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

Bisoprolol is highly selective beta₁adrenoblocker without sympathomimetic and membrane-stabilizing activity. The mechanism of action of bisoprolol in arterial hypertension is associated, first of all, with a decrease in the level of renin in the blood plasma and a decrease in the heart rate.

Hydrochlorothiazide is a diuretic from the group of thiazides with an antihypertensive effect. Its diuretic effect is due to the inhibition of the transport of sodium ions from the renal tubules into the blood, thus preventing its reabsorption.

In clinical studies, potentiation of the effects of the active substances of this combination was observed.Efficacy for the treatment of mild to moderate degree of hypertension was noted even when used in the lowest doses - 2.5 mg + 6.25 mg.

Side effects such as hypokalemia (using hydrochlorothiazide) and bradycardia, asthenia and headache (using bisoprolol) are dose-dependent. Therefore, in order to reduce the undesirable effects, the amount of each active ingredient in the preparation is reduced by a factor of 2-4.

Pharmacokinetics:

Bisoprolol

Suction and distribution

T_maxin blood plasma ranges from 1 to 4 hours. Binding to plasma proteins - about 30%.

Metabolism and excretion

40% of bisoprolol is metabolized in the liver. Metabolites are inactive.

The half-life of blood plasma is 11 hours. Kidney and liver clearance are equivalent. Half of the administered dose is excreted in the urine both in unchanged form and in the form of metabolites. The total ground clearance is about 15 l / h.

Hydrochlorothiazide

Suction and distribution

Bioavailability of hydrochlorothiazide ranges from 60% to 80%. T_maxin blood plasma is about 4 hours (from 1.5 to 5 hours). Binding to plasma proteins - 40%.

Hydrochlorothiazide penetrates the placental barrier, excreted in breast milk.

Metabolism and excretion

Hydrochlorothiazide is not metabolized and almost completely eliminated in unmodified form by glomerular filtration and active tubular secretion. The half-life of hydrochlorothiazide is about 8 hours.

Pharmacokinetics in special clinical cases

In the case of renal and heart failure, in elderly patients renal clearance of hydrochlorothiazide decreases, the elimination half-life increases.

Indications:

Arterial hypertension of mild and moderate severity.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

Contraindications:

- severe forms of bronchial asthma,

- chronic obstructive pulmonary disease,

- chronic heart failure in the stage of decompensation, not amenable to drug therapy,

- cardiogenic shock,

- syndrome of weakness of the sinus node, including sinoatrial blockade,

- AV-blockade II and III degree without an artificial pacemaker,

- pronounced bradycardia (heart rate <50 beats per minute),

- Variable angina (Prinzmetal angina),

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

- severe forms of peripheral circulation disorders (including Raynaud's disease),

- arterial hypotension,

- hypokalemia,

- hypovolemia,

- severe renal dysfunction (creatinine clearance <30 ml per minute),

- severe violations of the liver,

- simultaneous use with floktaphenin, sultopride, antiarrhythmics, lithium preparations,

- age under 18 years (efficiency and safety not established),

- hypersensitivity to bisoprolol and other components of the drug,

- hypersensitivity to hydrochlorothiazide and other sulfonamides.

Carefully:

Use with caution when AV blockade I degree, psoriasis, coronary heart disease, chronic heart failure in the stage of decompensation, thyrotoxicosis, water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), gout, in elderly patients.

Pregnancy and lactation:

It is not recommended for use in pregnancy, because the drug contains a diuretic from the group of thiazides.

At present, it is not known whether bisoprolol with breast milk.Diuretics from the thiazide group are excreted in breast milk. Breastfeeding during treatment with the drug is contraindicated.

Dosing and Administration:

The drug is recommended in the morning (during meals). Tablets should be swallowed whole with a small amount of liquid and not chewed.

The dose of the drug should be selected individually, using the following dosages of the drug:

- 2.5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide;

- 5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide;

- 10 mg of bisoprolol + 6.25 mg of hydrochlorothiazide.

The initial dose is 1 tablet of 2.5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide once a day. In case of insufficient effectiveness of treatment, the dose is increased to 1 tablet of 5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide once a day. If necessary, the dose can be increased to 1 tablet 10 mg bisoprolol + 6.25 mg hydrochlorothiazide once a day.

Have patients with impaired liver function or moderate impaired renal function (creatinine clearance> 30 ml per minute) a dose change is not required.

Side effects:

From the side of the central nervous system: sleep disorders, depression; possible - fatigue, fatigue,dizziness, headache (may occur at the beginning of treatment and usually take place during the first or second week of treatment).

From the cardiovascular system: bradycardia, AV-conduction disorder, exacerbation of chronic heart failure, orthostatic hypotension.

From the respiratory system: bronchospasm in patients with bronchial asthma or chronic obstructive pulmonary disease in anamnesis.

From the digestive system: nausea, vomiting, diarrhea, constipation, hepatitis, jaundice, increased activity hepatic transaminases.

From the urinary system: reversible increase in serum creatinine and urea levels.

From the musculoskeletal system: feeling of cold and numbness of limbs, muscle weakness, convulsions.

From the sense organs: hearing impairment, decreased lacrimal gland production (must be taken into account by patients using contact lenses), visual impairment.

From the side of metabolism: hypertriglyceridemia, hypercholesterolemia, hyperglycemia, glucosuria, hyperuricemia, disturbance of the water-electrolyte state, metabolic alkalosis.

On the part of the hematopoiesis system: leukopenia, thrombocytopenia.

From the skin: beta-blockers can cause or aggravate the course of psoriasis or cause psoriasis-like rashes, alopecia.

Other: impotence, allergic rhinitis.

Overdose:

Symptoms: excessive decrease in blood pressure, bradycardia. In newborns from mothers who received treatment with beta-blockers, it is possible to develop an overdose, manifested by cardiac decompensation.

Treatment: in the case of severe bradycardia or excessive reduction in blood pressure, the following drugs are injected intravenously: atropine in a dose of 1-2 mg; glucagon in a dose of 1 mg slowly bolus and then, if necessary, in the form of infusion at a dose of 1-10 mg / h; Further, if necessary, enter either epinephrine (epinephrine) at a dose of 15-85 μg, the administration can be repeated, its total amount should not exceed 300 μg, or dopamine in a dose of 2.5-10 μg / kg / min.

When an overdose in newborns, manifested by cardiac decompensation, is prescribed glucagon at the rate of 0.3 mg / kg; epinephrine (epinephrine) and dobutamine (usually in high doses). It is necessary to ensure observation in intensive care unit newborns. Long-term treatment is carried out under the supervision of a specialist.

Interaction:

The drug is contraindicated for use in combination with floktaphenin, sultopride.

The drug is not recommended for use in combination with amiodarone, lithium, or with agents that can initiate arrhythmias (astemizole, beprideil, erythromycin, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamycin).

Caution is required when using the drug simultaneously with baclofen, inhaled halogenated general anesthetics, slow calcium channel blockers (bepridil, diltiazem, verapamil), antiarrhythmics (propafenone, quinidine, hydroquinidine, disopyramide), insulin, urea preparations, lidocaine, iodine-containing contrast agents, anticholinesterase means, high doses of salicylates, drugs that cause hypokalemia - amphotericin (intravenous vve ) and mineralocorticoids (systemic use), tetracosactide,laxatives; cardiac glycosides, diuretics causing hyperkalemia (amiloride, canrenone, spironolactone, triamterene); ACE inhibitors, metformin.

It is possible to intensify the hypotensive effect with the simultaneous use of tricyclic antidepressants (including imipramine), neuroleptics, slow calcium channel blockers with dihydropyridine derivatives (including amlopidine, felopidine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine).

Application simultaneously with tricyclic antidepressants, including inhibitors monoamine oxidase, as well as neuroleptics, is not a contraindication. At the same time, their combined use should be taken into account, since a reduction in the dose of the antihypertensive agent due to additive hypotensive effect may be required.

With a joint appointment with mefloquine, bradycardia may develop.

When co-administered with calcium preparations, hypercalcemia may develop.

When co-administered with cyclosporine, an increase in serum creatinine is possible.

Possible weakening of hypotensive action with simultaneous administration with glucocorticosteroids (for systemic use), nonsteroidal anti-inflammatory drugs and tetracosactide.

Special instructions:

Precautions associated with the use of bisoprolol

Do not suddenly stop treatment, especially in patients with ischemic heart disease. The dose is recommended to be reduced gradually within 2 weeks. If necessary, simultaneous initiation of appropriate therapy to prevent angina attacks should be started.

If it is necessary to prescribe the drug to patients with bronchial asthma or chronic obstructive pulmonary disease, treatment should begin with a minimum initial dose. Before the start of therapy, functional respiratory tests are recommended. In the case of development of bronchospasm during therapy, beta-adrenomimetics should be prescribed.

Patients with chronic heart failure drug should be administered with caution and under the supervision of a doctor, in minimum doses.

It is necessary to reduce the dose of the drug at a heart rate at rest <50-55 beats per minute and in the presence of clinical symptoms of bradycardia.

Given the negative dromotropic effect of beta-blockers, they should be administered with caution to patients with grade I AV blockade.

In patients with peripheral circulatory disorders (Raynaud's disease), beta-adrenoblockers can cause an exacerbation of the course of the disease.

Patients with pheochromocytoma should not be prescribed until treatment with alpha-blockers is performed. It is necessary to control blood pressure.

In elderly patients, treatment should begin with a low dose of the drug, careful monitoring of the patient's condition is necessary.

Patients taking the drug should be warned about the possibility of hypoglycemia and the need for regular monitoring of blood glucose levels. Bisoprolol can mask symptoms of hypoglycemia (tachycardia, palpitations and increased sweating).

On the background of therapy with beta-blockers, the exacerbation of psoriasis is possible. Bisoprolol should be assigned only when necessary.

If you have an anamnesis for anaphylactic reactions, regardless of the cause of their occurrence, especially when taking fllctafenin, or when conducting desensitizing therapy,treatment with beta-blockers can exacerbate the occurrence of these reactions and cause the development of resistance to epinephrine (adrenaline) treatment in usual doses.

Athletes should be informed that the drug contains an active substance that can give positive results in doping tests.

Precautions associated with the application hydrochlorothiazide

Before the start of therapy and further regularly during therapy, it is necessary to control the level of sodium in the blood. Decrease in the level of sodium at the beginning of treatment can be asymptomatic, therefore regular monitoring is necessary. Particular attention is required in the presence of risk factors, for example, patients of senile age, patients with cirrhosis of the liver.

Control of potassium in blood is required in patients at high risk, for example, in elderly patients, in patients receiving thiazide and thiazide-like diuretics, as well as in patients with cirrhosis accompanied by edema, ascites, in patients with coronary artery disease or with heart failure, extended QT interval.

Hypokalemia increases the risk of arrhythmias, the toxicity of cardiac glycosides.The first determination of the level of potassium in the blood should be done during the first week of therapy.

Thiazide diuretics can reduce the excretion of calcium in the urine, which leads to minor and temporary hypercalcemia. Temporary hypercalcemia may be associated with undiagnosed hyperparathyroidism. Before the study of parathyroid function, treatment with thiazides should be discontinued.

It is necessary to monitor the blood glucose level in patients with diabetes mellitus, especially in the case of hypokalemia.

In patients with hyperuricemia, the risk of developing gout attacks is increased: the dose of the drug must be selected individually.

Thiazide diuretics are effective in normal kidney function or slightly reduced renal function (creatinine clearance <60 ml / min, serum creatinine content> 2.5 mg / dL or> 220 μmol / L). In elderly patients, the clearance of creatinine can be calculated taking into account the age, body weight and sex of the patient according to Cockcroft's formula:

For men: creatinine clearance (ml / min) = [140 - age] × body weight (kg) / 0.814 × serum creatinine (μmol / L);

For women: The resulting value is × 0.85.

Hypovolemia (loss of fluid and sodium), resulting from the use of diuretics at the beginning of therapy, leads to a decrease in glomerular filtration, which leads to an increase in the level of urea and creatinine in the blood in patients with normal renal function.

Temporary impairment of kidney function occurs without consequences in patients with normal renal function. In patients with impaired renal function, there may be an increase in existing disorders.

In case of prescribing with another antihypertensive drug, a dose reduction at the beginning of treatment is recommended.

Use in Pediatrics

Efficacy and safety of the drug children and adolescents under the age of 18 therefore, the use of the drug is contraindicated.

Impact on the ability to drive vehicles and manage mechanisms

Use with caution when driving and working with machinery in connection with the possibility of developing dizziness.

Instructions

Bisoprolol + Hydrochlorothiazide (Bisoprololum + Hydrochlorothiazidum)