Bisangil

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Bisangil: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Bisangil

ATX code: C07BB07

Active ingredient: bisoprolol (bisoprolol) + hydrochlorothiazide (hydrochlorothiazide)

Manufacturer: Ozone, LLC (Russia)

Description and photo update: 2019-23-08

Prices in pharmacies: from 244 rubles.

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Bisangil is a combined drug with an antihypertensive effect.

Release form and composition

Dosage form Bisangil - coated tablets: almost white or white, biconvex (10 or 30 pieces in blisters, 1-5 or 10 packs in a cardboard box; 10, 20, 30, 40, 50 or 100 pieces in polymeric containers, 1 container in a carton box).

Active ingredients in 1 tablet:

bisoprolol fumarate - 2.5 or 5 mg;
hydrochlorothiazide - 6.25 mg.

Additional components (2.5 mg + 6.25 mg / 5 mg + 6.25 mg):

core: croscarmellose sodium - 2/4 mg; magnesium stearate - 1/2 mg; lactose monohydrate - 62 / 130.25 mg; microcrystalline cellulose - 18/36 mg; corn starch - 4.75 / 9.5 mg; povidone - 3.5 / 7 mg;
shell: macrogol 4000 - 0.45 / 0.9 mg; hypromellose - 1.65 / 3.3 mg; titanium dioxide - 0.9 / 1.8 mg.

Pharmacological properties

Pharmacodynamics

The action of Bisangil is due to the properties of the active ingredients.

Bisoprolol is a selective β ₁ -adrenergic blocker without intrinsic sympathomimetic activity. It has antianginal, antiarrhythmic and antihypertensive effects.

Due to the blocking of β ₁ -adrenergic receptors of the heart, when using low doses, the formation of cAMP (cyclic adenosine monophosphate) from ATP (adenosine triphosphate) stimulated by catecholamines decreases, the intracellular flow of calcium ions decreases, there is a negative dromo-, chrono-, ino- and batmotropic effect, which is manifested in a decrease heart rate, inhibition of cardiac conduction, decrease in contractility and excitability of the myocardium.

When using higher doses, bisoprolol blocks β ₂ -adrenergic receptors. In the first 24 hours of therapy, OPSS (total peripheral vascular resistance) increases (associated with a reciprocal increase in the activity of α-adrenergic receptors and elimination of stimulation of β ₂ -adrenoreceptors), after 1–3 days the value returns to its original value, with prolonged administration the indicator decreases.

The antihypertensive properties of Bisangil are associated with such effects of bisoprolol as:

suppression of sympathetic stimulation of peripheral vessels;
decrease in minute blood volume;
effect on the central nervous system;
a decrease in the activity of the renin-angiotensin-aldosterone system by inhibition of β-adrenergic receptors of the juxtaglomerular apparatus of the kidneys (causes a decrease in renin secretion);
restoration of the sensitivity of the aortic arch baroreceptors (in response to a decrease in blood pressure, their activity does not increase).

The effect of bisoprolol in arterial hypertension develops in 2–5 days, a stable effect after 1–2 months of therapy.

The second active component of Bisangil, hydrochlorothiazide, is a thiazide diuretic. The substance interferes with the reabsorption of magnesium, chlorine, sodium, potassium ions in the distal nephron, and also delays the excretion of uric acid and calcium. With an increase in the renal excretion of these ions, an increase in the amount of urine is observed (due to the osmotic binding of water).

Hydrochlorothiazide increases the secretion of aldosterone and renin activity in the blood plasma, reduces the volume of blood plasma. High doses of hydrochlorothiazide increase the excretion of bicarbonates; with prolonged therapy, they decrease the excretion of calcium.

The antihypertensive effect of Bisangil is provided due to the following effects:

change in the reactivity of the vascular wall;
a decrease in the volume of circulating blood;
strengthening of the depressor effect on the ganglia;
decrease in the pressor effect of vasoconstrictor amines (adrenaline, norepinephrine).

Hydrochlorothiazide does not affect normal blood pressure. The development of the diuretic effect is observed after 1–2 hours, the maximum is achieved after 4 hours, the duration of action is from 6 to 12 hours.

The antihypertensive effect develops in 3-4 days, the optimal therapeutic effect is observed in 21-28 days.

Pharmacokinetics

Bisoprolol

The substance is absorbed in the gastrointestinal tract almost completely, food intake has no effect on absorption. The effect of the first pass through the liver is negligible, which provides high bioavailability (approximately 90%).

Bisoprolol is metabolized by oxidative means without subsequent conjugation. All metabolites of the substance have a strong polarity; excretion is carried out mainly by the kidneys. The main metabolites, which are found in urine and blood plasma, do not show pharmacological activity. As a result of the studies, it was found that bisoprolol is metabolized mainly by the CYP3A4 isoenzyme (approximately 95%), the CYP2D6 isoenzyme is involved only slightly.

The connection with blood plasma proteins is approximately 30%. V _d (volume of distribution) is 3.5 l / kg. The total ground clearance is about 15 l / h. C _max (maximum concentration of the substance) in blood plasma is reached in 2-3 hours. Has a low permeability across the blood-brain barrier and placental barrier.

T _1/2 (half-life) from blood plasma is 10-12 hours, which after taking a single daily dose provides an effect for 24 hours.

The excretion of the substance is carried out in two ways (50% of the dose is metabolized in the liver, resulting in the formation of inactive metabolites): approximately 98% is excreted by the kidneys (unchanged - about 50% of them), with bile through the intestines - less than 2%.

The pharmacokinetic processes of bisoprolol are linear, these values do not depend on age.

Hydrochlorothiazide

After oral administration of the substance, its absorption and bioavailability are approximately 70%. 60-80% binds to blood plasma proteins.

C _max after taking 12.5 mg of hydrochlorothiazide is 70 ng / ml and is achieved in 1.5-4 hours, for a dose of 25 mg these values correspond to 142 ng / ml and 2-5 hours.

The average value of AUC (area under the curve "concentration - time") when used in the therapeutic dose range increases in direct proportion to the increase in dose, the cumulation when administered once a day is insignificant.

Penetrates through the hematoplacental barrier and into breast milk.

T _1/2 ranges from 5 to 6 hours. It is metabolized in the liver slightly. Hydrochlorothiazide is excreted by the kidneys unchanged almost completely (from 95%), 50-70% of the dose taken orally is excreted within 24 hours.

Indications for use

According to the instructions, Bisangil is prescribed for the treatment of mild / moderate arterial hypertension.

Contraindications

Absolute:

AV block II and III degree without an artificial pacemaker;
bronchial asthma and chronic obstructive pulmonary disease in severe forms;
cardiogenic shock;
acute heart failure or chronic heart failure in the stage of decompensation, which requires inotropic therapy;
sick sinus syndrome, including sinoatrial block;
difficult to control diabetes mellitus;
severe bradycardia (with a heart rate of less than 50 beats / min);
pheochromocytoma (without the combined use of alpha-blockers);
peripheral circulatory disorders in the later stages, including Raynaud's syndrome;
renal failure in acute course;
severe arterial hypotension (with systolic pressure less than 100 mm Hg);
metabolic acidosis;
hyponatremia, refractory hypokalemia, hypercalcemia;
anuria, chronic renal failure (with creatinine clearance less than 30 ml / min);
functional liver disorders in severe course, including coma and precoma;
combined use with the following drugs: floktaphenin, sultopride, MAO (monoamine oxidase) inhibitors except MAO type B inhibitors;
glucose-galactose malabsorption or lactase deficiency, lactose intolerance;
age up to 18 years (the safety profile for this group of patients has not been studied);
pregnancy and the period of breastfeeding;
individual intolerance to the components of the drug, as well as other sulfonamide derivatives.

Relative (Bisangil is prescribed with caution in the presence of the following diseases / conditions):

heart and liver failure;
AV block I degree;
peripheral circulatory disorders;
Prinzmetal's angina;
cardiac ischemia;
renal failure (with creatinine clearance greater than 30 ml / min);
pheochromocytoma, which developed during treatment with alpha-blockers;
hyperthyroidism;
depression, including the presence of anamnestic data;
water-electrolyte disturbances, including hypokalemia, hyponatremia, hypercalcemia;
hyperuricemia;
myasthenia gravis;
psoriasis;
gout;
diabetes mellitus with significant fluctuations in blood glucose concentration;
bronchial asthma;
hypovolemia;
desensitizing therapy;
burdened history of bronchospasm;
adherence to a strict diet;
elderly age.

Instructions for the use of Bisangil: method and dosage

Bisangil tablets are taken orally with a small amount of liquid, preferably in the morning along with food. Do not chew tablets.

The daily dose is taken in 1 dose. The dosage regimen is determined by the doctor on an individual basis.

At the beginning of the course, the drug is prescribed 1 tablet 2.5 mg + 6.25 mg per day. If the therapeutic effect is insufficient, after 14 days the patient can be transferred to the reception of Bisangil 5 mg + 6.25 mg.

The daily dose of Bisangil with creatinine clearance more than 30 ml / min is up to 10 mg.

Side effects

The incidence of adverse reactions:> 10% - very often; > 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% taking into account individual messages - very rare.

Bisoprolol

digestive system: often - vomiting, nausea, diarrhea, constipation, abdominal pain, dryness of the oral mucosa; rarely - hepatitis, an increase in the concentration of bilirubin, the activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase), a change in taste;
respiratory system: infrequently - bronchospasm against the background of bronchial asthma or obstructive respiratory diseases; rarely - nasal congestion, allergic rhinitis;
genitourinary system: very rarely - weakening of libido, violation of potency;
musculoskeletal system: infrequently - back pain, arthralgia;
nervous system: often - depression, sleep disturbances, dizziness, asthenia, anxiety, headache, increased fatigue; rarely - short-term memory loss or confusion, hallucinations, nightmares, tremors, myasthenia gravis, muscle cramps (these disorders in most cases are transient, mild and do not require discontinuation of therapy);
cardiovascular system: very often - a decrease in the heart rate (development of bradycardia, especially in patients with chronic heart failure), a feeling of palpitations; often - a pronounced decrease in blood pressure (especially in chronic heart failure), angiospasm (manifests itself as an increase in peripheral circulatory disorders, a feeling of coldness in the extremities); infrequently - orthostatic hypotension, violation of atrioventricular conduction (up to the development of cardiac arrest and complete transverse blockade), arrhythmias, worsening symptoms of chronic heart failure (the appearance of peripheral edema - swelling of the ankles and feet), shortness of breath, chest pain;
sense organs: rarely - visual impairment, decreased tear production (it is important to consider for patients who wear contact lenses), hearing loss, noise / pain in the ears; very rarely - conjunctivitis, soreness / dry eyes, taste disturbances;
allergic reactions: rarely - rash, pruritus, urticaria;
laboratory indicators: rarely - an increase in the concentration of triglycerides in the blood; in some cases - agranulocytosis, thrombocytopenia, leukopenia;
skin: rarely - psoriasis-like skin reactions, increased sweating, skin flushing, exanthema; very rarely - alopecia, exacerbation of the course of psoriasis;
others: withdrawal syndrome (in the form of increased frequency of angina attacks, increased blood pressure).

Hydrochlorothiazide

hematopoietic system: very rarely - aplastic / hemolytic anemia, leukopenia, thrombocytopenia, agranulocytosis;
digestive system: anorexia, pancreatitis, cholecystitis, diarrhea, cholestatic jaundice, constipation, sialadenitis;
nervous system: paresthesias, blurry vision (temporarily), dizziness, headache;
cardiovascular system: orthostatic hypotension, arrhythmias, vasculitis;
water and electrolyte balance: hypomagnesemia, hypercalcemia, hypokalemia, hypochloremic alkalosis (in the form of dryness of the oral mucosa, thirst, irregular heart rate, muscle pain, changes in the psyche / mood, seizures, nausea, vomiting, weakness, unusual fatigue; possibly development of hepatic coma / encephalopathy), hyponatremia (in the form of confusion, convulsions, lethargy, slowing down of the thinking process, increased fatigue, excitability, muscle cramps);
metabolism: glucosuria, hyperglycemia, hyperuricemia (can cause a gout attack), impaired glucose tolerance (diabetes mellitus can manifest), an increase in serum lipid concentration in the blood (while taking high doses of Bisangil);
allergic reactions: photosensitivity, purpura, necrotizing vasculitis, urticaria, Stevens-Johnson syndrome, respiratory distress syndrome (including noncardiogenic pulmonary edema and pneumonitis), anaphylactic reactions up to shock;
others: interstitial nephritis, decreased potency, functional renal disorders.

Overdose

The main symptoms are:

bisoprolol: bronchospasm, marked decrease in blood pressure, bradycardia, atrioventricular block, hypoglycemia, acute heart failure;
hydrochlorothiazide: hypovolemia, dizziness, drowsiness, hypokalemia, nausea, marked decrease in blood pressure (clinical manifestations of acute / chronic overdose are due to significant loss of electrolytes or fluid).

Therapy: abolition of Bisangil, gastric lavage, the use of adsorbents, supportive symptomatic treatment.

Other possible measures (depending on the indication):

marked decrease in blood pressure: intravenous administration of plasma-substituting solutions;
severe bradycardia: intravenous atropine; in some cases, installation of an artificial pacemaker is required;
aggravation of the course of chronic heart failure: intravenous administration of diuretics, drugs with a positive inotropic effect, vasodilators;
atrioventricular block (II – III degree): constant monitoring of the condition is shown, epinephrine may be prescribed, in some cases an artificial pacemaker is required;
hypoglycemia: intravenous administration of a glucose solution (dextrose);
bronchospasm: bronchodilators, β ₂ -sympathomimetics and / or aminophylline may be prescribed.

special instructions

During the use of Bisangil, monitoring of the following indicators is required:

heart rate and blood pressure (at the beginning of the course it is carried out daily, then - once every 3-4 months; the patient should be able to independently calculate the heart rate);
the content of electrolytes and indicators of the acid-base state (more frequent monitoring of the potassium content is required for patients belonging to the high-risk group);
the concentration of glucose in the blood (with diabetes mellitus; once every 4–5 months);
functional state of the kidneys (in elderly patients; 1 time in 4-5 months).

With violations of peripheral circulation, Bisangil should be prescribed with caution.

Against the background of thyrotoxicosis, bisoprolol can mask clinical signs of the disease (for example, tachycardia).

Patients with pheochromocytoma can be prescribed Bisangil after prescribing alpha-blockers (under the control of blood pressure).

With mild bronchial asthma or chronic obstructive pulmonary disease, treatment begins with the use of minimal doses.

The development of depression associated with taking bisoprolol is the basis for discontinuing therapy.

Elderly patients at the beginning of the course should be prescribed a dosage form of Bisangil containing 2.5 mg of bisoprolol. The therapy is carried out under regular monitoring of the patient's condition.

It should be borne in mind that the results of the study of the function of the parathyroid glands may be distorted (due to the effect on calcium metabolism).

It is impossible to abruptly interrupt therapy, in particular this applies to patients with coronary heart disease. The daily dose of Bisangil should be reduced for 14 days simultaneously with the appropriate antianginal therapy.

Bisangil is canceled 48 hours before surgical interventions, and the anesthesiologist should be warned about the therapy. As a means for general anesthesia, you need to choose a drug that has a minimal negative inotropic effect.

Patients with psoriasis are prescribed Bisangil with caution, since an exacerbation of the condition may occur during therapy.

If there is a history of anaphylactic reactions, regardless of the cause of their occurrence, especially during desensitizing treatment, taking the drug may increase the likelihood of allergic reactions and contribute to the development of resistance to the use of epinephrine (adrenaline) at usual doses.

Bisangil can reduce the production of tear fluid, which should be taken into account by patients who wear contact lenses.

With hyperuricemia, the likelihood of an exacerbation of the course of gout increases. In such cases, the dose of Bisangil is selected individually under the control of the serum concentration of uric acid in the blood. Before conducting a study of the function of the parathyroid glands, Bisangil is canceled, since against the background of its administration, the development of transient hypercalcemia can be observed.

Bisangil can influence the results of doping control, which should be considered by athletes.

Influence on the ability to drive vehicles and complex mechanisms

When driving vehicles and mechanisms, care must be taken, since dizziness may develop during the period of therapy.

Application during pregnancy and lactation

Bisangil is not prescribed during pregnancy / lactation.

Pediatric use

Bisangil therapy is contraindicated in patients under 18 years of age.

With impaired renal function

acute / chronic renal failure (with creatinine clearance less than 30 ml / min), anuria: therapy is contraindicated;
renal failure (with creatinine clearance more than 30 ml / min): Bisangil should be used under medical supervision.

For violations of liver function

severe hepatic dysfunction, including coma and precoma: therapy is contraindicated;
liver failure: Bisangil should be used under medical supervision.

Use in the elderly

Bisangil therapy in elderly patients should be carried out with caution.

Drug interactions

Bisoprolol

Contraindicated combinations:

floktaphenin: in case of arterial hypotension or shock caused by its intake, the use of bisoprolol leads to a decrease in compensatory cardiovascular reactions;
MAO inhibitors type A: there is a high likelihood of a hypertensive crisis;
sultopride: there is a high likelihood of developing ventricular arrhythmias, including pirouette-type arrhythmias.

Combinations not recommended:

class I antiarrhythmic drugs, including propafenone, flecainide, disopyramide, quinidine, lidocaine, phenytoin: possible decrease in atrioventricular conduction and cardiac contractility;
centrally acting antihypertensive drugs, including clonidine, moxonidine, methyldopa, rilmenidine: there is a high likelihood of a decrease in heart rate, a decrease in cardiac output and vasodilation associated with a decrease in central sympathetic tone. In the case of a sharp withdrawal of these drugs, especially before the withdrawal of bisoprolol, the risk of rebound arterial hypertension increases;
blockers of slow calcium channels such as verapamil and diltiazem (to a lesser extent): a decrease in myocardial contractility and a violation of atrioventricular conduction is possible; in particular, intravenous administration of verapamil while taking bisoprolol can lead to the development of severe arterial hypotension and atrioventricular blockade.

Other combinations that require caution:

local beta-blockers, including eye drops for the treatment of glaucoma: an increase in the systemic effects of bisoprolol (in the form of a decrease in blood pressure, a decrease in heart rate);
class III antiarrhythmics, including amiodarone: increased atrioventricular conduction disorders;
parasympathomimetics: an increase in atrioventricular conduction disorders and an increase in the likelihood of developing bradycardia;
adrenergic agonists that affect alpha and beta adrenergic receptors, including epinephrine, norepinephrine: increased vasoconstrictor effects of these drugs, increased blood pressure (more likely with the use of non-selective beta-blockers);
beta-agonists, including dobutamine, isoprenaline: decrease in the effectiveness of both drugs;
allergens used for immunotherapy, or extracts of allergens for skin tests: an increase in the likelihood of developing systemic allergic reactions in severe course or anaphylaxis;
mefloquine: increased likelihood of bradycardia;
radiopaque iodine-containing diagnostic agents (intravenous administration): an increase in the likelihood of anaphylactic reactions;
insulin and oral hypoglycemic agents: a change in their effectiveness (masks the symptoms of developing hypoglycemia in the form of tachycardia, increased blood pressure);
means for inhalation anesthesia (derivatives of hydrocarbons), phenytoin when administered intravenously: an increase in the severity of the cardiodepressant effect and the likelihood of a decrease in blood pressure;
non-steroidal anti-inflammatory drugs, estrogens, glucocorticosteroids: decrease in the antihypertensive effect;
lidocaine, xanthines (except for theophylline): a decrease in their clearance, which is associated with an increase in their plasma concentration, especially with an initially increased clearance of theophylline under the influence of smoking;
sotalol, antiarrhythmic drugs that can lead to the development of pirouette-type tachycardia (class IA - hydroquinidine, quinidine, disopyramide; class III - dofetilide, amiodarone, ibutilide), other arrhythmic drugs, including astemizole, erythromycin for intravenous administration, pentamidine, halonadofantrine, terfanthrine, sparfloxacin, vincamine: the occurrence of pirouette-type tachycardia, the cause of which is hypokalemia;
methyldopa, cardiac glycosides, guanfacine, reserpine, slow calcium channel blockers, amiodarone and other antiarrhythmic drugs: an increase in the risk of occurrence or aggravation of bradycardia, heart failure, cardiac arrest, AV blockade;
hydralazine, diuretics, sympatholytics, clonidine and other antihypertensive drugs: excessive lowering of blood pressure;
nifedipine: a significant decrease in blood pressure;
tetracyclic / tricyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, drugs with hypnotic and sedative effects: increased depression of the central nervous system;
non-depolarizing muscle relaxants, coumarins: prolonging their action;
non-hydrogenated ergot alkaloids: increased risk of peripheral circulatory disorders;
MAO inhibitors: a significant increase in the antihypertensive effect (the combination is contraindicated, an interval of at least 14 days is required between therapy with these drugs);
sulfasalazine: an increase in the plasma concentration of bisoprolol in the blood;
ergotamine: an increase in the likelihood of peripheral circulatory disorders;
rifampicin: shortening the half-life of bisoprolol.

Hydrochlorothiazide

hypoglycemic agents (for oral administration and insulin): changes in glucose tolerance (a change in their dose may be required);
ethanol, narcotic drugs, barbiturates: potentiation of the risk of orthostatic hypotension;
colestipol, cholestyramine: a significant decrease in the absorption of hydrochlorothiazide;
other drugs with an antihypertensive effect: the development of an additive effect;
pressor amines, including norepinephrine, epinephrine: decreasing the severity of the response to their use;
non-steroidal anti-inflammatory drugs, including COX-2 inhibitors: reducing the diuretic, natriuretic and antihypertensive effects of hydrochlorothiazide;
corticosteroids, glycyrrhizic acid, adrenocorticotropic hormone: a marked decrease in electrolytes, an increase in the likelihood of hypokalemia;
lithium: a decrease in its renal clearance and an increase in the likelihood of its toxic effect (the combination is not recommended);
muscle relaxants of a non-depolarizing type of action, including tubocurarine: enhancing their action.

Analogs

Bisangil's analogs are: Aritel Plus, Bisoprolol + Hydrochlorothiazide, Lodoz, Combiso Duo.

Terms and conditions of storage

Store in a dark, dry place at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Bisangil

According to reviews, Bisangil is an effective drug. However, some users note that the remedy did not suit them, since it did not have the claimed therapeutic effect. There are reports of the development of adverse reactions, including exacerbation of the course of gout and psoriasis.

Price for Bisangil in pharmacies

The approximate price for Bisangil for 30 tablets of 2.5 mg + 6.25 mg or 5 mg + 6.25 mg is 275 or 317 rubles, respectively.

Bisangil: prices in online pharmacies

Drug name

Price

Pharmacy

Bisangil 2.5 mg + 6.25 mg film-coated tablets 30 pcs.

244 RUB

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Bisangil 5 mg + 6.25 mg film-coated tablets 30 pcs.

277 r

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!