Combined antihypertensive drug Hartil: instructions for use, analogues, reviews and price. Hartil instructions for use, contraindications, side effects, reviews Pharmacological action of Hartil

Compound

1 tablet Hartil 2.5 contains:
Ramipril – 2.5 mg;
Excipients, including lactose monohydrate.

1 tablet Hartil 5 contains:
Ramipril – 5 mg;
Excipients, including lactose monohydrate.

1 tablet Hartil 10 contains:
Ramipril – 10 mg;
Excipients, including lactose monohydrate.

pharmachologic effect

The severity of Hartil's therapeutic effect does not depend on the patient's age; the hypotensive effect is equally evident in patients in a standing and lying position.
The drug is well absorbed from gastrointestinal tract. Bioavailability is slightly more than 50%. Eating simultaneously with the drug does not affect bioavailability, but slows down the absorption of ramipril. The maximum concentration in blood plasma after a single dose of ramipril is achieved within 4 hours. Metabolized in the liver to form active and inactive metabolites. At the same time, the ramipril metabolite ramiprilat blocks the angiotensin-converting enzyme 6 times more actively than ramipril. Plasma protein binding of ramiprilat is lower than that of ramipril and is about 55% (the degree of plasma protein binding for ramipril is up to 75%). When taken regularly, a constant concentration of the active substance is maintained in the blood plasma. In patients suffering from heart failure and liver dysfunction, the concentration of ramipril in the blood is higher. The drug is excreted in urine and feces, both unchanged and in the form of metabolites.

Indications for use

Mode of application

Depending on the diagnosis, the following are usually prescribed:
For arterial hypertension, at the beginning of therapy, take 2.5 mg 1 time per day. After which the dose is increased depending on the patient’s condition, it is recommended to increase the dose every 2-3 weeks until the required therapeutic effect is achieved. The average maintenance dose is 2.5-5 mg once a day.
If a patient requires a dose of ramipril greater than 5 mg to maintain normal blood pressure, it is recommended that monotherapy with Hartil be supplemented with other antihypertensive drugs, since regular intake of more than 5 mg of ramipril increases the risk of side effects and is not advisable. The drug is usually combined with diuretics or calcium channel blockers.

For congestive heart failure, at the beginning of therapy, 1.25 mg of ramipril is usually prescribed once a day. The dose is then increased every 2-3 weeks depending on the individual needs of the patient.
For heart failure after acute heart attack myocardium, the drug is prescribed at an initial dose of 1.25-2.5 mg 2 times a day. Ramipril therapy is recommended to begin 2-9 days after acute myocardial infarction. If necessary, the dose of the drug is increased to 2.5-5 mg 2 times a day.

For diabetic and non-diabetic nephropathy, at the beginning of therapy, ramipril is prescribed at a dose of 1.25 mg 1 time per day, then if the therapeutic effect is insufficient, the dose of the drug is increased every 2-3 weeks.
It is not recommended to prescribe more than 5 mg of ramipril per day for the treatment of patients with diabetic and non-diabetic nephropathy.
For the prevention of stroke and myocardial infarction, an initial dose of 2.5 mg is prescribed once a day. If the drug Hartil is well tolerated, the dose is doubled after 1 week. 3 weeks after starting the dose, the dose is increased to 10 mg. The maintenance dose of the drug for the prevention of circulatory disorders is 10 mg once a day.

Maximum daily dose drug – 10 mg.
The maximum daily dose of the drug for patients suffering from renal failure is 5 mg.
The maximum daily dose for patients with severe liver dysfunction is 2.5 mg.
In patients taking diuretics, the need for ramipril is lower, so it is recommended to start therapy with Hartil at a dose of 1.25 mg.

Side effects

From the hematopoietic system: anemia, decrease in the amount of hemoglobin and hematocrit, hemolytic anemia, decrease in the number of red blood cells, inhibition of hematopoiesis in the bone marrow, thrombocytopenia, leukopenia, pancytopenia.

From the gastrointestinal tract: nausea, vomiting, stool disorders (both diarrhea and constipation are possible), abdominal pain, thirst, dry mouth, loss of appetite. Inflammatory diseases of the oral cavity (stomatitis), disorders of the pancreas (pancreatitis). Rarely, while taking the drug Hartil, the development of hepatitis, cholestatic jaundice, and liver dysfunction is possible.

From the outside genitourinary system: sexual dysfunction, impotence, decreased libido, worsening condition with renal failure, proteinuria, swelling of the limbs and face, oliguria.

From the outside nervous system: dizziness, headache, weakness, loss of consciousness. Fatigue, drowsiness, trembling limbs, muscle spasms, sudden mood swings, irritability, anxiety. When taking high doses, side effects such as sleep disturbances, depression, fear, and fainting are possible.

From the outside respiratory system: bronchospasm, nonproductive cough, shortness of breath, inflammatory diseases upper respiratory tract(rhinitis, sinusitis, laryngitis, bronchitis).

Allergic reactions: itchy skin, rash, urticaria, photosensitivity, conjunctivitis. Rarely, the development of Quincke's edema and allergic dermatitis is possible.

Other side effects: increased body temperature, increased sweating, baldness, muscle and joint pain.

When taking the drug, laboratory parameters may change, including the following:
Increased potassium levels in the blood;
Increased level of bilirubin in the blood;
Hypercreatininemia;
Increasing urea nitrogen levels;
Increased activity of liver enzymes;
Decreased sodium levels in the blood.

Contraindications

Pregnancy

Drug interactions

The hypotensive effect of ramipril is reduced when taken simultaneously with non-steroidal anti-inflammatory drugs, kitchen salt and drugs containing estrogens, due to the deterioration of the excretion of water and sodium from the body. NSAIDs inhibit the synthesis of prostaglandins in the kidneys, which also helps to reduce the Hartil effect. Patients forced to combine these drugs should be under constant control doctor
Drugs that increase the level of potassium in the blood (potassium-sparing diuretics, potassium preparations, potassium mixtures, salt substitutes), as well as milk and cyclosporine, contribute to the development of hyperkalemia in patients receiving Hartil therapy.

The use of myelosuppressive drugs simultaneously with ramipril significantly increases the patient's risk of developing neutropenia and agranulocytosis, and in some cases, death is possible.
Ramipril increases the concentration of lithium in the blood when taken simultaneously with lithium-containing drugs.
The drug promotes a stronger reduction in blood glucose levels when taken simultaneously with insulin and other hypoglycemic drugs.

Alopurinol, immunosuppressants, procainamide, cytostatics increase the risk of developing leukopenia in patients taking Hartil.
Ramipril, when taken simultaneously, enhances the inhibitory effect ethyl alcohol on the central nervous system.

Overdose

Pills light pink or orange-pink color, possibly with a marble surface, oval, flat, chamfered, with a score and engraving “R3” on one side, with marks on the side surfaces.

Excipients: sodium bicarbonate, lactose monohydrate, pregelatinized starch 1500, croscarmellose sodium, sodium stearyl fumarate, yellow iron oxide, red iron oxide.

Pills white or almost white, oval, flat, chamfered, with a score and engraving “R4” on one side, with marks on the side surfaces.

Excipients: sodium bicarbonate, lactose monohydrate, pregelatinized starch 1500, croscarmellose sodium, sodium stearyl fumarate.

7 pcs. - blisters (2) - cardboard packs.
7 pcs. - blisters (4) - cardboard packs.

Clinical and pharmacological group

pharmachologic effect

Antihypertensive drug, ACE inhibitor. As a result of suppression of ACE activity (regardless of plasma renin activity), a hypotensive effect develops (with the patient lying and standing) without a compensatory increase in heart rate.

Suppression of ACE activity reduces the level of angiotensin II, which in turn leads to a decrease in aldosterone secretion. As a result of a decrease in the concentration of angiotensin II, due to the elimination of negative feedback, there is an increase in plasma renin activity.

Ramipril acts on ACE, circulating in the blood and located in tissues, incl. vascular wall. Reduces peripheral vascular resistance (afterload), pressure in the pulmonary capillaries (preload); increases cardiac output and increases exercise tolerance.

With long-term use, ramipril promotes the reverse development of myocardial hypertrophy in patients with arterial hypertension.

Ramipril reduces the incidence of arrhythmia during myocardial reperfusion; improves blood supply to ischemic myocardium.

Ramipril prevents the breakdown of bradykinin and stimulates the formation of nitric oxide (NO) in the endothelium.

The antihypertensive effect begins 1-2 hours after taking the drug orally, the maximum effect develops within 3-6 hours and persists for 24 hours. With daily use, the antihypertensive effect increases within 3-4 weeks and persists with long-term treatment (1-2 of the year). Antihypertensive effectiveness does not depend on the gender, age and body weight of the patient.

In patients with acute myocardial infarction, ramipril limits the area of ​​necrosis and improves life prognosis; reduces mortality in the early and late stages of myocardial infarction, the incidence of repeated heart attacks; reduces the severity of manifestations of heart failure and slows its progression.

With long-term use (at least 6 months) it reduces the degree of pulmonary hypertension in patients with congenital and acquired heart defects.

Ramipril reduces portal vein pressure during portal hypertension; inhibits microalbuminuria (in the initial stages) and deterioration of renal function in patients with severe diabetic nephropathy. For non-diabetic nephropathy, accompanied by proteinuria (more than 3 g/day) and renal failure, it slows down further deterioration of renal function, reduces proteinuria, and reduces the risk of increasing creatinine levels or developing end-stage renal failure.

Pharmacokinetics

Ramipril has a multiphasic pharmacokinetic profile.

Suction

After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract. The degree of absorption is at least 50-60% of the administered dose. Cmax in blood plasma is achieved within 1 hour.

Distribution and metabolism

Almost completely metabolized (mainly in the liver) with the formation of active and inactive metabolites. Its active metabolite, ramiprilat, suppresses ACE activity approximately 6 times more strongly than ramipril. Cmax of ramiprilat in blood plasma is achieved after 2-4 hours. Among the known inactive metabolites are diketopiperazine ester, diketopiperazine acid, as well as glucuronides of ramipril and ramiprilat.

The binding of ramipril and ramiprilat to plasma proteins is approximately 73% and 56%, respectively.

When taken in usual doses 1 time/day, C ss of ramipril in blood plasma is achieved by the 4th day of taking the drug.

Removal

T 1/2 ramipril - 5.1 hours, T 1/2 ramiprilat 13-17 hours.

After oral administration, 60% of the dose is excreted in the urine (mainly in the form of metabolites) and about 40% in the feces. About 2% of the administered dose is excreted unchanged in the urine.

Pharmacokinetics in special clinical situations

Urinary excretion of ramipril, ramiprilat and inactive metabolites is reduced in renal failure (leading to increased concentrations of ramiprilat).

A decrease in enzymatic activity in the liver when its function is impaired leads to a slowdown in the conversion of ramipril to ramiprilat, which can cause an increase in the concentration of ramipril in the blood plasma.

Indications for use of the drug

- arterial hypertension;

— chronic heart failure;

— chronic heart failure after acute myocardial infarction in patients with stable hemodynamics;

- diabetic nephropathy and chronic diffuse kidney disease (non-diabetic nephropathy);

— in order to reduce the risk of developing myocardial infarction, stroke or coronary death in patients at high cardiovascular risk with coronary artery disease, including patients who have had myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting.

Dosage regimen

The tablets should be taken orally, swallowing them whole, without chewing, with plenty of liquid (about 1 glass). The tablets can be divided in half, breaking according to the risk. Tablets can be taken regardless of meal time. The dose is set individually, taking into account the therapeutic effect and tolerability.

At arterial hypertension The recommended initial dose is 2.5 mg 1 time / day (1 tablet of 2.5 mg daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. The standard maintenance dose is 2.5-5 mg/day (1 tablet 2.5 mg or 1 tablet 5 mg). The maximum daily dose is 10 mg.

At chronic heart failure The recommended initial dose is 1.25 mg 1 time/day (1/2 tablet of Hartil 2.5 mg daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If it is necessary to use the drug in a dose of more than 2.5 mg, this dose can be taken immediately or divided into 2 doses. The maximum daily dose is 10 mg.

For treatment after myocardial infarction It is recommended to start taking the drug 3-10 days after acute myocardial infarction. The recommended initial dose, depending on the patient’s condition and the time elapsed after acute myocardial infarction, is 2.5 mg 2 times/day (1 tablet 2.5 mg 2 times/day). Depending on the therapeutic effect, the initial dose can be doubled to 5 mg (2 tablets of 2.5 mg or 1 tablet of 5 mg) 2 times a day. The maximum daily dose is 10 mg. If the drug is intolerant, the dose should be reduced.

At non-diabetic or diabetic nephropathy The recommended initial dose is 1.25 mg (1/2 tablet 2.5 mg) 1 time/day daily. Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If it is necessary to take more than 2.5 mg of the drug, this dose can be taken immediately or divided into 2 doses. The recommended maximum daily dose is 5 mg.

With the aim of prevention of myocardial infarction, stroke or death from cardiovascular disorders The recommended initial dose is 2.5 mg 1 time / day. Depending on the tolerability of the drug, after 1 week of use the dose should be doubled compared to the initial one. This dose should be doubled again after 3 weeks of use. The recommended maintenance dose is 10 mg 1 time/day.

In elderly patients taking diuretics and/or with heart failure, as well as with impaired liver or kidney function, the dose should be adjusted by individual selection depending on the patient's response to treatment.

The initial dose is usually 1.25 mg 1 time / day (1/2 tablet 2.5 mg). The maximum daily dose is 5 mg.

If CK is not measured, it can be calculated from serum creatinine using the Cockcroft formula.

For men:

CC (ml/min) = (140 - age) x body weight (kg)/72 x serum creatinine (mg/dl)

For women: The calculation result should be multiplied by 0.85.

At liver dysfunction a reduced or increased effect of the drug Hartil ® may be observed equally often, therefore early stages Treatment of this category of patients requires careful medical supervision. The maximum daily dose in such cases is 2.5 mg.

U patients receiving diuretic therapy due to the risk of a significant decrease in blood pressure, you should consider temporarily discontinuing or at least reducing the dose of diuretics at least 2-3 days (or longer, depending on the duration of action of the diuretics) before starting Hartil. For patients previously treated with diuretics, the usual starting dose is 1.25 mg.

Side effect

From the cardiovascular system: decreased blood pressure, orthostatic hypotension, tachycardia; rarely - arrhythmia, increased circulatory disorders of organs caused by narrowing blood vessels. With an excessive decrease in blood pressure, mainly in patients with coronary artery disease and clinically significant narrowing of cerebral vessels, myocardial ischemia (angina pectoris or myocardial infarction) and cerebral ischemia (possibly with dynamic disturbances) may develop. cerebral circulation or stroke).

From the urinary system: development or intensification of renal failure, intensification of existing proteinuria, decrease in urine volume (at the beginning of taking the drug).

From the central nervous system and peripheral nervous system: dizziness, headache, weakness, drowsiness, paresthesia, nervous excitability, anxiety, tremor, muscle spasms, mood disorders; when used in high doses - insomnia, anxiety, depression, confusion, fainting.

From the senses: vestibular disorders, disturbances of taste (for example, metallic taste), smell, hearing and vision, tinnitus.

From the outside digestive system: nausea, vomiting, diarrhea or constipation, epigastric pain, dry mouth, thirst, decreased appetite, stomatitis, hypersensitivity or inflammation of the buccal mucosa, pancreatitis; rarely - hepatitis, cholestatic jaundice, impaired liver function with the development of acute liver failure.

From the respiratory system: dry cough, bronchospasm (in patients with increased excitability of the cough reflex), shortness of breath, rhinorrhea, rhinitis, sinusitis, bronchitis.

From the hematopoietic organs: anemia, decreased hemoglobin concentration and hematocrit, thrombocytopenia, leukocytopenia, neutropenia, agranulocytosis, pancytopenia, hemolytic anemia, decrease in the number of red blood cells, inhibition of bone marrow hematopoiesis.

Allergic reactions: skin rash, itching, urticaria, conjunctivitis, photosensitivity; rarely - angioedema of the face, extremities, lips, tongue, pharynx or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus (pemphigus), serositis, onycholysis , vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.

From the laboratory parameters: hypercreatininemia, increased levels of urea nitrogen, increased activity of liver transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia; extremely rarely - an increase in the titer of the antinuclear factor.

Others: decreased libido, alopecia, hyperthermia, sweating.

Contraindications to the use of the drug

- history of angioedema, incl. associated with previous therapy with ACE inhibitors;

- hemodynamically significant bilateral renal artery stenosis or stenosis of the artery of a single kidney;

- arterial hypotension or unstable hemodynamics;

- pregnancy;

- lactation period (breastfeeding);

- primary hyperaldosteronism;

- renal failure (KR

- hypersensitivity to the components of the drug.

WITH caution used for hemodynamically significant aortic or mitral stenosis (risk of excessive decrease in blood pressure with subsequent impairment of renal function), severe primary malignant arterial hypertension, severe lesions of the coronary and cerebral arteries (risk of decreased blood flow with excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias; terminal stage of CHF; decompensated cor pulmonale; for diseases requiring the use of corticosteroids and immunosuppressants (lack of clinical experience) - incl. at systemic diseases connective tissue, severe renal and/or liver failure, hyperkalemia, hyponatremia (including while taking diuretics and a diet with limited sodium intake); with initial or severe manifestations of fluid and electrolyte deficiency, conditions accompanied by a decrease in blood volume (including diarrhea, vomiting); diabetes mellitus; inhibition of bone marrow hematopoiesis; condition after kidney transplant; in elderly patients, in children and adolescents under 18 years of age (efficacy and safety have not been established).

There is only limited experience with the use of ramipril in patients on dialysis.

Use of the drug during pregnancy and lactation

Contraindicated for use during pregnancy and lactation.

The drug causes impaired development of the fetal kidneys, decreased blood pressure in the fetus and newborns, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnios, limb contracture, cranial deformation, pulmonary hypoplasia.

Use for liver dysfunction

At liver dysfunction a reduced or increased effect of the drug Hartil can be observed equally often, therefore, in the early stages of treatment of this category of patients, careful medical supervision is required. The maximum daily dose in such cases should not exceed 2.5 mg.

Use for renal impairment

Patients with renal failure correction of the dosage regimen is required. At moderate renal dysfunction (creatinine clearance from 20 to 50 ml/min per 1.73 m2 of body surface) the initial dose is usually 1.25 mg 1 time / day (1 tablet 1.25 mg / day). The maximum daily dose should not exceed 5 mg.

special instructions

During treatment with Hartil ®, regular medical monitoring is required.

After taking the first dose, as well as when increasing the dose of the diuretic and/or Hartil, patients should be under medical supervision for 8 hours to avoid the development of an uncontrolled hypotensive reaction; Repeated blood pressure measurements are recommended.

If possible, dehydration, hypovolemia, and a decrease in the number of red blood cells should be corrected before starting the drug. If these disorders are severe, ramipril should not be started or continued until measures are taken to prevent an excessive fall in blood pressure and renal dysfunction.

Careful observation is required for patients with lesions renal vessels(for example, clinically insignificant stenosis of the renal artery or hemodynamically significant stenosis of the artery of a single kidney), impaired renal function, with a marked decrease in blood pressure, mainly in patients with heart failure, as well as after kidney transplantation.

Renal dysfunction can be identified by increased levels serum urea and creatinine, especially if the patient is taking diuretics.

Due to a decrease in the synthesis of angiotensin II and the secretion of aldosterone in the blood serum, a decrease in sodium levels and an increase in potassium levels is possible. Hyperkalemia occurs more often with impaired renal function (for example, with diabetic nephropathy) or when taken concomitantly with potassium-sparing diuretics.

In case of an excessive decrease in blood pressure, the patient should be laid down and his legs elevated; Fluids and other measures may also be required.

Blood changes are more likely in patients with impaired renal function and concomitant connective tissue disease (for example, SLE and scleroderma), as well as in cases of use of other drugs that affect the hematopoietic and immune system.

Serum sodium levels should also be regularly monitored in patients taking diuretics concomitantly with Hartil ®. The white blood cell count should also be checked regularly to avoid the development of leukopenia. Monitoring should be more frequent at the beginning of therapy and in patients belonging to any risk group.

Experience with the use of ramipril in patients with severe renal failure (SC

There are reports of life-threatening anaphylactoid reactions, sometimes progressing to shock, in patients on hemodialysis using membranes with high hydraulic permeability (for example, polyacrylonitrile) with simultaneous administration of ACE inhibitors. Anaphylactoid reactions have also been reported in patients undergoing LDL apheresis with dextran sulfate uptake.

During desensitizing therapy carried out to reduce allergic reaction to insect bites (for example, bees and wasps), while taking ACE inhibitors, a severe, life-threatening anaphylactoid reaction (drop in blood pressure, respiratory failure, vomiting, skin reactions) may occur. Therefore, ACE inhibitors should not be given to patients receiving desensitization therapy.

In case of lactase deficiency, galactosemia or glucose/lactose malabsorption syndrome, it should be noted that each tablet of Hartil ® contains the following amounts of lactose: 1.25 mg tablets contain 79.5 mg of lactose, 2.5 mg tablets - 158.8 mg, 5 mg tablets - 96.47 mg , 10 mg tablets – 193.2 mg.

Use in pediatrics

Experience with the use of ramipril in children with severe renal failure (SC

Impact on the ability to drive vehicles and operate machinery

At the beginning of treatment, a decrease in blood pressure may affect the ability to concentrate. In this case, patients are advised to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions. In the future, the degree of restriction is determined for each patient individually.

Overdose

Symptoms: marked decrease in blood pressure, bradycardia, shock, water and electrolyte imbalance, acute renal failure.

Treatment: in case of mild overdose - gastric lavage, administration of adsorbents and sodium sulfate (preferably within 30 minutes after administration).

In case of acute overdose: control and support of vital functions in ICU conditions; when blood pressure decreases, administer catecholamines and angiotensin II. The patient should be placed on his back with his legs elevated, and additional amounts of fluid and sodium should be administered.

It is not known whether forced diuresis, hemofiltration and correction of urine pH accelerate the elimination of ramipril. This should be taken into account when considering hemodialysis and hemofiltration.

Drug interactions

When Hartil is used simultaneously with allopurinol, corticosteroids, procainamide, cytostatics and other substances that cause changes in the blood, the risk of disorders of the hematopoietic system increases.

When Hartil is used simultaneously with hypoglycemic drugs (insulin or sulfonylurea derivatives), an excessive decrease in blood sugar levels is possible. This phenomenon may be due to the fact that ACE inhibitors may increase tissue sensitivity to insulin.

When used simultaneously with other antihypertensive drugs (including diuretics) or other drugs that have a hypotensive effect (for example, nitrates, tricyclic antidepressants and anesthetics): the antihypertensive effect may be enhanced.

When used simultaneously with lithium preparations, an increase in the concentration of lithium in the blood serum is observed, which leads to an increased risk of cardio- and nephrotoxicity.

NSAIDs and sodium salts reduce the effectiveness of ACE inhibitors.

Ramipril may enhance the effects of ethanol.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature below 25°C. Shelf life - 2 years.

They are prescribed other medications to treat heart disease.

Hartil is a drug that acts not only on blood pressure. It helps relieve stress from the entire cardiovascular system.

If the muscle of the organ is hypertrophied, the medication restores its previous volume. Regular use of Hartil reduces the number of arrhythmias, improves breathing and heart nutrition.

Main active substance Hartila is ramipril, part of the group of drugs such as Monopril and. The main purpose of the medication is to lower blood pressure.

• heart failure;
• diabetic nephropathy.

The drug is prescribed to reduce the risk of complications arising from various cardiovascular diseases.

Release form, dosage

The medicine is available in one form - tablets. When taking them, it is better to drink them with plenty of water without chewing. If the dosage of the medicine prescribed by the doctor is less than indicated on the package, the tablets can be divided into two and four parts. The therapeutic effect will not become less pronounced.

Blood pressure tablets Hartil

The doctor selects the dosage individually for each patient. If there is a need to take a large daily dose, it can be taken in two doses.

Older patients, patients with severe impairment of liver and kidney function, taking the drug, should be regularly monitored by a doctor in order, if necessary, to adjust therapy or discontinue the drug completely.

How to use?

Hartil is indicated for oral administration. The initial dose is 2.5 mg per day.

For the next three weeks, if necessary, it can be doubled. The maximum dosage of the drug should not exceed 10 mg. The instructions for use accompanying the Hartil tablets do not indicate at what pressure exactly to use the drug.

For heart failure, 1.25 mg of the drug per day is initially prescribed with a gradual doubling of its amount. Maximum – 10 mg per day.

Contraindications

Like any medicine, Hartil has a number of contraindications for use:

• narrowing of the renal arteries;
• severe renal failure;
• individual intolerance to the components of the medication;
• a tendency to angioedema, which manifested itself when taking such medications.

Side effects

One of the most common side effects from Hartil treatment is orthostatic hypotension. It is characterized by a persistent decrease in blood pressure.

In some cases, taking the medicine may be accompanied by:

1. arrhythmia, circulatory disorders of various organs, myocardial and cerebral ischemia;
2. renal failure, decreased libido, decreased urine volume;
3. headaches, drowsiness, feeling of weakness, tremors of the limbs. The patient may experience nervous system excitability, sudden mood swings, and anxiety;
4. disorders of the organs of smell, vision, and hearing. The patient may lose his sense of taste.
5. loss of appetite, nausea, vomiting, constipation, or loose stools. In patients with pancreatitis, their general condition may worsen;
6. respiratory disorders: sinusitis, bronchitis, bronchospasm, dry cough;
7. various allergic reactions on the skin, urticaria, itching;
8. joint and muscle pain, swelling.

A patient taking Hartil may experience a drop in hemoglobin levels in the blood, conjunctivitis and thrombocytopenia, neutropenia, convulsions, increased sweating, hyperkalemia. The level of urea nitrogen sometimes increases in the patient's urine.

Hartil has a negative effect on fetal development expectant mother. He has problems with kidney activity, his blood pressure decreases, lung hypoplasia develops, and his skull becomes deformed.

A sharp decrease in blood pressure can lead to myocardial infarction and stroke.

Danger of overdose

An overdose of Hartil is extremely dangerous for humans.

A decrease in blood pressure can cause the heart rate to slow down, state of shock, the patient develops a water-salt imbalance, and the kidneys begin to work poorly.

When these symptoms occur, the patient is placed with his legs elevated and drugs that increase blood pressure are administered.

Interaction with other drugs

The combination of non-steroidal anti-inflammatory drugs and Hartil, as well as drugs containing estrogen, reduces this effect. If such interaction is necessary, the doctor must exercise strict control over the patient's condition.

Taking medications that increase the level of potassium in the blood, cyclosporine and milk together with Hartil can cause hyperkalemia. Hartil increases the amount of lithium when used together with lithium-containing drugs, reduces sugar levels when combined with hypoglycemic agents.

Alopurinol and immunosuppressants in combination with Hartil increase the likelihood of leukopenia. Alcoholic drinks increase its inhibitory effect on the central nervous system.

Analogues of the drug

Hartil has the following analogues:

• Tritace;
• Ramipril;
• Meryl;
• Pyramid;
• Ramizes;
• Ramimed;
• Cardipril;
• Topril;
• Ramigexal.

Are different similar drugs from each other only at cost.

This instruction is valid from 05/06/2014

Registration number:

Tradename:

International nonproprietary name:

Dosage form:

Compound

Composition per 1 tablet:

Active ingredient: ramipril 2.5/5/10 mg.

Excipients: sodium bicarbonate 2.5/5/10 mg, lactose monohydrate 155/94/193.2 mg, pregelatinized starch 1500 30/19.5/39 mg, croscarmellose sodium 4/2.6/5.2 mg, sodium stearyl fumarate 2/1.3/2.6 mg, Pigment Blend PB-24877 4/-/- mg, Pigment Blend PB-22960 -/2.6/- mg.

Pigment Blend PB-24877: lactose monohydrate 3.8 mg, yellow iron oxide 0.2 mg.

Pigment Blend PB-22960: lactose monohydrate 2.47 mg, red iron oxide 0.09 mg, yellow iron oxide 0.04 mg.

Description:

2.5 mg tablets: Yellow or light yellow, possibly with a marbled surface, flat oval tablets with a bevel, with a score and engraving R2 on one side of the tablet, and scores on the side surfaces.

5 mg tablets: Light pink or orange-pink, possibly with a marbled surface, flat oval tablets with a chamfer, with a score and engraving R3 on one side of the tablet, and marks on the side surfaces.

10 mg tablets: White or almost white flat oval tablets with a chamfer, with a score and engraving R4 on one side of the tablet, and marks on the side surfaces.

Pharmacotherapeutic group:

ATX Code S09AA05

Pharmacological properties

Pharmacodynamics

Ramipril inhibits the angiotensin-converting enzyme (ACE), as a result of which (regardless of plasma renin activity) a hypotensive effect develops (in the patient's "lying and standing" position without a compensatory increase in heart rate (HR).
Suppression of ACE activity reduces the level of angiotensin II, which in turn leads to a decrease in aldosterone secretion. As a result of a decrease in the concentration of angiotensin II, due to the elimination of negative feedback, an increase in plasma renin activity occurs. Ramipril acts on ACE, circulating in the blood and located in tissues, incl. vascular wall. Reduces total peripheral vascular resistance (TPVR) or afterload, pressure in the pulmonary capillaries (preload); increases cardiac output and increases exercise tolerance.
With long-term use, ramipril promotes the reverse development of myocardial hypertrophy in patients with arterial hypertension.
Ramipril reduces the frequency of arrhythmias during myocardial reperfusion and improves blood supply to ischemic myocardium.
Ramipril prevents the breakdown of bradykinin and stimulates the formation of nitric oxide (NO) in the endothelium.
The antihypertensive effect begins 1-2 hours after taking the drug orally, the maximum effect develops within 3-6 hours and lasts for 24 hours.
With daily use, the antihypertensive effect increases within 3-4 weeks and persists with long-term treatment (1-2 years). Antihypertensive effectiveness does not depend on the gender, age and body weight of the patient. In patients with acute myocardial infarction, ramipril limits the area of ​​necrosis and improves life prognosis; reduces mortality in the early and late periods of myocardial infarction, the incidence of recurrent infarctions; reduces the severity of manifestations of heart failure and slows its progression. With long-term use (at least 6 months) it reduces the degree of pulmonary hypertension in patients with congenital and acquired heart defects.
Ramipril lowers portal vein pressure in portal hypertension; inhibits microalbuminuria (in the initial stages) and deterioration of renal function in patients with severe diabetic nephropathy. For non-diabetic nephropathy, accompanied by proteinuria (over 3 g/day) and renal failure, it slows down further deterioration of renal function, reduces proteinuria, the risk of increased creatinine levels or the development of end-stage renal failure.

Pharmacokinetics

After oral administration, it is quickly absorbed from the gastrointestinal tract. The maximum concentration in blood plasma is achieved within 1 hour. The degree of absorption is at least 50-60% of the administered dose. Almost completely metabolized (mainly in the liver) with the formation of active and inactive metabolites. Its active metabolite, ramiprilat, suppresses ACE activity approximately 6 times more strongly than ramipril. The maximum concentration of ramiprilat in blood plasma is achieved after 2-4 hours. Known inactive metabolites include diketopiperazine ester, diketopiperazine acid, and the glucuronides of ramipril and ramiprilat. The binding of ramipril and ramiprilat to plasma proteins is approximately 73% and 56%, respectively. When taking usual doses once a day, the equilibrium concentration of the drug in the blood plasma is achieved by the 4th day of taking the drug.
The half-life (T 1/2) for ramipril is 5.1 hours, T 1/2 for ramiprilat is 13-17 hours. Ramipril has a multiphasic pharmacokinetic profile. After oral administration, 60% of the dose is excreted in the urine (mainly in the form of metabolites), and approximately 40% in the feces. Approximately 2% of the administered dose is excreted unchanged in the urine.
Urinary excretion of ramipril, ramiprilat and inactive metabolites is reduced in renal failure (which increases ramiprilat concentrations).
A decrease in enzymatic activity in the liver when its function is impaired leads to a slowdown in the conversion of ramipril to ramiprilat, which can cause an increase in ramipril levels.

Indications for use:

• Arterial hypertension. Chronic heart failure.
• Chronic heart failure after acute myocardial infarction in patients with stable hemodynamics.
• Diabetic nephropathy and chronic diffuse kidney disease (non-diabetic nephropathy).
• Reducing the risk of myocardial infarction, stroke or coronary death in patients with coronary disease heart, including patients who have suffered myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting.

Contraindications:

• Hypersensitivity to ramipril or any other component of the drug.
• History of angioedema, including that associated with previous therapy with ACE inhibitors.
• Hemodynamically significant bilateral renal artery stenosis and stenosis of the artery of a single kidney.
• Arterial hypotension or unstable hemodynamics.
• Pregnancy and lactation period.
• Primary hyperaldosteronism.
• Renal failure (creatinine clearance below 20 ml/min)

Carefully
Hemodynamically significant aortic or mitral stenosis(risk of excessive reduction in blood pressure with subsequent renal dysfunction);
severe primary malignant arterial hypertension;
severe damage to the coronary and cerebral arteries (danger of decreased blood flow due to excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, terminal stage CHF, decompensated “pulmonary” heart, diseases requiring the use of glucocorticosteroids and immunosuppressants (lack of clinical experience) - incl. with systemic connective tissue diseases, severe renal and/or liver failure, hyperkalemia, hyponatremia (including against the background of diuretics and a diet with limited Na+ intake), initial or severe manifestations of fluid and electrolyte deficiency;
conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting),
diabetes,
inhibition of bone marrow hematopoiesis,
condition after kidney transplant,
elderly age,
age under 18 years (efficacy and safety have not been established).
There is only limited experience with the use of ramipril in patients on dialysis.

Directions for use and dosage:

The dosage should be set for each patient individually, taking into account the therapeutic effect and tolerability.
The tablets can be divided in half, breaking according to the risk.

Arterial hypertension:
The recommended starting dose is 2.5 mg once a day (1 Hartil 2.5 mg tablet daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. The usual maintenance dose is 2.5-5 mg per day (1 Hartil 2.5 mg tablet or 1 5 mg tablet).

Chronic heart failure:
The recommended starting dose is 1.25 mg once a day (1/2 tablet of Hartil 2.5 mg daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If it is necessary to take more than 2.5 mg of the drug, this dose can be taken immediately or divided into 2 doses.
The maximum daily dose should not exceed 10 mg.

Treatment after myocardial infarction:
It is recommended to start taking the drug 3-10 days after acute myocardial infarction. The recommended initial dose, depending on the patient's condition and the time elapsed after acute myocardial infarction, is 2.5 mg 2 times a day (1 tablet of Hartil 2.5 mg 2 times a day). Depending on the therapeutic effect, the initial dose can be doubled to 5 mg (2 tablets of Hartil 2.5 mg or 1 tablet of Hartil 5 mg) 2 times a day.
The maximum daily dose should not exceed 10 mg.
If the drug is intolerant, the dose should be reduced.

Non-diabetic or diabetic nephropathy:
The recommended initial dose is 1.25 mg 1 time per day (1/2 tablet of Hartil 2.5 mg daily). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks. If it is necessary to take more than 2.5 mg of the drug, this dose can be taken at once or divided into two doses.
The recommended maximum daily dose is 5 mg.

Prevention of myocardial infarction, stroke, or cardiovascular death:
The recommended starting dose is 2.5 mg once daily. Depending on the tolerability of the drug, after one week of use the dose should be doubled compared to the initial one. This dose should be doubled again after 3 weeks of use.
The recommended maintenance dose is 10 mg once daily.

Special patient groups

Elderly patients: the use of ramipril in elderly patients taking diuretics and/or with heart failure, as well as impaired liver or kidney function, requires special attention. The dosage should be established by individual selection of doses depending on the response to the drug.

Patients with renal failure: for moderate renal impairment (creatinine clearance from 20 to 50 ml/min per 1.73 m2 of body surface), the initial dose is usually 1.25 mg 1 time per day (1/2 Hartil 2.5 tablet per day).
The maximum daily dose should not exceed 5 mg. If creatinine clearance is not measured, it can be calculated from serum creatinine using Cockroft's equation:
For men: creatinine clearance (ml/min) = [body weight in kg x (140 - age) / 72 × serum creatinine (mg/dl)].
For women: multiply the result of the calculation using the above equation by 0.85.

Liver dysfunction: in case of impaired liver function, a reduced or increased effect on taking the drug Hartil can be equally often observed, therefore, in the early stages of treatment, patients with impaired liver function require careful medical supervision. The maximum daily dose in such cases should not exceed 2.5 mg.

In patients receiving diuretic therapy, due to the risk of a significant decrease in blood pressure (BP), the possibility of temporarily discontinuing or at least reducing the dose of diuretics should be considered, at least 2-3 days (or longer, depending on the duration of action of the diuretics) before starting to take the drug Hartil.
For patients previously treated with diuretics, the usual starting dose is 1.25 mg.

Side effect

Overdose

Symptoms: marked decrease in blood pressure, bradycardia, shock, water and electrolyte imbalance, acute renal failure.
Treatment: in case of mild overdose - gastric lavage, administration of adsorbents and sodium sulfate (preferably within 30 minutes after administration).
In case of acute overdose: control and support of vital functions in the intensive care unit; when blood pressure decreases, administer catecholamines and angiotensin II. Place the patient on his back with his legs elevated, and administer additional fluids and sodium.
It is not known whether forced diuresis, hemofiltration and correction of urine pH accelerate the elimination of ramipril. This should be taken into account when considering the possibility of hemodialysis and hemofiltration (see also section "Contraindications").

Interaction with other drugs

Allopurinol, corticosteroids, procainamide, cytostatics and other substances, causing change blood:
increased risk of disorders of the hematopoietic system.

Antidiabetic drugs (insulin or sulfourea derivatives):
excessive decrease in blood sugar levels. This phenomenon may be due to the fact that ACE inhibitors may increase tissue sensitivity to insulin.

Antihypertensive drugs (eg, diuretics) or other drugs that have antihypertensive effects (eg, nitrates, tricyclic antidepressants and anesthetics):
the antihypertensive effect may be enhanced.

Potassium salts and potassium-sparing diuretics, heparin:
Concomitant use with ramipril is not recommended due to the risk of hyperkalemia.

Lithium salts:
Elevated serum lithium levels increase the risk of cardio- and nephrotoxicity.

Non-steroidal anti-inflammatory drugs and salts (sodium):
decreased effectiveness of ACE inhibitors.

High hydraulic permeability membranes and dextran sulfate:

For desensitization therapy used to reduce allergic reactions to insect stings (eg, bees and wasps) while taking ACE inhibitors:
A severe, life-threatening anaphylactoid reaction may occur (drop in blood pressure, difficulty breathing, vomiting, skin reactions). Therefore, ACE inhibitors should not be given to patients receiving desensitization therapy.

Alcohol: Ramipril may enhance the effects of alcohol.

special instructions

During treatment with Hartil, regular medical monitoring is required. After taking the first dose, as well as when increasing the dosage of the diuretic and/or Hartil, patients should be under medical supervision for 8 hours to avoid the development of an uncontrolled hypotensive reaction; multiple blood pressure measurements are recommended.

If possible, dehydration, hypovolemia, and a decrease in the number of red blood cells should be corrected before starting the drug. If these disorders are severe, ramipril should not be started or continued until measures are taken to prevent an excessive fall in blood pressure and renal dysfunction.

Careful monitoring is required for patients with damage to the renal vessels (for example, clinically insignificant stenosis of the renal artery or hemodynamically significant stenosis of the artery of a single kidney), impaired renal function, with a marked decrease in blood pressure, mainly in patients with heart failure, and also after kidney transplantation.

Impaired renal function can be identified by elevated serum urea and creatinine levels, especially if the patient is taking diuretics.

Due to decreased angiotensin II synthesis and aldosterone secretion, serum sodium levels may decrease and potassium levels may increase. Hyperkalemia occurs more often with impaired renal function (for example, with diabetic nephropathy) or when taken concomitantly with potassium-sparing diuretics.

If there is an excessive decrease in blood pressure, the patient should be placed and elevated lower limbs; Fluids and other measures may also be required.

Blood changes are more likely in patients with impaired renal function and concomitant connective tissue disease (for example, systemic lupus erythematosus and scleroderma), as well as in the case of the use of other drugs that affect the hematopoietic and immune systems. Serum sodium levels should also be checked regularly in patients taking diuretics concomitantly with Hartil. The white blood cell count should also be checked regularly to avoid the development of leukopenia. Monitoring should be more frequent at the beginning of therapy and in patients belonging to any risk group.

In case of lactase deficiency, galactosemia or glucose/lactose malabsorption syndrome, it should be noted that each Hartil tablet contains the following amounts of lactose: 1.25 mg tablets contain 79.5 mg of lactose, 2.5 mg tablets - 158.8 mg, 5 mg tablets - 96.47 mg, 10 mg tablets - 193.2 mg.

Membranes with high hydraulic permeability and dextran sulfate:
There are reports of life-threatening anaphylactoid reactions, sometimes progressing to shock, in patients on hemodialysis using membranes with high hydraulic permeability (for example, polyacrylonitrile) with simultaneous administration of ACE inhibitors. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate.
Experience with the use of ramipril in children, patients with severe renal failure (creatinine clearance less than 20 ml/min/1.73 m 2 body surface) and in patients undergoing dialysis is limited.

Impact on driving

At the beginning of treatment, a decrease in blood pressure may affect the ability to concentrate. In this case, patients are advised to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions. In the future, the degree of restriction is determined for each patient individually.

Release form:

Tablets of 2.5, 5 and 10 mg. 7 tablets in a blister.
2 or 4 blisters (14 or 28 tablets each) in a cardboard box along with instructions for use.

Storage conditions

Best before date

Conditions for dispensing from pharmacies

Manufacturer (holder registration certificate)

JSC Pharmaceutical Plant EGIS 1106 Budapest, st. Keresturi, 30-38 HUNGARY

Production:

JSC Pharmaceutical Plant EGIS, Hungary, 1165 Budapest, Bokenyfoldi ut 118-120 or

Actavis Ltd, Malta, BLB 016, Bulebel Industrial Estate, Zejtun ZTN3000

Consumer complaints should be sent to the address of the Representative Office of ZAO Pharmaceutical Plant EGIS (Hungary), Moscow 121108, Moscow, st. Ivana Franko, 8,

COMPOSITION AND FORM OF RELEASE:

table 1.25 mg, no. 28

Ramipril 1.25 mg

No. UA/3196/01/01 from 05/25/2005 to 05/25/2010

table 2.5 mg, No. 28 34.64 UAH.

Ramipril 2.5 mg

Other ingredients: sodium bicarbonate, lactose monohydrate, sodium salt croscarmellose, pregelatinized starch, sodium stearyl fumarate, pigment mixture PB24877 (lactose monohydrate, yellow iron oxide).

No. UA/3196/01/02 from 05/25/2005 to 05/25/2010

table 5 mg, No. 28 44.5 UAH.

Ramipril 5 mg

Other ingredients: sodium bicarbonate, lactose monohydrate, croscarmellose sodium salt, pregelatinized starch, sodium stearyl fumarate, pigment mixture PB22960 (lactose monohydrate, iron oxide red and yellow).

No. UA/3196/01/03 from 05/25/2005 to 05/25/2010

table 10 mg, No. 28 57.45 UAH.

Ramipril 10 mg

Other ingredients: sodium bicarbonate, lactose monohydrate, croscarmellose sodium salt, pregelatinized starch, sodium stearyl fumarate.

No. UA/3196/01/04 from 05.25.2005 to 05.25.2010

HARTIL ® -H

table 2.5 mg + 12.5 mg, No. 28

Ramipril 2.5 mg

Hydrochlorothiazide 12.5 mg

No. UA/6486/01/01 from 05/25/2007 to 05/25/2012

table 5 mg + 25 mg, No. 28

Ramipril 5 mg

Hydrochlorothiazide 25 mg

Other ingredients: lactose monohydrate, hypromellose, crospovidone, microcrystalline cellulose, sodium stearyl fumarate.

No. UA/6486/01/02 from 05/25/2007 to 05/25/2012

PHARMACOLOGICAL PROPERTIES: Ramiprilat, the active metabolite of ramipril, inhibits the enzyme dipeptidyl-carboxypeptidase I (synonyms: ACE, kininase II), which catalyzes the conversion of angiotensin I in tissues into the active vasoconstrictor angiotensin II, as well as the breakdown of the active vasodilator bradykinin. A decrease in the amount of angiotensin II and inhibition of the breakdown of bradykinin causes vasodilatation. Inhibition of ACE activity is accompanied by an increase in renin activity in the blood plasma and reduces the level of angiotensin II and aldosterone.

Increasing the activity of bradykinin enhances the cardioprotective effect of ramipril and protects the vascular endothelium.

The use of ramipril leads to a marked decrease in peripheral arterial resistance. Usually there are no significant changes in the rate of renal plasma flow and glomerular filtration.

Ramipril reduces blood pressure without a compensatory increase in heart rate. The antihypertensive effect is achieved 1–2 hours after taking a single dose. The maximum effect is achieved 3–6 hours after administration. As a rule, the antihypertensive effect after a single use lasts at least 24 hours. With long-term treatment with ramipril, the maximum antihypertensive effect is usually achieved after 2–4 weeks and can be maintained for 2 years. Abrupt cessation of ramipril does not cause a rapid and excessive increase in blood pressure.

Ramipril is rapidly absorbed in the gastrointestinal tract (at least 50–60% of the administered dose), the maximum concentration in the blood plasma is achieved within 1 hour. Ramipril is almost completely metabolized (mainly in the liver) with the formation of active and inactive metabolites. Its active metabolite ramiprilat is 6 times more active than ramipril. Its maximum concentration in the blood plasma is achieved after 2–4 hours. Among the known inactive metabolites are diketopiperazine ester, diketopiperazine acid, as well as the glucuronides of ramipril and ramiprilat. The binding of ramipril and ramiprilat to blood proteins is about 73 and 56%, respectively. When using normal doses (once a day), the equilibrium concentration in the blood plasma is achieved on the 4th day of drug use. After administration, 60% of the dose is excreted in the urine (mainly in the form of metabolites), and approximately 40% is excreted in the feces. Almost 2% of the administered dose is excreted unchanged in the urine.

The combination of ramipril and the diuretic hydrochlorothiazide has an antihypertensive and diuretic effect. The antihypertensive effects of both substances complement each other, and the hypokalemic effect of hydrochlorothiazide is reduced by ramipril.

Hydrochlorothiazide is a thiazide diuretic. It inhibits the reabsorption of sodium and chloride in the distal tubules. Increased renal excretion of these ions is accompanied by increased urine formation (due to osmotic binding of water). Excretion of potassium and magnesium increases, and uric acid- decreases. IN high dose the drug causes increased bicarbonate excretion, and long-term use reduces calcium excretion.

Possible mechanisms of antihypertensive action include changes in sodium balance, decreases in extracellular water and plasma volume, changes in renal vascular resistance, or decreased responses to norepinephrine and angiotensin II.

Excretion of electrolytes and water begins approximately 2 hours after administration, the maximum effect is achieved after 3–6 hours and lasts for 6–12 hours. The antihypertensive effect is achieved after 3–4 days of treatment and lasts for 1 week after the end of the drug.

With long-term treatment, a decrease in blood pressure is achieved by using the drug at a lower dose than necessary for the diuretic effect. The decrease in blood pressure is accompanied by a slight increase in glomerular filtration rate, renal vascular resistance and renin activity in the blood plasma.

Thiazide diuretics may interfere with breast milk secretion.

After oral administration 70% of hydrochlorothiazide is absorbed in the duodenum and upper colon. The maximum concentration in the blood plasma is reached after 1.5–4 hours. It binds to plasma proteins by approximately 40%. 95% of hydrochlorothiazide is excreted by the kidneys by tubular excretion. The half-life is 5–15 hours. Typically, the therapeutic effect of hydrochlorothiazide is achieved 2 hours after administration, the maximum after 2–4 hours.

The effect of this combination of the drug Hartil-N usually lasts up to 24 hours. An optimal reduction in blood pressure is observed after 3–4 weeks of treatment.

INDICATIONS:Hartil.

– congestive heart failure (as part of combination therapy);

– heart failure after acute myocardial infarction in patients with stable hemodynamics;

– severe diabetic or non-diabetic nephropathy, as well as its initial stages;

– prevention of circulatory disorders of the myocardium and brain - myocardial infarction, stroke or the threat of death from cardiovascular disorders.

Hartil-N.

APPLICATION: The tablets should be swallowed whole without chewing, with plenty of liquid, regardless of meals.

Hartil:

AG. The recommended starting dose is 2.5 mg once a day (1 tablet 2.5 mg). Depending on the patient’s condition, the daily dose can be doubled every 2–3 weeks. The usual maintenance dose is 2.5–5 mg/day (1 tablet 2.5 mg or 5 mg). The maximum daily dose is 10 mg.

If it is necessary to use a dose above 5 mg, instead of further increasing the dose of Hartil, consider combining it with other antihypertensive agents, such as diuretics or calcium channel blockers.

Congestive heart failure. The initial recommended dose is 1.25 mg 1 time per day (1 tablet 1.25 mg). Depending on the therapeutic effect, the daily dose can be increased, doubling it every 2-3 weeks. The maximum daily dose should not exceed 10 mg.

Heart failure after acute myocardial infarction. It is recommended to start using the drug on days 2–9 after myocardial infarction. The initial dose is 1.25–2.5 mg 2 times a day (1 tablet 1.25 or 2.5 mg). Depending on the therapeutic effect, the initial dose can be doubled to 2.5–5 mg (1 tablet of 2.5 or 5 mg) 2 times a day. The maximum daily dose should not exceed 10 mg.

Severe non-diabetic or diabetic nephropathy, as well as its initial stages. The recommended starting dose is 1.25 mg 1 time per day (1 tablet 1.25 mg). Depending on the therapeutic effect, the dose can be increased by doubling the daily dose every 2-3 weeks.

Prevention of circulatory disorders of the myocardium and brain - myocardial infarction, stroke or threat of death due to cardiovascular disorders.Initial dose - 2.5 mg 1 time per day (1 tablet 2.5 mg). Depending on the tolerability of the drug, after 1 week of use the daily dose should be doubled (1 tablet 5 mg). This dose can be doubled again after 3 weeks of use. The recommended maintenance dose is 10 mg 1 time per day (1 tablet of 10 mg or 2 tablets of 5 mg).

Elderly patients. The use of this drug in elderly patients taking diuretics and/or with signs of heart failure, as well as impaired liver or kidney function, requires special monitoring. Dosage should be set individually, depending on the response to the drug.

Patients with renal failure. With a moderate decrease in renal function (creatinine clearance 20–50 ml/min per 1.73 m2 of body surface), the initial dose is 1.25 mg 1 time per day (1 tablet 1.25 mg). The maximum daily dose should not exceed 5 mg. If it is not possible to determine creatinine clearance in a laboratory, it can be calculated from the serum creatinine level using the Cockroft equation:

For men. Creatinine clearance (ml/min) = [body weight in kg ´ (140 – age)/72 ´ serum creatinine (mg/dl)].

For women. Multiply the calculation result by 0.85.

Patients with impaired liver function. At the beginning of treatment with Hartil, patients with impaired liver function require careful medical supervision. The maximum daily dose in such cases should not exceed 2.5 mg.

In patients receiving diuretic therapy, the possibility of temporarily discontinuing or reducing the dose of diuretics should be considered for at least 2-3 days (or more, depending on the duration of action of the diuretics) before starting to use Hartil. For patients recently treated with diuretics, the usual starting dose is 1.25 mg (1 tablet 1.25 mg).

In patients with fluid and electrolyte imbalance, with severe hypertension and in cases where a significant decrease in blood pressure cannot be allowed (for example, with coronary or cerebral arteries), preference should be given to low initial doses, for example 1.25 mg/day.

Hartil-N.

The combined drug Hartil-H should be used once daily in the morning with a sufficient amount of liquid, regardless of meals.

Adults

Assign combination drug Hartil-H is recommended only after individual selection of doses of each component. The dose can be increased at intervals of at least 3 weeks. The usual starting dose is 2.5 mg ramipril and 12.5 mg hydrochlorothiazide. The usual maintenance dose is 2.5 mg ramipril and 12.5 mg hydrochlorothiazide or 5 mg ramipril and 25 mg hydrochlorothiazide. The maximum daily dose is 5 mg ramipril and 25 mg hydrochlorothiazide. Only in exceptional cases maximum dose can be increased to 10 mg ramipril and 50 mg hydrochlorothiazide.

Elderly patients and patients with impaired renal function

For elderly patients and patients with a creatinine clearance of 30–60 ml/min, individual doses of each component (ramipril and hydrochlorothiazide) must be carefully selected when switching to taking Hartil-H.

The dose of Hartil-H should be as low as possible. The maximum recommended daily dose is 5 mg ramipril and 25 mg hydrochlorothiazide.

Liver dysfunction

Before switching to Hartil-H, patients with mild or moderate liver dysfunction should adjust the dose of ramipril.

Patients with severe liver dysfunction and/or cholestasis should not take the drug Hartil‑H.

Combining fixed doses of the two ingredients of Hartil-H is indicated for those patients in whom the use of ramipril or hydrochlorothiazide alone does not reduce blood pressure.

CONTRAINDICATIONS:Hartil:

Hypersensitivity (history of angioedema associated with previous therapy with ACE inhibitors, hereditary or idiopathic angioedema);

Systemic lupus erythematosus, scleroderma (increased risk of developing neutropenia or agranulocytosis); inhibition of bone marrow hematopoiesis;

Hyperkalemia;

Bilateral renal artery stenosis, renal artery stenosis of a solitary kidney, kidney transplantation, renal failure;

Hyponatremia (risk of dehydration, hypertension, renal failure);

Liver failure;

Primary hyperaldosteronism;

During pregnancy and breastfeeding;

Children under 15 years of age.

Hartil-N:

Hypersensitivity to ramipril and other ACE inhibitors, thiazides or sulfonamide derivatives, as well as to any excipient of the drug;

History of angioedema due to administration of ACE inhibitors; hereditary/idiopathic angioedema;

Severe renal impairment (creatinine clearance<30 мл/1,73 м 2 площади поверхности тела) или анурия;

Severe liver dysfunction and/or cholestasis;

Pregnancy period (II and III trimester) and breastfeeding;

Age up to 18 years.

SIDE EFFECTS:Hartil

From the cardiovascular and blood systems: hypotension, angina, syncope, heart failure, myocardial infarction, vertigo, chest pain; very rarely - arrhythmia, tachycardia, hemolytic anemia, myelodepression, pancytopenia, thrombocytopenia, eosinophilia, agranulocytosis; vasculitis

From the gastrointestinal tract: nausea, vomiting, diarrhea; very rarely - dry mouth, anorexia, dyspepsia, dysphagia, constipation, abdominal pain, gastroenteritis, pancreatitis, hepatitis, liver dysfunction, increased transaminase levels.

From the nervous system and sensory organs: dizziness, headache, asthenia; very rarely - cerebrovascular disorders, amnesia, drowsiness, convulsions, depression, sleep disturbance, neuralgia, neuropathy, paresthesia, tremor, hearing loss, visual impairment.

From the respiratory system: dry cough, infectious diseases of the upper respiratory tract; very rarely - dyspnea, pharyngitis, sinusitis, rhinitis, tracheobronchitis, laryngitis, bronchospasm.

From the urinary system: renal dysfunction, proteinuria, oliguria, edema.

Allergic reactions: urticaria, skin rashes, erythema multiforme, photosensitivity, angioedema.

Others: weight loss, anaphylactoid reactions, increased levels of urea nitrogen and creatinine, angioedema, arthralgia/arthritis, myalgia, chills, hyperkalemia, increased activity of liver enzymes, concentrations of bilirubin, uric acid, glucose in the blood serum.

Hartil-N

In addition to those listed, it has the following side effects:

from the blood and hematopoietic system: rarely: decrease in hemoglobin and hematocrit, leukopenia, thrombocytopenia; very rarely: agranulocytosis, pancytopenia, eosinophilia, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency;

from the nervous system and sensory organs: dizziness, fatigue, headache, weakness, drowsiness, conjunctivitis, blepharitis, impaired sense of smell, balance, paresthesia, visual impairment (transient myopia, blurred vision), tinnitus;

from the psyche: apathy, anxiety, nervousness; fear, confusion, sleep disturbance;

metabolic and nutritional disorders: hypokalemia, increased levels of uric acid, urea and creatinine in the blood serum, gout; hyponatremia, decreased magnesium levels, hypercholesterolemia, hypercalcemia; disturbances of water and electrolyte balance, hypochloremia, metabolic alkalosis; increased TG levels in the blood serum, hypercholesterolemia, increased serum amylase, hyperglycemia and, as a consequence, decompensation of diabetes mellitus;

allergic reactions: when taking Hartil-N, they are more pronounced : urticaria, skin rashes, photosensitivity, angioedema; very rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, lupus erythematosus, alopecia.

SPECIAL INSTRUCTIONS: Caution must be exercised when prescribing Hartil-N to patients on a low- or low-salt diet (increased risk of developing arterial hypotension). In patients with heart failure, taking the drug can lead to the development of severe arterial hypotension, which is accompanied by oliguria or azotemia, and rarely - the development of acute renal failure.

Patients with an increased risk of severe arterial hypotension after taking the first dose of Hartil-N, as well as after increasing the dose of the drug or diuretic, should be under medical supervision, especially in the first 2 weeks of treatment.

Patients with malignant hypertension or with concomitant severe heart failure should begin treatment in a hospital setting.

Transient hypotension is not a contraindication for continuing treatment after stabilization of blood pressure. If severe hypotension reoccurs, the dose should be reduced or the drug discontinued.

When using a combination of ramipril and hydrochlorothiazide, treatment with other diuretics, if possible, should be discontinued 2-3 days before starting the drug. In the future, if necessary, the use of diuretics can be resumed under the supervision of a physician.

If chills, swollen lymph nodes and/or sore throat develop (these symptoms may be associated with the development of agranulocytosis), the patient should immediately consult a doctor.

At the beginning of treatment and regularly during drug therapy, the number of leukocytes, the level of hemoglobin in the peripheral blood, the level of potassium, creatinine and the activity of liver enzymes in the blood are monitored, especially in patients with impaired renal function, in patients receiving allopurinol or procainamide, immunosuppressants, including cytostatic agents.

In patients with autoimmune diseases and syndromes, the risk of developing neutropenia increases when using ramipril.

If urgent hemodialysis is necessary, the patient must first be transferred to another antihypertensive drug (not an ACE inhibitor).

The use of AN69 dialysis membranes together with ACE inhibitors is not recommended (due to the possibility of developing anaphylactoid reactions in patients). If the history shows indications of the development angioedema, not associated with taking ACE inhibitors, in which case these patients have an increased risk of developing it when taking the drug.

Lactose intolerance

The drug Hartil and Hartil-N contains lactose monohydrate. It should not be prescribed to patients with rare hereditary disorders of galactose tolerance, hereditary lactose deficiency or glucose/galactose malabsorption syndrome.

During pregnancy and lactation taking the drug Hartil and Hartil-H is contraindicated, therefore, before starting its use, pregnancy should be excluded in the patient, and it is also necessary to protect against pregnancy by using an adequate method of contraception. In the case of a planned or confirmed pregnancy, you should switch to an alternative drug that does not contain an ACE inhibitor as quickly as possible (before the end of the first trimester) to avoid the risk of fetal harm.

Taking Hartil and Hartil-H is contraindicated during the second and third trimesters of pregnancy, since it can cause symptoms of intoxication in the fetus (depression of renal function, oligohydramnios, delayed ossification of the skull bones) and the infant (renal failure in infants, hypotension, hyperkalemia ).

The drug Hartil and Hartil-H are contraindicated during breastfeeding. Both ramipril and hydrochlorothiazide are excreted into human breast milk, so breastfeeding should be discontinued if treatment with this drug is necessary for the mother.

The ability to influence reaction speed when driving vehicles or other mechanisms

Taking the drug Hartil and Hartil-H has a weak or moderate effect on the ability to drive a car and operate potentially dangerous mechanisms. Some people may have difficulty driving, operating machinery, or performing other types of work without proper support for their feet. This is especially pronounced at the beginning of treatment, after increasing the dose and while taking alcohol.

Special Security Measures

If possible, before surgery (including dentistry), treatment with the drug should be stopped or its dose reduced. When performing emergency operations, the dose of medications used for sedation and anesthesia should be reduced.

The drug is prescribed with caution to patients with gout, as well as diabetes mellitus, especially those receiving insulin and oral hypoglycemic agents.

INTERACTIONS:Hartil:

hypotensive, diuretic, opioid analgesics, anesthetics enhance the hypotensive effect of Hartil. NSAIDs (especially indomethacin), kitchen salt weaken the effect of Hartil, interfere with the antihypertensive effect by inhibiting the synthesis of prostaglandins in the kidneys and/or due to sodium and fluid retention in the body. Therefore, patients receiving combination therapy with Hartil and NSAIDs should be closely monitored.

Cyclosporine, potassium-sparing diuretics (amiloride, spironolactone, triamterene), milk, potassium supplements, potassium mixtures, salt substitutes increase the risk of hyperkalemia.

The combined use of myelosuppressive drugs and Hartil increases the risk of developing neutropenia and/or agranulocytosis, which can be fatal.

When Hartil is taken simultaneously with lithium preparations, the concentration in the blood of the latter increases.

Enhances the hypoglycemic effect of sulfonylurea derivatives and insulin.

The risk of developing leukopenia increases when used simultaneously with alopurinol, cytostatic agents, immunosuppressants, and procainamide.

Hartil enhances the inhibitory effect of ethanol on the central nervous system.

Estrogens weaken the hypotensive effect of the drug (cause fluid retention).

Hartil-N:

simultaneous use of antihypertensive, diuretic drugs, opioid analgesics, some anesthetics, tricyclic antidepressants and antipsychotics may increase the antihypertensive effect of the drug.

With the simultaneous use of NSAIDs (for example, acetylsalicylic acid, indomethacin), estrogens, sympathomimetics or salt, the hypotensive effect of the drug may be reduced.

When used simultaneously with potassium supplements and potassium-sparing diuretics (for example, amiloride, spironolactone, triamterene), the potassium content in the blood serum may increase.

The simultaneous use of ramipril with lithium preparations is not recommended, since such a combination may increase the risk of toxicity of lithium preparations.

In polyuria caused by lithium preparations, hydrochlorothiazide can cause a paradoxical antidiuretic effect.

Combined use with hypoglycemic agents (oral hypoglycemic agents, insulin) may lead to an increased hypoglycemic effect with the risk of hypoglycemia. This phenomenon was observed most often during the first weeks of combination treatment in patients with renal failure.

When used together with allopurinol, cytostatic drugs, immunosuppressants, corticosteroid drugs, procainamide, the risk of leukopenia increases.

Hydrochlorothiazide may enhance the toxic effect of salicylates (at a dose of >3 g/day) on the central nervous system.

The drug may potentiate the effect of alcohol.

OVERDOSE:Hartil:

Symptoms: severe hypotension, shock, electrolyte imbalance, renal failure.

Hartil-N:

Symptoms: urinary retention, severe hypotension, cardiac arrhythmia, tachycardia, impaired consciousness, seizures, shock, bradycardia, electrolyte imbalance, renal failure and paralytic ileus.

Treatment: general measures: gastric lavage, use of sorbents, sodium sulfate (if possible during the first 30 minutes); intravenous administration of an isotonic solution of sodium chloride, catecholamines, angiotensin II; for persistent bradycardia - use of an artificial pacemaker. Hemodialysis is ineffective.

If angioedema occurs, immediate subcutaneous administration of 0.3–0.5 ml of epinephrine or its slow intravenous administration; in the future - intravenous administration of corticosteroids, antihistamines and H 2 receptor antagonists.

STORAGE CONDITIONS: at a temperature not exceeding 25 °C.

Date added: 31/10/2007
Date modified: 20/11/2007

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