Instruction for use: Niperten

Trade name of the drug – Niperten

Dosage Form: tablets

Active substance: Bisoprololum

ATX

C07AB07 bisoprolol

Pharmacotherapeutic group: Beta1-selective blocker [Beta-blockers]

The nosological classification (ICD-10)

I10 Essential (primary) hypertension: hypertension; Arterial hypertension; Arterial hypertension crisis course; Essential Hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Primary hypertension; Arterial hypertension, complications of diabetes; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; arterial Hypertension; malignant Hypertension; Hypertonic disease; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; Isolated systolic hypertension

I15 Secondary hypertension: Arterial hypertension, complications of diabetes; hypertension; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; hypertension; arterial Hypertension; malignant Hypertension; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; hypertension; Arterial hypertension; Arterial hypertension crisis course; renovascular hypertension; Hypertension symptomatic; Renal hypertension; Renovascular hypertension; renovascular hypertension; Symptomatic hypertension

I20 Angina [angina]: Heberden disease; Angina pectoris; The attack of angina pectoris; recurrent angina; Spontaneous angina; Stable angina pectoris; Angina rest; Angina progressing; Angina mixed; Angina spontaneous; stable angina; Chronic stable angina; Angina Syndrome X

I25 Chronic ischemic heart disease: Coronary heart disease on the background of hypercholesterolemia; Coronary heart disease is a chronic; Coronary heart disease; Stable coronary artery disease; Percutaneous transluminal angioplasty; Myocardial ischemia, arteriosclerosis; Recurrent myocardial ischemia

I50.0 Congestive heart failure: anasarca heart; Decompensated congestive heart failure; Congestive heart failure; Congestive heart failure with high afterload; Congestive chronic heart failure; Cardiomyopathy with severe chronic heart failure; Compensated chronic heart failure; Swelling with circulatory failure; Edema of cardiac origin; Swelling of the heart; Edematous syndrome in diseases of the heart; Edematous syndrome in congestive heart failure; Edematous syndrome in heart failure; Edematous syndrome in heart failure or liver cirrhosis; right ventricular failure; Congestive Heart Failure; Heart failure stagnant; Heart failure with low cardiac output; Heart failure is a chronic; Cardiac edema; Chronic decompensated heart failure; Chronic Congestive Heart Failure; Chronic heart failure; Change of liver function in heart failure

Composition (per tablet):

active substance: bisoprolol fumarate 2.5 mg, 5 mg, 10 mg

Excipients: MCC - 95.5 / 93/186 mg; sodium carboxymethyl - 15/15/30 mg; povidone - 2/2/4 mg; colloidal silicon dioxide - 1/1/2 mg; magnesium stearate - 1/1/2 mg

shell film: Valium - 1.33 / 1.33 / 2.66 mg; macrogol 400 - 0.42 / 0.42 / 0.84 mg; titanium dioxide (E171) - 0.42 / 0.42 / 0.84 mg; talc - 0.83 / 0.83 / 1.66 mg

Description

Tablets 2.5 mg: oval, biconvex, film-coated white color, with Valium on one party.

Tablets 5 mg: Round, biconvex, film-coated white color, with Valium on one party.

Tablets 10 mg: Round, biconvex, film-coated white color, with Valium on one party.

View of the fracture: a rough mass of white or almost white, film-coated white.

Characteristic

Selective β1-blocker.

Pharmacological Properties of Niperten

Pharmachologic effect - antianginal, antihypertensive, antiarrhythmic, beta-adrenoceptor blocking.

Pharmacodynamics

Selective β1-blocker, without its own sympathomimetic activity, has no membrane stabilizing action. He has only a negligible affinity for the β2-adrenoceptor smooth muscles of the bronchi and vessels as well as the β2-adrenergic receptors, involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect the airway resistance and metabolic processes that are involved in the β2-adrenergic receptors.

The selective effect of the drug on the β1-adrenergic receptors and is stored outside of the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of the drug is achieved within 3-4 hours after ingestion. Even with bisoprolol 1 once daily its therapeutic effect is maintained for 24 hours through a 10-12 hour T1 / 2 from the blood plasma. As a rule, the maximum reduction in blood pressure is achieved within 2 weeks after initiation of treatment.

Bisoprolol reduces the activity simpatoadrenalovoj system by blocking the β1-adrenergic receptors of the heart.

For a single ingestion in patients with coronary artery disease with no evidence of heart failure bisoprolol slows heart rate, stroke volume decreases, as a result, reduces the ejection fraction and myocardial oxygen demand. When long-term therapy initially elevated peripheral vascular resistance is reduced. Reducing the activity of renin in blood plasma is considered as one of the components of the antihypertensive action of β-blockers.

Pharmacokinetics

Suction. Bisoprolol is almost completely (90%) absorbed from the gastrointestinal tract. Due to its low bioavailability metabolization during the initial passage through the liver (approximately 10%) is approximately 90% after oral administration. Food does not affect the bioavailability. Bisoprolol demonstrates linear kinetics, and its plasma concentration is proportional to the dose in the range of 5 to 20 mg. Cmax plasma levels achieved in 2-3 hours.

Distribution. Bisoprolol is distributed widely enough. Vd is 3.5 L / kg. Communication plasma protein reaches about 30%.

Metabolism. It is metabolized by oxidative way without subsequent conjugation. All metabolites are polar (water soluble) and the kidneys. Major metabolites detected in plasma and urine did not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes under conditions in vitro, suggest that bisoprolol is metabolized mainly via isoenzyme CYP3A4 (about 95%) and CYP2D6 isozyme plays only a minor role.

Withdrawal. The clearance of bisoprolol is determined by the equilibrium between the renal excretion as unchanged (about 50%) and metabolism in the liver (approximately 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l / h. T1 / 2 - 10-12 h.

Pharmacokinetics in different patient groups. There is no information on the pharmacokinetics of bisoprolol in patients with chronic heart failure and simultaneous impaired liver or kidney function.

Indications for Niperten

arterial hypertension;

Coronary heart disease: stable angina;

chronic heart failure.

Contraindications for Niperten

Hypersensitivity to bisoprolol or any of the excipients of the formulation;

acute heart failure, chronic heart failure decompensation requiring of inotropic therapy;

cardiogenic shock;

AV blockade II-III degree, without a pacemaker;

syndrome sick sinus;

sinoatrial block;

severe bradycardia (heart rate less than 60 beats / min.);

severe hypotension (Sad less than 100 mm Hg);

severe bronchial asthma and chronic obstructive pulmonary disease;

The expressed disturbances of peripheral arterial circulation or Raynaud's syndrome;

pheochromocytoma (without α-blockers simultaneous use);

metabolic acidosis;

age of 18 years (effectiveness and safety have been established).

Precautions: conducting desensitizing therapy, Prinzmetal angina, hyperthyroidism, diabetes mellitus type 1 and diabetes mellitus with significant fluctuations in blood glucose concentration, AV block I degree, severe renal impairment (Cl creatinine less than 20 mL / min), severe hepatic dysfunction, psoriasis, restrictive cardiomyopathy, congenital heart defects or heart disease valve with severe hemodynamic disturbances, heart failure with myocardial infarction within the last 3 months, a strict diet.

Pregnancy and breast-feeding

In pregnancy, the drug Niperten® should be advised to use only if the benefit to the mother outweighs the risk of side effects in the fetus and / or the child.

Typically, β-blockers decrease the blood flow in the placenta and can affect fetal development. It should monitor blood flow in the placenta and uterus, and also to observe the growth and development of the child and in the event of adverse events in respect of pregnancy and / or fetus, the use of alternative therapies use with proven safety profile during pregnancy. It is necessary to carefully examine the newborn after delivery. In the first 3 days of life symptoms of bradycardia and hypoglycemia may occur.

Data on the allocation of bisoprolol into breast milk is not. Therefore reception Niperten® drug is not recommended for women during breastfeeding. If reception Niperten® during lactation is necessary, breast-feeding should be discontinued.

Side effect of Niperten

The frequency of adverse reactions listed below was determined according to the following criteria recommended by WHO: very common (≥ / 10); commonly (≥1 / 100 to <1/10); uncommon (≥1 / 1,000 to <1/100); rare (≥1 / 10,000 to <1/1000); very rare (<1/10000).

From the nervous system: often - dizziness *, headache *; rare - loss of consciousness.

Mental disorders: rarely - depression, insomnia; rarely - hallucinations, nightmares.

From a sight organ: seldom - a decrease in lacrimation (to consider when wearing contact lenses); very rarely - conjunctivitis.

On the part of the ear and labyrinth disorders: rarely - a violation hearing.

On the part of the heart and blood vessels: very often - bradycardia (in patients with heart failure); often - current worsening heart failure symptoms (patients with CHF), cooling sensation or numbness in the extremities, marked reduction in blood pressure, especially in patients with CHF; rarely - a violation of AV conduction, bradycardia (in patients with hypertension or angina), worsening of heart failure symptoms flow (in patients with hypertension or angina), orthostatic hypotension.

The respiratory system, organs, thoracic and mediastinal disorders: rarely - bronchospasm in patients with asthma or airway obstruction in history; rarely - allergic rhinitis.

On the part of the digestive tract: often - nausea, vomiting, diarrhea, constipation.

On the part of the liver and biliary tract: rarely - hepatitis.

On the part of the musculoskeletal and connective tissue disorders: rarely - muscle weakness, muscle cramps.

Skin and subcutaneous tissue disorders: rarely - hypersensitivity reactions, such as itching, skin rash, redness of the skin; very rare: alopecia.

β-blockers may exacerbate psoriasis current symptoms or induce psoriasis-like rash.

From the genitals and breast: rarely - a violation of potency.

General disorders and administration in place: often - asthenia (patients with chronic heart failure), fatigue *; infrequently - asthenia (patients with arterial hypertension or angina).

Laboratory and instrumental data: rarely - increased triglyceride concentration and liver transaminases (ACT, ALT) in blood plasma.

* In patients with hypertension or angina, these symptoms most often occur at the start of treatment. Usually, these effects are mild and are usually within 1-2 weeks after starting treatment.

Interaction

On the efficacy and tolerability of the bisoprolol may affect concomitant use of other drugs. Such interaction may also occur in those cases when the two drugs taken after a short time.

You must inform the doctor about taking other medicines, even if they are received without a doctor's prescription (ie, non-prescription drugs).

Not recommended combinations

Treatment of chronic heart failure. Class I antiarrhythmic agents (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.

All indications for the drug Niperten®. CCB verapamil type and to a lesser extent diltiazem while the use of bisoprolol may lead to a decrease in myocardial contractility and AV conduction disorders. In particular, in / with the introduction of verapamil in patients receiving β-blockers may lead to severe hypotension and AV blockade.

Antihypertensive drugs central action (such as clonidine, methyldopa, moxonidine, rilmenidine) may lead to a slowing of the heart rate and reducing cardiac output and to vasodilatation due to the reduction of the central sympathetic tone. Abrupt withdrawal, particularly to cancellation β-blockers may increase the risk of rebound hypertension.

Combinations requiring special care

Treatment of hypertension and angina. Class I antiarrhythmics (eg quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.

All indications for the drug Niperten®. BPC, dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine), while the use of bisoprolol may increase the risk of hypotension. In patients with heart failure cannot eliminate the risk of further deterioration of the contractile function of the heart.

Class III antiarrhythmics (eg amiodarone) may increase the violation of AV conduction.

The action of β-blockers for topical application (eg eye drops for glaucoma treatment) may enhance the systemic effects of bisoprolol (lowering blood pressure, slowing of the heart rate).

Parasympathomimetics while the use of bisoprolol may increase the violation of AV conduction and increase the risk of bradycardia.

Hypoglycemic effect of insulin or hypoglycemic agents for oral administration can be enhanced. Symptoms of hypoglycemia, particularly tachycardia, may be masked or suppressed. Such interactions are more likely when using a nonselective β-blockers.

Funds for general anesthesia may increase the risk cardiodepressive action, resulting in hypotension (see. "Special Instructions").

Cardiac glycosides while the use of bisoprolol may lead to an increase of the pulse time, and thus - to the development of bradycardia.

NSAIDs may reduce the antihypertensive effect of bisoprolol.

Simultaneous application Niperten® drug with β-adrenergic agonists (e.g., isoprenaline, dobutamine) may reduce the effects of both drugs. Application of bisoprolol with agonists affecting the α and β-adrenergic receptors (such as norepinephrine, epinephrine), may enhance the effects of vasoconstrictor agents arising with α-adrenergic receptors, resulting in an increase in blood pressure. Such interactions are more likely when using a nonselective β-blockers.

Antihypertensives, as well as with other possible means antihypertensive effect (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may enhance the antihypertensive effect of bisoprolol.

Mefloquine while the use of bisoprolol may increase the risk of bradycardia.

MAO inhibitors (except MAO inhibitors) may increase the antihypertensive effect of β-blockers. Concomitant use can also lead to the development of hypertensive crisis.

Dosage and Administration

Inside, 1 time per day with a little liquid, in the morning, regardless of mealtime. Tablets should not be chewed or triturate.

Arterial hypertension and stable angina. In all cases of reception mode and selects the physician dose for each patient individually, in particular, given the patient's heart rate and condition. Typically, the initial dose is 5 mg Niperten® 1 time per day. If necessary, the dose may be increased to 10 mg 1 time per day. In the treatment of hypertension and stable angina, the maximum recommended dose is 20 mg Niperten® 1 time per day.

CHF: CHF Standard scheme of treatment includes the use of ACE inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), β-blockers, diuretics, and optionally cardiac glycosides. Start treating heart failure drug Niperten® requires mandatory special titration phase and regular medical supervision.

A prerequisite for treatment with Niperten® is stable chronic heart failure without acute symptoms.

CHF Niperten® drug treatment is started in accordance with the following titration scheme. This may require individual adaptation depending on how well the patient carries the prescribed dose, i.e. the dose can be increased only if the previous dose was well tolerated.

The recommended initial dose is 1.25 mg (1/2 tab. 2.5 mg) 1 every day. Depending on individual tolerance dose should be gradually increased to 2.5; 3.75; 5; 7.5 1 and 10 mg once a day. Each subsequent increase in dose should be administered at least 2 weeks.

If an increase in the dose of the drug is poorly tolerated by the patient, the dose may be reduced.

The maximum recommended dose for the treatment of chronic heart failure is 10 mg Niperten® 1 time per day.

During titration we recommend regular monitoring of blood pressure, heart rate and severity of heart failure symptoms. Worsening heart failure symptoms may flow from the first day of the drug.

If the patient does not tolerate the maximum recommended dose of the drug Niperten® should consider a gradual reduction of the dose.

During the titration phase, or it can occur after a temporary deterioration in the flow of CHF, hypotension or bradycardia. In this case it is recommended first of all carry out the correction of concurrent therapy doses of drugs. It may also require temporary dose reduction or cancellation Niperten®.

After stabilization, the patient should undertake a re-titration of the dose or continue the treatment.

The duration of treatment for all indications to the application Niperten® drug. Treatment with Niperten® is usually long-term therapy.

Special patient groups

Impaired renal or hepatic function. If abnormal liver or renal function mild to moderate dose adjustment is usually not required.

In severe violation of kidney (Cl creatinine less than 20 mL / min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be administered with extreme caution.

Elderly patients. Dose adjustment is not required.

Children. Since there is not enough of the drug for use Niperten® data in children, it is not recommended to use the drug in children under 18 years.

At present, insufficient data regarding the use of the drug Niperten® in patients with heart failure in combination with type 1 diabetes, severe violations of the kidneys and / or liver disease, restrictive cardiomyopathy, congenital heart disease or a heart defect valve with severe hemodynamic compromise. Also still not enough data was received with respect to CHF patients with myocardial infarction within the past 3 months.

Overdose

Symptoms: The most common - AV block, bradycardia, marked reduction in blood pressure, bronchospasm, acute cardiac insufficiency and hypoglycaemia. Sensitivity to single receiving high doses of bisoprolol varies greatly among individual patients, and probably with CHF patients have a high sensitivity.

Treatment: If overdose occurs, first of all, you need to stop taking the drug and start supporting symptomatic therapy. In severe bradycardia: atropine intravenous administration. If the effect is insufficient, you can enter with caution agent with positive chronotropic effect. Sometimes it may require temporary staging an artificial pacemaker.

In marked decrease in blood pressure - in / in a plasma-solutions and vasopressor drugs.

When AV blockade - patients should be under constant supervision and be treated with α- and β-adrenergic agonists such as epinephrine (adrenaline). If necessary - setting an artificial pacemaker.

When exacerbation of chronic heart failure: intravenous diuretics, drugs with positive inotropic effect and vasodilators. When bronchospasm - the use of bronchodilators, including β2-agonists and / or aminophylline.

When hypoglycemia - in / in a dextrose (glucose).

Special instructions

Do not interrupt treatment with Niperten® sharply and do not change the recommended dose without first consulting your doctor, because this may lead to a temporary worsening of cardiac activity. Treatment should not be interrupted suddenly, especially in patients with CAD. If discontinuation is necessary, the dose should be reduced gradually.

With simultaneous use of clonidine its reception can be terminated only after a few days after discontinuation of the drug Niperten®.

In the initial stages of treatment Niperten® patients need constant monitoring.

Control of the state receiving the drug Niperten® patients should include measurement of heart rate and blood pressure (at the beginning of treatment - daily, then - 1 every 3-4 months) holding an electrocardiogram, determination of blood glucose in patients with diabetes mellitus (1 times 4-5 months). In elderly patients it is recommended to monitor renal function (1 every 4-5 months).

It is necessary to train the patient's heart rate calculation method and instructed to consult a doctor if the heart rate less than 60 bpm. / Min.

Niperten® The drug should be used with caution in the following cases:

- Diabetes mellitus with significant fluctuations in plasma concentrations of glucose: symptom reduction of the concentration of glucose (hypoglycaemia) such as tachycardia, palpitations and sweating may be masked;

- strict diet;

- Conducting desensitizing therapy;

- AV block of I degree;

- Prinzmetal angina;

- Peripheral arterial circulatory disorders of mild to moderate degree (at the beginning of treatment may be increased symptoms);

- Psoriasis (including a history..).

In the case of elderly patients increasing bradycardia (heart rate less than 60 beats. / Min), marked reduction of blood pressure (SBP below 100 mm Hg), AV blockade bronchospasm, ventricular arrhythmias, severe liver dysfunction and / or kidney disease need to reduce dose or discontinue treatment.

It is recommended to discontinue therapy in the development of depression caused by taking β-blockers.

Respiratory system

Before therapy is recommended to study of respiratory function in patients with a history of bronchopulmonary history.

In bronchial asthma or COPD shows the simultaneous use of bronchodilator agents. Patients with asthma may increase airway resistance, which requires higher doses of β2-agonists.

Smokers effectiveness of β-blockers lower.

Allergic reactions

.beta.-blockers, including drug Niperten® may increase the sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of compensatory adrenergic regulation under the action of .beta.-blockers. Therapy epinephrine (adrenaline) does not always give the expected therapeutic effect.

general anesthesia

With general anesthesia, you should consider the risk of β-adrenoceptor blockade. If you want to stop therapy with Niperten® before surgery, this should be done gradually and completed within 48 hours prior to general anesthesia. It is necessary to warn the anesthesiologist that the patient takes the drug Niperten®.

pheochromocytoma

Patients with adrenal gland tumor (pheochromocytoma) Niperten® drug can be used only against the background of the simultaneous use of alpha-blockers.

hyperthyroidism

In the treatment of drug Niperten® symptoms of hyperthyroidism (hyperthyroidism) can be masked.

Patients who use contact lenses should bear in mind that during treatment may decrease the production of tear fluid.

Effects on ability to perform potentially hazardous activities that require attention and fast reactions (eg, road management, work with moving machinery). Niperten® The drug does not affect the ability to drive vehicles according to a study in patients with CAD. However, the ability to drive vehicles or operate technically complex mechanisms may be impaired as a result of individual reactions. It should be emphasized at the start of treatment, after changing the dose and while consuming alcohol.

Release Form

Tablets, film-coated, 2.5 mg, 5 mg, 10 mg. According to Table 10. in blisters made of PVC foil and aluminum foil; 2, 3, 5 or 10 contour cell packages are placed in a cardboard box.

Manufacturer

LLC "Krka-Rus", 143500, Russia, Moscow Region., Istra Str. Moscow, 50.

Representative office of JSC «Krka, dd, Novo mesto" in the Russian Federation / organization receiving consumer complaints: 125212, Moscow, Golovinskoye Highway 5, Bldg. 1 fl. 22.

A comment

In some data were obtained the following research:

Comparative evaluation of clinical efficacy and safety of the original product and its generic bisoprolol in patients with coronary artery disease, with concomitant COPD

The drug has proven Niperten® clinical equivalence to the original bisoprolol. The study was conducted in Russia for 12 weeks. The study involved 92 patients with stable angina, arterial hypertension (AH) and concomitant COPD. The study confirmed the equal anti-ischemic and anti-hypertensive effects of drugs. Niperten® original bisoprolol in patients with ischemic heart disease with concomitant COPD do not have a negative influence on bronchial patency. In appointing the drug Niperten® and original bisoprolol reached the target heart rate range, which allows us to speak about their positive influence on the prognosis of patients' lives.

The study of the effect of drug therapy on the indices Niperten® peripheral and central blood pressure, arterial stiffness, diastolic left ventricular function and quality of life in patients with arterial hypertension

The study included 30 patients, during the - 3 months. Research has shown that therapy with Niperten® leads to significant reductions in SBP by 10.5%, Dad - by 11.8%. At the same time, 93% of patients achieved target BP levels. In the group of drug Niperten® heart rate decreased from 81.1 to 68.7 bpm. / Min (p <0.001), improved mental and physical health components. It was well tolerated and metabolic neutrality Niperten® drug.

Literature

1. Grigoriev NY, Kuznetsov AN, Queen TV Comparative evaluation of clinical efficacy and safety of the original and generic bisoprolol in patients with coronary heart disease combined with chronic obstructive pulmonary disease // Serdtse.- 2012.- 11 (4) .- S. 223-226.

2. Orlov YA Mikhailov GV, Hezheva FM, Vitsenya MV Ageev F. Effect of bisoprolol therapy on the peripheral and central blood pressure, arterial stiffness, left ventricular diastolic function and quality of life in hypertensive patients (study key) // Heart: journal for practitioners vrachey.- 2012.- 11 (6) - (68).

Conditions of supply of pharmacies

On prescription.

Storage conditions of Niperten

The temperature is not above 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life

2 years.

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