maximum daily dose - 5 mg.

For patients with renal insufficiency (CC 20-50 ml / min) over the age of 65 years, with concomitant diabetes starting dose is 1.25 mg 1 time / day maintenance dose - 2.5 mg, the maximum daily dose - 5 mg.

Careful monitoring of patients taking diuretics, and for patients with heart failure and impaired renal and hepatic function. Amprilana dose should be selected depending on the target BP level. The drug, taken orally, drinking plenty of fluids, regardless of the meal.

Side effect

Since the cardiovascular system: reduction of blood pressure, orthostatic hypotension, Orthostatic hypotension, tachycardia, rarely (if excessive reduction of blood pressure) - arrhythmia, angina, myocardial infarction.

On the part of the urogenital system: the development or worsening symptoms of renal failure, proteinuria, reduced urine volume, decreased libido.

From the side of the central nervous system and peripheral nervous system: excessive lowering blood pressure (mainly in patients with clinically significant narrowing of the vessels of the brain) may develop cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, paresthesia, nervousness, restlessness, tremor , muscle cramps, mood disorder, convulsions, when used in high doses - insomnia, anxiety, depression, confusion, fainting.

From the senses: vestibular disorders, breach of taste (eg, a metallic taste), smell, hearing and vision, tinnitus.

On the part of the digestive system: nausea, vomiting, diarrhea or constipation, pain in the epigastric region, ileus, pancreatitis, hepatitis, cholestatic jaundice, abnormal liver function with the development of liver failure, dry mouth, thirst, decreased appetite, stomatitis, glossitis, increased activity of hepatic transaminases, hyperbilirubinemia.

On the part of the respiratory system: dry cough, bronchospasm, dyspnea, rhinorrhea, rhinitis, sinusitis, bronchitis. Allergic reactions: skin rash, itching, rash, conjunctivitis, photosensitivity, angioedema face, extremities, lips, tongue, pharynx and / or larynx, exfoliative dermatitis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus, serositis, oniholiz, vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.

Other: alopecia, pyrexia, increased sweating, hypercreatininemia, increased BUN, hyperkalemia, hyponatremia, the appearance of antinuclear antibodies.

Contraindications
angioedema in history (also associated with previous therapy with ACE inhibitors);
hemodynamically significant bilateral renal artery stenosis;
artery stenosis was the only kidney;
condition after kidney transplantation;
hemodialysis;
renal failure (CC less than 20 ml / min);
hemodynamically significant aortic or mitral stenosis (risk of excessive BP reduction with subsequent renal dysfunction);
hypertrophic obstructive cardiomyopathy;
primary hyperaldosteronism;
Pregnancy
Lactation (breastfeeding);
the age of 18 years (effectiveness and safety have not been established);
Hypersensitivity to ramipril or any other ingredient of a drug or other ACE inhibitors.

Precautions should be prescribed medication for severe coronary and cerebral arteries (risk reduction of blood flow under excessive blood pressure reduction), unstable angina, severe ventricular arrhythmias, congestive heart failure stage IV, decompensated pulmonary heart, kidney and / or liver failure, hyperkalemia, hyponatremia (including on the background of diuretics and diet with restriction of salt intake), the state, accompanied by a decrease in the bcc (including diarrhea, vomiting), systemic connective tissue disease, diabetes, depression of bone marrow hemopoiesis, elderly patients.

Bermennost and lactation

Ramipril is contraindicated during pregnancy and lactation (breastfeeding). Before therapy ramipril should exclude the presence of pregnancy. Ramipril is not recommended to women planning a pregnancy. If ramipril treatment is absolutely necessary, it should prevent pregnancy. If pregnancy occurs during treatment, the drug should be immediately repealed and replaced with other medicines.

Found that the drug reduces blood pressure of the fetus and newborn, causes impairment of renal function, promotes the development of hyperkalemia, hypoplasia of the skull bones, oligogidramniona, contractures of limbs, bone deformities of the skull, hypoplasia of the lungs. In experimental studies revealed no secretion of ramipril and milk in lactating animals.

Application for violations of liver function

With caution is prescribed for liver failure.

Application for violations of renal function

In patients with CC more than 0.5 ml / sec (30 ml / min) change in dose is required. For patients with CC is less than 0.5 ml / sec (30 ml / min) recommended initial daily dose of 1.25 mg, and maksmalnaya daily dose - 5 mg. For patients with renal insufficiency (CC 20-50 ml / min) over the age of 65 years and with concomitant diabetes starting dose is 1.25 mg 1 time / day maintenance dose - 2.5 mg, the maximum daily dose - 5 mg.

Cautions

You should not assign the drug to patients with hemodynamically significant stenosis of the aortic or mitral valve, or any obstacle outflow of blood from the left ventricle. At the beginning of treatment is necessary to evaluate kidney function. We must carefully monitor renal function during treatment Amprilanom (particularly in patients with impaired renal function, with lesion of renal vessels / clinically insignificant renal artery stenosis, or hemodynamically significant stenosis of the artery of a sole kidney /), congestive heart failure. The risk of hypersensitivity reactions and anaphylactoid reactions is increased among patients receiving both ACE inhibitors and undergoing hemodialysis using dialysis membrane AN69. Similar responses were detected in low density lipoprotein apheresis with dextran sulfate, so the treatment with ACE inhibitors should avoid using this method.

During treatment Amprilanom in patients with impaired renal function, especially with simultaneous treatment with diuretics, may increase the level of urea and creatinine in serum. In this case, treatment should be continued reduced doses Amprilana or repeal the drug.

Patients with impaired renal function and increased risk of hyperkalemia.

Patients with hepatic impairment due to decreased activity of hepatic esterases can be slowed metabolism of ramipril and formation of the active metabolite. In this regard, treatment of such patients should be started only under close medical supervision. Be careful when appointing Amprilana patients who are on low salt or salt-free diet (increased risk of arterial hypotension).

In patients with reduced BCC (as a result of diuretic therapy), during dialysis, diarrhea and vomiting may develop symptomatic hypotension. Transitory hypotension is not a contraindication for further treatment after stabilization of blood pressure. In the case of re-emergence of pronounced hypotension should reduce the dose or cancel the drug.

The therapy Amprilanom during extensive surgery during general anesthesia may be the development of angiotensin II blockade due to compensatory renin release. If the doctor connects the development of arterial hypotension with the above mechanism, hypotension may be adjusted to increase the volume of blood plasma.

In rare cases during treatment with ACE inhibitors observed agranulocytosis, erythropenia, thrombocytopenia, gemoglobinemiya or bone marrow suppression. At the beginning of and during treatment should control the number of white blood cells to detect possible neutropenia / agranulocytosis. More frequent monitoring is recommended in patients with renal failure, with connective tissue diseases (systemic lupus erythematosus or scleroderma) and in patients receiving both drugs that affect hematopoiesis. Counting of blood cells should be carried out also in the event of clinical signs of neutropenia / agranulocytosis and increased bleeding.

In patients with arterial hypertension, treatment Amprilanom rarely in the rise of potassium in the blood serum. The risk of hyperkalemia is increased in chronic heart failure, while treatment of potassium-sparing diuretics (spironolactone, amiloride, triamterene) and potassium administration of these drugs.

If you use ACE inhibitors during desensitizing treatment to a wasp or bee venom may arise anaphylactoid reactions (hypotension, dyspnea, vomiting, skin rash), which can be life threatening. Hypersensitivity reactions may occur with insect bites (bees or wasps).

If necessary, a desensitizing treatment with bee venom or Osin to cancel ACE inhibitors and continue treatment with suitable drugs from other groups.

Effects on ability to drive vehicles and Management

During treatment Amprilanom be careful when driving and busy with other potentially hazardous activities that require high concentration and quickness of psychomotor reactions (dizziness, especially after the initial dose of ACE inhibitor in patients taking diuretic drugs). Patients are encouraged to refrain from driving and working with the mechanisms so far as there is no defined response to treatment.

Overdose

Symptoms: marked reduction of blood pressure, bradycardia, shock, disruption of water and electrolyte balance, acute renal failure.

Treatment: In mild cases - gastric lavage, the introduction of adsorbents and sodium sulphate (preferably within 30 minutes after admission).

In marked decrease in blood pressure patient should be placed on their backs with a low headboard, shown in / at the introduction of catecholamines, angiotensin II, if necessary, BCC can be compensated by in / infusion 0.9% sodium chloride solution, with bradycardia - Pacemaker application. We must carefully monitor blood pressure, kidney function and the concentration of potassium in the blood serum. The effectiveness of hemodialysis for the removal of intoxication is not installed.

Drug Interactions

Ramipril increases the inhibitory effect of ethanol on the CNS. With simultaneous use of ramipril and other means that reduce blood pressure (diuretics, nitrates, tricyclic antidepressants, anesthetics), leads to increased hypotensive effect of ramipril. The simultaneous appointment of ramipril and potassium supplements or medications Potassium-sparing diuretics can cause hyperkalemia. Sympathomimetic vasopressor (epinephrine, norepinephrine) may reduce the hypotensive effect of ramipril. In this regard, while the treatment should be carefully monitored BP levels.

The simultaneous appointment of ramipril and allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics increases the likelihood of changes in the peripheral blood picture.

The simultaneous appointment of ramipril and lithium preparations leads to a decrease excretion of lithium. It is therefore necessary to control the concentration of lithium in blood serum to eliminate the risk of toxic effects. ACE inhibitors may increase the hypoglycemic effect of (insulin or sulfonylurea derivatives) that in some cases can cause hypoglycemia.

In this regard, blood glucose levels should be carefully monitored, especially in the beginning of the joint application. The simultaneous use of ramipril and NSAIDs (acetylsalicylic acid, indomethacin) may diminish the hypotensive effect of ramipril.

In addition, concurrent use may cause hyperkalaemia and increase the risk of renal dysfunction. The simultaneous use of heparin and ramipril may cause hyperkalemia. Anaphylactic and anaphylactoid reactions to Hymenoptera venom (and possibly other allergens) are more pronounced during treatment with ACE inhibitors. Increased intake of salt with food may decrease the hypotensive effect of ramipril.

Terms and Conditions of storage

The product should be stored out of reach of children, dry place at temperatures not above 25 ° C. Shelf life - 2 years.

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