Biprol plus - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate 129.10 mg or 111.60 mg, microcrystalline cellulose 10.00 mg or 10.00 mg, pregelatinized starch 10.00 mg or 10.00 mg, silicon dioxide colloid 2.00 mg or 2.00 mg, magnesium stearate 1.40 mg or 1.40 mg;

film coating: hypromellose 2.20 mg or 2.20 mg, dimethicone 350 0.025 mg or 0.025 mg, macrogol 400 0.53 mg or 0.53 mg, titanium dioxide E 171 1.00 mg or 1.00 mg, iron oxide dye red E 172 0.05 mg or 0.20 mg.

Description:

Tablets 5 mg + 12.5 mg

Round biconvex tablets, covered with a film coating of pink color. View at the break: the core of white color. On one side: the "B-H "," 5-12 "and risk, on the other - risk.

Tablets 10 mg + 25 mg

Round biconvex tablets, covered with a film shell of dark pink color with a brown tinge. View at the break: the core of white color. On one side: marking "B-H", "10-25" and risk; on the other - risk.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Biprol Plus is a combined antihypertensive drug consisting of bisoprolol and hydrochlorothiazide.

Bisoprolol - selective beta₁-adrenoceptor without internal sympathomimetic and membrane-stabilizing activity. Has antihypertensive, antiarrhythmic and anti-anginal action. Blocking in low doses of beta₁(adenosine triphosphate (ATP)), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect , reduces the excitability and contractility of the myocardium). As the dose increases, beta blocks₂-adrenoceptors.

The total peripheral vascular resistance at the beginning of beta-blockers application increases in the first 24 hours (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation beta₂-adrenoreceptors), after 1-3 days. Returns to the original, and for a long-term appointment decreases.

Antihypertensive effect is associated with a decrease in the minute volume of blood, suppression of sympathetic stimulation of peripheral vessels, reduction in the activity of the renin-angiotensin-aldosterone system by inhibiting the beta-adrenoreceptors of the juxtaglomerular renal apparatus (which leads to a decrease in renin secretion), restoration of the sensitivity of the aortic aortic baroreceptors (no increase in their activity in response to lowering arterial pressure), and influence on the central nervous system. With arterial hypertension, the effect develops after 2-5 days, stable effect - after 1-2 months.

Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions in the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of the convoluted renal tubules, enhances the excretion of potassium ions, hydrocarbonates and phosphates by the kidneys. Virtually does not affect the acid-base state. Increases the excretion of magnesium ions by the kidneys; It detains calcium ions in the body and inhibits the excretion of urates. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, the duration of the antihypertensive effect persists for a day.The diuretic effect decreases when the glomerular filtration rate decreases and stops at a value of less than 30 ml / min.

Pharmacokinetics:

Bisoprolol

Absorption does not depend on food intake. After ingestion, absorption from the gastrointestinal tract (GIT) is 80-90%. The maximum concentration (C_mOh) in blood plasma is achieved after 1-3 hours, the connection with plasma proteins is about 30%. Moderately soluble in lipids, poorly penetrates the blood-brain and placental barrier, excreted in breast milk (about 1%). Metabolised in the liver.

Outputs in two equivalent ways: approximately 50% of the dose Bisoprolol is excreted by the kidneys in an unchanged form and only 1-2% through the intestine. The half-life (T_1/2) - 10-12 hours.

Hydrochlorothiazide

When ingested quickly absorbed, but incomplete, 80% absorption, communication with plasma proteins 64%. Bioavailability of hydrochlorothiazide from 60 to 80%. Time to reach C_mOh comes in 2-5 hours, about 4 hours. It penetrates the placental barrier and is excreted into breast milk. T_1/2 - 9-13 hours. It is not metabolized.

It is excreted by the kidneys mainly (more than 95%) unchanged through glomerular filtration and active tubular secretion.

Indications:Arterial hypertension of mild to moderate severity.

Contraindications:

- Hypersensitivity to bisoprolol, hydrochlorothiazide and other sulfonamide derivatives, as well as to other components of the drug;

- severe forms of bronchial asthma;

- chronic obstructive pulmonary disease;

- cardiogenic shock;

- syndrome of weakness of the sinus node (including sinoatrial blockade);

- atrioventricular blockade of II and III degree without artificial pacemaker;

- pronounced bradycardia (heart rate less than 60 beats per minute);

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

- late stages of peripheral circulatory disorders (including Raynaud's syndrome);

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- refractory hypokalemia, hyponatremia, hypercalcemia;

- metabolic acidosis;

- dehydration;

- acute renal insufficiency;

- chronic renal failure (creatinine clearance (CK) less than 30 ml / min);

- simultaneous application with floktaphenin, sultopride;

- simultaneous administration of monoamine oxidase inhibitors (MAO) (with the exception of MAO type B inhibitors);

- age under 18 years (effectiveness and safety not established);

- severe hepatic insufficiency (including hepatic precoma and coma);

- gout.

Carefully:

Atrioventricular AV blockade of the 1st degree, variant angina (prinzmetal angina), ischemic heart disease (IHD), diabetes mellitus, impaired water-electrolyte balance, hepatic and / or renal failure (QC more than 30 ml / min), thyrotoxicosis, pheochromocytoma (against alpha treatment adrenoblockers), a strict diet, a decrease in the volume of circulating blood BCC (vomiting, diarrhea, dehydration), bronchospasm (in the anamnesis), psoriasis, advanced age.

Pregnancy and lactation:

The use of Biprol Plus during pregnancy and lactation is contraindicated.

Dosing and Administration:

Inside, in the morning (during a meal), not chewing with a small amount of liquid 1 time per day.

The dose of the drug is selected individually.

The initial dose of Biprol Plus is 1 tablet 5 / 12.5 (containing 5 mg of bisoprolol and 12.5 mg of hydrochlorothiazide) once a day. If the therapeutic effect is inadequate, the dose can be increased to a maximum daily dose of 10/25 - 1 tablet of Biprol Plus (containing 10 mg of bisoprolol and 25 mg of hydrochlorothiazide).

Application of the drug in old age

Usually dose adjustment is not required. It is recommended to start with the lowest possible dose.

Application in renal and / or liver failure

Patients with renal insufficiency (QC more than 30 ml / minute), as well as mild to moderate hepatic insufficiency, dose adjustment is not required.

Side effects:

The incidence of adverse reactions listed below was determined as follows: very often (≥ 1/10); often (≥ 1/100, but <1/10); infrequently: (≥ 1/1000, but <1/100); rarely (≥ 1/10000, but <1/1000); very rarely (<1/10000), including individual messages.

From the central and peripheral nervous system

Often: increased fatigue, dizziness, headache, which particularly occur at the beginning of treatment, are mild and pass during the first 1-2 weeks of treatment;

Infrequently: sleep disturbance, depression, convulsions;

Rarely: "nightmarish" dreams, hallucinations.

From the side of the cardiovascular system

Infrequently: bradycardia AV conduction, exacerbation of chronic heart failure, ventricular extrasystole, sensation of cold and numbness of limbs;

Infrequently: orthostatic hypotension;

Rarely: pain in the chest.

From the respiratory system

Infrequently: bronchospasm in patients with bronchial asthma and bronchospasm (in anamnesis);

From the digestive system

Often: nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa;

Infrequently: loss of appetite, discomfort in the gastrointestinal tract, pancreatitis.

From the musculoskeletal system

Infrequently: muscle weakness, cramps in the calf muscles, arthralgia.

From the sense organs

Rarely: hearing impairment, vision, decreased lacrimal gland production (it is necessary to consider patients who use contact lenses); Rarely: conjunctivitis.

From the side of the reproductive system

Rarely: violation of potency.

On the part of the hematopoiesis system

Rarely: leukopenia, thrombocytopenia;

Rarely: agranulocytosis.

Allergic reactions

Rarely: skin itch, rash, face redness, allergic rhinitis, increased sweating;

Rarely: possibly exacerbation of psoriasis, alopecia, discoid and red lupus.

From the laboratory indicators

Often: hypertriglyceridemia, hypercholesterolemia, hyperglycemia and glucosuria, hyperuricemia,violation of water-electrolyte balance (especially hypokalemia, hyponatremia, hypomagnesemia, hypochloraemia, as well as hypercalcemia), metabolic alkalosis;

Infrequently: an increase in the activity of amylase, a reversible increase in the concentration of creatinine and urea in the blood serum;

Rarely: increased activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase).

From the liver and biliary tract

Rarely: hepatitis, jaundice.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, acute heart failure, ventricular extrasystole, atrioventricular block, convulsions, bronchospasm.

Treatment: immediately after an overdose (within 2 hours) gastric lavage, the appointment of adsorbents, symptomatic therapy.

In the case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, to make up the volume of circulating blood.

When bradycardia intravenously injected atropine in a dose of 1-2 mg, glucagon 1 mg (slowly, bolus), if necessary - in the form of infusion 1-10 mg / h.

In the subsequent it is appointed epinephrine in a dose of 15-85 mcg (the administration of which can be repeated, but its total amount should not exceed 300 mcg) or dopamine in a dose of 2.5-10 μg / kg / min.

In acute heart failure, cardiac glycosides, diuretics, glucagon.

If there are no signs of pulmonary edema, then intravenously administered plasma-substituting solutions, if they are ineffective - epinephrine, dopamine, dobutamine.

When ventricular extrasystole is used lidocaine.

With the development of atrioventricular block, intravenous 1-2 mg of atropine, epinephrine, or a temporary pacemaker should be administered.

When convulsions are recommended diazepam intravenously.

When bronchospasm is inhaled, beta is injected₂-adrenomimetics.

Interaction:

Interaction with a combination of bisoprolol and hydrochlorothiazide

Biprol plus is contraindicated in combination with floktaphenin, sultopride, monoaminotransferase (MAO) inhibitors (with the exception of MAO type B inhibitors).

It is possible to strengthen the antihypertensive effect of Biprol plus plus with simultaneous use with tricyclic antidepressants, antipsychotics,blockers of "slow" calcium channels (AMB) (amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), angiotensin-converting enzyme (ACE) inhibitors (including captopril, enalapril), irbesartan, diuretics, clonidine, sympatholytic drugs, hydralazine and other antihypertensive drugs.

It is possible to attenuate the antihypertensive effect of Biprol Plus plus with simultaneous administration with glucocorticosteroids (for systemic use), estrogens, nonsteroidal anti-inflammatory drugs (indoleacetin, piroxicam, naproxen, phenylbutazone) and tetracosactide.

With the development of hypovolemia, the combined use of NSAIDs can induce the development of acute renal failure.

The combination of bisoprolol and hydrochlorothiazide with glucocorticosteroids, ACTH, carbenoxolone, amphotericin B, furosemide and laxatives can lead to hypokalemia. With simultaneous use with the drug Biprol Plus, the effects of nondepolarizing muscle relaxants and the anticoagulant effect of coumarin derivatives can be enhanced.

Cardiac glycosides, methyldopa, reserpine, guanfacine, BCCC (verapamil, diltiazem, amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), antiarrhythmics, as well as agents that can initiate arrhythmias such as pirouettes (astemizole, beprideil, erythromycin (iv), halofantrine, pentamidine, sparfloxacin, terfenadine), increase the risk of developing and / or strengthening bradycardia, AV blockade and chronic heart failure.

With simultaneous application with sotalol hypokalemia and development of ventricular arrhythmia such as "pirouette" is possible.

Cytostatics (in particular, cyclophosphamide, fluorouracil, methotrexate) - may increase myelotoxicity.

With the simultaneous use of the drug Biprol plus with lithium salts, it is possible to increase the concentration of the latter in the blood to a toxic level.

With the simultaneous use of Biprol plus with allergens used for immunotherapy, or with allergen extracts for skin tests, as well as with allopurinol or with iodine-containing radiopaque diagnostic agents for intravenous administration, the risk of allergic reactions increases.

With the simultaneous administration of Biprol Plus plus carbamazepine, the development of hyponatremia is possible; with cyclosporine - an increase in serum creatinine is possible.

Bisoprolol

With the simultaneous use of Biprol plus plus phenytoin (with intravenous administration) and means for inhalation anesthesia (derivatives of hydrocarbons), the severity of cardiodepressive action and the likelihood of excessive BP decrease may increase. The clearance of lidocaine and xanthines (except diphylline) may decrease due to a possible increase in their concentration in the blood plasma, especially in patients with initially elevated clearance of theophylline (under the influence of smoking).

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.

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 myocardial contractility and disruption AV conductivity.In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

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

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

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

Drugs foxglove with simultaneous application with bisoprolol may lead to an increase in the timing of the pulse, and thus, bradycardia.

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.

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

The combination of bisoprolol with sympathomimetics that affect beta, and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these agents that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using nonselective beta-blockers. For the treatment of hypersensitivity reactions, higher doses of epinephrine (epinephrine) may be required.

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

Sulfasalazine increases the concentration of bisoprolol in the blood plasma; rifampicin - shortens the half-life of bisoprolol.

Hydrochlorothiazide

With the simultaneous use of calcium and / or vitamin preparations D in high doses, hypercalcemia may develop and the risk of metabolic acidosis may increase.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

With the simultaneous use of hydrochlorothiazide with lithium salts, its toxicity increases, since the renal clearance of lithium decreases.

It is necessary to use caution hydrochlorothiazide together with the following preparations:

- hypotensive drugs (their effect is potentiated, there may be a need for dose adjustment);

- with cardiac glycosides, tk. may increase the possibility of manifestations of toxicity of digitalis preparations associated with hypokalemia and hypomagnesemia;

- with nondepolarizing muscle relaxants (enhances their effect);

- with amiodarone (increased risk of arrhythmias associated with hypokalemia);

- hypoglycemic agents for oral administration (their effectiveness decreases, hyperglycemia may develop);

- with corticosteroids or calcitonin (increased risk of hypokalemia);

- with salicylates (enhances their neurotoxicity);

- with quinidine (reduces its excretion);

- with methyldopa (possible development of hemolysis);

- with amantadine (clearance of amantadine may be reduced by hydrochlorothiazide, which leads to an increase in the concentration of amantadine in blood plasma and possible toxicity);

- colestyramine and colestipol, which reduce the absorption of hydrochlorothiazide;

- ethanol, barbiturates and narcotic analgesics, which increase the risk of orthostatic hypotension.

Medicines, intensely binding to proteins (indirect anticoagulants, clofibrate), enhance the diuretic effect.

Vasodilators, beta-adrenoblockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol increase the antihypertensive effect.

Nonsteroidal anti-inflammatory drugs, in particular indomethacin, reduce the antihypertensive and diuretic effect.

Simultaneous use of diflunisal with hydrochlorothiazide causes a significant increase in the level of the latter in blood plasma and reduces its hyperuricemic effect.

Hydrochlorothiazide weakens the effect of oral contraceptives, norepinephrine, epinephrine and antidotal drugs.

Thiazides can reduce the level of iodine in blood plasma associated with proteins.

Special instructions:

During the period of therapy with Biprol plus, control of heart rate and blood pressure is necessary (at the beginning of treatment - daily, then - once every 3-4 months),for the concentration of glucose in the blood in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended to monitor kidney function (1 every 4-5 months). It is necessary to teach the patient how to calculate heart rate.

It is necessary to reduce the dose of Biprol Plus (due to the content of bisoprolol) in it from 10 to 5 mg, if the heart rate at rest does not exceed 50-55 beats / min for 2 weeks.

Particular attention is required by patients with ischemic heart disease. Abrupt cancellation can lead to a sudden deterioration in the patient's condition.

During the period of therapy with Biprol Plus, it is also necessary to monitor the acid-base state and the content of electrolytes (potassium, sodium, calcium).

During treatment with Biprol plus, patients should consume an adequate amount of liquid and food rich in potassium (for example, bananas, vegetables, nuts), which is necessary to compensate for potassium losses. The risk of hypokalemia can be prevented or reduced by simultaneous administration of potassium-sparing diuretics.

Prior to the appointment of Biprol Plus, the BCC should be compensated.

In patients with peripheral circulatory disorders, caution should be exercised when prescribing Biprol Plus.

In thyrotoxicosis Biprol plus (due to the content of bisoprolol in it) can mask the clinical signs of the disease (for example, tachycardia).

Patients with pheochromocytoma should not be prescribed Biprol plus until treatment with alpha-blockers is prescribed. In this case, it is necessary to monitor blood pressure.

It is recommended to stop therapy with Biprol plus with the development of depression caused by taking a beta-blocker (due to the content of bisoprolol in it).

In elderly patients, treatment with Biprol Plus should be started with a dosage form containing a low dose of bisoprolol (5 mg). At the same time, regular monitoring of the patient's condition is necessary.

Particular attention is required in cases of surgical intervention under general anesthesia in patients taking beta - blockers. Such patients should cancel Biprol plus 48 hours prior to surgery, warn the anesthetist that the patient is taking Biprol plus. As a means for general anesthesia, a drug with a minimum negative inotropic effect should be chosen.

On the background of therapy with beta-blockers, the exacerbation of psoriasis is possible. Patients with this disease Biprol plus should be administered with caution.

With a history of anaphylactic reactions, regardless of the cause of their occurrence, especially when conducting desensitizing therapy, treatment with Biprol Plus (due to bisoprolol content) may increase the risk of allergic reactions and promote the development of resistance to epinephrine (adrenaline) treatment in conventional doses.

Patients who use contact lenses should be careful when using Biprol Plus, as beta-blockers can reduce the production of tear fluid.

Clonidine - increased risk of "ricochet" hypertension, as well as aggravation of bradycardia and disorders AV conductivity. First it is necessary to carry out gradual abolition of clonidine, and only then the use of Biprol Plus is possible.

With prolonged therapy with Biprol Plus, regular monitoring of the concentration of creatinine and urea, lipids (cholesterol and triglycerides), uric acid should be carried out.

In bronchial asthma or other chronic obstructive pulmonary diseases characterized by a risk of worsening, parallel bronchodilator therapy is necessary.

Hypokalemia can contribute to the development of severe arrhythmias, in particular, piruette-type arrhythmias.

It is possible to aggravate the course of metabolic alkalosis due to violations of the water-electrolyte balance.

Athletes should be informed that Biprol Plus contains hydrochlorothiazide, which can give positive results in the conduct of doping control.

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

During the period of treatment with Biprol Plus, care should be taken when driving vehicles and when practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions due to the possibility of developing dizziness.

Form release / dosage:Film-coated tablets are 5 mg / 12.5 mg and 10 mg / 25 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC / PE / Al.

For 3 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001783

Date of registration:24.07.2012

Expiration Date:24.07.2017

The owner of the registration certificate:SHTADA Artznajmittel AGSHTADA Artznajmittel AG Germany

Manufacturer: & nbsp

STADA Arzneimittel, AG Germany

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Biprol plus (Biprol plus)