Hartyl tablets 5 mg No. 28

Instructions for Hartil tablets 5 mg No. 28

Composition

active ingredient: ramipril;

1 tablet contains ramipril 5 mg;

excipients: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, red iron oxide (E 172), yellow iron oxide (E 172).

Dosage form

Pills.

Main physicochemical properties:

5 mg tablets – light pink, flat, oval tablets without a shell, with a bevel, with possible inclusions, with a score on one side and on the lateral surfaces, marked R3, size 8.8 x 4.4 mm.

Pharmacotherapeutic group

Agents acting on the renin-angiotensin system. Angiotensin-converting enzyme (ACE) inhibitors. ATC code C09A A05.

Pharmacological properties

Pharmacodynamics

Ramiprilat, the active metabolite of ramipril, inhibits the enzyme dipeptidylcarboxypeptidase (synonyms: angiotensin-converting enzyme, kininase II). In blood plasma and tissues, this enzyme catalyzes the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. The reduction in the formation of angiotensin II and the inhibition of the breakdown of bradykinin lead to vasodilation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat contributes to a decrease in aldosterone secretion.

Administration of ramipril causes a significant decrease in peripheral arterial resistance. In general, there are no significant changes in renal plasma flow and glomerular filtration rate. Administration of ramipril to patients with arterial hypertension leads to a decrease in blood pressure in the horizontal and vertical positions, without a compensatory increase in heart rate.

In most patients, the antihypertensive effect after a single dose occurs 1-2 hours after oral administration of the drug. The maximum effect after a single dose is usually achieved 3-6 hours after oral administration. The antihypertensive effect is maintained for 24 hours. The maximum antihypertensive effect with long-term treatment with ramipril is generally evident after 3-4 weeks. The antihypertensive effect has been shown to be maintained with long-term therapy for 2 years. Abrupt discontinuation of ramipril does not lead to a rapid and excessive rebound increase in blood pressure.

In addition to conventional therapy with diuretics and, if necessary, cardiac glycosides, ramipril has been shown to be effective in patients with NYHA functional classes II-IV. The drug has beneficial effects on cardiac hemodynamics (reduction of left and right ventricular filling pressures, total peripheral vascular resistance, increased cardiac output and improved cardiac index). It also reduces neuroendocrine activation.

Pharmacokinetics

Absorption: After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract: peak plasma concentrations are reached within one hour. Based on the amount of substance recovered in the urine, the extent of absorption is at least 56% and is not significantly affected by the presence of food in the gastrointestinal tract. The bioavailability of the active metabolite ramiprilat after oral administration of ramipril at a dose of 2.5 mg and 5 mg is 45%.

Peak plasma concentrations of ramiprilat, the only active metabolite of ramipril, are reached 2–4 hours after administration.

Under conditions of usual doses (once a day), steady-state plasma concentrations are achieved on the 4th day of drug administration.

Distribution

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

Metabolism: Ramipril is almost completely metabolized to ramiprilat, diketopiperazine ester, diketopiperazine acid, and the glucuronides of ramipril and ramiprilat.

Elimination. Excretion of metabolites is mainly renal. The decrease in plasma ramiprilat concentration occurs in several phases. Due to the strong saturable binding to ACE and slow dissociation from the enzyme, ramiprilat is characterized by a prolonged terminal elimination phase at very low plasma concentrations.

After repeated doses of ramipril once daily, the effective half-life is 13–17 hours for doses of 5–10 mg and longer for lower doses of 1.25–2.5 mg. The difference is due to the saturable capacity of the enzyme for binding ramiprilat.

Ramipril and its metabolite were not detected in breast milk after a single oral dose. However, the effect of multiple doses is unknown.

Renal excretion of ramiprilat is reduced in patients with impaired renal function, and renal clearance of ramiprilat is proportionally related to creatinine clearance. This results in increased plasma concentrations of ramiprilat, which decline more slowly than in subjects with normal renal function.

In patients with hepatic impairment, the metabolism of ramipril to ramiprilat is slowed due to reduced hepatic esterase activity, and plasma levels of ramipril are increased in these patients. Peak ramiprilat concentrations in these patients, however, were not different from those in subjects with normal hepatic function.

Indication

Treatment of arterial hypertension.

Prevention of cardiovascular disease: reduction of cardiovascular morbidity and mortality in patients with:

severe cardiovascular disease of atherothrombotic origin (history of ischemic heart disease or stroke or peripheral vascular disease); diabetes with at least one cardiovascular risk factor (see section "Pharmacological properties").

Treatment of kidney disease:

initial glomerular diabetic nephropathy as evidenced by microalbuminuria; severe glomerular diabetic nephropathy as evidenced by macroproteinuria in patients with at least one cardiovascular risk factor (see section "Pharmacodynamics"); severe glomerular non-diabetic nephropathy as evidenced by macroproteinuria ≥ 3 g/day (see section "Pharmacodynamics").

Treatment of heart failure accompanied by clinical manifestations

Secondary prevention after acute myocardial infarction: reduction of mortality during the acute stage of myocardial infarction in patients with clinical signs of heart failure, provided that treatment is started more than 48 hours after the onset of acute myocardial infarction.

Contraindication

Hypersensitivity to the active substance or to any of the excipients included in the preparation, or to other ACE inhibitors (see section "Composition").

History of angioedema (hereditary, idiopathic or previously experienced while taking ACE inhibitors or angiotensin II receptor antagonists).

Concomitant use with sacubitril/valsartan (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other forms of interaction”)

Significant bilateral renal artery stenosis or unilateral renal artery stenosis in the presence of a single functioning kidney.

Pregnant women or women planning to become pregnant (see section “Use during pregnancy or breastfeeding”).

Ramipril should not be used in patients with hypotension or hemodynamically unstable conditions.

Concomitant use with aliskiren-containing products in patients with diabetes or in patients with moderate or severe renal impairment (glomerular filtration rate (GFR)
< 60 ml/min/1.73 m2) (see sections “Interaction with other medicinal products and other types of interactions” and “Pharmacodynamics”).

The concomitant use of ACE inhibitors and extracorporeal treatments that result in contact of blood with negatively charged surfaces should be avoided, as such use may lead to severe anaphylactoid reactions. Such extracorporeal treatments include dialysis or hemofiltration using certain membranes with high hydraulic permeability (e.g. polyacrylonitrile) and low-density lipoprotein apheresis using dextran sulfate.

Interaction with other medicinal products and other types of interactions

Clinical trial data have shown that dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalemia and worsening renal function (including acute renal failure) compared with the use of a single agent affecting the RAAS (see sections 5.1, 5.3 and 5.4).

Contraindicated combinations. Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see sections "Contraindications" and "Special warnings and precautions for use"). Ramipril treatment should only be started 36 hours after the last dose of sacubitril/valsartan. Sacubitril/valsartan treatment should only be started 36 hours after the last dose of Hartil®.

Extracorporeal therapy methods that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain high flux membranes (e.g. polyacrylonitrile membranes) and low density lipoprotein apheresis using dextran sulfate, due to the increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is necessary, consideration should be given to using a different dialysis membrane or a different class of antihypertensive agent.

The combined use of Hartil® with aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or moderately severe renal impairment and is not recommended for other categories of patients (see sections “Contraindications” and “Special Instructions for Use”).

Combinations requiring precautions

Antihypertensive drugs (e.g. diuretics) and other substances that may lower blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). An increased risk of arterial hypotension should be expected (see section "Special warnings and precautions for use" for diuretics).

Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of Hartil®. Close monitoring of blood pressure is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may cause changes in the blood picture. Increased likelihood of hematological reactions (see section "Special instructions").

Lithium salts: ACE inhibitors may reduce lithium excretion, which may lead to increased lithium toxicity. Lithium levels should be carefully monitored.

Antidiabetic agents, including insulin. Hypoglycemic reactions may occur. Close monitoring of blood glucose levels is recommended.

Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. The antihypertensive effect of Hartil® is expected to be reduced. Furthermore, the concomitant use of ACE inhibitors and NSAIDs may be associated with an increased risk of worsening of renal function and an increase in blood potassium levels.

Salt. Excessive salt consumption may weaken the hypotensive effect of the drug.

Trimethoprim or a combination of trimethoprim and sulfamethoxazole (co-trimoxazole).

Patients taking ACE inhibitors together with the combination of trimethoprim and sulfamethoxazole are at increased risk of hyperkalemia.

Selective immunosuppressants or mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus) or vildagliptin. There may be an increased risk of angioedema in patients receiving concomitant treatment with mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus) or vildagliptin. Such therapy should be initiated with caution (see section 4.4).

Neprilysin (NEP) inhibitors: A potential increased risk of angioedema has been reported with the concomitant use of ACE inhibitors and a NEP (neutral endopeptidase) inhibitor, such as racecadotril (see section 4.4).

Application features

Special categories of patients

Pregnancy. Treatment with ACE inhibitors or angiotensin II receptor antagonists is contraindicated during pregnancy. Unless continued ACE inhibitor/angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with aliskiren-containing medicinal products.

Concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren has been shown to increase the risk of hypotension, hyperkalaemia and deterioration of renal function (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections 4.5 and 5.1).

If such dual blockade therapy is considered absolutely necessary, it should only be used under specialist supervision and with frequent and careful monitoring of renal function, electrolytes and blood pressure.

ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.

The combined use of Hartil® and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2) (see section "Contraindications").

Patients at particular risk of hypotension.

Patients with markedly increased activity of the renin-angiotensin-aldosterone system (RAAS). Patients with markedly increased RAAS are at risk of a sudden significant decrease in blood pressure and deterioration of renal function due to ACE inhibition, especially if an ACE inhibitor or concomitant diuretic is to be administered for the first time or the dose is to be increased for the first time.

with severe arterial hypertension; with decompensated congestive heart failure; with hemodynamically significant obstruction to the inflow or outflow of blood from the left ventricle (for example, with aortic or mitral valve stenosis); with unilateral renal artery stenosis in the presence of a second functioning kidney; in whom fluid or electrolyte depletion exists or may develop (including those receiving diuretics); with cirrhosis of the liver and/or ascites; who are undergoing major surgical interventions or during anesthesia with drugs that cause arterial hypotension.

It is generally recommended that dehydration, hypovolemia, or electrolyte depletion be corrected before treatment is initiated (however, in patients with heart failure, such corrective measures should be carefully weighed against the risk of volume overload).

In patients with impaired liver function, the response to treatment with Hartil® may be either enhanced or reduced. In addition, in patients with severe cirrhosis of the liver, accompanied by edema and/or ascites, the activity of the renin-angiotensin system (RAS) may be significantly increased; therefore, special caution should be exercised when treating these patients.

Transient or persistent heart failure after myocardial infarction.

Patients at risk of cardiac or cerebral ischemia in the event of acute arterial hypotension. Special medical supervision is required in the initial phase of treatment.

Elderly patients: See section "Method of administration and dosage".

Surgery: If possible, treatment with angiotensin-converting enzyme inhibitors such as ramipril should be discontinued 1 day before surgery.

Monitoring of renal function. Renal function should be assessed before and during treatment and the dose adjusted, especially in the first weeks of treatment. Particularly careful monitoring is required in patients with impaired renal function (see section "Method of administration and dosage"). There is a risk of deterioration of renal function, especially in patients with congestive heart failure or after kidney transplantation.

Angioedema: Angioedema has been reported in patients treated with ACE inhibitors, including ramipril (see section 4.8).

This risk is increased in patients receiving concomitant medicinal products such as mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, everolimus, sirolimus) or vildagliptin or racecadotril. The combination of ramipril with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see sections 4.3 and 4.5).

In case of angioedema, Hartil® should be discontinued. Emergency treatment should be initiated immediately. The patient should be under medical supervision for at least 12–24 hours and may be discharged after complete resolution of symptoms.

Cases of intestinal angioedema have been reported in patients treated with ACE inhibitors, including Hartil® (see section 4.8). These patients presented with abdominal pain (with or without nausea/vomiting).

Anaphylactic reactions during desensitization. When using ACE inhibitors, the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Before desensitization, Hartil® should be temporarily discontinued.

Electrolyte balance control. Hyperkalemia. Hyperkalemia has been observed in some patients treated with ACE inhibitors, including Hartil®. Patients at risk for hyperkalemia include patients with renal insufficiency, patients over 70 years of age, patients with uncontrolled diabetes mellitus, patients taking potassium salts, potassium-sparing diuretics, and other active substances that increase plasma potassium, or patients with conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. If the combined use of the above drugs is considered appropriate, regular monitoring of plasma potassium levels is recommended (see section "Interaction with other medicinal products and other types of interactions").

Electrolyte balance control. Hyponatremia. Syndrome of inappropriate antidiuretic hormone secretion with subsequent development of hyponatremia has been observed in some patients treated with ramipril. It is recommended to regularly monitor serum sodium levels in the elderly and in other patients at risk of developing hyponatremia.

Neutropenia/agranulocytosis: Cases of neutropenia/agranulocytosis, as well as thrombocytopenia and anemia, have been observed rarely. Bone marrow depression has also been reported.

Ethnic differences. ACE inhibitors cause angioedema more frequently in black patients than in non-black patients. As with other ACE inhibitors, the antihypertensive effect of ramipril may be less pronounced in black patients than in non-black patients. This may be because black patients with hypertension are more likely to have low-renin hypertension.

Cough. Cough has been reported with ACE inhibitors. The cough is typically non-productive, persistent, and resolves after discontinuation of therapy. The possibility of cough due to ACE inhibitors should be considered in the differential diagnosis of cough.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Ability to influence reaction speed when driving vehicles or other mechanisms

Some side effects (e.g. symptoms of low blood pressure such as dizziness) may impair the patient's ability to concentrate and affect the speed of reaction, especially at the beginning of treatment or when switching from treatment with other drugs.

After taking the first dose or a subsequent dose increase, it is not advisable to drive a car or operate other machinery for several hours.

Use during pregnancy or breastfeeding

Pregnancy: The drug should not be used by pregnant women or women planning to become pregnant.

Epidemiological data on the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy have not been conclusive; however, a small increased risk cannot be excluded. If ACE inhibitor therapy is continued, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy.

If pregnancy is confirmed during treatment with this medicine, its use should be discontinued immediately and replaced with another medicine approved for use in pregnant women.

Exposure to ACE inhibitors/angiotensin II receptor antagonists (ARBs) during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligoamnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Neonates whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia (see sections 4.3 and 4.4).

Breastfeeding. Due to the lack of information regarding the use of ramipril during breastfeeding (see section "Pharmacological properties"), this drug is not recommended for use in breastfeeding women and alternative treatments with better established safety profiles during lactation are preferable, especially while breastfeeding a newborn or preterm infant.

Method of administration and doses

Drug for oral use.

Hartil® is recommended to be taken at the same time each day. The drug can be taken before, during and after meals, as food intake does not affect the bioavailability of the drug. Hartil® tablets should be swallowed whole with water. They should not be chewed or crushed. To ensure proper administration, the tablets can be divided into equal doses along the score line.

Patients taking diuretics. At the beginning of treatment with Hartil®, arterial hypotension may occur, the development of which is more likely in patients who are simultaneously receiving diuretics. In such cases, caution is recommended, since these patients may experience a decrease in BCC and / or electrolytes.

It is advisable to discontinue the diuretic 2–3 days before starting treatment with Hartil®, if possible (see section “Special instructions”).

In patients with arterial hypertension who cannot discontinue the diuretic, treatment with Hartil ® should be initiated at a dose of 1.25 mg. Kidney function and blood potassium levels should be closely monitored. Subsequent dosage of Hartil ® should be adjusted depending on the target blood pressure level.

Arterial hypertension

The dose should be selected individually, depending on the characteristics of the patient's condition (see section "Features of use") and the results of control blood pressure measurements. Hartil® can be used as monotherapy or in combination with other classes of antihypertensive drugs (see sections "Contraindications", "Features of use", "Interaction with other drugs and other types of interactions" and "Pharmacodynamics").

Patients with a strongly activated renin-angiotensin-aldosterone system (RAAS) may experience a significant decrease in blood pressure after the initial dose. For such patients, the recommended starting dose is 1.25 mg and treatment should be initiated under medical supervision (see section 4.4).

Dose titration and maintenance dose. The dose can be doubled every 2–4 weeks until the target blood pressure level is reached; the maximum dose of Hartil® is 10 mg per day. The drug is recommended to be taken once a day.

Prevention of cardiovascular diseases

Initial dose. The recommended initial dose of Hartil® is 2.5 mg once daily.

Dose titration and maintenance dose. Depending on individual tolerability, the dose should be increased gradually. It is recommended to double the dose after 1–2 weeks of treatment, and then increase it after another 2–3 weeks to the target maintenance dose of 10 mg once daily.

(See also the above information regarding dosing for patients receiving diuretics.)

Kidney disease treatment

In patients with diabetes and microalbuminuria.

Initial dose. The recommended initial dose of Hartil® is 1.25 mg (in the appropriate dosage) once a day.

Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose should be increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.

Patients with diabetes and at least one cardiovascular risk factor.

Initial dose. The recommended initial dose of Hartil® is 2.5 mg once daily.

Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose should be increased during further treatment. After 1–2 weeks of treatment, it is recommended to double the daily dose of Hartil ® to 5 mg, and then to 10 mg after another 2–3 weeks of treatment. The target daily dose is 10 mg.

Patients with non-diabetic nephropathy, as evidenced by macroproteinuria ≥ 3 g/day.

Initial dose. The recommended initial dose of Hartil® is 1.25 mg (in the appropriate dosage) once a day.

Dose titration and maintenance dose. Depending on the individual patient's tolerance of the drug, the dose should be increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.

Heart failure with clinical manifestations

Initial dose: For patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg/day.

Dose titration and maintenance dose. The dose of Hartil® should be titrated by doubling it every 1–2 weeks until a maximum daily dose of 10 mg is reached. It is advisable to divide the dose into 2 doses.

Secondary prevention after acute myocardial infarction in the presence of heart failure.

Initial dose. 48 hours after the onset of myocardial infarction, patients who are clinically and hemodynamically stable should be given an initial dose of 2.5 mg twice daily for 3 days. If the initial dose of 2.5 mg is poorly tolerated, then 1.25 mg (in the appropriate dosage) twice daily for 2 days should be used, followed by an increase to 2.5 mg and 5 mg twice daily. If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued.

(See also the above information regarding dosing for patients receiving diuretics.)

Dose titration and maintenance dose: The daily dose should then be increased by doubling it at intervals of 1–3 days until the target maintenance dose of 5 mg twice daily is reached.

Whenever possible, the maintenance daily dose should be divided into 2 doses.

If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. There is still insufficient experience in patients with severe (NYHA class IV) heart failure immediately after myocardial infarction. If a decision is made to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg.
(in the appropriate dosage) once a day and any increase should be done with extreme caution.

Special categories of patients

Patients with renal impairment. The daily dose for patients with renal impairment depends on the creatinine clearance (see section "Pharmacological properties"):

Patients with impaired liver function (see section "Pharmacodynamics"). Treatment with Hartil® in patients with impaired liver function should be initiated under close medical supervision, and the maximum daily dose in such cases should be 2.5 mg.

Elderly patients. The initial dose should be lower and subsequent dose titration should be more gradual because of the higher likelihood of adverse effects, especially in very elderly and debilitated patients. In such cases, a lower initial dose of 1.25 mg (in the appropriate dosage) of ramipril should be prescribed.

Children

Hartil® is not recommended for use in children (under 18 years of age) as there is insufficient data on the safety and efficacy of this drug in such patients.

Currently available data on ramipril are described in the sections “Pharmacodynamics” and “Adverse reactions”.

Overdose

Symptoms of overdose with ACE inhibitors may include excessive peripheral vasodilation (with pronounced hypotension, shock), bradycardia, electrolyte disturbances, renal failure. The patient's condition should be closely monitored. Symptomatic and supportive treatment should be administered. Suggested measures include primary detoxification (gastric lavage, administration of sorbents) and measures to restore hemodynamic stability, including the administration of alpha-1-adrenergic agonists or angiotensin II (angiotensinamide). Ramiprilat, the active metabolite of ramipril, is poorly removed from the general circulation by hemodialysis.

Adverse reactions

The safety profile of Hartil® includes data on persistent cough and reactions caused by arterial hypotension. Serious adverse reactions include angioedema, hyperkalemia, impaired liver or kidney function, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

The frequency of adverse reactions is classified as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare
(< 1/10,000), unknown (cannot be estimated from the available data). Within each group, adverse reactions are presented in order of decreasing seriousness.

Adverse reactions by frequency

Organ system class
Often	Infrequently	Rarely	Very rare	Unknown
From the side of the hematopoietic and lymphatic systems		Eosinophilia	Decreased white blood cell count (including neutropenia or agranulocytosis), decreased red blood cell count, decreased hemoglobin level, decreased platelet count		Bone marrow failure, pancytopenia, hemolytic anemia
On the part of the immune system					Anaphylactic and anaphylactoid reactions, increased antinuclear antibodies
From the endocrine system					Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolic and nutritional disorders	Increased potassium levels in the blood	Anorexia, decreased appetite			Decreased blood sodium levels
Mental disorders		Decreased mood, anxiety, nervousness, restlessness, sleep disturbances including drowsiness	State of confused consciousness		Attention deficit disorder
From the nervous system	Headache, dizziness	Vertigo, paraesthesia, ageusia, dysgeusia	Tremor, balance disorder		Cerebral ischemia, including ischemic stroke and transient ischemic attack; psychomotor disorders Specifications Characteristics Active ingredient Ramipril Adults Can ATC code C MEDICINES AFFECTING THE CARDIOVASCULAR SYSTEM; C09 MEDICINES AFFECTING THE RENIN-ANGIOTENSIN SYSTEM; C09A ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS; C09A A ACE inhibitors, single-component; C09A A05 Ramipril Country of manufacture Malta Diabetics With caution Dosage 5 мг Drivers With caution For allergies With caution For children It is impossible. Form Tablets Method of application Inside, solid Nursing It is impossible. Pregnant It is impossible. Primary packaging blister Producer Aegis Quantity per package 28 pcs Trade name Hartyl Vacation conditions By prescription Reviews There are no reviews for this product. + Add review Write a review Hartyl tablets 5 mg No. 28 My mark: Continue There are no reviews for this product, be the first to leave your review. Answers & questions Add your question and we will answer as soon as possible. + Ask a question Ask a question Add your question and we will answer as soon as possible. * Your question Continue No questions about this product, be the first and ask your question. 399.47 грн. Add to Cart