Alotendin 10 mg / 10 mg N30 Tablet

Alotendin

Indications for use

• For arterial hypertension: in monotherapy or when needed, as required • First-degree AV block. • Information exists regarding the development of arterial spasm in Prinzmetal angina; despite B1-selectivity, when prescribing bisoprolol to patients with Prinzmetal angina, it is not possible to completely exclude the possibility of angina attacks. • Occlusive diseases of peripheral arteries (especially at the beginning of treatment, complaints may increase), • Presence of psoriasis in the patient’s history and/or currently — in this case, beta-blockers (e.g., bisoprolol) should be used only after carefully considering the benefits and risks; during treatment, in patients in whom symptoms of hyperthyroidism may be concealed, bisoprolol should be prescribed only after blockade of alpha receptors.

In patients undergoing general anesthesia, beta-blockade reduces the incidence of arrhythmia and myocardial ischemia during anesthesia induction and intubation, as well as in the postoperative period. It is recommended to continue beta-blockade during surgery due to the potential interactions that may occur with the preparations. This may lead to bradyarrhythmia, weakening of reflex tachycardia, and inhibition of reflex ability to compensate for blood loss; therefore, the anesthesiologist should be informed in advance about beta-blockade. If it is necessary to stop beta-blocker intake, it should be done gradually and completed approximately 48 hours before anesthesia. • Although cardioselective (B1-selective) beta-adrenergic blockers have less effect on lung function compared with non-selective beta-blockers, as with other beta-blockers, their use should be avoided in obstructive lung diseases. • In bronchial asthma and other chronic obstructive lung diseases that may cause symptoms, bronchodilator therapy should be administered. In patients with asthma, increased airway resistance may occur, and for this reason, it may be necessary to increase the dose of B2-stimulants. Special information: In each tablet of this product, there is less than 1 mmol of sodium (23 mg), i.e., it is practically sodium-free. Unknown.

Contraindications

Related to amlodipine • Severe hypotension, • shock (including cardiogenic shock), obstruction of blood flow from the left ventricle (severe aortic stenosis), hemodynamically unstable heart failure after a compensatory infarction; Related to bisoprolol • Acute heart failure and/or episodes of heart failure requiring intravenous inotropic preparations, • cardiogenic shock, • second- or third-degree atrioventricular block (without an electrocardiostimulator). sick sinus syndrome, sinoatrial block, • clinically significant bradycardia, clinically significant arterial hypotension, severe bronchial asthma, • severe forms of occlusive diseases of peripheral arteries and severe form of Raynaud’s syndrome,

Use during pregnancy and lactation

Pregnancy In humans, the safety of amlodipine during pregnancy has not been established. In studies conducted, reproductive toxicity was observed when high doses of amlodipine were used. Lactation It is not known whether amlodipine is excreted into human breast milk in the amount of approximately 3–7% of the dose taken by the mother (interquartile range, maximum 15%). For this reason, the use of Alotendin during lactation is not recommended. There is no information about the effect of the combined product on human fertility. In some patients treated with channel blockers, biochemical changes have been observed in the heads of spermatozoa. There is insufficient clinical information to assess the possible effect on fertility. Data show that bisoprolol has not been shown to affect the fertility and reproductive capacity of animals in an experimental study; however, the effect of amlodipine on male rat fertility has been described in an experimental study.

Use in children

Bisoprolol has pharmacological effects that may adversely affect pregnancy and/or the fetus/newborn. β-adrenergic blockers reduce placental perfusion, which can lead to growth retardation, intrauterine death, spontaneous abortion, and premature birth, and additional effects in newborns (e.g., hypoglycemia and bradycardia) may be observed. When treatment is necessary, unless there is a strong indication to prefer selective β1-adrenergic blockers, the use of Alotendin is not recommended. If treatment is considered necessary, uteroplacental blood circulation and fetal growth should be monitored carefully, and if there are adverse effects on the fetus, alternative treatment should be considered. It should be monitored carefully and bradycardia symptoms are usually expected within the first 3 days.

Effect on the ability to drive vehicles and operate other potentially dangerous machinery

Amlodipine may have a minor effect on the ability to control vehicles and machinery. In patients who experience dizziness, headache, fatigue, or nausea, their ability to react may be impaired. In a study conducted with patients with ischemic disease in the presence of participants, bisoprolol did not weaken the ability to control vehicles and other potentially dangerous machinery. However, considering the variability of individual responses to this product, the ability to drive and operate machinery may be impaired. This effect is most often noted at the beginning of treatment, when treatment is changed, and also during alcohol use.

How to use Alotendin and dosage

Alotendin is indicated for patients in whom adequate control of high blood pressure and/or coronary artery pathology can be achieved with simultaneous use of monocomponent preparations at doses contained in the recommended fixed combinations. In very rare cases: exfoliative dermatitis, A very rare: angioedema, multiform erythema, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke’s edema, not photosensitive: toxic epidermal necrolysis.

Interaction with other medicinal products

Effect of other medicinal substances on amlodipine: CYP3A4 isoenzyme inhibitors. Co-administration of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, antifungal preparations of the azole group, macrolides such as erythromycin or clarithromycin, verapamil and diltiazem) may lead to a significant increase in amlodipine concentration. In elderly people, the clinical picture of possible variants of parameters may be more pronounced; therefore, careful medical monitoring and dose adjustment may be required. When used together with clarithromycin, the risk of developing hypotension increases; patients should be closely monitored when clarithromycin is used concomitantly. CYP3A4 isoenzyme inducers. Co-administration of amlodipine with substances that are major inducers of CYP3A4 may change the concentration of amlodipine in blood plasma. Therefore, blood pressure monitoring should be performed and, first of all, when co-administered with strong CYP3A4 inducers (e.g., rifampicin, St. John’s wort/Hypericum perforatum preparations), dose adjustment should be considered both during and after such co-administration. Grapefruit or grapefruit juice is not recommended, because in some patients the bioavailability of amlodipine may increase and, as a result, the hypotensive effect may be enhanced (including with infusion). In animal studies, after administration of verapamil and intravenous administration of dantrolene, an increased risk of development of ventricular fibrillation and cardiovascular failure resulting in death associated with hyperglycemia has been observed. Therefore, in patients predisposed to malignant hyperthermia and treated for malignant hyperthermia, it is necessary to avoid the use of calcium channel blockers such as amlodipine. Concomitant use in the same tablet form: in patients in whom blood pressure and/or chronic stable angina can be adequately controlled, it is indicated as adjunctive therapy.

Studies of the interaction between amlodipine and cyclosporine in healthy volunteers or other groups have not been conducted. With the exception of patients who have undergone kidney transplantation, an increase in cyclosporine variable minimal concentration (0%–40%) has been observed. During combination therapy in patients who have undergone kidney transplantation, it is necessary to consider monitoring the cyclosporine concentration in blood plasma and, if necessary, reduce the cyclosporine dose. In interaction studies affecting pharmacokinetics, amlodipine with atorvastatin, digoxin, or

Special warnings and precautions

See the “Precautions” section), • in relation to metabolic acidosis preparations ⚫ active substances (bisoprolol, amlodipine), dihydropyridine derivatives and/or any excipient contained in the preparation. In cases of hypersensitivity crises, the effectiveness and safety of amlodipine are determined. In patients with renal insufficiency, the product should be prescribed with caution. According to the results of long-term, placebo-controlled studies involving patients with severe heart failure of class III/IV, the incidence of pulmonary edema in the amlodipine group was higher than in the placebo group. In patients with heart failure, calcium channel blockers, including amlodipine, should be used with caution because these preparations may increase the risk of serious cardiovascular complications and death. In patients with impaired liver function, the half-life and AUC of amlodipine increase. In this group of patients, dosing should be determined; it has not been established, and therefore amlodipine should be used with caution in them. In patients with impaired renal function, amlodipine can be used at usual doses in this group of patients. Changes in the concentration of amlodipine are associated with the degree of renal function impairment. It is removed by hemodialysis. Elderly patients: when increasing the dose in elderly patients, caution is required. If there are no specific indications for discontinuation, especially in ischemic heart disease, discontinuation of treatment with bisoprolol may be inappropriate (see “How to use and dosage”). Otherwise, it may cause temporary worsening of heart disease.

Bisoprolol should be used with extreme caution in patients with hypertension and/or angina pectoris with heart failure. It should be used with caution in the following cases: ⚫ diabetes with sudden changes in blood glucose levels; symptoms of hypoglycemia (tachycardia, strong heartbeat, excessive sweating) may be masked. During fasting/early hours, desensitization therapy performed. As with beta-blockers, bisoprolol may increase sensitivity to allergens and aggravate anaphylactic reactions; therefore, the therapeutic effect may not always be ensured. There is a risk of increased tacrolimus blood levels when taken together with amlodipine. In patients receiving treatment, to eliminate the risk of tacrolimus toxicity during amlodipine intake, it is necessary to monitor the required level and, if necessary, adjust the dose. mTOR inhibitors (the mechanical target of rapamycin in animals) such as sirolimus, temsirolimus, and everolimus are CYP3A4 substrates and weak inhibitors of CYP3A4 isoenzyme; when taken concomitantly, amlodipine increases their exposure. Cyclosporine. Simvastatin. Concomitant use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in simvastatin concentration by 77% compared with simvastatin monotherapy. In patients receiving such combination, the simvastatin dose should be limited to up to 20 mg per day.

Bisporalol Recommended not-to-use combinations. Calcium antagonists such as verapamil and, to a lesser extent, diltiazem. They have a negative effect on myocardial contractility and atrioventricular conduction. In patients taking β-blockers, intravenous administration of verapamil can cause severe hypotension and atrioventricular block. Centrally acting antihypertensives such as clonidine, methyldopa, moxonidine, rilmenidine. Concomitant use of centrally acting antihypertensive substances may reduce the frequency of heart contractions and heart rate and can lead to vasodilation; it should be taken as a combination that may increase the risk of “rebound syndrome as hypertension is abolished.” Calcium antagonists of the dihydropyridine type such as felodipine and nifedipine. Concomitant use increases the risk of developing arterial hypotension; it is not possible to exclude an increase in heart failure. In patients, there is a risk of subsequent worsening of ventricular pump function. (fenitoin, flecainide, propafenone) Class I antiarrhythmic drugs (e.g., disopyramide, quinidine, lidocaine). They increase atrioventricular conduction time and negative inotropic effect. Class III antiarrhythmic drugs (e.g., amiodarone). They may strengthen the effect on atrioventricular conduction time and increase the risk when taken, increasing atrioventricular conduction time and the development of bradycardia. Locally acting β-blockers (e.g., eye drops for glaucoma treatment). Bisoprolol’s systemic effect may be enhanced and symptoms of peroral antidiabetic drugs may be masked. The effect of blockade of hypoglycemia. Anesthetics. The risk of weakening reflex tachycardia and developing arterial hypotension. Increased glycoside levels of the heart (see “Special warnings and precautions”). Decreased frequency of heart contractions, prolongation of atrioventricular conduction time. Anti-inflammatory preparations (OSIǝP). Osiap may reduce the hypotensive effect of bisoprolol (e.g., isoprenaline, dobutamine). Combination with bisoprolol may reduce the effects of both preparations.

Also, sympathomimetics that activate α-adrenergic receptors (e.g., noradrenaline, adrenaline). Combination with bisoprolol may activate the vasodilatory effect of these preparations mediated by α-adrenergic receptors and lead to an increase in arterial pressure. In patients with impaired liver function, there are no specific recommendations regarding the dose related to reduced elimination of amlodipine; therefore, such patients should use the product with caution (see “Special warnings and precautions”). In severe liver failure, the daily dose of bisoprolol should not exceed 10 mg. In patients with mild or moderate renal impairment, dose adjustment is required. In renal impairment not removed by hemodialysis (creatinine clearance less than 20 ml/min), the daily dose of bisoprolol should not exceed 10 mg. Cases of marked and long-lasting arterial hypotension, even development of shock and death have been described. With amlodipine

Side effects

Additional effects observed when active substances are used separately are presented according to the following frequency parameters: very often (≥1/10); often (≥1/100–<1/10); sometimes (≥1/1000–<1/100); rarely (≥1/10000–<1/1000); very rarely (<1/10000); not known (frequency cannot be estimated from available data). The most frequently reported additional effects of amlodipine are: drowsiness, dizziness, headache, palpitations, bleeding, abdominal pain, nausea, edema in the ankles, edema, severe fatigue, and lymphatic system disorders. Very rarely: leukopenia, thrombocytopenia. System disorders: very rarely: allergic reactions.

Metabolism and nutrition disorders. Sometimes: disorders of hyperglycemia. Sometimes: insomnia, mood changes (including anxiety), depression. Rarely: confusion. Nervous system disorders. Often: headache, dizziness, drowsiness (especially at the beginning of treatment). Sometimes: syncope, hypesthesia, paresthesia, taste disturbance, tremor. Rarely: increased muscle tone, peripheral neuropathy. Not known: extrapyramidal disorders. Eye disorders. Sometimes: blurred vision (including diplopia). Ear and labyrinth disorders. Sometimes: tinnitus.

Cardiac disorders. Often: strong palpitations: arrhythmia (including bradycardia, ventricular tachycardia, and atrial fibrillation). Very rarely: myocardial infarction disorders. Often: hot bleeding.

Sometimes: arterial hypotension. In volunteers, after taking 10 mg amlodipine, administration of activated charcoal within 2 hours reduced amlodipine absorption. Because it has the ability to bind to proteins at high levels, dialysis has less effect. Symptoms. When overdose occurs with B-blockers, symptoms are observed more frequently than expected from overdose: bradycardia, arterial hypotension, bronchospasm, sudden heart failure, and hypoglycemia. There are large individual differences in sensitivity at high single doses. However, it is more likely that patients with heart failure have high sensitivity. When overdose occurs with bisoprolol, treatment should be discontinued and supportive and symptomatic therapy should be applied. Information indicates that bisoprolol is difficult to dialyze.

Based on expected pharmacological effects and recommendations for other β-blockers, when clinically necessary, the following general measures should be taken: in case of no effect from intravenous atropine administration, isoprenaline or other preparations with positive chronotropic effects may be administered with caution; in cases of hypotension, intravenous administration of fluids and vasopressor preparations may be effective. In AV block (second or third degree): carefully monitor the patient’s condition and apply an isoprenaline infusion and/or use a transvenous cardiostimulator device. In case of heart failure: intravenous administration of diuretics, positive inotropic preparations, and vasodilators.

In bronchospasm: when prescribing bronchodilators such as isoprenaline, B2-sympathomimetics and/or aminophylline, a number of data show that bisoprolol is poorly eliminated by hemodialysis.