Bisangil tablets: instructions for use, price and reviews

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Combined antihypertensive drug.

The beta-blocker bisoprolol has a hypotensive and antiarrhythmic effect, blocking cardiac adrenergic receptors and reducing the flow of calcium into the cell. Reduces heart rate , reduces myocardial excitability and inhibits cardiac conductivity. The effect appears after 2-5 days, and a persistent decrease in blood pressure after 1 month of treatment.

Hydrochlorothiazide is a diuretic that increases the excretion of sodium, potassium, chlorine and magnesium, which leads to an increase in the amount of urine. Reduces plasma volume, increases aldosterone . High doses of hypothiazide increase bicarbonate . The hypotensive effect is manifested by reducing the volume of blood volume , reducing the influence of adrenaline and norepinephrine . Does not affect normal blood pressure . The diuretic effect develops after 2 hours and lasts up to 12 hours.

Pharmacokinetics

Bisoprolol is completely absorbed from the gastrointestinal tract . There is a slight first-pass effect in the liver, so bioavailability is high. The maximum concentration is determined in plasma after 2 hours. Protein binding is 30%. Its metabolites are inactive and are excreted by the kidneys. The half-life is up to 12 hours, so the duration of action lasts 24 hours.

The bioavailability of hydrochlorothiazide is about 70%. The maximum concentration is determined after 2-4 hours. 80% binds to blood proteins. Metabolized in the liver. Excreted by the kidneys. The half-life is 6 hours.

Bisangyl tablet film 5 mg+6.25 mg x30

Clinical-pharmacological group: Antihypertensive drug Pharmaco-therapeutic group: Antihypertensive combined drug (beta1-blocker + diuretic)

pharmachologic effect

Bisoprolol is a selective beta1-blocker without intrinsic sympathomimetic activity. It has antihypertensive, antiarrhythmic and antianginal effects. By blocking β1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces heart rate, inhibits cardiac conduction, reduces myocardial excitability and contractility) . As the dose increases, it blocks β2-adrenergic receptors. OPSS at the beginning of the use of beta-adrenergic blockers increases in the first 24 hours (as a result of a reciprocal increase in the activity of α-adrenergic receptors and elimination of stimulation of β2-adrenergic receptors), after 1-3 days it returns to the original level, and with long-term administration it decreases.

The antihypertensive effect is associated with a decrease in minute blood volume, suppression of sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system by inhibiting β-adrenergic receptors of the juxtaglomerular apparatus of the kidneys (which leads to a decrease in renin secretion), restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure) and effects on the central nervous system. In case of arterial hypertension, the effect develops after 2-5 days, stable effect - after 1-2 months. therapy.

Hydrochlorothiazide is a thiazide diuretic that interferes with the reabsorption of sodium, chlorine, potassium, and magnesium ions in the distal nephron, and delays the excretion of calcium and uric acid. An increase in renal excretion of these ions is accompanied by an increase in the amount of urine (due to osmotic binding of water). Hydrochlorothiazide reduces blood plasma volume, increases plasma renin activity and aldosterone secretion. When taken in high doses, hydrochlorothiazide increases the excretion of bicarbonates; when taken for a long time, it reduces the excretion of calcium.

The antihypertensive effect develops due to a decrease in blood volume, a change in the reactivity of the vascular wall, a decrease in the pressor effect of vasoconstrictor amines (adrenaline, norepinephrine) and an increase in the depressor effect on the ganglia. Has no effect on normal blood pressure. The diuretic effect is observed after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. The antihypertensive effect occurs after 3-4 days, but 3-4 weeks are necessary to achieve the optimal therapeutic effect.

Pharmacokinetics

Bisoprolol

Bisoprolol is almost completely absorbed from the gastrointestinal tract; food intake does not affect absorption. The first pass effect through the liver is negligible, resulting in high bioavailability (about 90%).

Bisoprolol is metabolized via the oxidative pathway without subsequent conjugation. All metabolites have strong polarity and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.

Communication with blood plasma proteins is about 30%. Vd - 3.5 l/kg. Total ground clearance is approximately 15 l/h. Cmax in blood plasma is determined after 2-3 hours. Permeability through the blood-brain barrier and placental barrier is low.

The plasma half-life (10-12 hours) ensures effectiveness for up to 24 hours after a single daily dose.

Bisoprolol is excreted from the body in two ways; 50% of the dose is metabolized in the liver with the formation of inactive metabolites. About 98% is excreted by the kidneys, of which 50% is excreted unchanged, less than 2% through the intestines (with bile).

Since elimination occurs equally in the kidneys and liver, no dosage adjustment is required in patients with impaired liver function or renal failure. The pharmacokinetics of bisoprolol is linear and does not depend on age.

Hydrochlorothiazide

After oral administration, the absorption and bioavailability of hydrochlorothiazide is about 70%. Bonding with blood plasma proteins is 60-80%.

When administered orally 12.5 mg of hydrochlorothiazide, Cmax is achieved after 1.5-4 hours and is 70 ng/ml, and when administered orally 25 mg of hydrochlorothiazide, Cmax is achieved after 2-5 hours and is 142 ng/ml.

In the therapeutic dose range, the average AUC value increases in direct proportion to the increase in dose; when administered 1 time/day, the accumulation is insignificant. Penetrates through the hematoplacental barrier and into breast milk.

T1/2 - 5-6 hours. Hydrochlorothiazide is slightly metabolized in the liver. Hydrochlorothiazide is excreted almost completely (more than 95%) by the kidneys unchanged. 50-70% of the dose taken orally is eliminated within 24 hours.

Indications for the drug Bisangyl

arterial hypertension of mild to moderate severity. Open list of ICD-10 codes

Dosage regimen

Bisangil is recommended to be taken in the morning (during meals). The tablets should be swallowed whole, without chewing, with a small amount of liquid, 1 time/day.

The dose of the drug should be selected individually.

The initial dose of Bisangyl is 1 tablet 2.5 mg/6.5 mg (bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg) 1 time/day.

If the antihypertensive effect is insufficient, the dose is increased (after 2 weeks) - 1 tablet 5 mg/6.25 mg (bisoprolol 5 mg/hydrochlorothiazide 6.25 mg) 1 time/day.

Patients with impaired liver function, as well as elderly patients, do not require dosage adjustment.

In patients with impaired renal function (creatinine clearance more than 30 ml/min), the maximum daily dose of bisoprolol should not exceed 10 mg.

Side effect

The frequency of the adverse reactions listed below was determined according to the following (World Health Organization classification): very often - at least 10%, often - at least 1%, but less than 10%, infrequently - at least 0.1%), but less than 1%, rarely - at least 0.01%, but less than 0.1%, very rarely - less than 0.01%>, including individual messages.

From the heart and blood vessels: very often - a decrease in heart rate (bradycardia, especially in patients with chronic heart failure), a feeling of palpitations, often - a pronounced decrease in blood pressure (especially in patients with chronic heart failure), the manifestation of vasospasm (increased peripheral circulatory disorders, a feeling of coldness in the extremities (paresthesia), infrequently - impaired AV conduction (up to the development of complete transverse block and cardiac arrest), arrhythmias, orthostatic hypotension, worsening of chronic heart failure with the development of peripheral edema (swelling of the ankles, feet, shortness of breath), chest pain .

From the nervous system: often - dizziness, headache, asthenia, fatigue, sleep disturbances, depression, anxiety, rarely - confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremors, muscle cramps. Typically, these phenomena are mild in nature and usually disappear within 1-2 weeks after the start of treatment.

From the senses: rarely - blurred vision, decreased tearing (should be taken into account when wearing contact lenses), tinnitus, decreased hearing, ear pain, very rarely - dry and sore eyes, conjunctivitis, taste disturbances.

From the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or obstructive airway diseases, rarely - allergic rhinitis, nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dry oral mucosa, abdominal pain, rarely - hepatitis, increased activity of liver enzymes (ALT, AST), increased bilirubin concentration, change in taste.

From the musculoskeletal system: infrequently - arthralgia, back pain.

From the genitourinary system: very rarely - impaired potency, weakened libido.

Laboratory indicators: rarely - increased concentration of triglycerides in the blood, in some cases - thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rarely - itching, rash, urticaria.

From the skin: rarely - increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, very rarely - alopecia; beta-blockers can aggravate the course of psoriasis.

Other: withdrawal syndrome (increased frequency of angina attacks, increased blood pressure).

Hydrochlorothiazide

Fluid and electrolyte imbalance: hypokalemia, hypomagnesemia, hypercalcemia and hypochloremic alkalosis: dry oral mucosa, thirst, irregular heart rhythm, changes in mood or psyche, cramps and muscle pain, nausea, vomiting, unusual fatigue or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma. Hyponatremia: confusion, convulsions, lethargy, slow thinking, increased fatigue, excitability, muscle cramps.

Metabolic disorders: hyperglycemia, glycosuria, hyperuricemia with the development of an attack of gout.

Treatment with thiazides may impair glucose tolerance, and latent diabetes mellitus may manifest itself. When using high doses, serum lipid concentrations may increase.

From the digestive system: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the heart and blood vessels: arrhythmias, orthostatic hypotension, vasculitis.

From the nervous system: dizziness, temporarily blurred vision, headache, paresthesia.

From the hematopoietic organs: very rarely - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Allergic reactions: urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.

Other: decreased potency, impaired renal function, interstitial nephritis.

Contraindications for use

hypersensitivity to bisoprolol and other components of the drug, hypersensitivity to hydrochlorothiazide and other sulfonamide derivatives, severe forms of bronchial asthma and chronic obstructive pulmonary disease, acute heart failure or chronic heart failure in the decompensation stage, requiring inotropic therapy, cardiogenic shock, sick sinus syndrome node (including sinoatrial block), AV block of the second and third degree without an artificial pacemaker, severe bradycardia (heart rate less than 50 beats/min.), pheochromocytoma (without simultaneous use of alpha-blockers), difficult-to-control diabetes mellitus, late stages of peripheral circulatory disorders (including Raynaud's syndrome), severe arterial hypotension (systolic blood pressure less than 100 mm Hg), refractory hypokalemia, hyponatremia, hypercalcemia, metabolic acidosis, acute renal failure, chronic renal failure (creatinine clearance (CC) less than 30 ml/min.), anuria, severe liver dysfunction (incl. coma and precoma), simultaneous use with floctafenine, sultopride, simultaneous use of monoamine oxidase inhibitors (MAO inhibitors) with the exception of MAO type B inhibitors), age under 18 years (efficacy and safety have not been established), lactose intolerance, lactase deficiency or glucose-galactose malabsorption, pregnancy, lactation period.

Use with caution in heart failure, AV block of the first degree, Prinzmetal's angina, peripheral circulatory disorders, coronary heart disease, liver failure, renal failure (creatinine clearance more than 30 ml/min.), hyperthyroidism, pheochromocytoma (during treatment with alpha-blockers) , water and electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), depression (including a history), myasthenia gravis, gout, psoriasis, as well as in elderly patients, hyperuricemia, diabetes mellitus with significant fluctuations in blood glucose concentrations, severe diet, hypovolemia, bronchial asthma, bronchospasm (history), desensitizing therapy.

Use during pregnancy and breastfeeding

The use of Bisangyl is contraindicated during pregnancy.

It is currently unknown whether bisoprolol is excreted in breast milk. Thiazide diuretics are excreted in breast milk and therefore breastfeeding during treatment with Bisangyl is not recommended. If the use of the drug is necessary during lactation, breastfeeding should be discontinued.

Use for liver dysfunction

Contraindication: severe liver dysfunction (including coma and precoma).

Use for impaired renal function Use with caution in case of renal failure (creatinine clearance more than 30 ml/min.). Contraindicated: chronic renal failure (creatinine clearance (CC) less than 30 ml/min.), anuria.

Use in children Contraindication: under 18 years of age (efficacy and safety have not been established).

Use in elderly patients Use with caution in elderly patients.

special instructions

During therapy with Bisangyl, it is necessary to monitor heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), and blood glucose concentrations in patients with diabetes (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months). It is necessary to teach the patient how to calculate heart rate. During therapy with Bisangyl, it is also necessary to monitor the acid-base status and electrolyte content (potassium, sodium, calcium). More frequent monitoring of potassium levels is necessary in high-risk patients. In patients with peripheral circulatory disorders, caution must be exercised when prescribing Bisangyl.

In case of thyrotoxicosis, the drug Bisangil (due to the content of bisoprolol) can mask the clinical signs of the disease (for example, tachycardia).

Patients with pheochromocytoma should not be prescribed Bisangyl until treatment with alpha-blockers has been prescribed. In this case, it is necessary to control blood pressure.

In patients with mild bronchial asthma or chronic obstructive pulmonary disease, treatment begins with a minimum dose.

It is recommended to discontinue therapy with Bisangil if depression occurs due to the use of a beta-blocker (due to the bisoprolol content in it). In elderly patients, treatment with Bisangil should begin with a dosage form of the drug containing a low dose of bisoprolol (2.5 mg). In this case, regular monitoring of the patient’s condition is necessary.

Overdose

Bisoprolol

The most common symptoms of beta-blocker overdose are: marked decrease in blood pressure, bradycardia, AV block, bronchospasm, acute heart failure and hypoglycemia.

Hydrochlorothiazide

Clinical manifestations of acute or chronic overdose of hydrochlorothiazide are caused by significant loss of fluid or electrolytes.

The most common symptoms of hydrochlorothiazide overdose: dizziness, nausea, drowsiness, hypovolemia, marked decrease in blood pressure, hypokalemia.

Treatment: in case of overdose, first of all, it is necessary to stop taking the drug, rinse the stomach, prescribe adsorbents and begin supportive symptomatic therapy.

For severe bradycardia: intravenous administration of atropine. Sometimes temporary placement of an artificial pacemaker may be necessary. With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions. In case of AV block (II and III degrees): patients should be under constant supervision, epinephrine may be prescribed, and, if necessary, an artificial pacemaker should be placed. In case of exacerbation of chronic heart failure: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators. For bronchospasm: prescribing bronchodilators, beta2-sympathomimetics and/or aminophylline. For hypoglycemia: intravenous administration of dextrose (glucose) solution.

Drug interactions

Combinations whose use is contraindicated

In case of shock or arterial hypotension caused by taking floctafenine, beta-blockers cause a decrease in compensatory cardiovascular reactions.

Bisoprolol should not be used simultaneously with sultopride, since there is a high risk of ventricular arrhythmias, incl. "pirouette" type.

MAO type A inhibitors should not be taken simultaneously with bisoprolol, as there is a risk of developing a hypertensive crisis.

Not recommended combinations

Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and cardiac contractility. Slow calcium channel blockers (SCBCs) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block. Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal of centrally acting antihypertensive drugs, especially before discontinuation of beta-blockers, may increase the risk of developing “rebound” arterial hypertension.

Combinations requiring caution

Class III antiarrhythmic drugs (eg, amiodarone) may worsen AV conduction disturbances.

The effect of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

Parasympathomimetics, when used simultaneously with bisoprolol, may enhance AV conduction disturbances and increase the risk of developing bradycardia. The simultaneous use of Bisangyl with beta-agonists (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenergic agonists that affect beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine) may increase

the vasoconstrictor effects of these drugs occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.

Mefloquine, when used simultaneously with bisoprolol, may increase the risk of bradycardia.

Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol.

Iodine-containing radiopaque diagnostic agents for intravenous administration increase the risk of developing anaphylactic reactions.

Phenytoin, when administered intravenously, and agents for inhalation anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of lowering blood pressure.

The effectiveness of insulin and hypoglycemic agents for oral administration may change during treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

The clearance of lidocaine and xanthines (except theophylline) may be reduced due to a possible increase in their concentration in the blood plasma, especially in patients with an initially increased clearance of theophylline under the influence of smoking. The antihypertensive effect is weakened by nonsteroidal anti-inflammatory drugs (NSAIDs) (sodium ion retention and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure.

Antiarrhythmics that can cause torsade de pointes (class IA, eg, quinidine, hydrohidine, disopyramide and class III, eg, amiodarone, dofetilide, ibutilide) and sotalol: Hypokalemia may cause torsade de pointes.

Other arrhythmic drugs that can cause torsades de pointes (for example, astemizole, erythromycin IV, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamine): hypokalemia can provoke the development of torsades de pointes.

Nifedipine can lead to a significant decrease in blood pressure

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure.

The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins may be prolonged during treatment with bisoprolol.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression.

Concomitant use with MAO inhibitors is not recommended due to a significant increase in antihypertensive effect. The treatment break between taking MAO inhibitors and bisoprolol should be at least 14 days. Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.

Ergotamine increases the risk of developing peripheral circulatory disorders. Sulfasalazine increases the concentration of bisoprolol in the blood plasma. Rifampin shortens the half-life of bisoprolol. Hydrochlorothiazide

With thiazide diuretics, drugs such as ethanol, barbiturates and narcotics may potentiate the risk of orthostatic hypotension.

Hypoglycemic agents (oral and insulin) - dosage adjustment of hypoglycemic agents may be required.

Other antihypertensive drugs have an additive effect.

Cholestyramine and colestipol - in the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired. Cholestyramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, ACTH (adrenocorticotropic hormone) or glycyrrhizic acid (found in licorice root) - marked reduction in electrolytes, in particular the risk of hypokalemia.

Pressor amines (eg, epinephrine, norepinephrine) - decreased response to pressor amines.

Muscle relaxants of a non-depolarizing type of action (for example, tubocurarine) - enhance the effect of muscle relaxants.

Lithium - Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity; simultaneous use is not recommended.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors) - may reduce the diuretic, natriuretic and antihypertensive effects of diuretics.

In some patients with impaired renal function (eg, elderly or dehydrated patients, including those taking diuretics) receiving NSAID therapy, including COX-2 inhibitors, treatment with angiotensin II receptor antagonists or ACE inhibitors may cause further deterioration of renal function, including development of acute renal failure. These effects are reversible. The simultaneous use of these drugs should be used with caution in patients with impaired renal function.

Due to their effect on calcium metabolism, their intake may distort the results of studies of parathyroid function.

Therapy should not be abruptly discontinued, especially in patients with coronary artery disease. The dose should be reduced gradually over two weeks. If necessary, appropriate antianginal therapy should be initiated simultaneously.

Particular attention is required in cases of surgery under general anesthesia in patients taking beta-blockers. Such patients should discontinue the drug Bisangyl 48 hours before surgery, and warn the surgeon-anesthesiologist that the patient is taking the drug Bisangil. As a means of general anesthesia, you should choose a drug with minimal negative inotropic effect.

During therapy with beta-blockers, an exacerbation of psoriasis is possible. Bisangil should be prescribed to patients with this disease with caution. If there is a history of anaphylactic reactions, regardless of the cause of their occurrence, especially during desensitizing therapy, treatment with Bisangyl (due to the content of bisoprolol) may increase the risk of allergic reactions and contribute to the development of resistance to treatment with epinephrine (adrenaline) in normal doses .

Patients who wear contact lenses should be careful when using Bisangyl, as beta-blockers may reduce tear production.

Patients with hyperuricemia have an increased risk of developing an exacerbation of gout. In this case, the dose of Bisangyl should be selected individually under the control of the concentration of uric acid in the blood serum. Before studying the function of the parathyroid glands, treatment with Bisangyl must be stopped, since transient hypercalcemia may occur while taking it.

Athletes should be informed that Bisangil contains bisoprolol, which may give false positive results during doping control.

Impact on the ability to drive vehicles and operate machinery

Bisangil should be used with caution when driving vehicles and machinery due to the possibility of dizziness.

Storage conditions for the drug Bisangil

The drug should be stored in a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C.

Shelf life of the drug Bisangil Shelf life - 3 years. Do not use after expiration date.

Terms of sale The drug is available with a prescription.

Contacts for inquiries

OZONE LLC (Russia)

445351 Samara region. Zhigulevsk, st. Gidrostroiteley, 6 Tel.: (84862) 3-41-09, 7-18-51/54

Contraindications

increased sensitivity;
decompensated heart failure ;
severe bronchial asthma and obstructive pulmonary disease ;
cardiogenic shock;
severe bradycardia ;
AV block II and III degrees;
severe diabetes mellitus ;
metabolic acidosis;
Raynaud's syndrome;
hypokalemia , hypercalcemia ;
arterial hypotension;
renal and liver failure;
age under 18 years;
pregnancy;
taking with monoamine oxidase , sultopride and floctafenine .

It is prescribed with caution for AV block of the first degree, heart failure , peripheral circulatory disorders, hyperthyroidism , pheochromocytoma , depression , disorders of the water-electrolyte composition of the blood, gout , psoriasis , and in the elderly.

Bisangil

Precautions related to bisoprolol

Discontinuation of therapy

Do not abruptly stop therapy, especially in patients with coronary heart disease (angina). Abrupt cessation of therapy may result in severe cardiac arrhythmia, myocardial infarction, or sudden death.

Bronchial asthma and COPD

Although cardioselective beta blockers (beta1) may have less effect on pulmonary function than non-selective beta blockers, as with all beta blockers, their use should be avoided in patients with obstructive airway disease unless clinically convincing indications for their use. If such indications exist, the drug should be used with caution. In patients with obstructive airway diseases, treatment with bisoprolol begins with the lowest possible dose. Patients should be closely monitored for new symptoms (eg, shortness of breath, exercise intolerance, cough).

For symptomatic manifestations of bronchial asthma or COPD, simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be an increase in airway resistance, which requires a higher dose of beta2-agonists.

Chronic heart failure

Patients with compensated CHF who are indicated for treatment with beta-blockers should begin treatment with minimal doses of the drug, gradually increasing the dose under the supervision of a physician.

Bradycardia

When the heart rate is less than 50-55 beats/min at rest and in patients who experience symptoms associated with bradycardia, it is necessary to reduce the dose of the drug.

First degree atrioventricular block

Given the negative dromotropic effect of beta-blockers, they should be used with caution in patients with first-degree AV block.

Prinzmetal's angina

Beta blockers may increase the frequency and duration of vasospastic episodes in patients with Prinzmetal's angina. Beta1-selective blockers can be used for mild or mixed manifestations of Prinzmetal's angina with simultaneous use of vasodilators.

Peripheral circulation disorders

In patients with peripheral circulatory disorders or Raynaud's syndrome, beta-blockers may cause an exacerbation of the disease. It is preferable to prescribe beta1-selective beta blockers to such patients.

Pheochromocytoma

Patients with pheochromocytoma should not use Bisangil until they have been treated with alpha-blockers. Careful monitoring of blood pressure is necessary.

Elderly patients

Usually no dose adjustment is required. Treatment must be carried out under careful monitoring of the patient’s condition (see subsection “Water and electrolyte balance”).

Diabetes

Patients taking Bisangyl should be warned about the possibility of hypoglycemia and the need for regular monitoring of blood glucose concentrations at the beginning of therapy. Symptoms of a pronounced decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations, increased sweating, may be masked.

Psoriasis

During therapy with beta-blockers, an exacerbation of psoriasis is possible. Bisoprolol can be prescribed only if necessary.

Allergic reactions

In patients with a history of anaphylactic reactions, regardless of the cause of their occurrence, especially when using iodinated contrast agents or during desensitization therapy, treatment with beta-blockers may exacerbate the occurrence of these reactions and cause the development of resistance to treatment with epinephrine (adrenaline) in usual doses used in the treatment of hypersensitivity reactions.

General anesthesia

During general anesthesia, beta-adrenergic receptor blockade reduces the likelihood of arrhythmia and myocardial ischemia during induction of anesthesia and intubation, as well as in the postoperative period. It is currently recommended to continue beta-blocker therapy intraoperatively. The anesthesiologist should consider the risk of beta-adrenergic receptor blockade due to potential interactions with other drugs, which can cause bradyarrhythmia, suppression of reflex tachycardia and a decrease in the reflex ability to compensate for blood loss. If it is necessary to discontinue Bisangyl therapy before surgery, this should be done gradually and completed 48 hours before general anesthesia.

Thyrotoxicosis

When treated with bisoprolol, the symptoms of thyrotoxicosis from the cardiovascular system may be masked.

Strict diet

Bisangyl should be used with caution in patients on a strict diet.

Combination with verapamil, diltiazem or bepridil

Such combinations require careful monitoring of the patient's condition and ECG, especially in elderly patients and at the beginning of treatment.

Precautions associated with hydrochlorothiazide

In patients with impaired liver function, thiazide diuretics and their derivatives can cause hepatic encephalopathy. In this case, you must immediately stop taking the medications.

Non-melanoma skin cancer

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of non-melanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment. In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide.

Water and electrolyte balance

With long-term use of the drug Bisangyl, it is necessary to regularly monitor the content of serum electrolytes (especially potassium, sodium, calcium), creatinine and urea, serum lipids (cholesterol, triglycerides), uric acid and glucose.

Long-term use of thiazide diuretics can lead to disturbances in water-electrolyte balance, in particular hypokalemia and hyponatremia, as well as hypomagnesemia and hypochloremia, and hypercalcemia.

Sodium content in blood plasma

Before starting therapy and thereafter, it is necessary to regularly monitor sodium levels in the blood. Taking diuretics can provoke hyponatremia, in some cases with serious consequences. A decrease in sodium levels at the beginning of treatment may be asymptomatic, so regular monitoring is necessary, special attention is required in patients at high risk, for example, elderly patients, patients with cirrhosis of the liver.

Potassium content in blood plasma

The greatest risk associated with the use of thiazide and thiazide-like diuretics is potassium loss leading to hypokalemia (<3.5 mmol/L). More frequent monitoring of blood potassium is necessary in high-risk patients, such as those who are elderly and/or malnourished and/or taking multiple medications at the same time, and in patients with coronary artery disease or heart failure in whom hypokalemia increases the risk development of arrhythmias, toxicity of cardiac glycosides. Also at risk are patients with an increased QT interval, both congenital and acquired. Hypokalemia (as well as bradycardia) potentiates the development of severe arrhythmias, including tachycardia of the “pirouette” type, which can be fatal.

More frequent monitoring of potassium levels in blood plasma is indicated for all of the above groups of patients. The first determination of potassium content in blood plasma should be carried out during the first week of therapy with Bisangyl.

Calcium content in blood plasma

Thiazide diuretics may reduce renal excretion of calcium, resulting in mild and temporary hypercalcemia.

Significant hypercalcemia may be associated with undiagnosed hyperparathyroidism. Thiazide diuretics should be discontinued until parathyroid function studies are performed.

Plasma glucose concentration

Monitoring of blood glucose concentrations is necessary in patients with diabetes mellitus, especially in the case of hypokalemia.

Uric acid

In patients with hyperuricemia, the risk of developing gout attacks is increased: the dose of the drug must be selected individually, based on the concentration of uric acid in the blood plasma.

Kidney function

Thiazide diuretics are effective in normal or slightly reduced renal function (creatinine clearance less than 25 mg/ml or 220 µmol/l in adults). Creatinine clearance is calculated taking into account the age, body weight or gender of the patient using the Cockcroft equation.

For example: CC = (140 - age) x body weight/0.814 x serum creatinine,

where: age (years), body weight (kg), serum creatinine (in micromol/l).

This calculation formula is applicable for elderly male patients.

For elderly female patients, the result must be multiplied by 0.85.

Hypovolemia, in addition to the loss of fluid and sodium resulting from the use of diuretics at the beginning of therapy, leads to a decrease in glomerular filtration rate, which in turn leads to an increase in serum urea and creatinine concentrations. Temporary impairment of renal function occurs without consequences in patients with normal renal function. In patients with impaired renal function, existing disorders may worsen.

Combination with other antihypertensive drugs

If the drug is used with another antihypertensive agent, a dose reduction is recommended, at least at the beginning of therapy.

Photosensitivity

The use of thiazide diuretics in rare cases can cause photosensitivity reactions. If such reactions occur, it is recommended to discontinue therapy with Bisangyl. If therapy needs to be restarted, sensitive areas of the body should be protected from exposure to sunlight or artificial ultraviolet radiation.

Myopia (nearsightedness) and angle-closure glaucoma

Hydrochlorothiazide, as a sulfonamide, can cause idiosyncratic reactions manifested as acute short-term myopia and acute angle-closure glaucoma. Symptoms include: a sharp decrease in visual acuity or eye pain, which usually appears within a few hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. The first step in treatment is to stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: a history of an allergic reaction to sulfonamide derivatives or penicillin.

Precautions associated with bisoprolol and hydrochlorothiazide

Athletes

Athletes should be informed that the drug Bisangil contains the active ingredients bisoprolol and hydrochlorothiazide, which can give positive results during a doping test.

Side effects

hearing impairment;
bradycardia , hypotension, AV conduction ;
nausea, diarrhea , jaundice, hepatitis ;
bronchospasm;
hyperglycemia;
rhinitis;
hair loss;
psoriasis;
leukopenia , increased levels of ALT , AST , glucosuria , hypercholesterolemia .

Bisangil, instructions for use (Method and dosage)

The tablets are taken once a day, in the morning with meals. The doctor selects the dose individually for each patient.

The initial dose is 1 tablet per day (2.5 mg/6.25 mg). If the effect is insufficient, then after 2 weeks it is increased to 5 mg/6.25 mg. No dose changes are required for liver dysfunction. If renal function is impaired, the daily dose is up to 10 mg of bisoprolol .

During treatment, you need to monitor heart rate and blood pressure glucose levels (every 5 months) and electrolyte levels. Elderly persons need to monitor their kidney function. For mild bronchial asthma, a minimum dose is prescribed.

Also, a low dose (2.5 mg) is indicated for elderly people. depression develops during treatment, therapy should be discontinued.

Overdose

An overdose of Bisoprolol is manifested by severe bradycardia , decreased blood pressure , the appearance of AV block , bronchospasm and hypoglycemia .

Manifestations of an overdose of hydrochlorothiazide are associated with fluid loss: drowsiness , dizziness , nausea, hypokalemia , decreased blood pressure .

Treatment consists of gastric lavage, administration of enterosorbents and symptomatic therapy: administration of atropine for bradycardia , for bronchospasm - bronchodilators and epinephrine for AV block .

Bisangil

The frequency of adverse reactions that occur while taking the drug is indicated in accordance with the classification of the World Health Organization: very often - at least 10%; often - at least 1%, but less than 10%; infrequently - not less than 0.1%), but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%>, including individual messages.

From the heart and blood vessels: very often - decreased heart rate (bradycardia, especially in patients with chronic heart failure); sensation of palpitations, often - a marked decrease in blood pressure (especially in patients with chronic heart failure), increased peripheral circulatory disorders, a feeling of coldness in the extremities (paresthesia); infrequently - disturbance of atrioventricular conduction (up to the development of complete transverse block and cardiac arrest), arrhythmias, orthostatic hypotension, aggravation of chronic heart failure with the development of peripheral edema (swelling of the ankles, feet; shortness of breath), chest pain.

From the nervous system: often - dizziness, headache, asthenia, increased fatigue, sleep disturbances, depression, anxiety; rarely - confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremors, muscle cramps. Typically, these phenomena are mild in nature and usually disappear within 1-2 weeks after starting treatment with the drug.

From the senses: rarely - blurred vision, decreased lacrimation (must be taken into account when wearing contact lenses), tinnitus, hearing loss, ear pain; very rarely - dry and sore eyes, conjunctivitis, taste disturbances.

From the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or obstructive airway diseases; rarely - allergic rhinitis; nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dry oral mucosa, abdominal pain; rarely - hepatitis, increased activity of liver enzymes (ALT, AST), increased bilirubin concentration, change in taste.

From the musculoskeletal system: uncommon - joint pain, back pain.

From the genitourinary system: very rarely - impaired potency, weakened libido.

Laboratory indicators: rarely - increased concentration of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rarely - itching, rash, urticaria.

From the skin: rarely - increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions; very rarely - alopecia; beta-blockers can aggravate the course of psoriasis.

Other: withdrawal syndrome (increased frequency of angina attacks, increased blood pressure).

Hydrochlorothiazide, which is part of the drug, may cause the following side effects:

Metabolic disorders: hyperglycemia, glycosuria, hyperuricemia with the development of an attack of gout.

Treatment with thiazides may impair glucose tolerance, and latent diabetes mellitus may manifest itself. When using high doses, serum lipid concentrations may increase.

From the digestive system: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the heart and blood vessels: arrhythmias, orthostatic hypotension, vasculitis.

From the nervous system: dizziness, temporarily blurred vision, headache, paresthesia.

From the hematopoietic organs: very rarely - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Other: decreased potency, impaired renal function, interstitial nephritis.

In case of an overdose of the drug, a pronounced decrease in blood pressure, bradycardia, atrioventricular block, bronchospasm, acute heart failure and hypoglycemia may develop; dizziness, nausea, drowsiness, hypovolemia, hypokalemia. In such cases, the drug is stopped, gastric lavage is prescribed, adsorbents are taken, and supportive symptomatic therapy is started.

Interaction

Cannot be used simultaneously with sultopride (high risk of developing ventricular arrhythmias ). When taken with MAO inhibitors, there is a risk of hypertensive crisis .

Quinidine , lidocaine , disopyramide , phenytoin ; propafenone , flecainide may reduce AV conduction . When calcium channel blockers are prescribed simultaneously, AV conduction . Clonidine , moxonidine , methyldopa , rilmenidine cause a decrease in heart rate and reduce cardiac output.

Nifedipine , clonidine , and hydralazine lead to a pronounced decrease in blood pressure . Tricyclic antidepressants and antipsychotics increase central nervous system . Sulfasalazine significantly increases the concentration of bisoprolol . Rifampin shortens its half-life.

Corticosteroids taken with hypothiazide cause decreased electrolyte levels and increase the risk of hypokalemia .

Bisangyl

Combinations whose use is contraindicated

In case of shock or arterial hypotension caused by taking floctafenine, beta-blockers cause a decrease in compensatory cardiovascular reactions.

Bisoprolol should not be used simultaneously with sultopride, since there is a high risk of ventricular arrhythmias, incl. "pirouette" type.

MAO type A inhibitors should not be taken simultaneously with bisoprolol, as there is a risk of developing a hypertensive crisis.

Not recommended combinations

Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and cardiac contractility. Slow calcium channel blockers (SCBCs) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block. Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal of centrally acting antihypertensive drugs, especially before discontinuation of beta-blockers, may increase the risk of developing “rebound” arterial hypertension.

Combinations requiring caution