Instructions for use Alotendin tablets 5 mg/5 mg blister No. 30
Composition
active ingredients: amlodipine, bisoprolol;
1 tablet of Alotendin 5 mg/5 mg contains 5 mg of bisoprolol fumarate and 5 mg of amlodipine, corresponding to 6.95 mg of amlodipine besylate;
1 tablet of Alotendin 10 mg/5 mg contains 10 mg of bisoprolol fumarate and 5 mg of amlodipine, corresponding to 6.95 mg of amlodipine besylate;
1 tablet of Alotendin 5 mg/10 mg contains 5 mg of bisoprolol fumarate and 10 mg of amlodipine, which corresponds to 13.9 mg of amlodipine besylate;
1 tablet of Alotendin 10 mg/10 mg contains 10 mg of bisoprolol fumarate and 10 mg of amlodipine, corresponding to 13.9 mg of amlodipine besylate;
Excipients: microcrystalline cellulose, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
5 mg/5 mg tablets: white or almost white, oblong, slightly biconvex, odorless tablets, scored on one side and engraved with MS on the other side;
10 mg/5 mg tablets: white or almost white, oval, slightly biconvex, odorless tablets, scored on one side and engraved with MS on the other side;
5 mg/10 mg tablets: white or almost white, round, flat, beveled tablets, odorless, with a score on one side and engraved with MS on the other side;
10 mg/10 mg tablets: white or almost white, round, slightly biconvex, odorless tablets, scored on one side and engraved with MS on the other side.
Pharmacotherapeutic group
Selective β-blockers and other antihypertensive agents.
ATX code C07 FB.
Pharmacological properties
Pharmacodynamics
Amlodipine is a calcium ion antagonist (slow calcium channel blocker) that blocks the transmembrane flow of calcium ions into myocardial and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The antianginal effect of amlodipine is provided by two mechanisms:
- dilation of peripheral arterioles and, as a result, a decrease in total peripheral resistance (afterload). Since the heart rate does not change, a decrease in the load on the heart reduces myocardial energy consumption and its oxygen demand;
- dilation of the main coronary arteries and arterioles in both intact and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium
- in patients with vasospastic angina (Prinzmetal's angina or variant angina).
In patients with hypertension, once-daily administration of amlodipine provides clinically significant reductions in blood pressure over 24 hours. Due to the slow onset of action of amlodipine, a rapid decrease in blood pressure is not observed.
In patients with angina pectoris, amlodipine prolongs the total exercise time, the time to angina attack, and increases the time to significant ST-segment depression, as well as reducing the frequency of angina attacks and the need for nitroglycerin.
Amlodipine does not cause undesirable metabolic effects or changes in plasma lipid levels, so it can be used in patients with bronchial asthma, diabetes mellitus, and gout.
Bisoprolol is a selective β1-adrenoceptor blocker, without intrinsic sympathomimetic activity, and it also does not have significant membrane-stabilizing properties.
Blocks beta1-adrenergic receptors and reduces the effect of catecholamines on them. Has antihypertensive and antianginal effects.
The mechanism of antihypertensive action is carried out by reducing cardiac output, reducing sympathetic stimulation of peripheral vessels, and inhibiting the release of renin by the kidneys.
The antianginal effect is associated with the blockade of β1-adrenoreceptors, which leads to a decrease in myocardial oxygen demand due to negative chronotropic and inotropic effects. Thus, bisoprolol eliminates or reduces the symptoms of ischemia.
The maximum effect occurs 3-4 hours after oral administration. Usually the maximum hypertensive effect is observed after 2 weeks of use.
Pharmacokinetics
Amlodipine.
After oral administration of therapeutic doses, amlodipine is well absorbed and reaches peak blood concentrations 6-12 hours after administration. Food intake does not affect the bioavailability of amlodipine. Absolute bioavailability is 64% to 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately
93–98% of circulating amlodipine is bound to plasma proteins.
Amlodipine is metabolized in the liver to form inactive metabolites, 10% of the drug is excreted in the urine unchanged, 60% in the form of metabolites, 20-25% in the feces.
The half-life from blood plasma is approximately 35-50 hours, which allows the drug to be administered once a day.
Bisoprolol is almost completely (up to 90%) absorbed from the gastrointestinal tract. The effect of the first passage through the liver is expressed to a small extent (approximately 10%), absolute bioavailability is approximately 90%. The half-life from blood plasma is 10-12 hours, which provides a therapeutic effect for 24 hours after a single daily dose.
Bisoprolol is excreted from the body in two ways. 50% is metabolized by the liver to inactive metabolites, which are then excreted by the kidneys. The last 50% is excreted by the kidneys unchanged. Active metabolites are not formed in the human body.
Indication
Arterial hypertension, as monotherapy or in combination with other antihypertensive agents.
Chronic stable angina, as monotherapy or in combination with other antianginal agents.
As replacement therapy in patients whose blood pressure and/or chronic stable angina are adequately controlled by concomitant use of amlodipine and bisoprolol at the same dosages.
Contraindication
For amlodipine/bisoprolol tablets: hypersensitivity to amlodipine, dihydropyridine derivatives, bisoprolol and/or to any of the excipients.
For amlodipine.
– Unstable angina.
– Severe arterial hypotension.
– Shock (including cardiogenic shock).
– Obstruction of the left ventricular outflow tract (e.g. severe aortic stenosis).
– Hemodynamically unstable heart failure after acute myocardial infarction.
For bisoprolol:
- acute heart failure or heart failure in a state of decompensation requiring inotropic therapy;
- cardiogenic shock;
- AV block II-III degrees;
- sick sinus syndrome;
- sinoatrial block, bradycardia (heart rate less than 60 per minute), arterial hypotension (systolic blood pressure < 100 mm Hg) before starting treatment;
- bronchial asthma, chronic obstructive pulmonary disease;
- pronounced peripheral circulatory disorders, Raynaud's syndrome;
- untreated pheochromocytoma;
- metabolic acidosis.
Interaction with other medicinal products and other types of interactions
For amlodipine.
Drugs that require caution when used concomitantly: thiazide diuretics, beta-blockers, long-acting nitrates, sublingual nitroglycerin, nonsteroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.
Concomitant use of amlodipine with digoxin does not lead to changes in the concentration of digoxin in the blood plasma and does not affect its renal clearance.
Concomitant use of amlodipine with cimetidine does not affect the pharmacokinetics of amlodipine.
Concomitant use of amlodipine with warfarin does not significantly affect prothrombin time.
Effect of other drugs on amlodipine.
CYP3A4 inhibitors.
Concomitant use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine exposure, which may also lead to an increased risk of hypotension. The clinical significance of such changes may be more pronounced in elderly patients. Clinical monitoring of the patient and dose adjustment may be necessary.
It is not recommended to use amlodipine and grapefruit or grapefruit juice simultaneously, since in some patients the bioavailability of amlodipine may increase, which, in turn, leads to increased hypotensive effect.
CYP3A4 inducers.
There is no information on the effect of CYP3A4 inducers on amlodipine. Concomitant use of amlodipine and substances that are CYP3A4 inducers (e.g. rifampicin, St. John's wort) may lead to a decrease in amlodipine plasma concentrations, therefore such combinations should be used with caution.
Dantrolene (infusion).
Fatal ventricular fibrillation and cardiovascular collapse associated with hyperkalemia have been observed in animals following intravenous administration of verapamil and dantrolene. Due to the risk of hyperkalemia, it is recommended that calcium channel blockers such as amlodipine be avoided in patients predisposed to malignant hyperthermia and in the treatment of malignant hyperthermia.
The effect of amlodipine on other drugs.
The hypotensive effect of amlodipine potentiates the hypotensive effect of other antihypertensive agents.
Tacrolimus.
There is a risk of increased blood levels of tacrolimus when co-administered with amlodipine, but the pharmacokinetic mechanism of this interaction has not been fully established. To avoid tacrolimus toxicity when co-administered with amlodipine, regular monitoring of tacrolimus blood levels and, if necessary, dosage adjustment are required.
Cyclosporine.
Interaction studies of ciclosporin and amlodipine have not been conducted in healthy volunteers or other populations, except in renal transplant patients, where a variable increase in ciclosporin trough concentrations (mean 0-40%) was observed. In renal transplant patients receiving amlodipine, monitoring of ciclosporin concentrations should be considered and, if necessary, a reduction in the ciclosporin dose should be considered.
Simvastatin.
Clinical drug interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.
For bisoprolol.
Concomitant administration is not recommended.
Calcium antagonists (verapamil and to a lesser extent diltiazem): adversely affect contractions, atrioventricular conduction, and blood pressure. Intravenous administration of verapamil to patients taking β-blockers may result in significant hypotension and atrioventricular block.
Centrally acting antihypertensive drugs (clonidine, methyldopa, moxonidine, rilmenidine): Concomitant administration of these drugs may lead to a decrease in heart rate (heart rate), cardiac output, and vasodilation. Abrupt withdrawal of the drug may increase the risk of withdrawal syndrome in the form of arterial hypertension.
Drugs that require caution when used concomitantly
- Dihydropyridine-type calcium antagonists such as nifedipine: due to increased risk of arterial hypotension and risk of developing heart failure.
- Class 1 antiarrhythmic drugs (e.g. disopyramide, quinidine, lidocaine, phenytoin, flecainide, propafenone): due to increased negative effects on myocardial inotropic function, AV conduction.
- Class III antiarrhythmic drugs (e.g. amiodarone): due to increased effects on atrioventricular conduction.
- Parasympathomimetics: when used simultaneously, may cause an increase in atrioventricular conduction time and thereby increase the risk of bradycardia.
- Topical agents containing β-blockers (eye drops for the treatment of glaucoma) may complement the systemic effects of bisoprolol.
- Insulin and oral antidiabetic agents: increased hypoglycemic effect. Blockade of β-adrenergic receptors may mask signs of hypoglycemia.
- Cardiac glycosides: decrease in heart rate, prolongation of atrioventricular conduction.
- Nonsteroidal anti-inflammatory drugs: reduced antihypertensive effect.
- β-sympathomimetics (isoprenaline, dobutamine): combination with bisoprolol may reduce the effects of both drugs.
- Sympathomimetics that activate α- and ß-adrenergic receptors (e.g. adrenaline, noradrenaline): increase blood pressure. This interaction is more likely with non-selective β-blockers.
- Ergotamine derivatives: exacerbation of peripheral circulatory disorders.
- Tricyclic antidepressants, barbiturates, phenothiazines, and other antihypertensive agents: increase the risk of arterial hypotension.
Inhalation anesthetics, carbohydrate derivatives (chloroform, cyclopropane, halothane, methoxyflurane) when used simultaneously with β-blockers increase the risk of myocardial depression and the development of hypotensive reactions.
The action of non-depolarizing neuromuscular blockers may be enhanced and prolonged by β-blockers.
Drugs that require discussion when used concomitantly:
- Mefloquine: increased risk of bradycardia.
- Monoamine oxidase inhibitors (except MAO-B inhibitors): increased hypotensive effect of beta-blockers, as well as increased risk of hypertensive crisis.
- Rifampicin: a slight decrease in the half-life of bisoprolol is possible due to the effect on the metabolism of the drug by liver enzymes. However, dose adjustment is not required.
Application features
For amlodipine.
The safety and efficacy of amlodipine in hypertensive crisis have not been evaluated.
Patients with heart failure.
Amlodipine should be used with caution in this patient population. In a long-term placebo-controlled study in patients with severe heart failure (NYHA class III and IV), the incidence of pulmonary edema was higher with amlodipine than with placebo. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Patients with impaired liver function.
The half-life of amlodipine and AUC parameters are longer in patients with impaired liver function; there are no recommendations regarding the dosage of the drug. Therefore, this category of patients should start using the drug at the lowest dose. Caution should be exercised both at the beginning of the drug and when increasing the dose. Patients with severe hepatic insufficiency may require slow dose selection and careful monitoring of the patient's condition.
Elderly patients.
Increasing the dose of the drug in this category of patients should be done with caution.
Patients with renal failure.
This category of patients should use the usual doses of the drug. Changes in the concentration of amlodipine in the blood plasma do not correlate with the degree of renal dysfunction. Amlodipine is not removed by dialysis.
Amlodipine does not affect the results of laboratory tests.
It is not recommended to use amlodipine with grapefruit or grapefruit juice, as bioavailability may be increased in some patients, leading to increased hypotensive effect of the drug.
Reversible biochemical changes in the sperm head have been reported in some patients receiving calcium channel blockers. There is insufficient clinical information on the potential effect of amlodipine on fertility.
For bisoprolol.
In patients with coronary heart disease, treatment should not be stopped abruptly without urgent need, as this may lead to a transient deterioration of the condition. Bisoprolol should be prescribed with caution in patients with arterial hypertension or angina pectoris associated with heart failure.
Initiation and discontinuation of bisoprolol treatment requires regular monitoring.
Bisoprolol should be used with caution in the following conditions:
- diabetes mellitus with significant fluctuations in blood glucose levels; symptoms of hypoglycemia may be masked;
- strict fasting or diet;
- concomitant desensitization therapy. Bisoprolol may increase sensitivity to allergens and the severity of anaphylactoid reactions. In such cases, treatment with adrenaline does not always have a positive effect.
- first degree AV block;
- Prinzmetal's angina;
- peripheral arterial occlusive disease (at the beginning of therapy, complaints may worsen);
- patients with psoriasis or with a history of psoriasis, use only after careful assessment of the benefit/risk ratio);
- during treatment with bisoprolol, symptoms of thyrotoxicosis may be hidden;
- in patients with pheochromocytoma, bisoprolol can be used only after therapy with α-adrenergic blockers;
- before general anesthesia, it is necessary to inform the anesthesiologist about the use of β-adrenergic blockers. In patients who are scheduled for general anesthesia, the use of β-blockers reduces the incidence of arrhythmia and myocardial ischemia during anesthesia, intubation and the postoperative period. It is recommended to continue the use of β-blockers during the intraoperative period. The anesthesiologist should take into account the potential interaction with other drugs, which can lead to bradyarrhythmia, reflex tachycardia and a decrease in the ability of the reflex mechanism to compensate for a decrease in pressure. In case of discontinuation of bisoprolol before surgical interventions, the dose should be gradually reduced and the drug should be discontinued 48 hours before general anesthesia;
- in bronchial asthma and other chronic obstructive airway diseases; despite the fact that cardioselective β-blockers (β1) have a smaller effect on lung function compared to non-selective β-blockers, their use, like all β-blockers, in obstructive airway diseases should be avoided unless there are compelling reasons for therapy. If necessary, bisoprolol should be used with caution. In patients with obstructive airway diseases, treatment with bisoprolol should be started at the lowest dose and patients should be monitored for the appearance of new symptoms (such as shortness of breath, exercise intolerance, cough).
The specified drug contains an active substance that gives positive results in
anti-doping control.
Use during pregnancy or breastfeeding
For amlodipine.
The safety of amlodipine in women during pregnancy has not been established.
The use of amlodipine during pregnancy is recommended only in cases where there is no safer alternative and the risk associated with the disease itself outweighs the possible harm from treatment for the mother and fetus.
Reproductive toxicity was observed in animal studies at high doses.
Breastfeeding period.
It is not known whether amlodipine is excreted in human milk. A decision must be made whether to continue breastfeeding or to continue using amlodipine, taking into account the benefit of breastfeeding for the child and the benefit of the drug for the mother.
For bisoprolol.
Bisoprolol has pharmacological properties that may cause harmful effects on the course of pregnancy and/or the development of the fetus/newborn.
β-blockers reduce placental perfusion, which causes growth retardation, fetal death, spontaneous abortion, and preterm labor. Hypoglycemia and bradycardia may occur in the fetus and newborn. If treatment with β-blockers is necessary, selective β1-blockers are preferred.
Bisoprolol should not be used during pregnancy unless clearly necessary. If treatment with bisoprolol is deemed necessary, uteroplacental circulation and fetal growth should be monitored. In the event of adverse effects on pregnancy or the fetus, alternative treatment should be considered. Neonates should be closely monitored. Hypoglycemia and bradycardia can usually be expected in the first 3 days.
Breast-feeding.
It is not known whether bisoprolol passes into breast milk and if so, whether it could harm a nursing baby. Therefore, the use of amlodipine/bisoprolol tablets during breastfeeding is not recommended.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given the different individual patient response to the use of the drug, the ability to influence the reaction rate when driving vehicles or working with other mechanisms may be impaired, especially at the beginning of treatment, when changing treatment.
Method of administration and doses
The recommended daily dose is 1 tablet of the appropriate dosage; it is advisable to take the drug in the morning, regardless of meals, without chewing.
The maximum daily dose is 1 tablet of Alotendin 10 mg/10 mg per day.
The dosage range of the drug allows for flexible selection of the ratio of components depending on clinical needs.
Treatment should not be stopped abruptly, as this may lead to temporary deterioration of the clinical condition. This is especially true for patients with ischemic heart disease. A gradual dose reduction is recommended.
Liver and kidney dysfunction.
In case of hepatic insufficiency, the elimination of amlodipine is slowed down. There are no specific recommendations for the dosage of amlodipine, therefore the drug should be prescribed with caution in patients with impaired liver function. In case of severe hepatic insufficiency, the daily dose of bisoprolol should not exceed 10 mg.
In patients with mild or moderate renal insufficiency, there is no need to change the dosage. In case of severe renal insufficiency (creatinine clearance < 20 ml/min), the daily dose of bisoprolol should not exceed 10 mg.
Elderly patients can be prescribed the usual doses of the drug.
The combined drug amlodipine/bisoprolol is not recommended for use in children due to the lack of data on safety and efficacy.
Children
Alotendin is not recommended for use in children.
Bisoprolol. Clinical data on the efficacy and safety of the drug for the treatment of children are lacking.
Overdose
For amlodipine.
Experience with intentional overdose of the drug is limited.
Symptoms of overdose: Available information suggests that a significant overdose of amlodipine will result in excessive peripheral vasodilation and possibly reflex tachycardia. Significant and possibly prolonged systemic hypotension, including shock with fatal outcome, has been reported.
Treatment: Clinically significant hypotension due to amlodipine overdose requires active support of the cardiovascular system, including frequent monitoring of cardiac and respiratory functions, elevation of the lower extremities, monitoring of circulating fluid volume and urine output.
Vasoconstrictors can be used to restore vascular tone and blood pressure, making sure there are no contraindications to their use. Intravenous calcium gluconate may be useful for reversing the effects of calcium channel blockade.
Gastric lavage may be useful in some cases. Administration of activated charcoal to healthy volunteers within 2 hours of administration of 10 mg of amlodipine significantly reduced its absorption.
Since amlodipine is extensively protein bound, the effect of dialysis is negligible.
For bisoprolol.
The most common symptoms of overdose are bradycardia, hypotension, acute heart failure, bronchospasm, hypoglycemia. There is a wide variability in individual sensitivity to a single high dose of bisoprolol, patients with heart failure may be more sensitive to the drug.
In case of overdose, you should immediately consult a doctor.
Depending on the degree of overdose, treatment with the drug should be discontinued and supportive and symptomatic therapy should be administered. There is limited evidence that bisoprolol is difficult to dialyze.
For bradycardia: intravenous atropine. If there is no response, isoprenaline or another drug with a positive chronotropic effect should be administered with caution. In exceptional cases, an artificial pacemaker should be administered.
For arterial hypotension: taking vasoconstrictor drugs, intravenous administration of glucagon.
In case of atrioventricular block of the II and III degree: infusion of isoprenaline; if necessary, cardiac pacing.
In case of exacerbation of chronic heart failure: intravenous administration of diuretics and vasodilators.
For bronchospasm: bronchodilators (e.g. isoprenaline), β2-adrenomimetics and/or aminophylline.
For hypoglycemia: intravenous glucose administration.
Adverse reactions
Adverse reactions may be caused by each of the components of the drug.
When using amlodipine: the following side effects occur more often: headache, swelling (especially in the lower legs), increased fatigue, drowsiness, nausea, abdominal pain, hot flashes, palpitations, dizziness.
Laboratory tests: increased liver enzymes.
From the side of the cardiovascular system: increased heart rate; arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation); myocardial infarction.
From the blood and lymphatic system: leukopenia, thrombocytopenia, purpura.
Nervous system: headache, dizziness, drowsiness; peripheral neuropathy, syncope, hypoesthesia, paresthesia, taste disturbance, tremor; hypertonicity, peripheral neuropathy.
On the part of the organs of vision: visual impairment (including diplopia).
Respiratory system: shortness of breath, cough, rhinitis; dyspnea.
Gastrointestinal: nausea, abdominal pain; dyspepsia, gingival hyperplasia, pancreatitis, dry mouth, gastrointestinal motility disorders; gastritis; vomiting.
Renal and urinary disorders: frequent urination, urinary incontinence, nocturia.
Skin and subcutaneous tissue disorders: increased sweating, alopecia, skin discoloration; allergic reactions, rash, itching, angioedema, erythema multiforme exudative; urticaria; purpura, skin discoloration, exanthema; angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity.
Musculoskeletal system: arthralgia, myalgia, back pain, muscle cramps; swelling of the lower legs.
Metabolic disorders: hyperglycemia.
From the vascular system: hot flashes; vasculitis; arterial hypotension.
General disorders: edema, peripheral edema, fatigue; exhaustion, asthenia, weight gain or loss.
Hepatobiliary system: cholestasis, jaundice, hepatitis; increased liver enzymes (most often associated with cholestasis).
From the reproductive system: impotence, gynecomastia.
Psychiatric disorders: depression, mood changes (including anxiety), insomnia; confusion.
Similar to other calcium antagonists, adverse reactions such as myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation, angina pectoris) have been reported, but it is almost impossible to determine whether they are related to the underlying disease.
General disorders and administration site conditions: edema; fatigue, asthenia; chest pain, pain, malaise.
Investigations: Weight gain or loss; exceptional cases of extrapyramidal syndrome have been reported.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after a medicinal product has been authorised is important. This allows for continuous monitoring of the benefit-risk balance of the medicinal product. Physicians should report any suspected adverse reactions as required by law.
When using bisoprolol.
From the side of the cardiac system: bradycardia (in patients with chronic heart failure); AV conduction disorders, increased manifestations of heart failure; signs of worsening heart failure (in patients with chronic heart failure); bradycardia (in patients with arterial hypertension or ischemic heart disease), signs of worsening heart failure (in patients with arterial hypertension or ischemic heart disease).
Nervous system: headache*, dizziness*; sleep disturbances; syncope.
On the part of the organs of vision: decreased tear secretion, which must be taken into account in patients who use contact lenses; conjunctivitis.
From the side of the organs of hearing and labyrinth: hearing impairment.
On the part of the respiratory system: bronchospasm (especially in patients with bronchial asthma or a history of obstructive bronchial diseases); allergic rhinitis.
Gastrointestinal: nausea, vomiting, diarrhea, constipation.
Skin and subcutaneous tissue disorders: allergic reactions, rash, itching; alopecia, psoriatic rashes.
Musculoskeletal system: muscle weakness, cramps.
Metabolic disorders: increased triglyceride levels.
On the part of the vascular system: deterioration of peripheral blood circulation (feeling of cold in the extremities); arterial hypotension (especially in patients with heart failure).
General disorders: increased fatigue, exhaustion.
On the part of the hepatobiliary system: increased levels of liver enzymes (ALT, AST), hepatitis.
From the reproductive system: impotence.
Psychiatric disorders: depression; nightmares, hallucinations, sleep disturbances.
Laboratory indicators: increased triglyceride levels in the blood.
General disorders: asthenia (in patients with chronic heart failure), fatigue*; asthenia (in patients with arterial hypertension or ischemic heart disease).
*Symptoms such as dizziness, headache, fatigue, and exhaustion are common at the beginning of treatment and often disappear within 1-2 weeks.
In case of side effects or adverse reactions, you should immediately inform your doctor.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 °C out of the reach of children.
Packaging
7 tablets in a blister; 4 or 8 blisters in a cardboard box.
10 tablets in a blister; 3 or 9 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
CJSC Pharmaceutical Plant EGIS.
Location of the manufacturer and its business address
1165, Budapest, Bekenfeldi Street, 118-120, Hungary.
