Instructions for use Alotendin tablets 5 mg/10 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, which corresponds 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, corresponding 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, with a score on one side and engraved 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 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:
1) 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;
2) 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 time of possible physical exertion, the time to the onset of an angina attack and increases the time to the onset of significant ST-segment depression, and also reduces the frequency of angina attacks and reduces the need for nitroglycerin.
Amlodipine does not cause undesirable metabolic effects or changes in blood plasma lipid levels, so it can be used in patients with bronchial asthma, diabetes mellitus, and gout.
Bisoprolol is a potent, highly selective β1-adrenoceptor blocker, without intrinsic sympathomimetic activity and significant membrane-stabilizing properties.
It shows only low affinity for β2-receptors of bronchial and vascular smooth muscle, as well as for β-receptors involved in metabolic regulation. Thus, bisoprolol does not affect airway resistance and β2-mediated metabolic effects. The selectivity for β1-receptors is beyond the therapeutic dose range. Bisoprolol has no apparent negative inotropic effect.
The maximum effect appears 3–4 hours after oral administration.
The plasma half-life is 10–12 hours, which provides a therapeutic effect for 24 hours after a single daily dose.
Typically, the maximum hypertensive effect occurs after 2 weeks of use.
When administered acutely to patients with coronary heart disease without chronic heart failure, bisoprolol reduces heart rate and stroke volume, and therefore cardiac output and oxygen consumption. With continuous administration, the initially increased peripheral resistance decreases.
The antihypertensive effect of β-blockers is due to a decrease in renin activity.
Amlodipine/bisoprolol combination
This combination allows for increased antihypertensive and antianginal efficacy due to the complementary mechanism of action of the two active substances: the vasoselective action of the calcium channel blocker amlodipine (reduces peripheral resistance) and the cardioselective β-blocker bisoprolol (reduces cardiac output).
Pharmacokinetics.
Amlodipine
Absorption
After oral administration in therapeutic doses, amlodipine is well absorbed and reaches maximum blood concentrations 6–12 hours after administration. Food intake does not affect the bioavailability of amlodipine. Absolute bioavailability is from 64% to 80%.
The volume of distribution is approximately 21 l/kg. Steady-state plasma concentrations (5–15 ng/ml) are reached after 7–8 days of continuous administration. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
Biotransformation and excretion
Amlodipine is metabolized (about 90%) in the liver to form inactive metabolites. 10% of the drug is excreted in the urine unchanged, 60% as metabolites, 20-25% in the feces. The decrease in plasma concentration has biphasic characteristics.
The plasma half-life is approximately 35–50 hours, which allows the drug to be administered once daily.
Total clearance is 7 ml/min/kg (if the patient's weight is 60 kg, it is 25 l/h, in elderly patients it is 19 l/h).
Elderly patients
The time to reach peak plasma concentrations of amlodipine is similar in elderly and young subjects. In elderly patients, amlodipine clearance tends to decrease, leading to an increase in AUC and half-life. The increase in AUC and half-life in patients with congestive heart failure was in line with expectations for the age group studied (see section 4.4).
Patients with renal insufficiency
Amlodipine is extensively metabolized to inactive metabolites. 10% of the unchanged compound is excreted in the urine. Changes in plasma concentrations of amlodipine are not associated with the degree of renal insufficiency. These patients can be prescribed the usual doses of amlodipine. Amlodipine is not removed by dialysis.
Use in patients with impaired liver function
Very limited clinical data are available on the use of amlodipine in patients with hepatic impairment. In patients with hepatic impairment, the clearance of amlodipine is reduced, resulting in an increase in half-life and AUC by approximately 40-60%.
Bisoprolol
Absorption
Bisoprolol is almost completely (up to 90%) absorbed from the gastrointestinal tract.
The absolute bioavailability of bisoprolol is approximately 90% after oral administration - the effect of the first pass through the liver is very small (approximately 10%).
Distribution
The volume of distribution is 3.5 l/kg. Binding to plasma proteins is 30%.
Biotransformation and excretion
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 remaining 50% is excreted by the kidneys in an unchanged form.
Since bisoprolol is excreted equally by the kidneys and liver, no dose adjustment is required for patients with mild to moderate hepatic impairment or renal failure. Total clearance is approximately 15 l/h. The elimination half-life is 10–12 hours.
The kinetics of bisoprolol are linear and independent of age.
Amlodipine/bisoprolol combination
Pharmacokinetic interaction studies between these two compounds have not been conducted. Even if such an interaction exists, according to the results of a bioequivalence study, it should be the same when using Alotendin as when using amlodipine and bisoprolol separately at the same doses as in combination.
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
Hypersensitivity to the active substances or dihydropyridine derivatives, or to any of the excipients of the medicinal product.
Contraindications for the use of amlodipine:
Severe arterial hypotension.
Shock (including cardiogenic shock).
Left ventricular outflow tract obstruction (e.g. severe aortic stenosis).
Hemodynamically unstable heart failure after acute myocardial infarction.
Unstable angina.
Contraindications for the use of bisoprolol:
Acute heart failure or heart failure in a state of decompensation requiring inotropic therapy.
Cardiogenic shock.
Atrioventricular (AV) block II–III degrees.
Sick sinus syndrome.
Sinoatrial block, bradycardia (heart rate less than 60 per minute), arterial hypotension before the start of treatment (systolic blood pressure < 100 mm Hg).
Symptomatic hypotension.
Bronchial asthma, chronic obstructive pulmonary disease.
Severe peripheral circulatory disorders, Raynaud's syndrome.
Untreated pheochromocytoma.
Metabolic acidosis.
Interaction with other medicinal products and other types of interactions
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 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 result in a significant increase in amlodipine exposure, which may increase the risk of hypotension. The clinical significance of these changes may be more pronounced in elderly patients. Clinical monitoring of the patient and dose adjustment may be necessary.
CYP3A4 inducers: When used concomitantly with CYP3A4 inducers, the plasma concentration of amlodipine may change. Therefore, blood pressure should be monitored and the dose adjusted both during and after concomitant treatment, especially when using strong CYP3A4 inducers (e.g. rifampicin, St. John's wort).
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.
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 used concomitantly with amlodipine. To avoid tacrolimus toxicity when used concomitantly with amlodipine, monitoring of tacrolimus blood levels and, if necessary, dosage adjustment is required.
mTOR inhibitors (mammalian target of rapamycin)
mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are substrates of CYP3A. Amlodipine is a weak inhibitor of CYP3A. When amlodipine is used concomitantly with mTOR inhibitors, it may potentiate the effects of the latter.
Clarithromycin.
There is an increased risk of hypotension in patients receiving clarithromycin and amlodipine concomitantly, as clarithromycin is a CYP3A inhibitor. Clinical monitoring of these patients is recommended.
Cyclosporine.
Interaction studies with cyclosporine and amlodipine have only been performed in renal transplant patients, where variable increases in cyclosporine trough concentrations (mean 0-40%) were observed. In renal transplant patients receiving amlodipine, monitoring of cyclosporine concentrations should be considered and, if necessary, a reduction in the cyclosporine dose.
Simvastatin.
Co-administration of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. For patients taking amlodipine, the dose of simvastatin should be limited to 20 mg daily.
Clinical drug interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.
Bisoprolol
Simultaneous 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 increases the risk of withdrawal syndrome in the form of arterial hypertension.
Drugs that require caution when used concomitantly:
Dihydropyridine calcium antagonists such as felodipine, nifedipine: concomitant use with bisoprolol increases the risk of arterial hypotension, and the risk of further deterioration of ventricular pumping function in patients with heart failure cannot be excluded.
Class I antiarrhythmic drugs (e.g. disopyramide, quinidine, lidocaine, phenytoin, flecainide, propafenone): effect on AV conduction and negative effect on myocardial inotropic function.
Class III antiarrhythmic drugs (e.g. amiodarone): the effect on AV conduction may be enhanced.
Parasympathomimetics: when used simultaneously with bisoprolol, they 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 β-adrenergic receptors (e.g. adrenaline, noradrenaline): when used with bisoprolol, the α-adrenergic receptor-mediated vasoconstrictor effect of these drugs may occur, leading to an increase in blood pressure. Such an interaction is more likely with the use of non-selective β-blockers.
Antihypertensive agents, as well as other drugs with the potential to lower blood pressure (e.g. tricyclic antidepressants, barbiturates, phenothiazines), when used with bisoprolol, increase the risk of hypotension.
Drugs for which there are precautions regarding simultaneous use:
Mefloquine: increased risk of bradycardia.
Monoamine oxidase inhibitors (except MAO-B inhibitors): increased hypotensive effect of β-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 hepatic enzymes. However, dose adjustment is not required.
Ergotamine derivatives: exacerbation of peripheral circulatory disorders.
Application features
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 because they 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, in this category of patients, amlodipine should be started at the lowest dose. Caution should be exercised both when starting the drug and when increasing the dose. Patients with severe hepatic insufficiency may require slow dose titration and careful monitoring.
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.
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.
Bisoprolol should be used with caution in the following cases:
diabetes with significant fluctuations in blood glucose levels - symptoms of hypoglycemia (such as tachycardia, rapid heartbeat, or sweating) 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; cases of coronary vasospasm have been observed. Despite high beta 1 selectivity, angina attacks cannot be completely stopped when bisoprolol is prescribed to patients with Prinzmetal's angina;
peripheral arterial occlusive disease (at the beginning of therapy, complaints may worsen);
Psoriasis. Patients with psoriasis or a history of psoriasis should use bisoprolol only after careful assessment of the benefit/risk ratio;
Thyrotoxicosis. When treated with bisoprolol, symptoms of thyrotoxicosis may be hidden;
Pheochromocytoma. In patients with pheochromocytoma, bisoprolol can be used only after therapy with α-adrenergic blockers;
bronchial asthma and other chronic obstructive airway diseases. Although cardioselective β-blockers (β1) have less effect on lung function than non-selective β-blockers, their use, like all β-blockers, should be avoided in obstructive airway diseases unless there are compelling reasons for therapy. If necessary, bisoprolol should be used with caution. In bronchial asthma and other chronic obstructive airway diseases that may cause symptoms, bronchodilator therapy should be used concomitantly. Sometimes, patients with asthma may have increased airway resistance, so the dose of β2-stimulants may need to be increased.
Use during pregnancy or breastfeeding
Pregnancy.
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.
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.
The drug should not be used during pregnancy unless clearly indicated. If treatment with Alotendin is considered necessary, uteroplacental circulation and fetal growth should be monitored. In case of adverse effects on pregnancy or the fetus, alternative treatment should be considered. Newborns should be closely monitored. Hypoglycemia and bradycardia can usually be expected in the first 3 days.
Breast-feeding.
Amlodipine is excreted in breast milk. The proportion of the initial maternal dose received by the infant was estimated in the interquartile range to be 3–7%, with a maximum of 15%. The effects of amlodipine on infants are unknown.
It is not known whether bisoprolol passes into breast milk.
Therefore, the use of amlodipine/bisoprolol tablets during breastfeeding is not recommended.
The ability to influence the reaction speed when driving or working with other mechanisms
Amlodipine may have a minor or moderate influence on the reaction rate when driving vehicles or using other mechanisms. If patients taking amlodipine suffer from dizziness, headache, fatigue or nausea, the ability to react may be impaired.
In a study of patients with coronary heart disease, bisoprolol did not affect reaction time.
Under the influence of the drug Alotendin, the ability to drive or operate other mechanisms may be impaired, depending on the individual patient's reaction. Such an effect is possible mainly at the beginning of therapy, during a change in therapy and with simultaneous use of alcohol.
Method of administration and doses
The recommended daily dose of the drug Alotendin is 1 tablet of the appropriate dosage, taken regardless of meals, preferably in the morning. Swallow the tablets without chewing.
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 dysfunction
In case of hepatic insufficiency, the elimination of amlodipine is slowed down. There are no specific dosage recommendations for amlodipine, so the drug should be prescribed with caution to patients with impaired liver function. In case of severe hepatic insufficiency, the daily dose of bisoprolol should not exceed 10 mg.
Patients with renal insufficiency
No dosage adjustment is required for patients with mild or moderate renal impairment. Amlodipine is not dialysable. In severe renal impairment (creatinine clearance < 20 ml/min), the daily dose of bisoprolol should not exceed 10 mg.
Elderly patients
Elderly people can be prescribed the usual doses of the drug, but caution is recommended when increasing the dose (see the section "Pharmacological properties").
Children.
The efficacy and safety of the drug in children and adolescents (under 18 years of age) have not been established.
Alotendin is not recommended for use in children.
Overdose
Amlodipine
Experience with intentional overdose of the drug is limited.
Treatment: Clinically significant hypotension due to amlodipine overdose requires active cardiovascular support, including monitoring of cardiac and respiratory function, monitoring of circulating fluid volume and urine output. The patient should be in a supine position with the lower extremities elevated.
To restore vascular tone and blood pressure, vasoconstrictor drugs can be used, making sure there are no contraindications to their use. Intravenous administration of calcium gluconate can help to neutralize 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 amlodipine significantly reduced its absorption.
Since amlodipine is extensively protein bound, the effect of dialysis is negligible.
Bisoprolol
Symptoms
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.
Treatment
In case of overdose, you should immediately consult a doctor.
Depending on the severity of the overdose, treatment with the drug should be discontinued and supportive and symptomatic therapy should be administered. According to some reports, bisoprolol is difficult to dialyze. General measures in case of overdose are given below, based on the expected pharmacological action and recommendations for the treatment of overdose with other beta-blockers.
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, a pacemaker may be necessary.
For arterial hypotension: taking vasoconstrictor drugs, intravenous administration of glucagon.
In case of second and third degree atrioventricular block: patients should be closely monitored and treated with isoprenaline infusion or pacemaker implantation.
In case of exacerbation of chronic heart failure: intravenous diuretics, agents with positive inotropic effects, and vasodilators should be used.
For bronchospasm: bronchodilators (e.g. isoprenaline), β2-adrenomimetics and/or aminophylline should be administered.
For hypoglycemia: intravenous glucose administration.
Side effects
The following are adverse reactions that may be caused by the active substances amlodipine and bisoprolol.
The frequency of adverse reactions is defined as follows:
very common (≥1/10);
common (≥1/100 to <1/10);
uncommon (≥1/1000 to <1/100);
rare (≥1/10,000 to <1/1000);
very rare (<1/10,000);
frequency unknown (cannot be estimated from the available data).
The most common side effects of amlodipine include: drowsiness, dizziness, headache, palpitations, flushing, abdominal pain, nausea, swelling (especially in the lower legs), and fatigue.
Blood and lymphatic system disorders
Very rare: leukopenia, thrombocytopenia.
On the part of the immune system
Very rare: allergic reactions.
Metabolic disorders
Very rare: hyperglycemia.
Mental disorders
Uncommon: insomnia, mood changes (including anxiety), depression.
Rare: confusion.
From the nervous system
Common: headache, dizziness, drowsiness (especially at the beginning of treatment).
Uncommon: syncope, decreased sensitivity, paraesthesia, dysgeusia, tremor.
Very rare: hypertension, peripheral neuropathy.
Frequency unknown: extrapyramidal disorder.
From the organs of vision
Common: visual disturbances (including diplopia).
From the side of the organs of hearing and labyrinth
Uncommon: tinnitus (ringing in the ears).
From the side of the cardiovascular system
Common: increased heart rate.
Uncommon: arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation).
Very rare: myocardial infarction.
From the vascular system
Often: hot flashes.
Uncommon: hypotension.
Very rare: vasculitis.
Respiratory, thoracic and mediastinal disorders
Common: dyspnea.
Uncommon: cough, rhinitis.
Gastrointestinal tract
Common: nausea, abdominal pain, dyspepsia, intestinal motility disorders (including diarrhea and constipation).
Uncommon: vomiting, dry mouth.
Very rare: gastritis, gingival hyperplasia, pancreatitis.
Hepatobiliary system
Very rare: hepatitis, jaundice, increased liver enzymes (in most cases with cholestasis).
Skin and subcutaneous tissue disorders
Uncommon: alopecia, purpura, skin discoloration, increased sweating, itching, rash, exanthema, urticaria.
Very rare: angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity.
Frequency unknown: toxic epidermal necrolysis.
Musculoskeletal system
Common: leg swelling, muscle cramps.
Uncommon: arthralgia, myalgia, back pain.
Renal and urinary disorders
Uncommon: urinary disorders, nocturia, increased urinary frequency.
Reproductive system and breast disorders
General disorders and administration site conditions
Very common: edema.
Common: fatigue, asthenia.
Uncommon: chest pain, pain, malaise.
Research
Uncommon: weight gain, weight loss.
When using bisoprolol
Metabolic and eating disorders
Rare: increased blood triglyceride levels.
Mental disorders
Uncommon: depression.
Rare: nightmares, hallucinations.
From the nervous system
Common: dizziness*, headache*.
Uncommon: sleep disorders.
Rare: syncope.
From the organs of vision
Rare: decreased tear production (to be considered if the patient wears contact lenses).
Very rare: conjunctivitis.
From the side of the organs of hearing and labyrinth
Rare: hearing impairment.
From the side of the cardiovascular system
Uncommon: AV conduction disturbances, exacerbation of existing heart failure, bradycardia.
Respiratory, thoracic and mediastinal disorders
Uncommon: bronchospasm (especially in patients with bronchial asthma or a history of obstructive bronchial disease).
Rare: allergic rhinitis.
Gastrointestinal tract
Common: nausea, vomiting, diarrhea, constipation.
Hepatobiliary system
Rare: hepatitis.
Skin and subcutaneous tissue disorders
Rare: hypersensitivity reactions including itching, redness, rash, angioedema.
Very rare: alopecia, psoriasis or exacerbation of psoriasis.
Musculoskeletal and connective tissue disorders
Uncommon: muscle weakness and cramps.
From the vascular system
Common: deterioration of peripheral circulation (feeling of coldness in the extremities).
Uncommon: hypotension (especially in patients with heart failure).
Reproductive system and breast disorders
Rare: impotence, erectile dysfunction.
General violations
Common: fatigue*.
Uncommon: fatigue.
Research
Rare: increased liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)].
* These symptoms occur primarily at the beginning of therapy. They are usually mild and often disappear within 1–2 weeks.
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.
Address
1165, Budapest, Bekenfeldi Street, 118-120, Hungary.
