Нипертен®

General characteristics. Structure:

Active agent: the bisoprolola fumarates (2:1) 2,5 mg, 5 mg and 10 mg.
Excipients: cellulose microcrystallic, sodium carboxymethylstarch, povidone, silicon dioxide colloid, anhydrous, magnesium stearate.
Cover: gipromelloza, macrogoal, titanium dioxide, talc.

Description:
Tablets of 2,5 mg: oval, biconvex tablets, film coated white color, with risky on one party.
Tablets of 5 mg: round, biconvex tablets, film coated white color, with risky on one party.
Mg tablets 10: round, biconvex tablets, film coated white color, with risky on one party.

Pharmacological properties:

Pharmacodynamics. The selection ß1 — adrenoblocker, without own sympathomimetic activity, does not possess membrane stabilizing action.
Reduces activity of a renin of a blood plasma, reduces the need of a myocardium for oxygen, urezhat the heart rate (HR) (at rest and at loading). Has hypotensive, antiarrhytmic and anti-anginal effect. Blocking in low doses of ß1 - heart adrenoceptors, reduces stimulated catecholamines formation of cyclic adenosinemonophosphate (tsAMF) from adenosinetriphosphate (ATP), reduces intracellular current of calcium ions (Sa2+), renders negative hrono-, dromo-, batmo-and inotropic action, reduces atrioventricular conductivity and excitability.
At exceeding of a therapeutic dose renders ß2 - adrenoceptor blocking action.
The general peripheric vascular resistance at the beginning of drug use, in the first 24 h, increases (as a result of reciprocal increase of activity α - adrenoceptors and elimination of stimulation of ß2 - adrenoceptors), in 1-3 days is returned to initial, and at prolonged use - decreases. The hypotensive effect is connected with reduction of minute volume of blood, sympathetic stimulation of peripheral vessels, recovery of sensitivity in response to a lowering of arterial pressure (ABP) and influence on the central nervous system (CNS). At arterial hypertension the effect occurs in 2-5 days, stable action is noted in 1-2 months.
The anti-anginal effect is caused by reduction of need of a myocardium for oxygen as a result of an urezheniye of the heart rate (HR) and decrease in contractility of a myocardium, lengthening of a diastole, improvement of perfusion of a myocardium. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles oxygen requirement, especially at patients with the chronic heart failure (CHF) can increase.
The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of atrioventricular (AV) carrying out (it is preferential in antegrade and, to a lesser extent, in the retrograde direction through an AV node) and on additional ways. At use in average therapeutic doses, unlike non-selective ß adrenoblockers, exert less expressed impact on the bodies supporting ß2 - adrenoceptors (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism; does not cause a delay of ions of sodium (Na+) in an organism; expressiveness of atherogenous action does not differ from effect of propranolol.

Pharmacokinetics. Absorption - 80-90%, meal does not influence absorption. The maximum concentration in a blood plasma is observed in 1-3 h, communication with proteins of a blood plasma - about 30%. Permeability through a blood-brain barrier and a placental barrier - low.
50% of a dose are metabolized in a liver with formation of inactive metabolites, an elimination half-life (Т½) of 10-12 hours. About 98% are removed by kidneys, 50% are brought out of them in not changed look; less than 2% - with bile.

Indications to use:

• arterial hypertension;
• coronary heart disease: prevention of attacks of an angina of exertion;
• chronic heart failure (CHF).

Route of administration and doses:

Inside, in the morning on an empty stomach, without chewing, once.
Arterial hypertension and coronary heart disease: prevention of attacks of an angina of exertion
 It is recommended to accept 5 mg once. If necessary the dose is increased to 10 mg of 1 times a day. The maximum daily dose - 20 mg.
Patients with a renal failure at the clearance of creatinine (CC) have less than 20 ml/min., or with the expressed abnormal liver functions the maximum daily dose - 10 mg.
Dose adjustment is not required from elderly patients.
Chronic heart failure
 Initiation of treatment of chronic heart failure drug Niperten demands obligatory carrying out the special period of selection of doses.
Preliminary conditions to start therapy following:
• HSN without aggravation signs in the previous six weeks,
• almost unchangeable basic therapy in the previous two weeks,
• treatment by optimum doses of inhibitors of an angiotensin-converting enzyme (APF) (and vasodilators, in case of intolerance of APF inhibitors), diuretics and, if necessary, cardiac glycosides.
Treatment is appointed according to the specified scheme of selection of doses.
Individual reaction of the patient to the appointed therapy, i.e. dose is possible it is possible to increase only if the previous dose was well transferred.
1 week: 1,25 mg (1/2 tablets on 2,5 mg) once a day
2 week: 2,5 mg once a day
3 week: 3,75 mg once a day
4-7 week: 5 mg once a day
8-11 week: 7,5 mg once a day
12 week and further:  10 mg once a day as a maintenance therapy

The maximum recommended drug dose Niperten makes 10 mg once a day.
After an initiation of treatment drug in a dose of 1,25 mg (1/2 tablets of 2,5 mg) of the patient it is necessary to observe within about 4 hours (control of ChSS, the ABP, disturbance of conductivity on an ECG, signs of deterioration in chronic heart failure).
During the period of selection of doses or after it there can be a temporary deterioration in a current of HSN, a liquid delay in an organism, arterial hypotension or bradycardia. In this case Niperten is recommended to pay, first of all, attention to selection of a dose of the accompanying basic therapy (to optimize a dose of diuretic and/or APF inhibitor), before a drug dose decline. Treatment by drug should be interrupted only in urgent cases.
After stabilization of a condition of the patient it is necessary to carry out repeated titration, or to continue treatment.

Features of use:

 Control of the patients accepting drug Niperten has to include measurement of ChSS and the ABP (in an initiation of treatment - daily, then - 1 time in 3-4 months), carrying out an ECG, determination of level of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months). At elderly patients it is recommended to monitor function of kidneys (1 times in 4-5 months).
It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS less than 50 уд. / min.
Before an initiation of treatment it is recommended to conduct a research of function of external respiration at patients with the burdened bronchopulmonary anamnesis.
Approximately at 20% of patients with stenocardia of ß adrenoblockers are inefficient. Main reasons: the expressed coronary atherosclerosis with a low threshold of ischemia (ChSS less than 100 уд. / min.) and the increased final diastolic volume of a left ventricle breaking a subendocardial blood stream.
At smokers efficiency of ß adrenoblockers is lower.
The patients using contact lenses have to consider that against the background of treatment reduction of products of the lacrimal liquid is possible.
When using patients with a pheochromocytoma have a risk of development of paradoxical arterial hypertension (if it is previously not reached effective α - an adrenoblokada).
At a thyrotoxicosis бисопролол can disguise certain clinical signs of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology. At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective ß adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose in blood to normal level does not detain.
At a concomitant use of a clonidine its reception can be stopped only in several days after drug withdrawal Niperten.
Strengthening of expressiveness of hypersensitivity reaction and lack of effect of usual doses of Epinephrinum against the background of the burdened allergological anamnesis is possible. In case of need performing planned surgical treatment carry out drug withdrawal for 48 h prior to the beginning of the general anesthesia. If the patient accepted drug before surgical intervention, it should pick up medicine for the general anesthesia with minimum negative inotropic effect. Reciprocal activation of a vagus nerve can be eliminated with intravenous administration of atropine (1-2 mg).
The medicines reducing stocks of catecholamines (including Reserpinum), can strengthen action of ß adrenoblockers therefore the patients accepting such combinations of medicines have to be under constant observation of the doctor regarding identification of the expressed decrease in the ABP or bradycardia. Patients with bronkhospastichesky diseases can appoint cardioselective ß adrenoblockers in case of intolerance and/or inefficiency of other antihypertensives. The overdose is dangerous by development of a bronchospasm. In case of identification at patients of advanced age of the accruing bradycardia (less than 50 уд. / min.), the expressed decrease in the ABP (systolic the ABP is lower than 100 mm hg), AV of blockade, it is necessary to reduce a dose or to stop treatment. It is recommended to stop therapy at development of a depression.
It is impossible to interrupt sharply treatment because of danger of development of a syndrome of "cancellation" (heavy arrhythmias and a myocardial infarction). Cancellation is carried out gradually, reducing a dose within 2 weeks and more (lower a dose by 25% in 3-4 days). It is necessary to cancel before a research of content in blood and urine of catecholamines, a normetanefrin and vanilinmindalny acid, credits of antinuclear antibodies.

Influence on ability to drive the car and others mechanical to means:
the question of a possibility of occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions should be solved with only after assessment of individual reaction of the patient to drug (especially in an initiation of treatment, in connection with a possibility of development of dizziness).

Side effects:

From TsNS and peripheral nervous system: increased fatigue, weakness, dizziness, a headache, frustration of a dream, a depression, concern, confusion of consciousness or short-term loss of memory, a hallucination, an adynamy, a myasthenia, paresthesias in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), a tremor, spasms (including gastrocnemius muscles).
From an organ of sight: vision disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis.
From cardiovascular system: a sinus bradycardia, heartbeat, disturbance of conductivity of a myocardium, AV blockade (up to development of total cross block and a cardiac standstill), arrhythmias, easing of contractility of a myocardium, development (aggravation) of HSN (puffiness of anklebones, feet; asthma), decrease in the ABP, orthostatic hypotension, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, cold snap of the lower extremities, Reynaud's syndrome), stethalgia.
From the alimentary system: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain, lock or diarrhea, abnormal liver functions (dark urine, yellowness of scleras or skin, cholestasia), taste changes.
From respiratory system: a nose congestion, difficulty of breath at appointment in high doses (selectivity loss) and/or at predisposed patients - laringo-and a bronchospasm.
From endocrine system: a hyperglycemia (at patients with non-insulin-dependent diabetes), a hypoglycemia (at the patients receiving insulin), a hypothyroid state. Allergic reactions: skin itch, rash, small tortoiseshell.
From integuments: sweating strengthening, dermahemia, dieback, psoriazopodobny skin reactions, aggravation of symptoms of psoriasis, alopecia.
Laboratory indicators: thrombocytopenia (unusual bleedings and hemorrhages), agranulocytosis, leukopenia, change of activity of enzymes of a liver (increase in alaninaminotranspherase (ALT), asparaginaminotransferaza (ACT), level of bilirubin, triglycerides.
Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia. Other: dorsodynia, arthralgia, weakening of a libido, decrease in a potentiality, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP).

Interaction with other medicines:

The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving бисопролол.
Yodosoderzhashchy X-ray contrast intravenous agents increase risk of development of anaphylactic reactions.
Phenytoinum at intravenous administration, means for inhalation anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.
Changes efficiency of insulin and hypoglycemic means for intake, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP).
Reduces clearance of lidocaine and xanthines (except theophylline) and increases their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.
Hypotensive effect non-steroidal anti-inflammatory drugs (NPVP) (a delay of ions of sodium (Na+) and blockade of synthesis of prostaglandin kidneys) weaken, glucocorticosteroids and estrogen (a delay of ions of Na+).
Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of "slow" calcium channels (verapamil, diltiazem), Amiodaronum and other antiarrhytmic means increase risk of development or aggravation of bradycardia, AV of blockade, a cardiac standstill and heart failure.
Nifedipine can lead to considerable decrease in the ABP.
Diuretics, clonidine, sympatholytics, гидралазин and other antihypertensives can lead to excessive decrease in the ABP.
Extends action of not depolarizing muscle relaxants and increases anticoagulating effect of coumarins.
Rub - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and somnolent medicines strengthen oppression of TsNS.
Simultaneous use with MAO inhibitors, owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of MAO inhibitors and a bisoprolola has to make not less than 14 days.
Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.
Ergotamine increases risk of development of disturbance of peripheric circulation;
Sulfasalazinum increases concentration of a bisoprolol in a blood plasma; rifampicin reduces Т½.

Contraindications:

Hypersensitivity to components of drug and other ß adrenoblockers, shock (including cardiogenic), a collapse, a fluid lungs, an acute heart failure, chronic heart failure in a decompensation stage, atrioventricular (AV) blockade of the II-III degree, sinuatrial blockade, a sick sinus syndrome, the expressed bradycardia, Printsmetal's stenocardia, a cardiomegaly (without symptoms of heart failure), arterial hypotension (systolic the ABP less than 100 mm hg, especially at a myocardial infarction); severe forms of bronchial asthma and the chronic obstructive pulmonary disease (COPD) in the anamnesis; a concomitant use of inhibitors of a monoaminooxidase (MAO) (except for MAO-B), late stages of disturbance of peripheric circulation, a Raynaud's disease, a pheochromocytoma (without simultaneous use α - adrenoblockers), a metabolic acidosis, age up to 18 years (efficiency and safety are not established).
With care: a liver failure, a chronic renal failure, a myasthenia, a thyrotoxicosis, a diabetes mellitus, AV blockade of the I degree, a depression (including in the anamnesis), psoriasis, allergic reactions (in the anamnesis), advanced age.
Use at pregnancy and in the period of a lactation: perhaps if the advantage for mother exceeds risk of development of side effects in a fruit and the child.
There are no data on allocation of a bisoprolol in breast milk. Therefore in need of use of drug in the period of a lactation, breastfeeding needs to be stopped.

Overdose:

Symptoms: arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, AV blockade, the expressed decrease in the ABP, HSN, cyanosis of nails of fingers or palms, breath difficulty, a bronchospasm, dizziness, unconscious states, spasms.
Treatment: a gastric lavage and purpose of the adsorbing means; symptomatic therapy: at the developed AV to blockade - intravenous administration of 1-2 mg of atropine, Epinephrinum or temporary statement of a pacemaker; at ventricular premature ventricular contraction - lidocaine (the drugs IA of a class are not used); at decrease in the ABP - the patient has to be in the provision of Trendelenburga; if there are no fluid lungs signs — intravenous administration of plasma substituting solutions, at inefficiency - introduction of Epinephrinum, dopamine, Dobutaminum (for maintenance of chronotropic and inotropic action and elimination of the expressed decrease in the ABP); at heart failure - cardiac glycosides, diuretics, a glucagon; at spasms — intravenously diazepam; at a bronchospasm - ß2-adrenostimulyatory is inhalation.

Storage conditions:

List B. To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use drug after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 2,5 mg, 5 mg and 10 mg.
On 10 tablets in a blister strip packaging. 2, 3, 5 or 10 planimetric packagings together with the application instruction place in a pack from a cardboard.