Bisoprolol-Vertex, 2.5mg 30 pcs.

Pharmacodynamics

Bisoprolol is a selective beta1-adrenoblocker without sympathomimetic activity of its own; it has antihypertensive, antiarrhythmic and antianginal effects. By blocking in low doses beta1-adrenoreceptors of the heart, it reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), decreases intracellular calcium ions (Ca2+) flow, has negative chrono-, dromo-, batmo- and inotropic effects (decreases heart rate, inhibits conduction and excitability, decreases myocardial contractility).

With increasing dose has beta2-adrenoblocking effect.
Total peripheral vascular resistance at the beginning of administration of beta-adrenoblockers, in the first 24 hours increases (as a result of reciprocal increase of activity of alpha-adrenoreceptors and elimination of stimulation of beta2-adrenoreceptors) which in 1-3 days returns to baseline and decreases with prolonged administration.

The antihypertensive effect is connected with decrease of the minute blood volume, sympathetic stimulation of peripheral vessels, decrease of renin-angiotensin-aldosteron system activity (it is more important for patients with initial renin hypersecretion), restoration of aortic arch baroreceptors sensitivity (their activity in response to arterial pressure (AP) decrease is not increased) and the influence on the central nervous system. In case of arterial hypertension the effect comes in 2-5 days, stable effect – in 1-2 months.

The antianginal effect is caused by decrease of myocardial oxygen demand as the result of shortening of heart rate and contractility, prolongation of diastole, improvement of myocardial perfusion. By increasing left ventricular end-diastolic pressure and increasing ventricular muscle fiber stretch may increase myocardial oxygen demand, especially in patients with chronic heart failure (CHF).

In contrast to non-selective beta-adrenoblockers when administered in medium therapeutic doses, it has less pronounced effect on the organs containing beta2-adrenoreceptors (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause delay of sodium ions (Na+) in the body. When used in high doses has a blocking effect on both subtypes of beta-adrenoreceptors.

Pharmacokinetics.

Bisoprolol is almost completely absorbed from the gastrointestinal tract (80-90%). Food intake has no effect on absorption of the drug. Maximum plasma concentration is reached after 2-3 hours. Binding with plasma proteins is approximately 35%. Hematoencephalic barrier and placental barrier permeability is low, secretion with breast milk is low.

It is metabolized in the liver. Period of semi-elimination (T1/2) is 9-12 hours, it is prolonged in patients with kidney function disorders (in creatinine clearance less than 40 ml/min – 3 times), in elderly people, in liver diseases (in cirrhosis it is increased up to 21.7 hours). Excreted by the kidneys – 50% unchanged, less than 2% through the intestines.

Indications

Active ingredient

Composition

1 film-coated tablet contains:

acting substance:

bisoprolol fumarate 2.5 mg.

Auxiliary substances:

lactose monohydrate,

microcrystalline cellulose,

p> colloidal silicon dioxide,

crospovidone,

magnesium stearate.

How to take, the dosage

In the morning on an empty stomach, without chewing, 5 mg once.

If necessary, the dose is increased to 10 mg once daily. The maximum daily dose is 20 mg/day.

In patients with impaired renal function and creatine clearance less than 20 ml/min or with significant hepatic impairment the maximum daily dose is 10 mg.

Dose adjustment in elderly patients is not required;

Interaction

When concomitant use of antacids and antidiarrheals may decrease the absorption of beta-adrenoblockers.

Concomitant use of antiarrhythmic agents may cause a sharp decrease in BP, lower HR, development of arrhythmias and/or heart failure.

The simultaneous use of antihypertensive agents may increase the antihypertensive effect.

Concomitant use of cardiac glycosides may cause conduction disorders.

The concomitant use of sympathomimetics (including those contained in cough products, nasal drops, eye drops) decreases the effectiveness of bisoprolol.

Concomitant use of verapamil, diltiazem may cause a sharp decrease in BP, lower HR, development of arrhythmia and/or heart failure.

Concomitant use of guanfacine may cause marked bradycardia and conduction disturbances.

In concomitant use of insulin, hypoglycemic agents for oral administration, the effect of insulin or other hypoglycemic agents increases (regular monitoring of plasma glucose levels is necessary).

When clonidine is used concomitantly there may be severe bradycardia, arterial hypotension and conduction disorders.

In case of abrupt clonidine withdrawal, patients receiving bisoprolol may experience a sharp increase in BP.

The simultaneous use of nifedipine, other calcium channel blockers, dihydropyridine derivatives increases the antihypertensive effect of bisoprolol.

The simultaneous use of reserpine, alpha-methyldopa may cause marked bradycardia.

Concomitant use of rifampicin may slightly decrease T1/2 of bisoprolol.

The concomitant use of ergotamine derivatives (including migraine medications containing ergotamine) increases symptoms of peripheral circulatory disorders.

Special Instructions

Control of patients taking Bisoprolol should include measurement of HR and BP (at the beginning of treatment – daily, then once every 3-4 months), ECG, determination of blood glucose level in diabetic patients (once every 4-5 months). In elderly patients it is recommended to monitor kidney function (once every 4-5 months).

The patient should be trained in the method of heart rate calculation and instructed to consult a physician if the heart rate is less than 50 bpm. Prior to treatment, it is recommended that patients with a history of bronchopulmonary disease have an external respiratory function study. In about 20% of patients with angina pectoris, beta-adrenoblockers are ineffective.

The main causes are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100 bpm) and increased left ventricular end-diastolic volume that impairs subendocardial blood flow.

The effectiveness of beta-adrenoblockers is lower in “smokers. Patients who use contact lenses should take into account that against the background of treatment a decrease of lacrimal fluid production is possible. When used in patients with pheochromocytoma, there is a risk of paradoxical arterial hypertension (if effective alpha-adrenoblockade has not been previously achieved).

In thyrotoxicosis, Bisoprolol may mask certain clinical signs of thyrotoxicosis (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can exacerbate the symptoms. In patients with diabetes mellitus it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-adrenoblockers practically does not increase insulin-induced hypoglycemia and does not delay the recovery of blood glucose concentration to normal levels.

If clonidine is taken concomitantly, its administration may be discontinued only after several days of Bisoprolol withdrawal.

The severity of hypersensitivity reactions and lack of effect of usual doses of epinephrine with a history of allergy may increase. In case of necessity of elective surgical treatment the drug shall be withdrawn 48 hours prior to the beginning of general anesthesia. If the patient has taken the drug before the surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect.
Reciprocal activation of the vagus nerve can be eliminated by intravenous injection of atropine (1-2 mg).

Drugs that reduce catecholamine stores (including reserpine) may potentiate the effects of beta-adrenoblockers, so patients taking such combinations of drugs should be under constant medical supervision for pronounced lowering of BP or bradycardia.

Patients with bronchospastic disorders may be prescribed cardioselective adrenoblockers if other hypotensive medications are intolerant and/or ineffective.
Overdose is dangerous with bronchospasm.

In elderly patients with increasing bradycardia (less than 50 beats/min), significant BP lowering (systolic BP below 100 mmHg), AV-blockade it is necessary to decrease the dose or discontinue treatment. It is recommended to discontinue therapy if depression develops.

The treatment should not be abruptly interrupted because of the risk of severe arrhythmias and myocardial infarction. Withdrawal is carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% every 3-4 days). It should be discontinued before testing the blood and urine content of catecholamines, normetanephrine and vanillinmindalic acid, and antinuclear antibody titers.

During treatment, caution should be exercised when driving motor vehicles and engaging in other potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

Side effects

Nervous system disorders:weakness, fatigue, dizziness, headache, sleep disorders, mental disorders (depression, rarely – hallucinations), cold sensation and paresthesias in the extremities.

Cardiovascular system disorders: Orthostatic hypotension, bradycardia, AV conduction disorders, appearance of symptoms of heart failure, worsening of intermittent claudication and basic clinical symptoms in Raynaud’s syndrome.

Visual side: decreased tear fluid secretion, conjunctivitis.

From the digestive system: diarrhea, constipation, nausea, abdominal pain.

Muscular system disorders: muscular weakness, muscle cramps.

Skin and subcutaneous tissues:cutaneous itching; in some cases – aggravation of psoriasis, the appearance of psoriasis-like rashes.

In the respiratory system:in predisposed patients there may be symptoms of bronchial obstruction.

Others:Sweating, hot flashes, impaired potency, decreased glucose tolerance in diabetic patients, allergic reactions.

Overdose

Symptoms: arrhythmia, ventricular extrasystole, marked bradycardia, AV blockade, marked BP decrease, chronic heart failure, cyanosis of finger nails or palms, difficulty breathing, bronchospasm, dizziness, fainting, seizures.

Treatment:Gastric lavage and administration of adsorptive drugs;
symptomatic therapy:

In case of developed AV blockade – intravenous injection of 1-2 mg of atropine, epinephrine or placement of a temporary pacemaker; If ventricular extrasystole – lidocaine (Class IA drugs are not used);

If BP decreases – the patient should be in Trendelenburg; If there are no signs of pulmonary edema – intravenous plasma exchange solutions, if ineffective – administration of epinephrine, dopamine, dobutamine (to maintain chronotropic and inotropic action and to eliminate marked BP decrease);

In case of heart failure – cardiac glycosides, diuretics, glucagon;

In case of seizuresFor seizures – intravenous diazepam; for bronchospasm – inhaled beta2-adrenergic stimulants

Pregnancy use

The use in pregnancy and lactation is not recommended and is possible when the expected benefit to the mother exceeds the potential risk of side effects in the fetus and child.

In exceptional cases of use in pregnancy, bisoprolol should be discontinued 72 hours before expected delivery due to the possibility of bradycardia, arterial hypotension, hypoglycemia and respiratory depression in the newborn. If cancellation is not possible, the newborn’s condition should be carefully monitored for 72 hours after delivery.

If bisoprolol has to be used during lactation, breastfeeding must be stopped.

Similarities