Ramipril-SZ, pills 5mg, 30pcs

Composition

Active ingredient:

ramipril – 5 mg;

Auxiliary substances:

lactose monohydrate 143.5 mg,

magnesium stearate 1.5 mg

Pharmacological action

ACE inhibitor. It is a prodrug from which the active metabolite ramiprilate is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II, which is a powerful vasoconstrictor. As a result of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during renin release and a direct decrease in aldosterone secretion. Due to its vasodilating action, it reduces OPSS (afterload), jamming pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases the minute volume of the heart and load tolerance.

In patients with signs of chronic heart failure after a myocardial infarction, ramipril reduces the risk of sudden death, progression of heart failure to severe/resistant failure, and reduces the number of hospitalizations for heart failure.

Ramipril is known to significantly reduce the incidence of myocardial infarction, stroke, and cardiovascular death in patients with an increased cardiovascular risk due to vascular diseases (CHD, stroke, or peripheral vascular disease) or diabetes mellitus who have at least one additional risk factor (microalbuminuria, hypertension, elevated total cholesterol, low HDL, smoking). Reduces overall mortality and the need for revascularization procedures, and slows the onset and progression of chronic heart failure. In both diabetic and non-diabetic patients, ramipril significantly reduces existing microalbuminuria and the risk of developing nephropathy. These effects are observed in patients with both elevated and normal blood pressure.

The hypotensive effect of ramipril develops in approximately 1-2 hours, reaches a maximum within 3-6 hours, and lasts at least 24 hours.

 When taken orally, absorption is 50-60%, food does not affect the degree of absorption, but slows down absorption. Cmax is reached in 2-4 hours. In the liver, it is metabolized to form the active metabolite ramiprilate (6 times more actively inhibits ACE than ramipril), inactive diketopiperazine, and glucuronized.

All the metabolites formed, with the exception of ramiprilate, have no pharmacological activity. Plasma protein binding for ramipril was 73%, ramiprilate-56%. Bioavailability after oral use of 2.5-5 mg ramipril – 15-28%; for ramiprilat-45%. After daily use of ramipril at a dose of 5 mg/day, a stable concentration of ramiprilate in plasma is reached by day 4.

T1 / 2 for ramipril is 5.1 hours; in the phase of distribution and elimination, the concentration of ramiprilate in the blood serum decreases with T1 / 2-3 hours, followed by a transition phase with T1 / 2-15 hours, and a long final phase with very low plasma concentrations of ramiprilate and T1 / 2-4-5 days. T1 / 2 increases in chronic renal failure.

Vd ramipril – 90 l, ramiprilat – 500 l. 60% is excreted by the kidneys, and 40% is excreted through the intestines (mainly in the form of metabolites). With impaired renal function, the excretion of ramipril and its metabolites slows down in proportion to the decrease in creatinine clearance; with impaired liver function, the conversion to ramiprilate slows down; with heart failure, the concentration of ramiprilate increases 1.5-1.8 times.

Indications

• hypertension;
• congestive heart failure, including acute myocardial infarction in patients with stable haemodynamics,
• diabetic nephropathy and chronic diffuse renal disease (non-diabetic nephropathy);
• reduction in the risk of myocardial infarction, stroke, or coronary death in patients with coronary artery disease, with an increased risk of cardiovascular diseases, including patients after myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting (when clinically stable condition).

Use during pregnancy and lactation

Contraindicated in children under 18 years of age.

Contraindicated in pregnancy. Before starting treatment, you should make sure that there is no pregnancy. If the patient becomes pregnant during treatment, it is necessary to replace ramipril drug therapy with another therapy as soon as possible. Otherwise, there is a risk of damage to the fetus, especially in the first trimester of pregnancy.

Effect on the fetus:  impaired fetal kidney development, decreased blood pressure Fetal and newborn blood pressure, renal dysfunction, hyperkalemia, cranial hypoplasia, oligohydramnion, limb contracture, cranial deformity, lung hypoplasia.

Category of action on the fetus according to the FDA-D.

Breast-feeding should be discontinued for the duration of treatment.

Contraindications

• severe renal and hepatic dysfunction, bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• condition after kidney transplantation;
• primary hyperaldosteronism, hyperkalemia, aortic stenosis,
• hypersensitivity to ramipril and other ACE inhibitors.

Side effects

Cardiovascular and blood disorders (hematopoiesis, hemostasis):  hypotension (10.7%), including postural (2.2%), angina (2.9%), syncope (2.1%), heart failure (2%), myocardial infarction (1.7%), vertigo (1.5%), chest pain (1.1%), less than 1% — arrhythmia, palpitations, hemolytic anemia, myelodepression, pancytopenia, thrombocytopenia, eosinophilia, agranulocytosis; vasculitis.

From the digestive tract:  nausea (2.2%), vomiting (1.6%), diarrhea (1.1%), less than 1% — dry mouth or increased salivation, anorexia, dyspepsia, dysphagia, constipation, abdominal pain, gastroenteritis, pancreatitis, hepatitis, liver dysfunction (cholestatic jaundice, fulminant liver necrosis with fatal outcome), changes in the level of transaminases.

Nervous system and sensory disorders:  dizziness (4.1%), headache (1.2%), asthenia (0.3%), less than 1% — cerebrovascular disorders, amnesia, drowsiness, seizures, depression, sleep disorders, neuralgia, neuropathy, paresthesia, tremor, hearing loss, visual impairment.

Respiratory system disorders:  unproductive cough (7.6%), upper respiratory tract infections, less than 1% — dyspnoea, pharyngitis, sinusitis, rhinitis, tracheobronchitis, laryngitis, bronchospasm.

From the genitourinary system:  impaired renal function (1.2%), less than 1% — proteinuria, oliguria, edema; impotence.

From the side of the skin:  urticaria, prurigo, rash, erythema multiforme, photosensitization.

Other services:  less than 1% — weight loss, anaphylactoid reactions, increased levels of urea nitrogen and creatinine, angioedema (0.3%), arthralgia/arthritis, myalgia, fever, increased titer of antinuclear antibodies, hyperkalemia, changes in enzyme activity, bilirubin, uric acid, glucose concentrations.

Interaction

With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to potassium retention in the body against the background of limiting the excretion of potassium or its additional intake into the body.

When used concomitantly with NSAIDs, the hypotensive effect of ramipril may decrease, and renal function may be impaired.

When used concomitantly with loop or thiazide diuretics, the antihypertensive effect increases. Severe hypotension, especially after taking the first dose of a diuretic, appears to occur due to hypovolemia, which leads to a transient increase in the hypotensive effect of ramipril. There is a risk of hypokalemia. The risk of impaired renal function increases.

When used concomitantly with drugs that have a hypotensive effect, it is possible to increase the hypotensive effect.

Concomitant use with immunosuppressants, cystostatics, allopurinol, procainamide may increase the risk of leukopenia.

When used concomitantly with insulin, hypoglycemic agents, sulfonylureas, and metformin, hypoglycemia may develop.

Concomitant use with allopurinol, cystostatics, immunosuppressants, procainamide may increase the risk of leukopenia.

When used concomitantly with lithium carbonate, it is possible to increase the concentration of lithium in the blood serum.

How to take it, course of use and dosage

They are taken orally. The initial dose is 1.25-2.5 mg 1-2 times / day.

If necessary, a gradual increase in the dose is possible.

The maintenance dose is set individually, depending on the indications for use and the effectiveness of treatment.

Overdose

Symptoms:  excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, water and electrolyte disorders, acute renal failure, stupor.

Treatment: gastric lavage, intake of adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a marked decrease in blood pressure, the use of alpha-1-adrenergic agonists (norepinephrine, dopamine) can be added to therapy to replenish the volume of circulating blood and restore electrolyte balance. If bradycardia is refractory to medical treatment, it may be necessary to install a temporary artificial pacemaker. In case of overdose, serum creatinine and electrolyte concentrations should be monitored.

Special instructions

In patients with concomitant renal impairment, doses are selected individually in accordance with the values of creatinine clearance. All patients should be evaluated for renal function before starting treatment.

During treatment with ramipril, regular monitoring of renal function, blood electrolyte composition, liver enzymes in the blood, as well as the picture of peripheral blood (especially in patients with diffuse connective tissue diseases, in patients receiving immunosuppressants, allopurinol) is carried out.

Patients who have a fluid and/or sodium deficiency should have their water and electrolyte disorders corrected before starting treatment. During treatment with ramipril, hemodialysis using polyacrylonitrile membranes should not be performed (the risk of anaphylactic reactions is increased).

Form of production

Pills.

Storage conditions

At a temperature not exceeding 25 °C

Shelf

life is 3 years.

Active ingredient

Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Diabetic Nephropathy, Heart Failure, Hypertension, Kidney damage, Prevention of heart attacks and strokes