Bisoprolol

Pharmacological properties

bisoprolol (inn - bisoprololum) is a selective blocker of β-adrenergic receptors. when used in therapeutic doses, does not show internal sympathomimetic activity and clinically pronounced membrane-stabilizing properties. It has an antianginal effect: it reduces myocardial oxygen demand due to lower heart rate, decreased cardiac output and decreased hell, increases myocardial oxygen supply by reducing the final diastolic hell and lengthening the diastole.

It has a hypotensive effect due to a decrease in cardiac output, inhibition of renin secretion by the kidneys, as well as the effect on the baroreceptors of the aortic arch and carotid sinus. With prolonged use of bisoprolol, primarily increased peripheral vascular resistance decreases. In chronic heart failure, it suppresses the activated sympathoadrenal and renin-angiotensin-aldosterone systems. It has a very low affinity for β blockers₂-adrenoreceptors of the mast muscles of the bronchi and blood vessels, as well as β blockers₂-receptors of the endocrine system. The drug only in isolated cases can affect the obese muscles of the bronchi and peripheral arteries, as well as glucose metabolism. With a single use, its effect persists for 24 hours.

Pharmacokinetics Absorption. After oral administration, the drug is well adsorbed in the digestive tract. Bioavailability is about 90% and is independent of food intake. WITH_max in blood plasma is achieved 1-3 hours after eating. Binding to plasma proteins is about 30%.

Metabolism and excretion. The effect of the first passage through the liver is not very pronounced (less than 10%). In the liver, approximately 50% of the dose is biotransformed with the formation of inactive metabolites. About 98% is excreted from the body by the kidneys, 50% - unchanged, the rest - in the form of metabolites, approximately 2% - through the intestines. T¹/₂ - 10-12 hours. The pharmacokinetics of bisoprolol is linear; its indices are not dependent on age. Dose adjustment in patients with impaired liver or kidney function of mild to moderate degree is not required.

Indications

Ag, IHD (angina pectoris), chronic heart failure (CHF).

Application

The recommended dose is 5 mg / day (1 tablet of 5 mg).

In hypertension of the second degree (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg / day may be prescribed at the beginning of treatment (¹/₂ 5 mg tablets).

If necessary, the daily dose can be increased to 10 mg (1 tablet of 10 mg).

Increasing the dose is allowed only in individual cases.

The maximum daily dose is 20 mg / day.

Patients with hepatic and renal failure. Dose adjustment in patients with impaired liver or kidney function of mild to moderate degree is usually not required.

In patients with severe impaired renal function (creatinine clearance of 20 ml / min) and / or severe impaired liver function, the maximum daily dose should not exceed 10 mg of Biprolol.

In elderly people (unless they have significant impairment of kidney or liver function), dosage adjustment of Biprolol is usually not required, however, this category of patients may be hypersensitive even to normal doses of the drug.

The drug is taken 1 time per day without chewing, regardless of food intake, preferably in the morning. The course of treatment is long. The duration of therapy depends on the nature and course of the disease. It is not recommended to stop treatment abruptly. This should be done slowly, gradually reducing the dose, especially in patients with angina pectoris, since a sudden cessation of treatment can lead to a sharp deterioration in the clinical picture.

Contraindications

• Hypersensitivity to bisoprolol or other components of the drug; heart failure in the decompensation phase; cardiogenic shock; av blockade of degrees II and III (with the exception of patients with an artificial pacemaker); sick sinus syndrome; severe sinoatrial block; bradycardia (heart rate 50 beats / min before treatment); arterial hypotension (systolic hell below 90 mm Hg. Art.); severe forms of peripheral circulation disturbance, Raynauds disease; severe ba or hobble; concomitant use of MAO inhibitors (with the exception of MAO-B inhibitors); combination with flactaphenin and sultopride; metabolic acidosis; untreated pheochromocytoma; psoriasis (including a family history); the period of pregnancy (except in cases where the expected benefit to the mother outweighs the potential risk to the fetus) and breastfeeding; childhood.

Side effects

Adverse reactions, information about which is given below, are classified by organs, systems and their frequency of occurrence: very often (≥10%); often (≥1% and 10%); sometimes (≥0.1% and 1%); rarely (≥0.01% and 0.1%); very rarely (0.01%).

The cardiovascular system. Very often: bradycardia (has a dose-dependent effect); often: a feeling of cold or numbness of the extremities, paresthesia, the appearance / intensification of manifestations of heart failure, arterial hypotension, at the beginning of treatment - worsening of patients with intermittent claudication or other peripheral circulation disorders; infrequently: palpitation or other rhythm disturbances, violation of AV conduction, orthostatic hypotension; very rare: pain in the chest, shortness of breath during physical exertion.

Nervous system. often: dizziness, headache, fatigue (especially at the beginning of treatment, symptoms are usually mild, disappear within 1–2 weeks), asthenia; infrequently: sleep disturbance, depression; rarely: anxiety, nervousness, confusion (especially in the elderly), hallucinations, paresthesia, decreased speed of motor and mental reactions, nightmares, syncope.

Respiratory system. Infrequently: shortness of breath, cough, bronchospasm (especially in patients with AD or with obstructive pulmonary diseases in history); rarely: nasal congestion, allergic rhinitis, sinusitis (dose-dependent effect).

GIT / hepatobiliary system. Often: dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation; rarely: cases of hepatotoxic action of bisoprolol - increased activity of hepatic enzymes in blood plasma (AsAT, AlAT), hepatitis.

Skin and subcutaneous tissue. rarely: hypersensitivity reactions, such as pruritus, skin rash (including urticaria, exfoliative dermatitis), angioedema, hot flashes, excessive sweating; very rare: allopecia, psoriasis-like rash, development or worsening of psoriasis symptoms.

Organ of vision. Rarely: decreased secretion of tear fluid (should be considered when wearing contact lenses); very rarely: impaired vision, eye pain / sensation of pressure, conjunctivitis.

Organ of hearing. Rarely: hearing loss, tinnitus, ear pain is possible.

Musculoskeletal system. Infrequently: muscle weakness, tremors / cramps, pain in muscles and / or joints, arthropathy.

Genitourinary organs. Rarely: impaired potency (decreased libido / impotence), dysuria, renal colic.

Endocrine system. Perhaps a decrease in glucose tolerance (with latent diabetes mellitus) and masking signs of hypoglycemia, weight gain.

Blood and lymphatic system. Agranulocytosis, thrombocytopenia, thrombocytopenic purpura are possible.

The immune system. Antinuclear antibodies may appear with the development of clinical symptoms of lupus-like syndrome, which usually disappears after treatment with bisoprolol is discontinued.

Laboratory indicators. Sometimes a slight increase in the level of TG in the blood, the concentration of uric acid, urea, creatinine, potassium in the blood serum, glucose and phosphorus, a decrease in the concentration of leukocytes, platelets. These changes, as a rule, have no clinical significance and rarely lead to discontinuation of bisoprolol.

The appearance of side effects requires immediate correction of the prescribed dose.

special instructions

Treatment with biprolol, as a rule, is long and requires regular medical supervision.the drug cannot be canceled suddenly due to the possible development of the withdrawal syndrome, which is manifested by an exacerbation of the disease, so the course of treatment should end smoothly, with a gradual decrease in dose, under the supervision of a doctor, taking into account the individual reactions of the patient.

Use with caution:

• in patients with diabetes mellitus with significant fluctuations in blood glucose levels, the symptoms of hypoglycemia (for example, tachycardia, palpitations, increased sweating) may be masked;
• subject to a strict diet;
• with AV blockade of the first degree, vasospastic angina (Prinzmetal angina), desensitizing therapy;
• in patients with a stable course of heart failure. Biprolol is contraindicated in case of exacerbation of heart failure or during episodes of decompensation of heart failure. Biprolol can be prescribed subject to compensation for their clinical condition and the possibility of medical control. Treatment begins with a minimum dose, observing careful dose titration. In case of intolerance or with the progression of symptoms of heart failure (severe arterial hypotension, acute pulmonary edema) during an increase in dose, it is recommended, first of all, to reduce the dose of Biprolol or stop taking the drug;
• in patients with COPD, BA in history;
• Before starting treatment with the drug, it is recommended to conduct a study of the function of external respiration;
• during desensitization specific immunotherapy. The drug may increase sensitivity to allergens and the incidence of anaphylactic reactions. Epinephrine should be prescribed with caution, as it may not exhibit the usual effects in the treatment of anaphylaxis. An alternative to the use of high doses of adrenaline is intensive supportive measures, in particular the administration of fluids and the use of β-agonists (parenteral administration of salbutamol or isoproterenol) to eliminate bronchospasm or norepinephrine - to eliminate arterial hypotension.

The appointment of Biprolol in patients with pheochromocytoma is permitted only after taking α-adrenoreceptor blockers.

In patients with myasthenia gravis in the presence of depression (including a history), the use of the drug should be carried out only after a thorough assessment of the benefit / risk ratio. The appointment of bisoprolol with thyrotoxicosis can mask the adrenergic symptoms of the disease.

General anesthesia Before surgery, it is necessary to warn the anesthetist about taking bisoprolol. It is not recommended to use β-adrenergic receptor blockers during surgical interventions, since the risk of arrhythmia and myocardial ischemia increases. The dose should be gradually reduced and the drug should be discontinued approximately 48 hours before general anesthesia.

In patients with impaired carbohydrate tolerance, such as congenital galactosemia, glucose-galactose malabsorption syndrome, lactase deficiency, the use of the drug is contraindicated due to the fact that it contains lactose.

The drug gives a positive result with anti-doping control.

Use during pregnancy and lactation. During pregnancy, the drug is used only if the expected benefit to the mother outweighs the potential risk to the fetus. As a rule, β-adrenergic receptor blockers reduce blood flow in the placenta and can affect fetal development. It is necessary to control blood flow in the placenta and uterus. After birth, the newborn should be under close medical supervision. Symptoms of hypoglycemia and bradycardia can be expected during the first 3 days. There are no data on the excretion of bisoprolol in breast milk or safety effects on infants. Therefore, the drug is not recommended for use during lactation.

Children.There are no clinical data on the efficacy and safety of the drug in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Due to the individual nature of the reactions when taking the drug, the reaction rate can be reduced, so during treatment you should avoid driving vehicles and working with other mechanisms.

Interactions

With the simultaneous use of bisoprolol with:

• nifedipine and other calcium channel blockers (dihydropyridine derivatives) may increase the hypotensive effect of bisoprolol;
• antiarrhythmic drugs (phenytoin, disopyramide, lidocaine, flecainide, amiodarone) - conduction disturbance and negative inotropic effect may occur;
• parasympathomimetic drugs - AV conduction time may increase and the risk of bradycardia may increase;
• β-adrenoreceptor blockers (contained in eye drops for the treatment of glaucoma) - the effect of bisoprolol may be enhanced;
• insulin and antidiabetic drugs for oral use - a hypoglycemic effect may occur;
• β-adrenoreceptor blockers - symptoms of hypoglycemia can be hidden;
• means for anesthesia - the risk of arrhythmia and myocardial ischemia may increase;
• cardiac glycosides (digitalis preparations) - can lead to a decrease in heart rate, a violation of AV conduction;
• NSAIDs - the hypotensive effect of bisoprolol is weakened;
• β-sympathomimetics (dobutamine, orciprenaline) - the effect of both drugs is reduced;
• sympathomimetics that activate α- and β-adrenergic receptors (adrenaline, norepinephrine) - blood pressure may increase and the phenomenon of intermittent claudication may intensify;
• tricyclic antidepressants, barbiturates, phenothiazine - the hypotensive effect is enhanced;
• MAO inhibitors (with the exception of MAO-B inhibitors) - the hypotensive effect of β-adrenergic receptor blockers increases;
• calcium channel blockers (verapamil, diltiazem), antihypertensive agents (clonidine, methyldopa, moxinidine, reserpine) should not be used simultaneously with bisoprolol therapy - development / strengthening of bradycardia, AV-blockade, heart failure, decrease in blood pressure is possible.

Overdose

Symptoms: bradycardia, arterial hypotension, heart failure, bronchospasm, respiratory failure, convulsions, arrhythmia (including av-block II and III degree), dizziness, hypoglycemia.

Treatment: drug withdrawal, gastric lavage, intake of activated carbon. If necessary, symptomatic treatment:

• with bradycardia: iv administration of atropine;
• with arterial hypotension: taking vasoconstrictor drugs, iv administration of glucagon;
• with AV blockade of the II and III degree: infusion administration of orciprenaline;
• if necessary - pacemaker;
• deterioration in heart failure: iv administration of diuretics;
• with bronchospasm: bronchodilators (e.g. orciprenaline), β₂-adrenomimetics and / or aminophylline;
• with hypoglycemia: iv glucose administration.

Hemodialysis is ineffective. The patient should be under strict medical supervision.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.