Instructions Ampril tablets 5 mg blister No. 30
Composition
active ingredient: ramipril;
1 tablet contains ramipril 1.25 mg or 2.5 mg, or 5 mg, or 10 mg;
excipients:
tablets of 1.25 mg and 10 mg: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate;
2.5 mg tablets: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, Pigment Blend PB 22886 Yellow (contains lactose monohydrate, iron oxide yellow (E 172));
5 mg tablets: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, Pigment blend PB 24899 Pink (contains lactose monohydrate, iron oxide yellow (E 172), iron oxide red (E 172)).
Dosage form
Pills.
Main physicochemical properties:
1.25 mg tablets – oval, flat tablets without a shell, white or almost white in color;
2.5 mg tablets – oval, flat tablets without a shell, yellow in color;
5 mg tablets – oval, flat tablets without a shell, pink in color;
10 mg tablets – oval, flat tablets without a shell, white or almost white in color.
Pharmacotherapeutic group
. Agents acting on the renin-angiotensin system. ACE inhibitors. Ramipril. ATC code C09A A05.
Pharmacological properties
Pharmacodynamics
Ramipril is a prodrug, after absorption it is broken down in the liver to form ramiprilat. Ramiprilat is a potent long-acting angiotensin-converting enzyme (ACE) inhibitor. ACE catalyzes the conversion of angiotensin I into the vasoconstrictor substance angiotensin II. ACE is an analogue of kininase, an enzyme that catalyzes the breakdown of bradykinin. Inhibition of ACE activity leads to a decrease in the concentration of angiotensin II, an increase in plasma renin activity, an increase in the action of bradykinin and a decrease in aldosterone secretion. The latter may lead to an increase in serum potassium.
In patients with hypertension, the antihypertensive and hemodynamic effects of ramipril are due to the expansion of stable vessels and a decrease in total peripheral vascular resistance, resulting in a gradual decrease in blood pressure. The heart rate is mostly unchanged. During long-term treatment, there is a decrease in left ventricular hypertrophy without affecting cardiac function. The hypotensive effect after a single dose is manifested 1-2 hours after administration, reaches a maximum within 3-6 hours and usually lasts for 24 hours. Ramipril is also an effective drug for the treatment of congestive heart failure. In patients with clinical signs of chronic heart failure after acute myocardial infarction, it reduces the risk of sudden death, progression of heart failure to severe or persistent heart failure and reduces the frequency of hospitalizations for heart failure.
According to published data, ramipril significantly reduces the incidence of myocardial infarction, stroke and reduces cardiovascular mortality in patients at increased risk due to cardiovascular disease (e.g., active coronary artery disease, previous stroke or peripheral vascular disease) or diabetes mellitus, who have at least one additional risk factor (microalbuminuria, hypertension, increased total cholesterol, low high-density lipoprotein cholesterol, smoking). The drug also reduces overall mortality and the need for revascularization and delays the onset and progression of congestive heart failure. In patients with diabetes, as well as other patients, ramipril significantly reduces the likelihood of microalbuminuria and the risk of developing nephropathy.
Pharmacokinetics
Ramipril is rapidly absorbed from the gastrointestinal tract. Absorption is 50-60% and is independent of food intake. Maximum serum concentrations are reached within 1 hour. The elimination half-life of ramipril is 1 hour.
Ramipril is metabolized in the liver. The main metabolite is ramiprilat, which is 6 times more potent as an ACE inhibitor than ramipril. In addition to ramiprilat, inactive metabolites (diketopiperazine ester and diketopiperazine acid, as well as compounds) have also been identified.
The maximum concentration of ramiprilat in the blood serum is reached 2-4 hours after administration, a constant concentration in the serum is reached after 4 days.
Approximately 73% of ramipril and 56% of ramiprilat are bound to serum proteins.
Ramipril and ramiprilat are mainly excreted in the urine (approximately 60%), mainly as metabolites, and less than 2% of the administered dose is excreted as unchanged ramipril.
Ramiprilat is eliminated in several stages. After administration of ramipril in therapeutic doses, the terminal half-life is 13 to 17 hours.
Animal studies have shown that this drug passes into breast milk.
In patients with renal insufficiency, the excretion of ramipril, ramiprilat and their metabolites is slowed down, therefore the dosage of ramipril should be adjusted depending on renal function (see "Method of administration and dosage").
In patients with hepatic insufficiency (possibly due to decreased hepatic esterase activity), the metabolic conversion of ramipril to ramiprilat may be slowed down and serum ramipril concentrations may increase.
Indication
Treatment of arterial hypertension. Prevention of cardiovascular diseases: reduction of the incidence of cardiovascular diseases and mortality in patients with:
- severe cardiovascular disease of atherothrombotic origin (history of ischemic heart disease or stroke or peripheral vascular disease);
- diabetes, who have at least one cardiovascular risk factor (see section "Pharmacological properties").
Treatment of kidney disease:
- initial glomerular diabetic nephropathy, as evidenced by the presence of microalbuminuria;
- severe glomerular diabetic nephropathy, as evidenced by the presence of macroproteinuria, in patients who have at least one cardiovascular risk factor (see section "Pharmacological properties");
- severe glomerular non-diabetic nephropathy, as evidenced by the presence of macroproteinuria ≥ 3 g per day (see section "Pharmacological properties").
Treatment of heart failure accompanied by clinical manifestations. Secondary prevention after acute myocardial infarction: reduction of mortality during the acute phase 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 (angiotensin-converting enzyme) inhibitors (see section “Composition”).
– History of angioedema (hereditary, idiopathic or previously experienced while taking ACE inhibitors or angiotensin II receptor antagonists).
– Significant bilateral renal artery stenosis or renal artery stenosis in the presence of a single functioning kidney.
– Pregnancy (see section “Use during pregnancy and breastfeeding”).
– Ramipril should not be used in patients with hypotension or hemodynamically unstable conditions.
– Should not be used with aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal impairment (GFR < 60 mL/min).
– 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
Contraindicated combinations.
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 "Contraindications"). If such treatment is necessary, the use of a different dialysis membrane or the use of a different class of antihypertensive agents should be considered.
The combined use of Ampril® with aliskiren-containing medicinal products 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.
Potassium salts, heparin, potassium-sparing diuretics and other active substances that increase plasma potassium levels (including angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin). Hyperkalaemia may occur, therefore careful monitoring of plasma potassium levels is necessary.
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 Ampril®. Close monitoring of blood pressure is recommended.
Increased likelihood of hematological reactions (see section "Special warnings and precautions for use").
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. A reduction in the antihypertensive effect of Ampril® is expected. Furthermore, 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.
Specific hyposensitization. ACE inhibition increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that this effect may also be observed for other allergens.
Application features
Special categories of patients.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with aliskiren-containing medicinal products.
Dual blockade of the renin-angiotensin-aldosterone system through the combined use of Ampril® and aliskiren is not recommended, as there is an increased risk of developing arterial hypotension, hyperkalemia, and changes in renal function.
The combined use of Ampril® and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR 60 ml/min) (see section "Contraindications").
Patients at particular risk of hypotension.
Patients with a strongly activated renin-angiotensin-aldosterone system. Patients with a strongly activated renin-angiotensin-aldosterone system are at risk of a sudden significant fall in blood pressure and deterioration of renal function due to ACE inhibition, particularly when an ACE inhibitor or concomitant diuretic is given for the first time or when the dose is increased for the first time. A strongly activated renin-angiotensin-aldosterone system, requiring medical supervision, including regular monitoring of blood pressure, may be expected, for example, in patients:
- 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 there is or may develop a lack of fluid or electrolytes (including those receiving diuretics);
- with liver cirrhosis and/or ascites;
- who are undergoing extensive surgical interventions or during anesthesia with the use of 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 applied with consideration of the risk of volume overload).
In patients with impaired liver function, the response to treatment with Ampril® 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 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 kidney function.
Renal function should be assessed before and during treatment and the dose adjusted, especially in the first weeks of treatment. Patients with impaired renal function should be monitored particularly closely (see section 4.2). There is a risk of worsening 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). If angioedema develops, Ampril should be discontinued. Emergency treatment should be initiated immediately. The patient should be kept under medical observation for at least 12-24 hours and may be discharged after complete resolution of symptoms.
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, Ampril® should be temporarily discontinued.
Hyperkalemia.
Hyperkalemia has been observed in some patients treated with ACE inhibitors, including Ampril®. 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 concomitant use of the above-mentioned drugs is considered appropriate, regular monitoring of plasma potassium levels is recommended (see section "Interaction with other medicinal products and other forms of interaction").
Neutropenia/agranulocytosis.
Cases of neutropenia/agranulocytosis, as well as thrombocytopenia and anemia have been observed rarely. Bone marrow suppression has also been reported. In order to detect possible leukopenia, it is recommended to monitor the number of white blood cells in the blood. More frequent monitoring is advisable at the beginning of treatment and in patients with impaired renal function, concomitant collagen disease (e.g. systemic lupus erythematosus or scleroderma) or those taking other drugs that can cause changes in the blood picture (see sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).
Ethnic differences. ACE inhibitors cause angioedema more often in black patients than in non-blacks. As with other ACE inhibitors, the antihypertensive effect of ramipril may be less pronounced in black patients than in non-blacks. 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.
Use during pregnancy or breastfeeding
Pregnancy.
Ampril® is contraindicated for use during pregnancy (see section "Contraindications"). Therefore, pregnancy should be excluded before starting treatment. Pregnancy should be avoided if treatment with ACE inhibitors is necessary.
If the patient plans to become pregnant, treatment with ACE inhibitors should be discontinued, i.e. replaced with another type of treatment.
If the patient becomes pregnant during treatment, Ampril® should be replaced with therapy without ACE inhibitors as soon as possible.
Breastfeeding: Because no information is available regarding the use of ramipril during breastfeeding (see section 5.1), this drug is not recommended for use in nursing mothers and alternative treatments with better established safety profiles during lactation are preferable, especially while nursing a newborn or preterm infant.
The ability to influence the reaction speed when driving or working with other mechanisms
Some side effects (certain symptoms of low blood pressure, such as dizziness or vertigo) may affect the ability to drive or operate machinery. Patients should be advised not to drive or operate hazardous machinery until they are sure that they respond normally to the treatment.
Method of administration and doses
Drug for oral use.
It is recommended to take Ampril® at the same time every day. The drug can be taken before, during and after meals, as food intake does not affect the bioavailability of the drug. Ampril® tablets should be swallowed whole with water (approximately ½ glass). They should not be chewed or crushed.
Adults.
Patients taking diuretics. At the beginning of treatment with Ampril®, 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 Ampril®, if possible (see section "Special instructions").
In patients with arterial hypertension who cannot discontinue the diuretic, treatment with Ampril® should be initiated at a dose of 1.25 mg. Renal function and blood potassium levels should be closely monitored. Subsequent dosage of Ampril® should be adjusted depending on the target blood pressure level.
The dose should be selected individually, depending on the characteristics of the patient's condition (see section "Special instructions for use") and the results of control blood pressure measurements. Ampril® can be used as monotherapy or in combination with other classes of antihypertensive drugs.
Initial dose. Treatment with Ampril® should be initiated gradually, starting with the recommended initial dose of 2.5 mg per day.
In patients with a strongly activated renin-angiotensin-aldosterone system, a significant decrease in blood pressure may occur after the initial dose. In 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 Ampril® is 10 mg per day. As a rule, the drug is taken once a day.
Prevention of cardiovascular diseases.
Initial dose. The recommended initial dose of Ampril® 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 - after another 2-3 weeks - increase it to the target maintenance dose of 10 mg 1 time per day.
Also see above for dosing information for patients receiving diuretics.
Treatment of kidney disease.
In patients with diabetes and microalbuminuria.
Initial dose. The recommended initial dose of Ampril® is 1.25 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is 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.
In patients with diabetes and at least one cardiovascular risk factor.
Initial dose. The recommended initial dose of Ampril® is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is increased during further treatment. After 1-2 weeks of treatment, it is recommended to double the daily dose of Ampril® to 5 mg, and then to 10 mg after another 2-3 weeks of treatment. The target daily dose is 10 mg.
In patients with non-diabetic nephropathy, as evidenced by macroproteinuria ≥ 3 g/day.
Initial dose. The recommended initial dose of Ampril® is 1.25 mg once daily.
Dose titration and maintenance dose. Depending on the individual patient's tolerance of the drug, the dose is 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 Ampril® is 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 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.
Also see above for dosing information for patients receiving diuretics.
Dose titration and maintenance dose. The daily dose is then 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 is divided into 2 doses.
If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. Experience in the treatment of patients with severe (NYHA class IV) heart failure immediately after myocardial infarction is still insufficient. If a decision is nevertheless made to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg once daily and any increase should be carried out 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"):
- if creatinine clearance is ≥ 60 ml/min, there is no need to adjust the initial dose (2.5 mg/day), and the maximum daily dose is 10 mg;
- if creatinine clearance is 30-60 ml/min, there is no need to adjust the initial dose (2.5 mg/day), and the maximum daily dose is 5 mg;
- patients with arterial hypertension undergoing hemodialysis: ramipril is removed to a small extent during hemodialysis; the initial dose is 1.25 mg, and the maximum daily dose is 5 mg; the drug should be taken a few hours after the hemodialysis session.
Patients with impaired liver function (see section "Pharmacological properties"). Treatment with Ampril® 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 ramipril should be prescribed.
Children.
The use of ramipril in children has not been studied, therefore this drug is not recommended for their treatment.
Overdose
Overdose may cause excessive peripheral vasodilation (accompanied by severe hypotension, shock), bradycardia, electrolyte imbalance and renal failure.
If hypotension occurs, the patient should be placed in a horizontal position, with the head placed on a low pillow, and the legs raised. If necessary, it is recommended to increase the plasma volume by infusion of 0.9% sodium chloride solution. After taking a large number of tablets, it is recommended to perform gastric lavage and administer adsorbents and sodium sulfate (in the first 30 minutes, if possible). It is necessary to carefully monitor blood pressure, renal function and serum potassium. In case of hypotension, in addition to volume and salt compensation, an alpha-1 adrenergic receptor agonist (e.g. noradrenaline, dopamine) and angiotensin II (angiotensin amide) can be administered.
The effectiveness of dialysis in treating intoxication has not been proven.
Adverse reactions
The safety profile of Ampril® 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.
Within each group, adverse reactions are presented in order of decreasing seriousness.
Cardiac disorders: myocardial ischemia, including angina pectoris or myocardial infarction; tachycardia; arrhythmia; palpitations; peripheral edema.
Blood and lymphatic system disorders: 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.
Nervous system: headache, dizziness, vertigo, paresthesia, ageusia, dysgeusia, tremor, balance disorders, cerebral ischemia, including ischemic stroke and transient ischemic attack; impaired psychomotor functions; burning sensation; parosmia.
From the organs of vision: visual disturbances, including blurred vision, conjunctivitis.
From the side of the organs of hearing and labyrinth: hearing impairment, tinnitus.
Respiratory, thoracic and mediastinal disorders: non-productive irritating cough, bronchitis, sinusitis, dyspnea, nasal congestion, bronchospasm, including exacerbation of asthma.
Gastrointestinal: gastrointestinal inflammation, indigestion, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting, pancreatitis (in isolated cases, fatal outcomes have been reported with the use of ACE inhibitors), increased pancreatic enzymes, angioedema of the small intestine, upper abdominal pain, including gastritis, constipation, dry mouth, glossitis, aphthous stomatitis.
On the part of the kidneys and urinary tract: impaired renal function, including acute renal failure; increased diuresis, worsening of background proteinuria, increased blood urea; increased blood creatinine.
Skin and subcutaneous tissue disorders: rash, particularly maculopapular, angioedema; in exceptional cases, airway obstruction due to angioedema, which may be fatal; pruritus, hyperhidrosis, exfoliative dermatitis, urticaria, onycholysis, photosensitivity reaction, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriatic dermatitis, pemphigoid or lichenoid exanthema or enanthema, alopecia.
Musculoskeletal and connective tissue disorders: muscle spasms, myalgia, arthralgia. Endocrine disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Metabolic and nutritional disorders: increased blood potassium levels, anorexia, decreased appetite, decreased blood sodium levels.
Vascular disorders: hypotension, orthostatic hypotension, syncope, flushing, vascular stenosis, hypoperfusion, vasculitis, Raynaud's phenomenon.
General disorders: chest pain, fatigue, pyrexia, asthenia.
Immune system disorders: anaphylactic and anaphylactoid reactions, increased antinuclear antibody levels
Hepatobiliary disorders: increased levels of liver enzymes and/or bilirubin conjugates, cholestatic jaundice, liver cell damage, acute liver failure, cholestatic or cytolytic hepatitis (in very exceptional cases - fatal).
Reproductive system and breast disorders: transient erectile impotence, decreased libido, gynecomastia.
On the part of the psyche: decreased mood, anxiety, nervousness, restlessness, sleep disturbances, including drowsiness, a state of confusion, impaired attention.
Expiration date
1.25 mg tablets – 2 years.
Tablets of 2.5 mg, 5 mg and 10 mg – 3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging to protect from moisture. Keep out of the reach of children.
Packaging
10 tablets in a blister; 1 or 3, or 6, or 9 blisters in a cardboard box;
7 tablets in a blister; 2 or 4, or 8, or 12, or 14 blisters in a cardboard box.
Vacation conditions
According to the recipe.
Producer
KRKA, dd, Novo mesto, Slovenia.
Location
Address of the production site responsible for bulk production, primary and secondary packaging, batch control and batch release:
Smarjeska cesta 6, 8501 Novo mesto, Slovenia.
Address of the production site responsible for "in bulk" production, primary and secondary packaging:
Novomeška cesta 22, Sentjernej (Beta), 8310, Slovenia.
