Amprilan NL, pills 2.5+12.5mg, 30pcs

Composition

Active ingredient:

ramipril-2.5 mg,

hydrochlorothiazide 12.5.

Auxiliary substances:

sodium bicarbonate 2.5 mg;

lactose monohydrate — 155 mg;

croscarmellose sodium — 4 mg

; starch pregelatinization — 30 mg;

sodium fumarate — 2 mg,

mixture of dyes “RV 22886 yellow” (lactose monohydrate, dye iron oxide yellow (E 172) — 4 mg.

Pharmacological action

of the enzyme catalyzes the conversion of angiotensin I to angiotensin II. ACE is identical to kininase, an enzyme that catalyzes the breakdown of bradykinin.

ACE inhibition leads to a decrease in the concentration of angiotensin II, an increase in the activity of renin in blood plasma, an increase in the effect of bradykinin and an increase in the secretion of aldosterone, which may cause an increase in the level of potassium in the blood serum.

The antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of vasodilation and a decrease in OPSS, which in turn gradually reduces blood pressure. Your heart rate usually doesn’t change. Long-term therapy reduces left ventricular hypertrophy without adversely affecting heart function.

The antihypertensive effect after taking a single dose of the drug inside is manifested in 1-2 hours, reaches a maximum in 3-6 hours and persists for 24 hours.

Ramipril is effective in the treatment of CHF. In patients with signs of CHF after a previous myocardial infarction, ramipril reduces the risk of sudden death, progression of heart failure, and reduces the number of hospitalizations for exacerbation of CHF.

Both in patients with and without diabetes mellitus, the drug significantly reduces the existing microalbuminuria and the risk of developing nephropathy. These effects are observed in patients with both elevated and normal blood pressure.

Indications

• Arterial hypertension.
• Chronic heart failure (as part of combination therapy), including those that developed on the 2nd-9th day after myocardial infarction.
• Diabetic nephropathy and nephropathy against the background of chronic diffuse kidney diseases (preclinical and clinical stages), including chronic glomerulonephritis with pronounced proteinuria.
• Reduction of the risk of myocardial infarction, stroke, and cardiovascular mortality in patients at high cardiovascular risk, including patients with confirmed coronary artery disease (with or without a history of myocardial infarction), patients undergoing percutaneous transluminal coronary angioplasty, coronary bypass grafting, a history of stroke, and patients with occlusive peripheral artery disease.

Use during pregnancy and lactation

The drug Amprilan® is contraindicated for use during pregnancy, because it can have an adverse effect on the fetus (including impaired renal function, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs).

Therefore, before starting the use of Amprilan® in women of childbearing age, pregnancy should be excluded.

When pregnancy is diagnosed, Amprilan should be discontinued as soon as possible.

If it is necessary to use the drug Amprilan® during lactation, breastfeeding should be discontinued.

Contraindications

• Hypersensitivity to ramipril and any other component of the drug or other ACE inhibitors.
• A history of angioedema (hereditary, idiopathic, or angioedema due to taking ACE inhibitors).
• Hemodynamically significant bilateral renal artery stenosis.
• Stenosis of the artery of a single kidney.
• Condition after kidney transplantation.
• Hemodialysis.
• Renal failure (Creatinine clearance
• Hemodynamically significant aortic and / or mitral stenosis (risk of excessive lowering of blood pressure with subsequent renal dysfunction).
• Hypertrophic obstructive cardiomyopathy (HOCMP).
• Chronic heart failure in the stage of decompensation.
• Severe hypotension (blood pressure less than 90 mm Hg) or unstable hemodynamics.
• Primary hyperaldosteronism.
• Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.
• Nephropathy treated with corticosteroids, NSAIDs, immunomodulators, and / or cytostatics.
• Pregnancy.
• Lactation period.
• Age up to 18 years (efficacy and safety have not been established).

With caution: severe lesions of the coronary and cerebral arteries (risk of decreased blood flow due to excessive BP reduction); malignant arterial hypertension; unstable angina; aortic and/or mitral stenosis; severe ventricular arrhythmias; chronic heart failure (NYHA functional class IV); decompensated pulmonary heart; renal and/or hepatic insufficiency; hyperkalemia; hyponatremia (including on the background of diuretics and diarrhoea, vomiting; systemic connective tissue diseases; diabetes mellitus; inhibition of bone marrow hematopoiesis; advanced age; hemodialysis using high — flow polyacrylonitrile membranes-the risk of developing anaphylactoid reactions; before the procedure of LDL apheresis; simultaneous desensitizing therapy with allergens (for example, hymenopteran venom).

Side effects

Classification of the frequency of side effects (WHO):

• Very often – ≥1/10.
• Often – ≥1/100 to
• Infrequently-from ≥1/1000 to < 1/100.
• Rarely-from ≥1/10000 to
• Very rarely-from

From the cardiovascular system: often-a marked decrease in blood pressure (at the beginning of therapy, with an increase in the dose or joining diuretic therapy), orthostatic hypotension, syncopal states; rarely-peripheral edema, palpitation, angina pectoris, arrhythmia; very rarely-myocardial ischemia, myocardial infarction, increased circulatory disorders against the background of stenosing vascular lesions, Raynaud’s syndrome, vasculitis, tachycardia, flushes of blood to the skin of the face.

From the nervous system: often-headache, weakness; rarely-increased fatigue, nervousness, depression, tremor, balance disorders, confusion, anxiety, dizziness, motor restlessness, sleep disorders; very rarely-paresthesia, impaired perception of odors (parosmia), transient ischemic attacks, ischemic stroke, cerebral ischemia, impaired concentration.

From the genitourinary system: rarely-transient impotence, decreased libido, impaired renal function, up to acute renal failure, increased urinary excretion, increased pre-existing proteinuria, increased urea and creatinine concentrations; very rarely — gynecomastia.

From the respiratory system: often-dry, unproductive cough, worse at night and in the supine position, more often occurring in women and non-smoking patients, sinusitis, bronchitis, shortness of breath; rarely — nasal congestion, pharyngitis, bronchospasm, including exacerbation of the course of bronchial asthma.

From the skin: often — maculopapular skin rash; rarely — pruritus, increased sweating (against the background of a decrease in blood pressure); very rarely — maculopapular exanthema and erythema, pemphigus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening of psoriasis, psoriasis — like, pemphigoid and lichenoid lesions of the skin and mucous membranes, alopecia; very rarely rarely-urticaria, onycholysis, exfoliative dermatitis, photosensitization.

From the digestive system: often — inflammation of the gastrointestinal mucosa, digestive disorders, abdominal discomfort, dyspepsia, nausea, diarrhea, vomiting; rarely — increased activity of liver enzymes, increased bilirubin concentration, cholestatic jaundice, acute liver failure, cholestatic hepatitis, hepatocellular lesions, dry oral mucosa, abdominal pain, gastritis, constipation, pancreatitis, including and with fatal outcome (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were observed extremely rarely), intestinal angioedema, decreased appetite, anorexia; very rarely — glossitis; aphthous stomatitis.

From the musculoskeletal system: often-myalgia, muscle cramps; rarely-arthralgia.

From the sensory organs: rarely-visual disorders, including blurred vision, conjunctivitis, hearing disorders, smell and taste disorders (for example, metallic taste, partial or temporary loss of taste sensations).

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

Laboratory parameters: rarely-hyperkalemia, moderate (sometimes severe) hypohemoglobinemia or neutropenia, erythropenia and thrombocytopenia, increased activity of pancreatic enzymes; very rarely-hyponatremia, proteinuria (although usually ACE inhibitors reduce previous proteinuria) or increased diuresis (in combination with impaired heart function), agranulocytosis, pancytopenia, bone marrow depression, hemolytic anemia.

Other: rarely-hyperthermia; very rarely-fever.

Interaction

Vasopressor sympathomimetics (epinephrine, norepinephrine) may reduce the hypotensive effect of ramipril. With the simultaneous use of these drugs, the level of blood pressure should be carefully monitored.

ACE inhibitors enhance the inhibitory effect of ethanol on the central nervous system.

Lithium preparations: Cases of reversible increases in serum lithium concentrations have been reported with concomitant use of lithium preparations and ACE inhibitors. Concomitant use with thiazide diuretics may increase the concentration of lithium and the risk of its toxic effect against the background of taking an ACE inhibitor.

NSAIDS: a combination of ACE inhibitors with NSAIDs (non-selective COX-1 and COX-2 inhibitors from the NSAID group, for example, acetylsalicylic acid in doses that have an anti-inflammatory effect): the hypotensive effect of ACE inhibitors decreases; the risk of impaired renal function increases, up to the development of acute renal failure; the serum potassium content increases in patients with pre-existing renal dysfunction.

Tricyclic antidepressants, antipsychotics (neuroleptics): increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect).

CORTICOSTEROIDS, tetracosactide: reduction of the hypotensive effect (fluid retention).

Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium preparations: the combined use of ramipril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.

Care should be taken and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

Hypoglycemic agents for oral use (sulfonylureas) and insulin: the use of ACE inhibitors may increase the hypoglycemic effect of hypoglycemic agents for oral use and insulin in patients with diabetes mellitus; when they are used together, glucose tolerance may increase, which may require dose adjustment of hypoglycemic agents for oral use and insulin.

Allopurinol, cytostatic drugs, immunosuppressants, corticosteroids (with systemic use) and procainamide: concomitant use of these drugs with ACE inhibitors may increase the risk of leukopenia.

General anaesthetics: ACE inhibitors may increase the hypotensive effect of some general anaesthetics.

Gold preparations: when prescribing ACE inhibitors, including ramipril, to patients receiving gold preparation (sodium aurothiomalate) intravenously, nitrate-like reactions (nausea, vomiting, a marked decrease in blood pressure, hyperemia of the facial skin) were noted.

How to take, course of use and dosage

Inside, whole, without chewing, regardless of food intake, with a sufficient amount of liquid.

The dose is selected depending on the therapeutic effect and tolerability of the drug by the patient.

Treatment with Amprilan® is long-term, its duration is determined by the doctor in each specific case.

Arterial hypertension: the recommended initial dose of Amprilan® is 2.5 mg once a day. Depending on the patient’s response, the dose may be doubled at 1-2-week intervals. Usually, the maintenance dose is 2.5-5 mg / day, the maximum daily dose is 10 mg. Patients taking diuretics should discontinue or reduce their dose at least 3 days before starting Amprilan.

CHF: The recommended starting dose of Amprilan is 1.25 mg once daily. Depending on the therapeutic effect, the dose can be doubled at intervals of 1-2 weeks.

The maximum daily dose is 10 mg.

In patients receiving high doses of diuretics, the dose of diuretics should be reduced before starting therapy with Amprilan®.

Heart failure that develops within a few days (from day 2 to day 9) after acute myocardial infarction: the recommended initial 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 the second in the evening. If the patient does not tolerate the initial dose (there is an excessive decrease in blood pressure), it should be reduced to 1.25 mg 2 times a day. Then, depending on the patient’s response, the dose can be doubled again (2.5 mg) at intervals of 1-3 days. Later, the daily dose, which was first divided into two, can be given once. The maximum daily dose is 10 mg. If the patient does not tolerate an increase in the dose to 2.5 mg 2 times a day, then treatment with the drug should be discontinued.

Diabetic nephropathy and nephropathy associated with chronic diffuse kidney disease: the recommended starting dose of Amprilan® is 1.25 mg once a day. Depending on the patient’s tolerance to ramipril, the dose of the drug may increase in the future: it is recommended to double the dose every 2 weeks to a maintenance dose of 5 mg once a day.

Reducing the risk of myocardial infarction, stroke and cardiovascular mortality: the recommended initial dose of Amprilan® is 2.5 mg once a day, which subsequently gradually increases depending on the drug’s tolerability: it is recommended to double the dose after 1 week of therapy, and then after another 2-3 weeks — until the target maintenance dose of 10 mg once a day is reached.

Special patient groups.

Impaired renal function: in patients with creatinine clearance greater than 30 ml/min, no dose adjustment is required. For patients with creatinine clearance less than 30 ml / min, the initial daily dose is 1.25 mg, and the maximum daily dose is 5 mg. Liver function disorders. The initial dose is 1.25 mg once a day. The maximum dose is 2.5 mg once a day.

Elderly patients: Elderly patients (over 65 years of age) who are taking diuretics should be carefully monitored. The dose of Amprilan® should be selected depending on the level of blood pressure.

Overdose

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

Treatment: in mild cases of overdose-gastric lavage, use of adsorbents and sodium picosulfate (preferably within 30 minutes after oral use). With a pronounced decrease in blood pressure — iv use of catecholamines, alpha-1-adrenergic agonists (norepinephrine, dopamine), angiotensin II (angiotensinamide), the patient should be laid on his back on a surface with a low headboard, if necessary, the BCC can be replenished by infusion of 0.9% sodium chloride solution; with bradycardia, a temporary artificial pacemaker can be set. Blood pressure, kidney function, and serum potassium should be carefully monitored. The effectiveness of hemodialysis has not been established.

Special instructions

Renal function should be evaluated at the beginning of treatment. Renal function should be carefully monitored in patients with impaired renal function, heart failure, bilateral renal artery stenosis or stenosis of the artery of a single kidney, as well as in patients after kidney transplantation.

Liver failure

In rare cases, against the background of the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice occurs or there is a significant increase in hepatic transaminase activity while taking ACE inhibitors, the use of Amprilan® should be discontinued.

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

• Patients with severe CHF: treatment is initiated with the lowest possible dose of Amprilan® (1.25 mg).
• Taking diuretics: if possible, it is necessary to cancel the diuretic in advance or reduce its dose; treatment begins with a minimum dose of Amprilan® (1.25 mg).
• Patients at risk of developing hypovolemia due to insufficient fluid intake, diarrhea, vomiting, or excessive sweating in conditions of insufficient compensation for salt and fluid loss. It is usually recommended to adjust the BCC before starting treatment, but if these conditions become clinically significant, treatment with Amprilan® can be initiated and / or continued with a minimum dose (1.25 mg) and under medical supervision.

Aortic stenosis/mitral stenosis/HOCMP

ACE inhibitors should be used with caution in patients with left ventricular exit tract obstruction and aortic and / or mitral stenosis.

Neutropenia/agranulocytosis

Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves independently after the withdrawal of ACE inhibitors.

Ramipril should be used with great caution in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially in patients with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If ramipril is used, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if there are any signs of an infectious disease (sore throat, fever), it is necessary to immediately consult a doctor.

Hyperkalemia

It may develop during treatment with ACE inhibitors, including ramipril.Risk factors for hyperkalemia include renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, and the use of other drugs that increase the potassium content in blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal.

Potassium-sparing diuretics and potassium supplements

The combined use of Amprilan® and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes, is not recommended.

Surgical interventions/general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.

It is recommended to stop taking ACE inhibitors, including ramipril,12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

Cough

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of drugs of this group. If a dry cough occurs, you should be aware of the possible association of this symptom with taking an ACE inhibitor.

Anaphylactoid reactions during desensitization procedures

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions, undergoing desensitization procedures. Avoid prescribing an ACE inhibitor to patients receiving hymenopteran venom immunotherapy. However, the development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions

During treatment, caution should be exercised when engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions, as dizziness, drowsiness, confusion and other side effects are possible.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf life

3 years

Active ingredient

Hydrochlorothiazide, Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Heart failure, Prevention of heart attacks and strokes, Kidney damage