Rami Sandoz 10 mg tablet number 30

Rami Sandoz (Ramipril) user manual

Composition

active ingredient: ramipril; 1 tablet contains ramipril 2.5 mg or 5 mg or 10 mg;
auxiliary substances: cellulose microcrystalline, corn starch, silicon dioxide precipitated, glycine hydrochloride, glycerin dibehenate, iron oxide yellow (E172) (for tablets of 2.5 mg), iron oxide red (E172) (for tablets 5 mg each).

Dosage form

Pills.

Basic physical and chemical properties:

2.5 mg tablets: pale yellow, slightly patchy capsule-like, with a notch on one side;
pills of 5 mg: light pink, slightly patchy capsule-like, with a notch on one side;
tablets of 10 mg: white or almost white capsule-like, with a notch on one side.

Pharmacological group

ACE inhibitors (ACE). ATX Code C09A A05.

Pharmacological properties

Ramiprilate, the active metabolite of ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: ACE, kininase II). In plasma and tissues, this enzyme catalyzes the conversion of angiotensin I into an active vasoconstrictor angiotensin II, as well as the cleavage of the active bradykinin vasodilator. Reducing the formation of angiotensin II and inhibiting the splitting of bradykinin leads to the expansion of blood vessels.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat helps reduce the secretion of aldosterone. The response to monotherapy with ACE inhibitors was, on average, less pronounced in Negroid (Afro-Caribbean) patients with arterial hypertension (a population characterized by a low level of renin in hypertension) than in representatives of other races.

Pharmacodynamics.

Taking ramipril leads to a significant decrease in peripheral arterial resistance. As a rule, significant changes in renal plasma flow or glomerular filtration rate do not occur. The administration of ramipril to patients with arterial hypertension leads to a decrease in blood pressure in both the horizontal and vertical position of the patient, not accompanied by a compensatory increase in the heart rate.

In most patients, the antihypertensive effect occurs 1-2 hours after taking a single dose. The maximum single dose effect is usually achieved in 3-6 hours. The antihypertensive effect after taking a single dose is usually maintained for 24 hours.

The maximum antihypertensive effect with long-term treatment with ramipril is generally observed after 3-4 weeks. With prolonged therapy, it persists for 2 years.

After a sudden stopping of ramipril, there is no rapid and excessive increase in blood pressure.

In patients with nondiabetic or diabetic nephropathy, ramipril reduces the rate of progression of renal failure and the onset of the terminal stage of renal failure, which necessitates dialysis or kidney transplantation. In patients who have a nondiabetic or diabetic initial nephropathy, ramipril reduces the excretion of albumin.

Studies have shown that ramipril statistically significantly reduces the incidence of myocardial infarction, stroke or mortality from cardiovascular diseases. In addition, ramipril reduces overall mortality and the need for revascularization, as well as delaying the onset and progression of heart failure. Ramipril reduces the risk of developing nephropathy in the general group of patients and among patients with diabetes mellitus. Ramipril also significantly reduces the incidence of microalbuminuria. Such effects were observed in patients with both arterial hypertension and normotension.

Pharmacokinetics.

Suction. After taking ramipril quickly absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is reached within 1:00. Given the amount of substance found in the urine, the degree of absorption is at least 56% and it is not significantly affected by the presence of food in the gastrointestinal tract. Bioavailability of the active metabolite ramiprilata after oral administration of ramipril in a dose of 2.5 mg and 5 mg is 45%.

The maximum concentration in the blood plasma of ramiprilata, a single active metabolite of ramipril, is reached 2-4 hours after taking ramipril. After applying the usual doses of ramipril once a day, the equilibrium concentration of ramiprilate in the blood plasma is reached on the 4th day of treatment.

Distribution. The binding of ramipril with plasma proteins is approximately 73%, and ramiprilata is 56%.

Metabolism. Ramipril is almost completely metabolized to ramiprilate, diketopiperazine ether, diketopiperazinovoy acid and glucuronide ramipril and ramiprilata.

Conclusion. Excretion of metabolites occurs mainly by renal excretion. Reducing the concentration of ramiprilate in the blood plasma multiphase. Because of the powerful saturating binding with ACE and slow dissociation due to the enzyme linkage, ramiprilate has a prolonged terminal phase of withdrawal at very low concentrations in the blood plasma.

After taking repeated doses of ramipril once a day, the effective half-life is 13-17 hours at a dose of 5-10 mg or more for low doses (1.25-2.5 mg). The difference is due to the fact that the ability of the enzyme to bind to ramiprilate is saturating.

When administered orally to a single dose of the drug, neither ramipril nor its metabolite was shown in breast milk.However, it is not known what effect repeat doses have.

Patients with impaired renal function (see Section "Method of administration and dose"). In patients with impaired renal function, renal excretion of ramiprilate is reduced, and renal clearance of ramiprilata is proportional to the creatinine clearance. This leads to an increase in the concentration of ramiprilata in the blood plasma, which decrease more slowly than in individuals with normal renal function.

Patients with impaired hepatic function (see Section "Method of administration and dose"). In patients with impaired liver function, ramipril metabolism with ramiprilate formation was slowed due to a decrease in hepatic esterase activity, and plasma ramipril levels in these patients were increased. However, the maximum concentrations of ramiprilate in these patients did not differ from those in individuals with normal liver function.

Indications

Treatment of arterial hypertension.

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

• expressed cardiovascular diseases of atherothrombotic genesis (presence in the anamnesis of ischemic heart disease or stroke or peripheral vascular disease)
• diabetes mellitus, have at least one factor of cardiovascular risk.

Treatment of kidney disease.

initial glomerular diabetic nephropathy, which is indicated by the presence of microalbuminuria;
expressed glomerular diabetic nephropathy, which is indicated by the presence of macroproteinuria, in patients with at least one cardiovascular risk factor;
expressed glomerular nondiabetic nephropathy, which is indicated by the presence of macroproteinuria ≥ 3 g / day.

Treatment of heart failure, accompanied by clinical manifestations.

Secondary prophylaxis after acute myocardial infarction: a decrease in mortality in the acute stage of myocardial infarction in patients with clinical signs of heart failure at the beginning of treatment more than 48 hours after the onset of acute myocardial infarction.

Contraindications

Hypersensitivity to the active substance, to any other component of the drug or to other ACE inhibitors angioedema in the anamnesis (hereditary, idiopathic or associated with the use of ACE inhibitors); stenosis of the renal artery (bilateral or stenosis of the artery of one kidney); severe renal failure primary hyperaldosteronism.

The drug should not be used in patients with arterial hypotension or hemodynamically unstable conditions.

The drug is contraindicated for women planning a pregnancy.

Do not use with drugs containing aliskiren, patients with diabetes mellitus or moderate or severe renal failure (GFR <60 mL / min).

It is necessary to avoid the simultaneous use of ACE inhibitors and extracorporeal methods of treatment, contact the blood with negatively charged surfaces, since such application can lead to severe anaphylactic reactions. Such extracorporeal treatments include dialysis or hemofiltration using certain membranes with high hydraulic permeability (eg, polyacrylonitrile) and low density lipoprotein apheresis using dextran sulfate.

Interaction with other drugs and other interactions

Contraindications are combinations.

Extracorporeal therapies that result in blood contact with negatively charged surfaces such as dialysis or hemofiltration using certain high flux intensity membranes (for example, polyacrylonitrile membranes) and low density lipoprotein apheresis using dextran sulfate - given the increased risk of severe anaphylactic reactions. If such treatment is necessary, consideration should be given to the use of dialysis membranes of a different type or antihypertensive agents of another class.

Double blockade of renin-angiotensin (RAAS) angiotensin II receptor antagonists, ACE inhibitors or aliskiren.

The combination of ACE inhibitors (including ramipril) or angiotensin II receptor antagonists with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m 2) and is not recommended for other patient categories.

Combinations that require action.

Potassium salts, heparin, potassium-sparing diuretics and other substances that increase the level of potassium in the blood plasma (including angiotensin II antagonists, trimethoprim, tacrolimus, cyclosporine): hyperkalaemia may occur, so careful monitoring of the potassium level in the blood plasma is necessary.

Antihypertensive drugs (eg, diuretics) and other drugs that can reduce blood pressure (eg nitrates, tricyclic antidepressants, anesthetics, ethanol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): an increase in the hypotensive effect is expected.

Vasopressor sympathomimetics and other substances (for example, isoproterenol, dobutamine, dopamine, epinephrine), which can reduce the antihypertensive effect of ramipril: it is recommended to control blood pressure.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that can change the number of blood cells: an increased likelihood of hematologic reactions.

Lithium salts inhibitors of ACE reduce the excretion of lithium, so the likelihood of lithium toxicity may increase. It is recommended to control the level of lithium.

Antidiabetic drugs, including insulin : possible hypoglycemic reactions. It is recommended to monitor the level of glucose in the blood plasma.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid are expected to reduce the antihypertensive effect of ramipril. In addition, the combined use of ACE inhibitors and NSAIDs may be accompanied by an increased risk of impaired renal function and an increase in the level of potassium in the blood plasma.

Food does not significantly change the absorption of the drug.

Salt. Increased salt intake can reduce the hypotensive effect of ramipril.

Specific hyposensitization. Due to the inhibition of ACE, the likelihood of occurrence and severity of anaphylactic and anaphylactoid reactions to insect venom increases. It is believed that this effect can also be observed for other allergens.

Application features

Special categories of patients.

Double blockade of RAAS with drugs containing aliskiren.

The combined use of ramipril and aliskiren is not recommended, as there is an increased risk of arterial hypotension, hyperkalemia and changes in kidney function.

Patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min) are contraindicated in the simultaneous use of ramipril and aliskiren (see Section "Contraindications").

Patients with a special risk of hypotension.

Patients with a pronounced activation of RAAS.

The risk of a sudden significant decrease in blood pressure with impaired renal function due to ACE inhibition is increased in patients with severe activation of RAAS, especially if an ACE inhibitor or concomitant diuretic is prescribed for the first time or at the first dose increase.

A significant increase in the activity of RAAS, which requires medical supervision, including continuous monitoring of blood pressure, can be expected, for example, in patients:

• with severe arterial hypertension;
• with decompensated congestive heart failure;
• with a hemodynamically significant obstruction to the inflow or outflow of blood from the left ventricle. (For example, with stenosis of the aortic or mitral valve);
• with unilateral stenosis of the renal artery in the presence of a second functioning kidney;
• in which there is or may develop a lack of fluid or electrolytes (Including those who receive diuretics);
• with cirrhosis of the liver and / or ascites;
• who undergo extensive surgery or during anesthesia with drugs that cause arterial hypotension.

As a rule, it is recommended to correct dehydration, hypovolemia or lack of electrolytes before starting treatment (however, for patients with heart failure such corrective measures should be carefully weighed against the risk of overload with volume).

In patients with impaired hepatic function, the response to treatment with ramipril may be either increased or decreased.In addition, in patients with severe cirrhosis accompanied by edema and / or ascites, the activity of the renin-angiotensin system can be significantly increased; therefore during treatment of these patients it is necessary to exercise special care.

Treatment of persistent heart failure after myocardial infarction.

Patients with a risk of cardiac or cerebral ischemia in the case of acute arterial hypotension. The initial phase of treatment requires special medical control.

Patients of advanced age. See section "Method of administration and dose".

Surgical interventions. It is recommended to stop treatment with ACE inhibitors, such as ramipril, if possible, 1 day before surgery.

Control of kidney function. The kidney function should be evaluated before and during treatment and dose adjustment, especially in the first weeks of treatment. In the presence of kidney damage, careful monitoring is required. There is a risk of impaired renal function, mainly in patients with congestive heart failure or after kidney transplantation.

Angioedema. Individual cases of angioedema have been reported in patients receiving ACE inhibitors, including ramipril.In the case of angioedema, the drug should be discontinued and immediate emergency treatment should be instituted.Patients should be under the supervision of a doctor for at least 12-24 hours before the symptoms disappear completely.

In the treatment of ACE inhibitors, cases of angioedema of the intestine were observed. These patients complained of abdominal pain (with or without nausea / vomiting). Symptoms of angioedema edema disappeared after the removal of ramipril.

Anaphylactic reactions during desensitization. The probability and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increase with the administration of ACE inhibitors. Before desensitization it is necessary to consider the possibility of a temporary discontinuation of taking ramipril.

Hyperkalemia. In some patients who received ACE inhibitors, including ramipril, hyperkalemia was observed. The risk of hyperkalemia is higher in patients with renal failure, age 70, in patients with uncontrolled diabetes mellitus, in those who receive potassium salts, potassium-sparing diuretics, and other potassium-active substances, or in conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. If joint use of the above drugs is deemed advisable, regular monitoring of the potassium level in the blood plasma is recommended.

Neutropenia / agranulocytosis. Cases of neutropenia / agranulocytosis, as well as thrombocytopenia and anemia were rare. Also reported on the inhibition of bone marrow function. In order to identify possible leukopenia, it is recommended to control the number of leukocytes in the blood plasma. Most often desirable to control the beginning of treatment and in patients with impaired renal function, concomitant collagenosis (e.g., systemic lupus erythematosus or scleroderma) or those who are taking other medications which may cause changes in the blood picture.

Ethnic differences.

ACE inhibitors are more likely to cause angioedema in blacks patients than in Caucasians. Like other ACE inhibitors, ramipril may be less effective in reducing blood pressure levels in patients blacks. This may be due to the fact that patients blacks with hypertension is more common in hypertension with low renin activity.

Cough. In applying the ACE inhibitors were reported occurrence of cough. Characteristically, the cough unproductive, long and disappears after discontinuation of therapy. In the differential diagnosis of cough should be remembered at possibility of cough due to the use of ACE inhibitors.

Use during pregnancy or lactation

Pregnancy. Ramipril is contraindicated during pregnancy. Thus, it is necessary to exclude pregnancy before treatment. Pregnancy should be avoided if treatment with ACE inhibitors is a must.

If a patient plans to become pregnant, you need to stop treatment with ACE inhibitors, ie replace them with another type of treatment.

If a patient becomes pregnant during the treatment, the use of drug therapy must be replaced without ACE inhibitors can be faster.

Breastfeeding. Due to lack of information on the use of ramipril during breast feeding is not recommended for this drug to women who are breastfeeding and it is desirable to give preference to other drugs the use of which during lactation is safer, particularly in breast feeding infants or premature infants.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Some side effects (e.g., the symptoms of lowering blood pressure, such as dizziness) can disrupt a patient's ability to concentrate and to reduce its rate of reaction is risky situations where these qualities are of particular importance (e.g., operating a vehicle or other machinery ).

It is usually possible at the beginning of treatment or during the transition from therapy for the treatment of other drugs ramipril. After the first dose or further dose escalation is not desirable to operate a vehicle or work with other mechanisms for several hours.

Dosing and Administration

A preparation for oral administration.

Ramipril is recommended to take daily at the same time. The drug can be taken before, during and after eating, because food intake does not affect the bioavailability of the drug. Tablets of 2.5 mg, 5 mg and 10 mg are used for the bisection for receiving a dose of 1.25 mg, 2.5 mg and 5 mg respectively. They can not chew or crush.

Adults.

Patients who used diuretics. Early treatment can occur hypotension, whose development is more likely in patients who simultaneously receive diuretics. In such cases it is advisable to exercise caution, as these patients may reduce blood volume and / or quantity of electrolytes.

It is advisable to discontinue the use of diuretics 2-3 days prior to initiation of treatment with ramipril, if possible. In patients with hypertension, which can not be undone diuretic treatment should be started at a dose of 1.25 mg. One should carefully monitor renal function and potassium levels in the blood. Further ramipril dosage should be adjusted according to the target blood pressure levels.

Arterial hypertension .

The dose should be adjusted individually, depending on the particular condition of the patient and the results of reference blood pressure measurement. Ramipril can be used as monotherapy or in combination with antihypertensive drugs of other classes.

The initial dose. drug treatment should begin gradually, starting with a recommended starting dose of 2.5 mg per day.

Patients with significant activation of the RAAS after receiving the initial dose may occur a significant reduction in blood pressure. For these patients, the recommended dose is 1.25 mg and their treatment should begin under control.

Titrating dose and the maintenance dose. The dose may be doubled every 2-4 weeks to achieve target blood pressure levels; ramipril maximum dose is 10 mg per day. Typically, the drug should be taken one time a day.

Prevention of cardiovascular diseases.

The initial dose. The recommended starting dose is 2.5 mg 1 time per day.

Titrating dose and the maintenance dose. Depending on individual tolerance dose should be gradually increased. Double the dose recommended after 1-2 weeks of treatment, and then - after 2-3 weeks - to increase its target maintenance dose of 10 mg 1 time per day (see also the information provided above dosage formulation for patients receiving diuretics.).

The treatment of kidney disease.

Patients with diabetes mellitus and microalbuminuria.

The initial dose. The recommended starting dose is 1.25 mg 1 time per day.

Titrating dose and the maintenance dose. Depending on individual tolerability further treatment dose can be increased. After 2 weeks of treatment, a single dose is recommended doubled to 2.5 mg, and then 5 mg after 2 weeks of treatment.

Patients with diabetes and at least one factor of cardiovascular risk.

The initial dose. The recommended starting dose is 2.5 mg 1 time per day.

Titrating dose and the maintenance dose. Depending on the individual tolerability of the drug in the further treatment dose should be increased. After 1-2 weeks of treatment the daily dose is recommended to double to 5 mg and then 10 mg after 2-3 weeks of treatment. The target daily dose of 10 mg.

Patients with non-diabetic nephropathy, which indicates the presence makroproteinurii ≥ 3 g / day.

The initial dose. The recommended starting dose is 1.25 mg 1 time per day.

Titrating dose and the maintenance dose. Depending on the individual tolerability of the drug in the further treatment dose should be increased. After 2 weeks of treatment, a single dose is recommended doubled to 2.5 mg, and then 5 mg after 2 weeks of treatment.

Heart failure with clinical manifestations.

The initial dose. For patients whose condition has stabilized after treatment with diuretics, the recommended starting dose is 1.25 mg per day.

Titrating dose and the maintenance dose. Dose ramipril titrated by its doubled every 1-2 weeks, to a maximum daily dose of 10 mg. It is desirable to distribute the dose to 2 doses.

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

The initial dose. At 48 hours after the onset of myocardial infarction patients whose condition clinically and hemodynamically stable, prescribe a starting dose of 2.5 mg 2 times a day for 3 days. If the initial dose of 2.5 mg poorly tolerated, then it is necessary to apply a dose of 1.25 mg 2 times a day for 2 days followed by an increase to 2.5 mg and 5 mg 2 times a day. If the dose can be increased to 2.5 mg 2 times a day, the treatment should be discontinued (see also. The above-mentioned information on the dosage of the drug to patients receiving diuretics).

Titrating dose and the maintenance dose. Subsequently daily dose enhanced by doubling it at intervals of 1-3 days until the target maintenance dose of 5 mg 2 times a day.

When possible, the maintenance dose to allocate 2 admission.

If the dose can be increased to 2.5 mg 2 times a day, the treatment should be discontinued. Experience in treating patients with severe heart failure (IV FC NYHA classification) immediately after myocardial infarction is still not enough. If, however, the decision on the treatment of patients with ramipril is recommended to start treatment with a dose of 1.25 mg 1 time a day, any increase in spending with extreme caution.

Specific categories of patients.

Patients with impaired renal function. The daily dosage for patients with impaired kidney function is dependent on the creatinine clearance:

• If creatinine clearance ≥ 60 ml / min, initial dose correction needed (2.5 mg / day) is not present, and the maximum daily dose is 10 mg;
• If creatinine clearance of 30-60 ml / min, initial dose correction needed (2.5 mg / day) is not present, and the maximum daily dose is 5 mg;
• If creatinine clearance of 10-30 ml / min, the initial dose is 1.25 mg / day and the maximum daily dose of - 5 mg;
• Patients with hypertension who are on hemodialysis: hemodialysis ramipril appears slightly; starting dose is 1.25 mg and a maximum daily dose of - 5 mg drug should be taken within a few hours after hemodialysis.

Patients with impaired liver function. Treatment of ramipril in patients with impaired liver function should be initiated under close supervision, and the maximum daily dose of such cases must be 2.5 mg.

Patients of advanced age. The initial dose should be lower, and further dose titration should be carried out more gradually, given the high risk of side effects, particularly in patients who are very elderly and infirm patients. In such cases, prescribe minimum initial dose - 1.25 mg of ramipril.

Children

Ramipril is not recommended for children, because the data on the efficacy and safety of this drug in these patients is not enough.

Overdose

Overdose symptoms ACE inhibitors may include excessive peripheral vasodilatation (with severe arterial hypotension, shock), bradycardia, electrolyte imbalance, renal failure. Status of the patient should be carefully monitored. Appoint symptomatic and supportive treatment. The measures proposed include primary detoxification (gastric lavage, sorbents) and means for recovery of hemodynamic stability, including the designation α 1 adrenergic agonists or angiotensin II (Angiotensinamide). Ramiprilat, the active metabolite of ramipril, is bad is output from the systemic circulation by hemodialysis.

Adverse Reactions

The safety profile of ramipril product contains data on persistent cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalemia, impaired liver or kidney function, pancreatitis, severe skin reactions and neutropenia / agranulocytosis.

Adverse reactions are classified according to frequency of occurrence as follows: very often (≥ 1/10), often (≥ 1/100, <1/10), rare (≥ 1/1000, <1/100), rare (≥ 1/10000 <1/1000), very rare (<1/10000), unidentified (can not be established from the available data).

With the cardiovascular system: often - arterial hypotension, orthostatic fall in blood pressure, fainting; rare - myocardial ischemia including angina pectoris or myocardial infarction; tachycardia, arrhythmia, feeling heart palpitations, peripheral edema, redness, feeling the tides; rarely - vascular stenosis, hypoperfusion, vasculitis unidentified - Raynaud's syndrome.

From the hematopoietic system: sometimes - eosinophilia; rarely - reducing the number of leukocytes (including neutropenia or agranulocytosis), reduction in the number of erythrocytes, hemoglobin levels decrease, reducing the number of platelets; unidentified - bone marrow failure, pancytopenia, haemolytic anemia.

From the nervous system: often - headache, dizziness, and sometimes - vertigo, paraesthesia, ageusia, dysgeusia; rarely - tremor, imbalance; unidentified - cerebral ischemia, including ischemic stroke and transient ischemic attack, impaired psychomotor functions, burning sensation, parosmiya.

On the part of the organ of vision: rarely - blurred vision, including blurred vision; rarely - conjunctivitis.

On the part of the ear and labyrinth: rarely - hearing loss, tinnitus.

The respiratory system: often - unproductive irritating cough, bronchitis, sinusitis, shortness of breath; rarely - bronchospasm, including exacerbation of asthma, nasal congestion.

On the part of the digestive tract: often - inflammation in the gastrointestinal tract, digestive disturbances, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting rarely - pancreatitis (in rare cases been reported lethal effects of the application of ACE inhibitors), increased levels of pancreatic enzymes prostate, small bowel angioedema, pain in the upper part of the stomach, including gastritis, constipation, dry mouth rarely - glossitis; unidentified - stomatitis.

From the urinary system: rarely - renal function, including acute renal failure, increase the amount of urine, worsening background proteinuria, increased levels of urea and creatinine in the blood.

Skin and subcutaneous tissue disorders: often - a rash, maculopapular in particular; rarely - angioedema, in very exceptional cases - violation airway due angioedema, which can be fatal; itching, rash; rarely - exfoliative dermatitis, urticaria, onycholysis; very rarely - photosensitivity reactions; unidentified - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis flow, psoriatic dermatitis, and lichenoid rash pemfigoidnaya or enanthema, alopecia.

On the part of the musculoskeletal system: often - muscle cramps, myalgia, rarely - arthralgia.

Endocrine disorders: Unidentified - syndrome of inappropriate secretion of ADH.

Metabolic disorders: often - increased levels of potassium in the blood rarely - anorexia, a decrease in appetite unidentified - a decrease in the level of sodium in the blood.

Common disorders: often - chest pain, fatigue; sometimes pyrexia; rarely - asthenia.

On the part of the immune system: unidentified - anaphylactic and anaphylactoid reactions, an increase in the level of antinuclear antibodies.

Hepatobiliary system: rarely - increased levels of hepatic enzymes and / or conjugates of bilirubin rarely - cholestatic jaundice, damage to the liver cells; unidentified - acute liver failure, cholestatic or cytolytic hepatitis (in very exceptional cases - with a fatal outcome).

On the part of the reproductive function: sometimes - transient erectile impotence, decreased libido unidentified - gynecomastia.

Mental disorders: rarely - decreased mood, anxiety, nervousness, anxiety, sleep disturbances, including drowsiness rarely - a state of confusion; unidentified - violation of attention.

Shelf life

2 years.

Storage conditions

Store at a temperature of no higher than 25 ° in the original packaging. Keep out of the reach of children.

Packaging

For 10 tablets in a blister, 3 (10 × 3) blisters in a cardboard box.

Category of leave

On prescription.