Amlodipine + Bisoprolol - instructions for use, dose, side effects, contraindications

Active substanceAmlodipine + BisoprololAmlodipine + Bisoprolol

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Amlodipine + Bisoprolol

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NORTH STAR, CJSC Russia

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Merck KGaA Germany

Niperten® Combi

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KRKA-RUS, LLC Russia

Dosage form: & nbsppills

Composition:

1 tablet contains:

dosage of 5 mg +5 mg:

active ingredients: 5 mg of amlodipine besylate (in terms of amlodipine) and 5 mg of bisoprolol fumarate;

Excipients: cellulose microcrystalline - 132.5 mg; sodium carboxymethyl starch 5.0 mg; magnesium stearate - 1.5 mg; silicon dioxide colloidal anhydrous (aerosil anhydrous) - 1.0 mg.

dosage of 5 mg + 10 mg:

active ingredients: 5 mg of amlodipine besylate (in terms of amlodipine) and 10 mg of bisoprolol fumarate;

Excipients: cellulose microcrystalline - 174.0 mg; sodium carboxymethyl starch - 7.0 mg; magnesium stearate - 2.0 mg; silicon dioxide colloidal anhydrous (aerosil anhydrous) 2.0 mg.

dosage of 10 mg + 5 mg:

active ingredients: 10 mg of amlodipine besylate (in terms of amlodipine) and 5 mg of bisoprolol fumarate;

Excipients: cellulose microcrystalline - 222.0 mg; sodium carboxymethyl starch - 8.5 mg; magnesium stearate - 2.5 mg; silicon dioxide colloidal anhydrous (aerosil anhydrous) 2.0 mg.

dosage of 10 mg + 10 mg:

active ingredients: 10 mg of amlodipine besylate (in terms of amlodipine) and 10 mg of bisoprolol fumarate;

Excipients: cellulose microcrystalline - 265.0 mg; sodium carboxymethyl starch - 10.0 mg; magnesium stearate - 3.0 mg; silicon dioxide colloidal anhydrous (aerosil anhydrous) 2.0 mg.

Description:

Dosages of 5 mg + 5 mg and 5 mg + 10 mg: tablets white or almost white, round, flat-cylindrical with a bevel.

Dosages of 10 mg + 5 mg and 10 mg + 10 mg: tablets of white or almost white color, round, flat-cylindrical with facet and risk on one side.

Pharmacotherapeutic group:A combined hypotensive drug (beta 1-blocker selective + blocker of "slow" calcium channels (BCCC)

ATX: & nbsp

C.07.F.B Selective beta-1 blockers in combination with other antihypertensive drugs

Pharmacodynamics:

This drug has pronounced antihypertensive and antianginal effects due to the complementary action of two active ingredients: BCCC-amlodipine and selective beta 1-adrenoblocker-bisoprolol.

The mechanism of action of amlodipine:

Amlodipine blocks the calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in the resistance of peripheral vessels.

The mechanism of antianginal action is not fully understood, perhaps it is associated with the following two effects:

- Expansion of peripheral arterioles reduces the overall peripheral resistance, i.e. afterloading. Because the amlodipine does not cause reflex tachycardia, energy consumption and oxygen myocardium decreases.

- Expansion of large coronary arteries and coronary arterioles improves the supply of oxygen to both normal and ischemic zones of the myocardium. Due to these effects, the supply of oxygen to the myocardium improves, even with spasm of the coronary arteries (Prinzmetal angina or unstable angina).

In patients with hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the "lying" and "standing" positions throughout the 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.

In patients with angina, taking the drug once a day increases the overall time of exercise, the time before the onset of an attack of angina, as well as the time to a significant decrease in the interval ST, and also reduces the frequency of angina attacks and the need for sublingual administration of nitroglycerin.

There was no negative effect of amlodipine on the exchange of blood plasma lipids, blood glucose and serum uric acid.

The mechanism of action of bisoprolol:

Bisoprolol is a selective beta 1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.

He has only a slight affinity for beta2-adrenergic receptors of the smooth muscles of the bronchi and vessels, as well as for beta2-adrenoreceptors involved in the regulation of metabolism. Consequently, bisoprolol in general, does not affect the resistance of the respiratory tract and the metabolic processes in which beta2-adrenergic receptors are involved.

The selective effect of the drug on beta 1-adrenergic receptors persists beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect;

The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol 1 time per day, its therapeutic effect persists for 24 hours due to a 10-12 hour half-life from the blood plasma.

Typically, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system (CAS) by blocking the beta 1-adrenoreceptors of the heart.

With a single oral intake in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol it reduces the heart rate (heart rate), reduces the stroke volume of the heart and, as a consequence, reduces the ejection fraction and the myocardial oxygen demand. With prolonged therapy, initially increased total peripheral vascular resistance (OPSS) is reduced. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of beta-blockers.

Pharmacokinetics:

Amlodipine:

Suction:

Amlodipine is well absorbed after ingestion. The maximum concentration in the blood plasma is observed after 6-12 hours.Taking the drug with food does not affect its absorption. Absolute bioavailability is 64 - 80%.

Distribution:

The apparent volume of distribution is 21 l / kg. The equilibrium concentration in the blood plasma (5-15 ng / ml) is achieved 7-8 days after the start of the drug.

In vitro studies have shown that circulating amlodipine approximately 93-98% is associated with blood plasma proteins.

Metabolism and excretion:

Amlodipine undergoes intensive metabolism in the liver. Approximately 90% of the accepted dose is converted to inactive pyridine derivatives. Approximately 10% of the dose taken is excreted unchanged in urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestine. The decrease in plasma concentration is biphasic. The final half-life is approximately 35-50 hours, which allows the administration of the drug once a day. The total clearance is 7 ml / min / kg (25 l / h in patients weighing 60 kg). In elderly patients, it is 19 l / h.

In elderly patients and patients with renal insufficiency, there was no significant change in the pharmacokinetics of amlodipine.

Due to lower clearance, patients with hepatic insufficiency should be given a lower initial dose.

Amlodipine penetrates the blood-brain barrier.

Bisoprolol:

Suction. Bisoprolol almost completely (more than 90%) is absorbed from the gastrointestinal tract. Its bioavailability due to an insignificant metabolism "during the first passage" through the liver (at about 10%) is about 90% after ingestion. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the range of 5 to 20 mg. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution. Bisoprolol distributed fairly widely. The volume of distribution is 3.5 l / kg. The connection with plasma proteins is approximately 30%.

Metabolism. Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine, do not show pharmacological activity. The data obtained as a result of experiments with human liver microsomes in vitro, show that bisoprolol is metabolized primarily with the help of the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.

Excretion.Bisoprolol clearance is determined by the balance between excretion by the kidneys in an unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites that are also excreted by the kidneys. The total ground clearance is 15 liters per hour. The half-life is 10-12 hours.

Indications:

Arterial hypertension: replacement therapy with monocomponent preparations of amlodipine and bisoprolol in the same doses.

Contraindications:

For amlodipine:

- unstable angina (with the exception of Prinzmetal's stenocardia);

- hemodynamically unstable heart failure after myocardial infarction;

- clinically significant aortic stenosis.

By bisoprolol:

- acute heart failure or chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy;

- atrioventricular (AV) blockade of II and III degree, without an electrocardiostimulator;

- syndrome of weakness of the sinus node (SSSU);

- sinoatrial blockade;

- pronounced bradycardia (heart rate less than 60 beats / min);

- severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD);

- severe peripheral arterial circulation or Raynaud's syndrome;

- pheochromocytoma (without simultaneous use of alpha-blockers);

- metabolic acidosis;

By combination of amlodipine / bisoprolol:

- hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and / or any of the excipients;

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

- shock (including cardiogenic);

- children under 18 years of age (efficacy and safety not established).

Carefully:

CHF (including non-ischemic etiology III-IV functional class by classification NYHA), hepatic insufficiency, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in the concentration of glucose in the blood, AV blockade I, degree, angina prinzmetal, occlusive diseases of peripheral arteries, psoriasis (including in the anamnesis), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), bronchial asthma and COPD, concomitant desensitizing therapy , general anesthesia, elderly age, arterial hypotension, type 1 diabetes mellitus, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).

Pregnancy and lactation:

For amlodipine:

In experimental studies fetotoxic and embryotoxic effects of the drug have not been established, but use in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

There is no evidence of excretion of amlodipine in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, if it is necessary to prescribe amlodipine during lactation, the question of stopping breastfeeding should be resolved.

By bisoprolol:

The use of bisoprolol in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. Beta-adrenoblockers reduce blood flow in the placenta and can affect the development of the fetus.

Blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored, and if alternative pregnancy and / or fetal events occur, alternative therapies should be adopted.You should carefully examine the newborn after delivery. In the first three days of life, bradycardia and hypoglycemia may occur.

There is no data on the isolation of bisoprolol in breast milk. Therefore, its administration is not recommended for women during lactation. If bisoprolol is required during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Tablets for oral administration. Tablets should be taken in the morning, regardless of food intake, without chewing.

The recommended daily dose is 1 tablet per day of a certain dosage. The choice and titration of the dose individually for each patient is performed by the doctor during the appointment of monocomponent drugs containing the active substances included in the preparation Amlodipine + Bisoprolol.

Duration of treatment

Treatment with drug Amlodipine + Bisoprolol is usually a long-term therapy.

Impaired liver function

In patients with impaired liver function, excretion of amlodipine can be slowed down. A special dosing regimen for this group of patients is not defined, but the drug should in this case be prescribed with caution.

For patients with severe impairment of liver function, the maximum daily dose of bisoprolol is 10 mg.

Impaired renal function

Patients with impaired renal function of mild or moderate severity of dosing regimen are generally not required. Amlodipine not output by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme caution.

For patients with severe renal impairment (creatinine clearance less than 20 ml / min), the maximum daily dose of bisoprolol is 10 mg.

Elderly patients

Elderly patients may be given regular doses of the drug. Caution is required only when the dose is increased.

Children

The drug is not recommended for use in children under the age of 18 due to lack of data on efficacy and safety.

Treatment should not be stopped abruptly, as this may lead to a temporary deterioration in the clinical condition. Especially, treatment should not be abruptly discontinued in patients with ischemic heart disease. A gradual dose reduction is recommended.

Side effects:

Unwanted adverse reactions observed with the use of active ingredients separately are presented in accordance with the following frequency grouping criteria:

Very frequent ≥ 1/10; frequent ≥ 1/100 - <1/10; Infrequent ≥ 1/1 000 - <1/100; rare ≥ 1/10 000 - <1/1 000; very rare (<1/10 000), unknown (estimate based on available data can not be performed).

For amlodipine:

Violations from the blood and lymphatic system: very rarely - leukopenia, thrombocytopenia.

Immune system disorders: very rarely - allergic reactions.

Disorders from the metabolism and nutrition: very rarely - hyperglycemia.

Disorders of the psyche: infrequently - insomnia, mood changes (including anxiety), depression; rarely confusion.

Impaired nervous system: often - headache, dizziness, drowsiness (especially at the beginning of treatment); infrequently - fainting, hypoesthesia, paresthesia, dysgeusia, tremor; very rarely - muscle hypertension, peripheral neuropathy;

Disorders from the side of the organ of vision: infrequently - impaired vision (including diplopia).

Hearing disorders and labyrinthine disturbances: infrequently - noise in ears.

Disorders from the gastrointestinal tract: often - nausea, abdominal pain; infrequent - vomiting, changing the mode of defecation (including constipation or diarrhea); dyspepsia, dryness of the oral mucosa; very rarely - gastritis, gingival hyperplasia, pancreatitis.

Disorders from the liver and bile ducts: very rarely - hepatitis *, jaundice *.

Heart Disease: often - a feeling of palpitations; very rarely - myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation).

Vascular disorders: often: "tides" of blood to the face, infrequent - a pronounced decrease in blood pressure; very rarely - vasculitis.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - shortness of breath, rhinitis; very rarely - cough.

Disorders from the kidneys and urinary tract: infrequently - pollakiuria, painful urge to urinate, nocturia.

Violations of the genitals and breast: infrequently - impotence, gynecomastia.

General disorders and disorders at the site of administration: often: peripheral edema, increased fatigue; infrequently - chest pain, asthenia, pain, general malaise.

Disturbances from the musculoskeletal and connective tissue: often - swelling of the ankles; infrequently - arthralgia, myalgia, muscle cramps, back pain.

Disturbances from the skin and subcutaneous tissue: infrequently - alopecia, purpura, discoloration of the skin,increased sweating, itching, rash, exanthema; very rarely - angioedema, erythema multiforme exudative, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity.

Laboratory and instrumental data: infrequently - weight gain, weight loss; very rarely - an increase in the activity of "liver" enzymes *.

* In most cases with cholestasis.

By bisoprolol:

Disorders from the metabolism and nutrition: rarely - an increase in the concentration of triglycerides.

Disorders of the psyche: infrequently - depression; rarely - hallucinations, nightmares.

Impaired nervous system: often - headache **, dizziness **; infrequently - insomnia; rarely - faint.

Disorders from the side of the organ of vision: rarely - a decrease in lacrimation (should be considered when wearing contact lenses); very rarely - conjunctivitis.

Hearing disorders and labyrinthine disturbances: rarely - hearing impairment.

Heart Disease: infrequently infringement AV conductivity, bradycardia, aggravation of symptoms of CHF.

Vascular disorders: often - a feeling of cold or numbness in the extremities, a pronounced decrease in blood pressure; infrequently orthostatic hypotension.

Disturbances from the respiratory, thoracic and mediastinal organs: infrequently bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis; rarely allergic rhinitis.

Disorders from the gastrointestinal tract: often: nausea, vomiting, diarrhea, constipation.

Disorders from the liver and bile ducts: rarely - hepatitis.

Disturbances from the skin and subcutaneous tissue: rarely - hypersensitivity reactions, such as pruritus, rash, hyperemia of the skin; very rarely - alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

Disturbances from the musculoskeletal and connective tissue: infrequently - muscle weakness, muscle cramps.

Violations of the genitals and breast: rarely - impotence.

General disorders and disorders at the site of administration: often - increased fatigue **; infrequently, exhaustion **.

Laboratory and instrumental data: rarely - increased activity of "hepatic" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).

** Especially often these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

Overdose:

For amlodipine:

Symptoms: marked decrease in blood pressure with possible development reflex tachycardia and excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal, maintaining the function of the cardiovascular system, monitoring the parameters of the function of the heart and lungs, elevated limb position, monitoring the volume of circulating blood and diuresis. Intensive symptomatic therapy. To restore the vascular tone - the use of vasoconstrictive drugs (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is not effective.

By bisoprolol

Symptoms: AV blockade, pronounced bradycardia; marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients, and probably patients with CHF have high sensitivity.

Treatment: In case of an overdose, first of all, it is necessary to stop taking the drug and begin supporting symptomatic therapy.

With severe bradycardia: intravenous atropine. If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With a marked decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations. Intravenous administration of glucagon may also be indicated.

When AV blockade: patients should be under constant observation, and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.

With exacerbation of the course of CHF: intravenous diuretics, preparations with a positive inotropic effect, as well as vasodilators.

When bronhospazme: the appointment of bronchodilators, including beta2-adrenomimetics and / or aminophylline.

When hypoglycemia: intravenous dextrose (glucose).

Bisoprolol practically does not give in to dialysis.

Interaction:

For amlodipine:

The simultaneous use of amlodipine with thiazide diuretics, beta-adrenoblockers, long-acting nitrates, sublingual preparations of nitroglycerin, nonsteroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration is considered safe.

Inhibitors CYP3A4: Use with caution amlodipine concomitantly with inhibitors CYP3A4.

Strong and moderate inhibitors CYP3A4 (eg, protease inhibitors, antifungal agents of the azole group, macrolides of the type erythromycin or clarithromycin, verapamil or diltiazem) can increase the concentration of amlodipine in the blood plasma to clinically significant values.

Inductors CYP3A4: Simultaneous application with inducers CYP3A4 (incl. rifampicin, St. John's wort perforated) can lead to a decrease in the concentration of amlodipine in the blood plasma. Use with caution amlodipine simultaneously with inductors CYP3A4.

Simvastatin: Simultaneous use with amlodipine may lead to an increase in the concentration of simvastatin in the blood plasma.

Patients receiving amlodipine, the use of simvastatin in a dose exceeding 20 mg per day is not recommended.

Grapefruit juice, cimetidine, aluminum / magnesium (in the composition of antacids) and sildenafil do not affect the pharmacokinetics of amlodipine.

Amlodipine may enhance the antihypertensive effect of other antihypertensive drugs.

Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (beverages containing alcohol), warfarin or cyclosporine. Amlodipine does not affect the laboratory performance.

By bisoprolol:

Not recommended combinations

The blockers of "slow" calcium channels (BCCC) such as verapamil and to a lesser extent, diltiazem, with simultaneous application with bisoprolol may lead to a decrease in contractility of the myocardium, expressed by a decrease in blood pressure and violation AV conductivity.In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) with simultaneous application with bisoprolol may lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tone. Abrupt cancellation, especially before the abolition of beta-blockers may increase the risk of developing "ricochet" hypertension.

Combinations that require caution

BCCC derivatives of dihydropyridine (for example, nifedipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out. Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

Antiarrhythmic drugs of the III class (for example, amiodarone) can increase the violation AV conductivity.

Parasympatomimetics with simultaneous use with bisoprolol may increase the disruption AV conductivity and increase the risk of developing a bradycardia.

The action of beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

The hypoglycemic effect of insulin or hypoglycemic agents for oral ingestion may be enhanced. Symptoms of hypoglycemia - in particular tachycardia - can be masked. Such interactions are more are likely when using nonselective beta-blockers.

Means for general anesthesia can weaken reflex tachycardia and increase the risk of developing arterial hypotension (see section "Special instructions").

Cardiac glycosides with simultaneous application with bisoprolol may lead to an increase in the timing of the impulse and to the development of a bradycardia.

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the antihypertensive effect of bisoprolol.

The simultaneous use of bisoprolol with beta-adrenomimetics (eg, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics, affecting beta and alpha-adrenoreceptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these agents that occur with alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using nonselective beta-blockers. Hypotensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the antihypertensive effect of bisoprolol.

Combinations that need to be considered

Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.

MAO inhibitors (with the exception of MAO B inhibitors) can enhance the antihypertensive effect of beta-blockers. Simultaneous application can also lead to the development of hypertensive crisis. Rifampicin slightly shortens the half-life (T1 / 2) of bisoprolol. As a rule, dose adjustment is not required.

Derivatives of ergotamine with simultaneous application with bisoprolol increase the risk of peripheral circulatory disturbance.

Special instructions:

Amlodipine

In patients with impaired liver function T₁_/2 Amlodipine increases. When appointing such patients should be observed caution and regularly monitor the activity of "liver" enzymes.

Care should be taken when prescribing amlodipine in patients with chronic heart failure.

In patients with CHF (including non-ischemic etiology III-IV functional class by classification NYHA), Amlodipine increases the risk of pulmonary edema, which is not associated with worsening symptoms of CHF.

During the period of amlodipine therapy, it is necessary to control body weight and intake of table salt, the purpose of the appropriate diet is indicated.

It is necessary to maintain oral hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

In Vitro Fertilization (IVF)

In isolated cases with IVF on the background of BCCC, reversible biochemical changes in the head of spermatozoa were noted, which led to a disruption of their functions.

With unsuccessful attempts of IVF and with the exclusion of other causes of infertility, one should take into account the probability of influence on spermatozoa BCCC, provided they are used.

Bisoprolol

Monitoring the status of patients receiving bisoprolol, should include measurement of heart rate and blood pressure, ECG, determination of blood glucose concentration in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients it is recommended to monitor the kidney function (1 time in 4-5 months).

It is necessary to teach the patient how to calculate the heart rate and instruct him about the need for medical consultation at a heart rate of less than 60 beats per minute.

Before the start of treatment, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis. Patients who use contact lenses should take into account that against the background of drug treatment, a decrease in the production of tear fluid is possible.

When bisoprolol is used in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless an effective blockade of α-adrenergic receptors has been previously achieved).

With hyperthyroidism bisoprolol can mask certain clinical signs of hyperthyroidism (eg, tachycardia). It should be avoided abrupt discontinuation of the drug in patients with hyperthyroidism to avoid increased symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to non-selective β-adrenoblockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

With the simultaneous use of clonidine, its administration can be stopped only a few days after the withdrawal of bisoprolol. It is possible to increase the severity of the reaction of hypersensitivity and the lack of effect from the usual doses of epinephrine (adrenaline) against the background of a weighed allergic anamnesis.

In case of need for planned surgical treatment bisoprolol should be discontinued 48 hours before general anesthesia. If the patient has accepted bisoprolol before surgical intervention, he should choose a medicine for general anesthesia with minimally negative inotropic action.

Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Medicines that deplete the catecholamine depot (incl. reserpine), can strengthen the action βadrenoblokatorov, so patients taking such drug combinations should be under the constant supervision of a physician to identify pronounced reduction in blood pressure and bradycardia.

Patients with bronchospastic diseases can be cautiously prescribed cardioselective β- adrenoblockers in case of intolerance and / or ineffectiveness of other antihypertensive drugs against simultaneous application of bronchodilating agents. On the background of admission β- adrenoblockers in patients with concomitant bronchial asthma may increase airway resistance. When the dose of bisoprolol is exceeded in such patients, there is a danger of developing bronchospasm.

In case of patients increasing bradycardia (heart rate less than 60 bpm. / Min.), Pronounced decrease in blood pressure (systolic blood pressure less than 100 mm Hg) AV blockade, it is necessary to reduce the dose or stop treatment.

It is recommended to stop therapy with bisoprolol in the development of depression. Do not abruptly interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction.Cancellation of the drug is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days).

It is necessary to cancel the drug before the study of the concentration in the blood and urine of catecholamines, normetanefrin, vanillylmandelic acid, antinuclear antibody titers.

Smokers have efficacy β-adrenoconcretors below.

Effect on the ability to drive transp. cf. and fur:

During the period of drug treatment, care should be taken in the management of vehicles and work with technically complex mechanisms.

Form release / dosage:Tablets 5 mg + 5 mg, 5 mg + 10 mg, 10 mg + 5 mg and 10 mg + 10 mg.

Packaging:

For 10 tablets in a planar cell package.

For 30 tablets in a plastic can or in a polymer bottle.

Each bank or vial, 3, 5, 6 contour cell packs of 10 tablets, 2, 3 contour packs of 30 tablets together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004185

Date of registration:15.03.2017

Expiration Date:15.03.2022

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp04.04.2017

Illustrated instructions

Instructions

Amlodipine + Bisoprolol (Amlodipine + Bisoprolol)