KORDINORM

Active material: Bisoprolol
When ATH: C07AB07
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): I10, i20
When CSF: 01.01.01.02
Manufacturer: ACTAVIS GROUP hf. (Iceland)

DOSAGE FORM, STRUCTURE AND PACKAGING

Pills, Film-coated white, round, convex, with Valium on one side, risks and side engraving “B 5” – another.

Excipients: microcrystalline cellulose, mannitol, sodium croscarmellose, magnesium stearate, gipromelloza, Titanium dioxide, macrogol 6000.

10 PC. – blisters (3) – packs cardboard.

Pills, Film-coated white, round, convex, with Valium on one side, risks and side engraving “B 10” – another.

Excipients: microcrystalline cellulose, mannitol, sodium croscarmellose, magnesium stearate, gipromelloza, Titanium dioxide, macrogol 6000.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Selective beta₁-blocker without intrinsic sympathomimetic activity and membrane stabilizing properties. Blocking in low doses β₁-adrenergic receptors of the heart, bisoprolol reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current. It has a negative chrono, dromo-, ʙatmo- and inotropic effect, oppressing conductivity and anxiety, slows AV-conduction, reducing myocardial oxygen demand. It reduces heart rate at rest and during exercise. It reduces plasma renin activity. It has hypotensive, antiarrhythmic and antianginal.

By increasing the dose of bisoprolol has beta₂-adrenoceptor blocking action.

At the beginning of the drug (first 24 no) as a result of reciprocal increase in the activity of α-adrenergic stimulation and removal of β₂-adrenoceptor PR increases slightly. Through 1-3 d PR returns to baseline, and long-term use – decreases.

The hypotensive effect of bisoprolol caused a decrease in the IOC, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (It is of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure and the influence of the central nervous system. When hypertension effect after 2-5 days, stable operation – through 1-2 Months.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. At the expense of increasing end-diastolic pressure in the left ventricle and increased tensile ventricular muscle fibers can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, hypertension), as well as the decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing of AV- (mainly in the antegrade and, less, in retrograde direction through the AV-node) and on additional routes.

In contrast, non-selective beta-blockers when given in therapeutic doses, the average bisoprolol has a less pronounced effect on the organs, содержащие b₂-adrenoreceptory (pancreas, skeletal muscle, smooth muscle peripheral arteries, bronchial and uterine) and carbohydrate metabolism, causes sodium retention. Intensity of atherogenic action is different from that of propranolol.

When used in large doses it has a blocking effect on both β-adrenoceptor subtype.

Pharmacokinetics

Absorption

After oral administration is absorbed from the gastrointestinal tract 80-90% bisoprolol. Receiving simultaneously with food did not affect the absorption. C_max plasma levels achieved after 1-3 no.

Distribution

The binding to plasma proteins – about 35%. The permeability of the BBB and placental barrier, and the degree of penetration into breast milk low.

Metabolism and excretion

50% the dose is metabolized in the liver with the formation of active metabolites. 50% – excreted unchanged.

T_1/2 sostavlyaet9-12 h. About 98% substances excreted by the kidneys, less 2% – the bile.

Testimony

- Arterial hypertension;

- CHD (prevention of angina attacks).

Dosage regimen

A single dose of 2.5-5 mg. Typically, the initial dose is 5 mg 1 time / day. If necessary, increase the dose to 10 mg 1 time / day. The maximum daily dose for adults – 20 mg.

The tablets should be taken orally, morning, fasting, without chewing.

Treatment patients with impaired hepatic function or kidney mild or moderate typically does not require dose adjustments. In patients with severe renal impairment (CC<20 ml / min) or liver the maximum daily dose – 10 mg.

In patients Seniors dose adjustment is required.

Side effect

CNS: fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesias in extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor.

From the senses: blurred vision, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis.

Cardio-vascular system: sinusovaya bradycardia, heartbeat, conduction disturbances infarction, violation of AV-conduction (until the development of a full cross-blockade and heart failure), Arrhythmia, weakening of myocardial contractility, development (aggravation) chronic heart failure (swelling of the ankles, stop; breathlessness), decrease in blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), chest pain.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, abnormal liver function (dark urine, yellow skin or sclera, cholestasis), changes in liver enzymes (ALT increase, ACT), bilirubin, triglycerides, changes in taste.

The respiratory system: nasal congestion, difficulty breathing when administered at high doses (due to the loss of selectivity) and / or in predisposed patients – laringo- and bronchospasm.

On the part of the endocrine system: giperglikemiâ (in patients with non-insulin dependent diabetes mellitus), gipoglikemiâ (patients, receiving insulin), hypothyroid state.

Dermatological reactions: increased sweating, dermahemia, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms, alopecia.

From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

On the part of the musculoskeletal system: muscular weakness, cramps in the calf muscles, backache, arthralgia.

On the part of the reproductive system: weakening of libido and reduced potency.

Allergic reactions: itching, rash, hives.

Other: withdrawal (increasing angina attacks, increased blood pressure).

Effect on the fetus: intrauterine growth, gipoglikemiâ, bradycardia.

Contraindications

- Shock (incl. cardiogenic);

- Collapse;

- Pulmonary edema;

- Acute heart failure;

- Chronic heart failure decompensation;

— AV-blockade II and III degrees (without pacemaker);

- Sinoatrialynaya blockade;

- SSS;

- Vыrazhennaya bradycardia (Heart Rate<50 u. / min);

- Prinzmetal angina;

- Kardiomegalija (without signs of heart failure);

- Hypotension (systolic blood pressure<100 mm Hg. Art., especially in myocardial infarction);

- Asthma and COPD history;

- Simultaneous MAO inhibitors (except MAO type B);

- Late stages of peripheral circulatory disorders;

- Raynaud's disease;

- Pheochromocytoma (without the simultaneous use of alpha-blockers);

- Metabolic acidosis;

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to other beta-blockers;

- Hypersensitivity to the drug.

FROM caution should be prescribed the drug for liver failure, chronic renal failure, myasthenia, thyrotoxicosis, diabetes, AV-blockade I degree, depression (in t. no. history), psoriaze, old age.

Pregnancy and lactation

Use in pregnancy and lactation is possible in the case, if the benefit to the mother outweighs the risk of side effects in the fetus and child (such as intrauterine growth retardation, gipoglikemiâ, bradycardia).

Cautions

The patient should know, that should not be abruptly discontinue or change the recommended dose without first consulting your doctor.

Control of patients, host Kordinorm, should include monitoring of heart rate and blood pressure (at the beginning of treatment – daily, then 1 once every 3-4 Months), conduct an electrocardiogram, determination of blood glucose in patients with diabetes (1 once every 4-5 Months). In elderly patients, it is recommended to monitor renal function (1 once every 4-5 Months).

It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 u. / min.

Before treatment, patients with a history of bronchopulmonary anamnesis recommended study of respiratory function.

Approximately 20% patients with angina Beta-blockers are ineffective. The main reasons for this is a severe coronary atherosclerosis with a low threshold of ischemia (HR less 100 u. / min) and increased end-diastolic volume of the left ventricle, violates the subendocardial blood flow.

If tobacco use effectiveness of beta-blockers lower.

Sick, use contact lenses, We should take into account, that against the background of treatment may decrease the production of tear fluid.

When using Kordinorma in patients with pheochromocytoma has the paradoxical risk of hypertension (if not previously achieved effective alpha adrenoblockade).

In patients with thyrotoxicosis Kordinorm may mask certain clinical signs of hyperthyroidism (eg, taxikardiju). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, because the symptoms can increase.

In diabetes the effect of bisoprolol may mask tachycardia, induced hypoglycemia. In contrast, non-selective beta-blockers Kordinorm little increase insulin-induced hypoglycemia and delay recovery of blood glucose to normal levels.

In simultaneous treatment with clonidine its reception can be terminated only a few days after the cancellation Kordinorma.

Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine (adrenaline) with aggravated allergic history. In the case of the need for a planned surgical treatment is carried out for the abolition of the drug 48 h before general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate I / atropine (1-2 mg).

Drugs, reducing stocks catecholamines (eg, reserpine), may enhance the action of beta-blockers, so patients, taking such drug combinations, should be under constant medical supervision to identify arterial hypotension or bradycardia.

Patients with diseases bronhospasticheskimi cardioselective blockers can be administered in case of intolerance and / or ineffectiveness of other antihypertensive drugs, but it should be strictly control the dose. Overdose danger of developing bronchospasm. In the case of elderly patients increasing bradycardia (less 50 u. / min), hypotension (systolic BP below 100 mmHg.), AV-blockade, bronchospasm, ventricular arrhythmias, Serious liver and kidneys need to reduce the dose or stop treatment.

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

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. The abolition of a gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 day).

The drug should be removed before the test content in the blood and urine catecholamines, normetanefrina, vanillylmandelic acid, antinuclear antibodies.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: arrhythmia, ventricular premature beats, vыrazhennaya bradycardia, AV блокада, decrease in blood pressure, congestive heart failure, cyanosis of nails of fingers or hands, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage and appointment of adsorbing drugs; simptomaticheskaya therapy: at razvivšejsâ AV-blockade – in / introduction 1-2 mg atropine, epinephrine (adrenaline) or setting a temporary pacemaker; when ventricular arrhythmia – lidocaine (drugs IA class shall not apply); with a decrease in blood pressure – the patient must be in the Trendelenburg position; if there are no signs of pulmonary edema, – should be in / enter plazmozameschayuschie solutions, the ineffectiveness – administration of epinephrine (adrenaline), dopamine, doʙutamina (to maintain chronotropic and inotropic effects and eliminate significant decrease in blood pressure); Heart failure – introduction of cardiac glycosides, diuretics, glucagon; with cramps – in / diazepam; with bronchospasm – inhaled beta₂-adrenostimulyatorov.

Drug Interactions

Patients, receiving bisoprolol, allergens, used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis.

Iodine radiopaque drugs for i / v administration increase the risk of anaphylactic reactions.

Phenytoin in in / in the introduction and drugs for inhalation general anesthesia (hydrocarbon derivatives) cardiodepressive increase the severity of the action and the probability of reduction of blood pressure.

In a joint application bisoprolol alters the effectiveness of insulin and oral hypoglycemic agents, masking the symptoms of developing hypoglycemia (taxikardiju, increased blood pressure).

With simultaneous use of bisoprolol reduces the clearance of lidocaine and xanthine (except difillina) and increases their concentration in the plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

The hypotensive effect of the drug in the combined use of NSAIDs weaken (due to the delay of sodium ions and the blockade of prostaglandin synthesis by the kidneys), SCS and estrogens (due to the delay of sodium ions).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs when combined with bisoprolol increase the risk of developing or worsening of bradycardia, AV-blockade, heart failure and congestive heart failure.

With simultaneous use of nifedipine can lead to a significant reduction in blood pressure.

Diuretic, klonidin, simpatolitiki, hydralazine, and other antihypertensive drugs, while the application may cause an excessive decrease of blood pressure.

Kordinorm udlinyaet action nedepolyarizuyushtih miorelaksantov and antikoagulyantnыy эffekt coumarin.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and sleeping drugs dampening effect of bisoprolol on the CNS.

Not recommended simultaneous application with MAO inhibitors due to a significant increase in the hypotensive action, a break in treatment between the reception of MAO inhibitors and bisoprolol must not be less than 14 days.

Non-hydrogenated ergot alkaloids when used together increase the risk of peripheral circulatory disorders.

Ergotamine in a joint application increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol plasma.

Rifampicin, while the application shortens T_1/2 bisoprolol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life 2 year.