Metoprolol Organica - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrogenphosphate dihydrate -20 mg or 40 mg sodium carboxymethyl starch (Primogel) - 8.9 mg or 17.8 mg microcrystalline cellulose - 34 mg or 68 mg, povidone K90 (K90 plasdon) - 1.2 mg or 2, 4 mg, magnesium stearate monohydrate 0.9 mg or 1.8 mg.

Description:

Tablets are white or white with a yellowish hue of color, flat-cylindrical shape, with a bevel.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Metoprolol Organica refers to cardioselective blockers of beta-adrenergic receptors,not possessing internal sympathomimetic activity and membrane-stabilizing properties. It has antihypertensive, antianginal and antiarrhythmic action.

Blocking in low doses of beta₁-adrenoceptors of the heart, reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic action (urezhaet heart rate (heart rate), inhibits conduction, excitability and reduces myocardial contractility).

Total peripheral vascular resistance at the beginning of application beta₁-adrenoconvertor (in the first 24 hours after ingestion) - increases (as a result of the reciprocal increase in the activity of alpha-adrenoreceptors and elimination of beta stimulation₂-adrenoreceptors), which after 1-3 days returns to the original, and with a long-term appointment - decreases.

Antihypertensive action is due to a decrease in cardiac output and renin synthesis in the kidneys, inhibition of the activity of the renin-angiotensin-aldosterone system (is of greater importance in patients with initial renin hypersecretion) and the central nervous system,restoration of the sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in blood pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces elevated blood pressure (BP) at rest, with physical stress and stress.

The antihypertensive effect develops rapidly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours, the diastolic blood pressure changes more slowly: a stable decrease is observed after several weeks of regular intake of the drug.

Antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastolic elongation and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance.

Antiarrhythmic effect is caused by elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, arterial hypertension),a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, retrograde directions through the AV node and along additional pathways).

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and hyperthyroidism, the heart rate decreases or even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it exerts a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism. When used in large doses (more than 100 mg / day) has a blocking effect on both subtypes of beta adrenoreceptors.

Pharmacokinetics:

After taking the drug inside almost completely (approximately 95%) is absorbed from the gastrointestinal tract (GIT). The maximum concentration in the blood plasma is achieved after 1.5-2 hours.Bioavailability increases with food intake by 20-40% and increases during course treatment. Binding to plasma proteins -10%. Penetrates through the BBB and placental barrier, excreted in breast milk. Intensively biotransformed in the liver with the formation of metabolites, 2 metabolites Metoprolol Organica have beta-adrenoblocking activity. In the metabolism of Metoprolol Organic is involved the isoenzyme CYP2D6. The plasma half-life is about 3.5 hours. The total plasma clearance (clearance) is approximately 1 L / min. It is excreted mainly by the kidneys (95%), about 3% - unchanged, the rest - in the form of metabolites.

In case of impaired renal function the excretion of metabolites decreases and the excretion of unchanged metoprolol of Organic practically does not change.

With cirrhosis of the liver bioavailability of Metoprolol Organic increases.

In elderly patients There is no significant change in the pharmacokinetics of Metoprolol Organic compared to young patients.

Violation of the kidney function does not require a reduction in the dose of the drug, and for violations of the liver, the dose of the drug should be reduced.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);

- functional disorders of cardiac activity, accompanied by tachycardia;

- Ischemic heart disease: myocardial infarction (secondary prevention - complex therapy), prevention of angina attacks;

- heart rhythm disturbances (supraventricular tachycardia, ventricular extrasystole);

- hyperthyroidism (complex therapy);

- prevention of migraine attacks.

Contraindications:

- Hypersensitivity to Metoprolol Organica or other components of the drug, other beta-blockers; cardiogenic shock;

- atrioventricular blockade of II-III degree (without artificial pacemaker);

- Sinoatrial blockade;

- syndrome of weakness of the sinus node;

- severe bradycardia (heart rate less than 50 beats per minute);

- chronic heart failure in the stage of decompensation;

- Prinzmetal angina;

- Acute myocardial infarction (heart rate less than 45 beats / min, PQ interval more than 0.25 sec, systolic blood pressure less than 100 mmHg);

- lactation period;

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels (BCCC) such as verapamil, diltiazem;

- Age 18 years (effectiveness and safety not established);

- pheochromocytoma (without simultaneous use of alpha-blockers);

severe violations of peripheral circulation;

- severe forms of bronchial asthma and chronic obstructive pulmonary disease.

Carefully:Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, enphysema, chronic obstructive bronchitis, violations of liver function, kidneys (creatinine clearance less than 40 ml / min), myasthenia gravis, pheochromocytoma (with simultaneous use of alpha-blockers) thyrotoxicosis, depression (including history), psoriasis, peripheral circulatory disorders ("intermittent" lameness, Raynaud's syndrome), pregnancy; children's age (safety is not defined), old age, weighed allergic anamnesis, atrioventricular blockade of the degree.

Pregnancy and lactation:

During pregnancy prescribe taking into account the careful weighing of the benefit / risk ratio, especially in the early stages of pregnancy (due to the possible development of a newborn bradycardia, hypotension, hypoglycemia and respiratory paralysis). Treatment should be interrupted for 48-72 hours before childbirth.In cases where this is not possible, it is necessary to ensure strict observation of the newborn within 48-72 hours after delivery.

If taking Metoprolol Organic is necessary during lactation, breast-feeding it is necessary to stop.

Dosing and Administration:

Tablets are taken orally at the same time as eating or immediately after eating, the tablets can be divided in half, but not chewed and washed down with liquid.

Arterial hypertension

The initial daily dose is 50-100 mg in 1-2 doses (morning and evening). With insufficient therapeutic effect, the daily dose can be gradually increased to 100-200 mg and / or additionally prescribed other antihypertensive agents. The maximum daily dose is 200 mg.

Secondary prevention of myocardial infarction

200 mg per day in two divided doses (morning and evening).

Angina pectoris, arrhythmias, prevention of migraine attacks

100-200 mg per day in two divided doses (morning and evening).

Functional disorders of cardiac activity, accompanied by tachycardia

100 mg per day in two divided doses (morning and evening).

With hyperthyroidism

150-200 mg per day in 3-4 divided doses.

In elderly patients, with violations of kidney function (creatinine clearance (CC) is less than 40 ml / min), and if the need for hemodialysis dose do not change.

When expressed violations of liver function the dose of the drug should be reduced depending on the clinical condition.

Side effects:

The incidence of adverse reactions was classified as follows: often (> 1% and <10%), infrequently (> 0.1% and <1%), rarely (> 0.01% and <0.1%), very rarely <0.01%).

From the nervous system: often: weakness, dizziness and headache; infrequent: decreased concentration, drowsiness / insomnia, nightmares, depression, muscle cramps, paresthesia in the extremities (in patients with "intermittent" lameness and Raynaud's syndrome); rarely: nervousness, anxiety, tremors, convulsions, depression, decreased attention; very rarely: lethargy, fatigue, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia gravis.

From the sense organs: rarely: decreased vision, xerophthalmia, reduced lacrimal fluid secretion, dry and sore eyes, conjunctivitis, tinnitus, hearing loss.

From the side of the cardiovascular system: often: sinus bradycardia, palpitation, lowering of blood pressure (BP), orthostatic hypotension (dizziness,sometimes loss of consciousness), coldness of the lower extremities; infrequently: heart failure, AV-blockade, edematous syndrome, chest pain; rarely: decreased myocardial contractility, arrhythmia, manifestation of angiospasm (increased peripheral circulatory disturbance), impaired myocardial conductivity, cardialgia; very rarely: aggravation of pre-existing AV conduction disorders.

From the digestive system: often: nausea, abdominal pain, constipation, or diarrhea; infrequently: vomiting; rarely: dryness of the oral mucosa, in some cases - a violation of liver function (dark urine, icteric sclera or skin, cholestasis), a violation of taste.

From the skin: infrequent: rash, dystrophic skin changes; rarely: reversible alopecia; very rarely: photosensitizer, exacerbation of psoriasis, itching, erythema, urticaria, hyperhidrosis.

From the respiratory system: often: dyspnea; infrequently: bronchospasm; rarely: vasomotor rhinitis, dyspnoea.

From the endocrine system: rarely: hyperglycemia (in patients with type 2 diabetes), hypoglycemia (type 1 diabetes mellitus), hypothyroidism.

Allergic reactions: very rarely: urticaria, itching, rash.

Laboratory indicators: rarely: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of "hepatic" enzymes; very rarely: hyperbilirubinemia.

Influence on the fetus: very rarely: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: infrequently: pain in the back or joints, increase or decrease in body weight, decreased libido and / or potency, with a sharp cessation of treatment - withdrawal syndrome (increased angina attacks, increased blood pressure), rhinitis, arthritis, Peyronie's disease.

Overdose:

Symptoms: severe sinus bradycardia, dizziness, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), marked decrease in blood pressure, fainting, arrhythmia, ventricular extrasystole, acute heart failure, cardiogenic shock, cardiac arrest, bronchospasm, unconsciousness, coma, nausea, vomiting, cyanosis, hypoglycemia, convulsions. The first signs of an overdose appear after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage and administration of adsorptive drugs (LS),symptomatic therapy: with a pronounced decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive decrease in blood pressure, bradycardia and heart failure - intravenous injection with an interval of 2-5 min beta-adrenostimulyatorov - to achieve the desired effect, or intravenous injection of 0.5-2 mg atropine sulfate. In the absence of a positive effect - dopamine, dobutamine or norepinephrine. As a follow-up, a transvenous intracardiac electrostimulator is possible. When bronhospazme enter intravenously beta-adrenomimetiki. With convulsions - a slow, intravenous injection of diazepam. Hemodialysis is ineffective.

Interaction:

With simultaneous application:

- antiarrhythmic drugs (quinine-like drugs and amiodarone) it is possible to enhance inotropic and dromotropic effects;

- calcium channel blockers (verapamil, diltiazem, nifedipine) or other antiarrhythmics, there is a decrease in the minute and stroke volume of the heart, the number of heartbeats (HR), and with intravenous administration of verapamil there is a threat of cardiac arrest;

- barbiturates metabolism Metoprolol Organica is accelerated, which leads to a decrease in its effectiveness;

- inductors or inhibitors of microsomal enzymes, it is possible to change the concentration of Metoprolol Organic in plasma - decrease with rifampicin, increase in the intake of cimetidine, ethanol, hydralazine, serotonin reuptake inhibitors (paroxetine, fluoxetine, sertraline), oral contraceptives;

- indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibitors of cyclooxygenase may reduce antihypertensive effects;

- calcium channel blockers, cardiac glycosides, reserpine, nitrates, increases the risk of arterial hypotension, bradycardia, AV blockade, negative inotropic effect;

- Insulin and oral antidiabetics increase the risk of developing hypoglycemia;

- narcotic drugs, inhalational anesthetics and some other drugs affecting the central nervous system (CNS), in particular hypnotics (bromazepam, lorazepam), tranquilizers (chlordiazepoxide, trimethocin, tophysopam), tri- and tetracyclic antidepressants, mutual potentiation of the cardiodepressive effect;

- allergens used for immunotherapy, or allergen extracts for skin tests increases the risk of developing severe systemic reactions and anaphylaxis;

- iodine-containing radiocontrast drugs (LS) for intravenous administration increase the risk of anaphylactic reactions;

- norepinephrine, epinephrine and other sympathomimetics increases the risk of developing arterial hypertension;

- Phenylpropanolamine in high doses - a paradoxical increase in blood pressure (right up to the hypertensive crisis);

- clonidine - the risk of a pronounced increase in blood pressure with a sharp abolition of clonidine on the background of simultaneous administration of Metoprolol Organic, therefore, in the event of the withdrawal of clonidine, the gradual discontinuation of Metoprolol Organic should be started several days before its cancellation;

- sympathomimetic agents, ganglion blockers, other blockers β-adrenoreceptors (eg eye drops), MAO inhibitors type B, careful monitoring of the patient's condition is necessary;

- Diazepamum may decrease clearance and increase AUC of diazepam,which can lead to an increase in its effects and a decrease in the rate of psychomotor reactions;

- Lidocaine - a disruption of lidocaine withdrawal;

- fluoxetine leads to inhibition of metabolism of Metoprolol Organica and its cumulation, which can enhance cardiodepressive action and cause bradycardia, the probability of drug interaction persists even a few days after the abolition of fluoxetine. A case of lethargy development is described;

- ciprofloxacin reduced clearance of Metoprolol Organica from the body;

- ergotamine may increase peripheral circulatory disorders;

- estrogen decreases the antihypertensive effect of Metoprolol Organica;

- mibefradil in patients with a low activity of the isoenzyme CYP2D6, an increase in the concentration of metoprolol in the blood plasma and an increased risk of toxic effects.

Special instructions:

Control of patients taking beta-blockers includes monitoring of heart rate and blood pressure (at the beginning of administration - every day, then once every 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 every 4-5 months). You should teach the patient how to calculate heart rate and instruct you about the need for medical consultation at a heart rate of less than 50 / min.It is possible to increase the severity of allergic reactions (against the background of a burdensome allergic anamnesis) and the absence of the effect of the administration of usual doses of epinephrine.

In elderly patients, it is recommended that the kidney function is monitored (once every 4-5 months).

It can intensify the symptoms of peripheral arterial circulation.

With angina pectoris, the selected dose of the drug should provide a heart rate at rest within 55-60 beats / min, with a load - no more than 110 beats / min.

In smokers, the effectiveness of beta-blockers is lower.

Metoprolol Organica may mask certain clinical manifestations of thyrotoxicosis (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to non-selective beta-blockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood to a normal value.

If it is necessary to use in patients with concomitant bronchial asthma, it is necessary to additionally use beta₂-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If surgery is necessary, an anesthesiologist should be warned about taking Metoprolol Organic (choice of drugs for general anesthesia with minimal negative inotropic effect), drug cancellation is not recommended.

If there is an increasing bradycardia (less than 50 / min), arterial hypotension (systolic blood pressure below 100 mmHg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney function, it is necessary to reduce the dose or stop treatment.

It is recommended to stop therapy with skin rashes and the development of depression caused by the use of beta-blockers.

Cancellation of the drug is carried out gradually, reducing the dose for 10 days. With a sharp cessation of treatment, there may be a "cancellation" syndrome (increased angina attacks, increased blood pressure). Special attention should be paid to stenocardia when the drug is withdrawn.

Patients using contact lenses should take into account that against the background of treatment with beta-adrenoblockers, tear production can be reduced.

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

During the period of treatment, care must be taken when driving vehicles and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, 25 mg and 50 mg.

Packaging:

For 2, 3, 5 or 6 contour packs of 10 tablets together with instructions for medical use in a cardboard bundle.

For 20, 30, 50 or 60 tablets in a can of light-protective glass or a polymer, together with instructions for medical use in a cardboard bundle.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-000754

Date of registration:29.09.2011

Expiration Date:29.09.2016

The owner of the registration certificate:ORGANICS, JSC ORGANICS, JSC Russia

Manufacturer: & nbsp

ORGANICS, JSC Russia

Information update date: & nbsp24.07.2016

Illustrated instructions

Instructions

Metoprolol Organica (Metoprolol Organica)