Niperten® Combi (Niperten® Combi)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceAmlodipine + BisoprololAmlodipine + Bisoprolol
Similar drugsTo uncover
  • Amlodipine + Bisoprolol
    pills inwards 
    NORTH STAR, CJSC     Russia
  • Concor® AM
    pills inwards 
    Merck KGaA     Germany
  • Niperten® Combi
    pills inwards 
    KRKA-RUS, LLC     Russia
    • Dosage form: & nbsppills
    Composition:

    Composition

    1 tablet 5 mg + 5 mg

    Active substance:

    Amlodipine + Bisoprolol, substance - granules, 5 mg + 5 mg 152 mg Active substance substances - granules: Amlodipine besylate (amlodipine besylate) 6.935 mg, equivalent to amlodipine 5.00 mg, Bisoprolol fumarate 5.00 mg

    Auxiliary substances of substance - granules: microcrystalline cellulose - 133,065 mg, sodium carboxymethyl starch 5.00 mg, silica colloidal dioxide 1.00 mg, magnesium stearate 1.00 mg]

    Excipients: magnesium stearate 1.00 mg

    1 tablet 5 mg + 10 mg

    Active substance:

    Amlodipine + Bisoprolol, substance - granules, 5 mg + 10 mg 304 mg [Active substances of substance - granules: Amlodipine besylate (amlodipine besylate) 6.935 mg, equivalent to amlodipine 5.00 mg, Bisoprolol fumarate 10.00 mg

    Auxiliary substances of substance - granules: microcrystalline cellulose 273,065 mg, sodium carboxymethyl starch 10.00 mg, silicon dioxide colloid 2.00 mg, magnesium stearate 2.00 mg]

    Excipients: magnesium stearate 2.00 mg

    1 tablet 10 mg + 5 mg

    Active substance:

    Amlodipine + Bisoprolol, substance - granules, 10 mg + 5 mg 304 mg [Active substances of substance - granules: Amlodipine besylate (amlodipine besylate) 13.87 mg, equivalent to amlodipine 10.00 mg, bisoprolol fumarate 5.00 mg

    Auxiliary substances of substance - granules: microcrystalline cellulose - 271,13 mg, sodium carboxymethyl starch 10.00 mg, silicon dioxide colloid 2.00 mg, magnesium stearate 2.00 mg]

    Excipients: magnesium stearate 2.00 mg

    on 1 tablet of 10 mg + 10 mg

    Active substance:

    Amlodipine + Bisoprolol, substance - granules, 10 mg + 10 mg 304 mg

    [Active substances of substance - granules: Amlodipine besylate (amlodipine besylate) 13.87 mg, equivalent to amlodipine 10.00 mg, Bisoprolol fumarate 10.00 mg

    Auxiliary substances of substance - granules: microcrystalline cellulose 273.66 mg, sodium carboxymethyl starch 10.00 mg, silicon dioxide colloid 2.00 mg, magnesium stearate 2.00 mg]

    Excipients: magnesium stearate 2.00 mg

    Description:

    Tablets 5 mg + 5 mg: Round, biconvex tablets are white, with a facet on both sides and risk on one side.

    Tablets 5 mg + 10 mg: Oval, biconvex tablets are white, with a risk on one side.

    Tablets 10 mg + 5 mg: Round, slightly biconcave tablets of white color, with a facet and a risk on one side and engraved "CS" on the other side.

    Tablets 10 mg + 10 mg: Round, slightly biconvex tablets of white color, with a facet and a risk on one side.

    Pharmacotherapeutic group:antihypertensive drug combined (beta 1-adrenoblocker selective + blocker of "slow" calcium channels)
    ATX: & nbsp

    C.07.F.B   Selective beta-1 blockers in combination with other antihypertensive drugs

    Pharmacodynamics:

    The drug Niperten® Combi has a pronounced antihypertensive and antianginal effect due to the complementary action of two active substances: a slow calcium channel blocker (amlodipine) and selective beta 1-adrenoblocker-bisoprolol.

    The mechanism of action of amlodipine

    Amlodipine blocks "slow" calcium channels and reduces the transmembrane current of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

    The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in the total peripheral vascular resistance (OPSS).

    The mechanism of antianginal action until the end of nc has been studied, presumably it is associated with two effects:

    - Expansion of peripheral arterioles reduces OPSS (postnagruzku). Due to the absence of reflex tachycardia, the consumption of energy and oxygen by the myocardium decreases.

    - Expansion of large coronary arteries and coronary arterioles improves the delivery of oxygen to both normal and ischemic areas of the myocardium, including coronary artery spasm (Prinzmetal angina or unstable angina).

    In patients with arterial hypertension, amlodipine once a day causes a clinically significant decrease in blood pressure (BP) in the "lying" and "standing" for 24 hours. In connection with the slow development of antihypertensive effect amlodipine does not cause a sharp decrease in blood pressure. In patients with angina, receiving amlodipine 1 time per day increases the total time of exercise, the time before the onset of an attack of angina and to a significant depression of the segment ST, and also reduces the frequency of angina attacks and the need for taking nitroglycerin (short-acting forms).

    There was no negative effect of amlodipine on the concentration of lipids, glucose and uric acid in the blood plasma.

    Mechanism of action of bisoprolol

    Bisoprolol is a selective beta 1-blocker that does not have its own sympathomimetic activity and membrane-stabilizing action and is characterized by only a slight affinity for the beta2-adrenoreceptors of the smooth muscles of the bronchi and vessels, as well as for beta2-adrenoreceptors involved in the regulation of metabolism. therefore bisoprolol practically does not affect the resistance of the respiratory tract and metabolic processes that are mediated through the action of pa-beta2-adrenergic receptors. The selective effect of bisoprolol on beta1-adrenergic receptors persists beyond the therapeutic range. Bisoprolol ns has a pronounced negative inotropic effect. The maximum effect is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol I once a day, its therapeutic effect persists for 24 hours, since its half-life (T1/2) from the blood plasma - 10-12 hours. Typically, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment. Bisoprolol reduces the activity of the sympathoadrenal system by blocking the beta 1-adrenergic receptor of the heart. With a single oral intake in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol it reduces the heart rate (heart rate), reduces the shock volume of the heart and, as a consequence, reduces the ejection fraction and myocardial oxygen demand. With prolonged therapy, the initially increased OPSS decreases. Reduction of renin activity in blood plasma is considered as one of the mechanisms of anti-hypertensive action of beta-blockers.

    Pharmacokinetics:

    Amlodipine

    Suction

    After oral administration amlodipine well absorbed. The maximum concentration (CmOh) in the blood plasma is observed after 6-12 hours. The intake of food does not affect the absorption of amlodipine. Absolute bioavailability is from 64 to 80%.

    Distribution

    The apparent volume of distribution is about 21 l / kg. The equilibrium concentration in the blood plasma (5-15 ng / ml) is achieved 7-8 days after the start of the drug. In studies in vitro binding to plasma proteins is 93-98%. Metabolism and excretion

    Amlodipine is actively metabolized in the liver. About 90% of the dose is converted to inactive derivatives of pyridine. Approximately 10% of the dose taken is excreted in the night in unchanged form. Approximately 60% of inactive metabolites are excreted by the kidneys, 20-25% through the intestine. Reducing the concentration of amlodipine in the blood plasma occurs in two phases. The final T1/2 is about 35-50 hours, which allows take the drug once a day. The total clearance is 7 ml / min / kg (25 l / hour in a patient with a body weight of 60 kg), in elderly patients - 19 l / h.

    In elderly patients and patients with renal insufficiency, there was no significant change in the pharmacokinetics of amlodipine. Due to reduced clearance, patients with hepatic insufficiency should use lower initial doses.

    Bisoprolol

    Suction

    Bisoprolol is almost completely (more than 90%) absorbed in the gastrointestinal tract (GIT). Its bioavailability due to low biotransformation at the "primary passage" through the liver (about 10%) is about 90% after ingestion. Eating does not affect bioavailability. The pharmacokinetics of bisoprolol is linear in the dose range of 5-20 mg. FROMmax in blood plasma is achieved in 2-3 hours.

    Distribution

    Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l / kg. The connection with blood plasma proteins is about 30%.

    Metabolism

    Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine, do not have pharmacological activity. Research in vitro on human liver chips showed that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only an insignificant role.

    Excretion

    Bisoprolol clearance is determined by the balance between excretion by the kidneys in unchanged form (about 50%) and metabolism in the liver (about 50%) with the formation of metabolites, which are also excreted by the kidneys. The total ground clearance is 15 liters per hour.

    T1/2 - 10-12 hours.

    Indications:

    Arterial hypertension (to replace amlodipine and bisoprolol in the same doses when used in monotherapy).

    Contraindications:

    Amlodipine

    - Unstable angina (with the exception of Prinzmetal angina).

    - Hemodynamically unstable heart failure after myocardial infarction.

    - Clinically significant aortic stenosis.

    Bisoprolol

    - Acute heart failure or chronic heart failure in the stage of decompensation, requiring inotropic therapy.

    - Atrioventricular block (AV) II and III degree without a pacemaker.

    - Syndrome of weakness of the sinus node.

    - Sinoatrial blockade.

    - Pronounced bradycardia (heart rate less than 60 beats / min).

    - Severe forms of bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD).

    - Severe disturbances of peripheral arterial blood circulation or Reynaud's syndrome.

    - Pheochromocytoma (without simultaneous use of alpha-blockers).

    - Metabolic acidosis.

    Combination of amlodipine / bisoprolol

    - Hypersensitivity to amlodipine, other derivatives of dihydropyridine, bisoprolol and / or any auxiliary substances.

    - Severe arterial hypotension (systolic blood pressure less than 100 mm Hg).

    - Shock (including cardiogenic).

    - Children under 18 years of age (efficiency and safety ns installed).

    Carefully:

    CHF (including non-ischemic etiology III-IV functional class by classification NYHA), hepatic insufficiency, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in the concentration of glucose in the blood plasma, AV blockade of I degree, angina of Prinzmetal, occlusive diseases of peripheral arteries, psoriasis (including in the anamnesis), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-adrenoblockers), BA and COPD, while desensitizing therapy, general anesthesia, use in elderly patients, arterial hypotension, type 1 diabetes mellitus, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).

    Pregnancy and lactation:

    Application of the drug Niperten® Combi in pregnancy is possible if the benefit to the mother exceeds the risk of side effects in the fetus and the newborn.

    If you need to use the drug Niperten® Combi during lactation breastfeeding should be discontinued.

    Amlodipine

    In experimental studies, embryotoxic and fetotoxic effects of the drug have not been established. However, the use of amlodipine during pregnancy is possible if the potential benefit to the mother exceeds the possible risk to the fetus. There are no data on excretion of amlodipine with breast milk.However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. If it is necessary to treat amlodipine during lactation, it is recommended to stop breastfeeding.

    Bisoprolol

    The use of bisoprolol in pregnancy is possible if the potential benefit to the mother exceeds the possible risk to the fetus.

    Beta-adrenoblockers reduce the blood supply of the placenta and can affect the development of the fetus. It is necessary to monitor blood flow in the placenta and uterus, as well as the growth and development of the fetus. In case of appearance of undesirable phenomena in relation to pregnancy and / or fetus, alternative therapy should be prescribed. It is necessary to carefully examine a newborn, in the first 3 days of life symptoms of hypoglycemia and bradycardia may appear.

    There are no data on excretion of bisoprolol with breast milk. If it is necessary to treat bisoprolol during lactation, it is recommended to stop breastfeeding.

    Dosing and Administration:

    Inside, preferably in the morning, regardless of time of meal. Do not chew. The recommended daily dose is 1 tablet of a certain dosage.

    Selection and titration of the dose is carried out by the attending physician individually for each patient when used in monotherapy of the drugs that make up the drug

    Niperten® Combi.

    Duration of therapy

    Niperten therapy® The combi is long.

    Impaired liver function

    In patients with impaired liver function, excretion of amlodipine can be slowed down. The special dosing regimen in such patients is not defined, but the drug should be used with caution in this case. For patients with severe liver dysfunction, the maximum daily dose of bisoprolol is 10 mg. Impaired renal function

    In patients with impaired renal function of mild or moderate severity, dose adjustment, as a rule, is not required. Amlodipine not excreted by hemodialysis. In patients on hemodialysis, amlodipine should be used with extreme caution.

    In patients with severe impairment of the function of the nights (creatinine clearance (CK) less than 20 ml / min), the maximum daily dose of bisoprolol is 10 mg.

    Elderly patients

    In elderly patients, Niperten is recommended® Combi in usual doses.Care should be taken when increasing the dose.

    Children

    The drug Niperten® Combi is not recommended for use in children under the age of 18, there is no safety or efficacy data.

    When the drug is withdrawn, a gradual dose reduction is recommended, a sharp cessation of therapy can lead to a temporary deterioration in the clinical state, especially in patients with ischemic heart disease.

    Side effects:

    The undesirable side effects observed with the use of the active substances separately are presented in accordance with the World Health Organization (WHO) classification of the incidence of adverse events: very often> 1/10; often> 1/100 - <1/10; infrequently> 1/1000 - <1/100; rarely> I / 10000 - <1/1000; very rarely <1/10000; frequency is unknown (can not be estimated from available data).

    Amlodipine

    Violations from the blood and lymphatic system: Very rarely: leukopenia, thrombocytopenia.

    Immune system disorders: very rarely: allergic reactions.

    Disorders from the metabolism and nutrition: very rarely: hyperglycemia.

    Disorders of the psyche: infrequently: insomnia, mood lability (including anxiety), depression; rarely: confusion.

    Impaired nervous system: often: headache, dizziness, drowsiness (especially at the beginning of treatment); infrequently: fainting, hypoesthesia, paresthesia, dysgeusia, tremor; very rarely: muscle hypertension, peripheral neuropathy.

    Disorders from the side of the organ of vision: infrequently: impaired vision (including diplopia).

    Hearing disorders and labyrinthine disturbances: infrequently: noise in the ears.

    Disorders from the digestive system: often: nausea, abdominal pain; infrequently: vomiting, changing the bowel movement (including constipation or diarrhea), indigestion, dryness of the oral mucosa; Very rarely: gastritis, gingival hyperplasia, pancreatitis.

    Disorders from the liver and bile ducts: very rarely: hepatitis *, jaundice *.

    Heart Disease: often: palpitations; very rarely: myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation).

    Vascular disorders: often: sensation of "tides" of blood to the skin of the face; infrequent: marked decrease in blood pressure; very rarely: vasculitis.

    Disturbances from the respiratory system, chest and mediastinal organs: infrequently: dyspnea, rhinitis; very rarely: cough.

    Disorders from the kidneys and urinary tract: infrequently: pollakiuria, painful urge to urinate, nocturia.

    Violations of the genitals and breast: infrequently: impotence, gynecomastia.

    General disorders and disorders at the site of administration: often: peripheral edema, increased fatigue; infrequently: chest pain, asthenia, pain of unspecified localization, general malaise.

    Disturbances from the musculoskeletal and connective tissue: often: swelling of the ankles; infrequently: arthralgia, myalgia, muscle cramps, back pain.

    Disturbances from the skin and subcutaneous tissues: infrequently: alopecia, purpura, discoloration, increased sweating, itchy skin, skin rash, exanthema; rarely: angioedema, multiforme exudative erythema, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity.

    Laboratory and instrumental data: infrequently: weight gain, weight loss; very rarely: an increase in the activity of "liver" enzymes * in the blood plasma.

    * In most cases, it is associated with cholestasis

    Bisoprolol

    Disorders from the metabolism and nutrition: rarely: an increase in the concentration of triglycerides in the blood plasma.

    Disorders of the psyche: infrequently: depression; rarely: hallucinations, nightmares.

    Impaired nervous system: often: headache **, dizziness **; infrequently: insomnia; rarely: faint.

    Disorders from the side of the organ of vision: rarely: reduced tearing (should be considered when wearing contact lenses); very rarely: conjunctivitis.

    Hearing disorders and labyrinthine disturbances: rarely: hearing loss.

    Heart Disease: infrequently: violation AV conduction, bradycardia, aggravation of CHF symptoms.

    Vascular disorders: often: a feeling of cold or numbness in the limbs, a pronounced decrease in blood pressure; infrequently: orthostatic hypotension.

    Disturbances from the respiratory system, chest and mediastinal organs: infrequently: bronchoconstriction in patients with asthma or with airway obstruction in anamnesis; rarely: allergic rhinitis.

    Disorders from the gastrointestinal tract: often: nausea, vomiting, diarrhea, constipation.

    Disorders from the liver and bile ducts: rarely: hepatitis.

    Disturbances from the skin and subcutaneous tissues: rarely: hypersensitivity reactions, such as itchy skin, skin rash, hyperemia of the skin; very rarely: alopecia. Beta-adrenoblockers can exacerbate psoriasis or cause a psoriasis-like rash.

    Disturbances from the musculoskeletal and connective tissue: infrequently: muscle weakness, muscle cramps.

    Violations of the genitals and breast: rarely: impotence.

    General disorders and disorders at the site of administration: often: increased fatigue **; infrequently: exhaustion **.

    Laboratory and instrumental data: rarely: increased activity of "hepatic" transaminases (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)) in the blood plasma.

    ** Especially often these symptoms appear at the beginning of treatment. Usually they are light in nature and pass, usually 1-2 weeks after the start of treatment.

    Overdose:

    Amlodipine

    Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including with the development of shock and death).

    Treatment: gastric lavage, the use of activated charcoal, maintenance of cardiovascular function, monitoring of heart and lung function, elevated position of the lower extremities, control of the volume of circulating blood and diuresis. Intensive symptomatic therapy. To restore vascular tone, vasoconstrictive drugs are used (in the absence of contraindications to their use), with the goal of eliminating calcium channel blockade - intravenous calcium gluconate. Hemodialysis ns is effective.

    Bisoprolol

    Symptoms: AV blockade, pronounced bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

    The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with CHF have high sensitivity.

    Treatment: In case of an overdose, it is necessary to stop taking bisoprolol and start supporting symptomatic therapy.

    With severe bradycardia: intravenous atropine. They sang the effect insufficient, with caution it is possible to introduce a drug,possessing a positive chronotropic action. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

    With a marked decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor agents. Intravenous administration of glucagon may also be indicated. When AV blockade: the patient should be under constant observation and receive treatment with beta-adrenomimetics, such as epinephrine (adrenalin). If necessary - staging an artificial pacemaker.

    With an exacerbation of the course of CHF: intravenous injection of diuretics, drugs, possessing a positive inotropic effect, as well as vasodilators.

    When bronhospazme: the use of bronchodilators, including beta2-adrenomimetics and / or aminophylline.

    In hypoglycemia: intravenous administration of a solution of dextrose (glucose).

    Bisoprolol is not practically excreted by hemodialysis.

    Interaction:

    Amlodipine

    Simultaneous use of amlodipine with thiazide diuretics, beta-adrenoblockers, prolonged action nitrates, nitroglycerin (short-acting forms), nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics and hypoglycemic agents for oral administration is considered safe.

    Simultaneous use with strong or moderate isoenzyme inhibitors CYP3A4 (protease inhibitors, verapamil or diltiazem, antifungal drugs from the azole group, macrolides such as erythromycin or clarithromycin) can lead to a significant increase in the systemic exposure of amlodipine.

    Use with caution amlodipine simultaneously with inhibitors of isoenzyme CYP3A4, although no adverse events associated with the above interaction were reported.

    Simultaneous use of amlodipine with isoenzyme inducers CYP3A4 (including, rifampicin, St. John's wort perforated) can lead to a decrease in the concentration of amlodipine in the blood plasma. Caution should be exercised while using amlodipine with isoenzyme inducers CYP3A4. Simultaneous multiple application of amlodipine in a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in the exposure of simvastatin by 77%. In such cases, the dosage of simvastatin should be limited to 20 mg per day.

    Grapefruit juice, cimetidine, aluminum hydroxide / magnesium hydroxide (as part of antacids) and sildenafil do not affect the pharmacokinetics of amlodipine.

    Amlodipine may enhance the antihypertensive effect of other antihypertensive drugs. Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (beverages containing alcohol), warfarin or cyclosporine.

    Amlodipine does not affect laboratory performance.

    Bisoprolol

    Not recommended combinations of drugs

    BCCI (verapamil and to a lesser extent diltiazem) with simultaneous application with bisoprolol may lead to a decrease in the contractility of the myocardium, a pronounced decrease in blood pressure and impairment AV conductivity. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to the development of severe arterial hypotension and AV blockade.

    Hypotensive drugs of central action (clonidine, methyldopa, moxonidine, rilmenidine) with simultaneous application with bisoprolol can lead to a decrease in heart rate, a reduction in cardiac output and vasodilation due to a decrease in the central sympathetic tone.Abrupt withdrawal of these drugs, especially before the termination of beta-blockers, may increase the risk of developing "ricochet" arterial hypertension.

    Combinations of medicines requiring caution

    BCCC, dihydropyridine derivatives (for example, nifedipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out.

    Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium. Antiarrhythmic drugs of the III class (for example, amiodarone) with simultaneous application with bisoprolol may increase the disruption AV conductivity. Parasympatomimeticheskie means with simultaneous application with bisoprolol can strengthen the violation AV conductivity and increase the risk of developing a bradycardia. Simultaneous application with beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

    Simultaneous use with insulin and hypoglycemic agents for oral administration may increase their hypoglycemic effects. Symptoms of hypoglycemia, in particular tachycardia, can be masked. Such interactions are more likely when using nonselective beta-blockers.

    Means for general anesthesia can weaken reflex tachycardia and increase the risk of developing arterial hypotension (see section "Special instructions"). Cardiac glycosides with simultaneous application with bisoprolol may lead to an increase in the timing of the impulse and to the development of a bradycardia.

    NSAIDs can reduce the antihypertensive effect of bisoprolol.

    The simultaneous use of bisoprolol with beta-adrenomimetics (eg, isoprenaline, dobutamine) can lead to a decrease in the effect of each drug. The simultaneous use of bisoprolol with adrenomimetics that affect beta and alpha-adrenergic receptors (eg, porepinephrine, epinephrine) can enhance the vasoconstrictive effects of these agents that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure.Such interactions are more likely when using nonselective beta-blockers. Hypotensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can enhance the antihypertensive effect of bisoprolol.

    Combinations of medicines that should be considered

    Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.

    Inhibitors of monoamine oxidase (MAO) (with the exception of MAO B inhibitors) can enhance the antihypertensive effect of beta-blockers. Simultaneous application can also lead to the development of hypertensive crisis.

    Rifampicin causes a slight shortening of T1/2 bisoprolol. As a rule, dose adjustment is not required.

    Derivatives of ergotamine with simultaneous application with bisoprolol increase the risk of peripheral circulatory disturbance.

    Special instructions:

    Amlodipine

    In patients with CHF (III and IV functional class by classification NYHA) treatment is carried out with caution in connection with the possibility of developing pulmonary edema, which is not associated with worsening of the symptoms of CHF.

    Bisoprolol

    Discontinuation of bisoprolol therapy should not be sudden, especially in patients with IVS, except for the presence of clear indications for withdrawal of the drug. Sudden abolition of bisoprolol may lead to a temporary worsening of the cardiovascular pathology. Bisoprolol Use with extreme caution in patients with hypertension or angina in combination with CHF. Like other beta-blockers, bisoprolol can increase sensitivity to allergens and intensify anaphylactic reactions, so care must be taken while performing desensitizing therapy. The use of epinephrine (adrenaline) does not always produce the expected therapeutic effect.

    The use of bisoprolol can "mask" the symptoms of hyperthyroidism.

    In patients with pheochromocytoma bisoprolol can be used only against the background of the use of alpha-blockers.

    Before the general anesthesia, the anesthetist should be informed that the patient is taking beta-blockers. If it is necessary to stop the therapy with beta-blockers before surgery, discontinuation of the drug should be carried out gradually and be completed 48 hours before the general anesthesia.

    Patients with asthma or COPD show simultaneous use of bronchodilating agents. In patients with asthma, an increase in respiratory tract resistance is possible, which requires an increase in the dose of beta2-adrenomimetics.

    Effect on the ability to drive transp. cf. and fur:

    During therapy with Niperten® Combi must be careful when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Tablets, 5 mg + 5 mg, 5 mg + 10 mg, 10 mg + 5 mg, 10 mg + 10 mg.

    Packaging:

    For 10 or 7 tablets in a contour acheikova packing of the combined material OPA / Al / PVC and aluminum foil.

    3, 6, 9 contour cell packs of 10 tablets or 4, 8, 12 contour cell packs of 7 tablets together with the instructions for use are placed in a pack of cardboard.
    Storage conditions:

    At a temperature of no higher than 25 ° C, in the original packaging.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002872
    Date of registration:24.02.2015
    The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspKRKA KRKA Slovenia
    Information update date: & nbsp24.02.2015
    Illustrated instructions
      Instructions
      Up