Corvitol 50 - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 110.5 mg, povidone (K value = 30) 3.5 mg, croscarmellose sodium 8.0 mg, magnesium stearate 2.0 mg, talc 2.5 mg, silicon dioxide colloidal anhydrous 1 , 0 mg.

Description:

White, round, flat cylindrical tablets with a facet and a risk on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Metoprolol is a weakly lipophilic β-adrenoblocker with relative selectivity to β₁adrenoreceptors ("cardioselectivity"). It has a weakly expressed membrane-stabilizing effect and does not possess internal sympathomimetic activity.

Metoprolol reduces the heart rate (heart rate), myocardial contractility, atrioventricular conduction and renin activity of blood plasma. The severity of these effects depends on the tone of sympathetic innervation.

It has antihypertensive, anti-anginal and antiarrhythmic effects.

Blocking in low doses (less than 100 mg / day) β₁-adrenoceptors of the heart, reduces 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 effect (reduces heart rate, inhibits conduction and excitability, reduces myocardial contractility ).

The total peripheral resistance at the beginning of the use of β1-blockers (in the first 24 hours after ingestion) increases (as a result of the reciprocal increase in α-adrenergic receptor activity and elimination of β stimulation₂-adrenoreceptors), which after 1-3 days returns to the original, and with a long-term appointment - decreases.

Antihypertensive action due to a decrease in cardiac output and synthesis of a renin inhibition of the renin-angiotensin-aldosterone system (of great importance in patients with initial hypersecretion renin) and central nervous system, reduction of baroreceptor sensitivity of the aortic arch (not going to increase their activity in response to a decrease in blood pressure) and in the end, 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 begins to decrease after 15 minutes, the maximum - after 2 hours) and lasts for 6 hours and diastolic blood pressure changes slower: a steady decline in diastolic blood pressure was observed after several weeks of continuous administration.

Antianginal action determined by the reduction of myocardial oxygen demand by decreasing the heart rate (diastole elongation and improving myocardial perfusion) and contractility and decreased sensitivity to the effects of myocardial sympathetic innervation.Reduces the number and severity of angina attacks and increases the tolerance of exercise.

Antiarrhythmic action is caused by the 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) conductivity mainly in antegrade and, to a lesser extent, in retrograde directions through the atrioventricular node and along additional paths.

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 attacks.

When used in average therapeutic doses, in contrast to non-selective β-adrenoblockers, metoprolol has a less pronounced effect on organs containing β₂-adrenoceptors (pancreas, skeletal muscles and 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 βadrenoreceptors. When blocking β₂-adrenorets spptor metoprolol can cause an increase in the tone of smooth muscles.

Pharmacokinetics:

Suction

After oral administration metoprolol almost completely (about 95%) is absorbed from the gastrointestinal tract. As metoprolol is subjected to intensive presystemic metabolism, its systemic bioavailability is 50% at the first admission. The maximum concentration in the blood plasma is achieved after 1.5-2 hours after administration.

Distribution

The connection with blood plasma proteins is 12%, the apparent volume of distribution is 5.6 l / kg.

Metabolism

Metoprolol is almost completely metabolized in the liver by oxidation. In the metabolism of the drug takes part isoenzyme cytochrome P450 (mainly isoenzyme CYP2D6). Two of the three major metabolites of metoprolol have poorly expressed β-adrenergic blocking properties, the clinical effect of whicheznachitelen.

Between different ethnic groups there is a significant difference in the incidence of persons with "slow" metabolism.The incidence of persons with a "slow" metabolism among persons of the European race is about 7%, among the Mongoloids - less than 1%. In patients with a "slow" metabolism through an isoenzyme system CYP2D6 the concentration of metoprolol in the blood plasma can be several times higher than the concentrations of metoprolol in individuals with a normal metabolic rate. Nevertheless, the metabolism of metoprolol through the isoenzyme system CYP2D6, apparently, does not influence or negatively affects the safety and tolerability of metoprolol. With cirrhosis of the liver, an increase in the concentration of unchanged metoprolol in the blood plasma should be expected due to the slowing of its metabolism.

Excretion

Metoprolol and ego metabolites are excreted mainly (95%) by the kidneys, about 10% of metoprolol is excreted unchanged. The half-life (T_1/2) of metoprolol is 3-5 hours. Metoprolol penetrates the blood-brain and placental barrier, penetrates into breast milk.

Hemodialysis is ineffective.

Indications:

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

Functional disorders of cardiac activity, accompanied by tachycardia.

Cardiac ischemia:

- myocardial infarction (secondary prevention - complex therapy);

- prevention of angina attacks.

Violations of the rhythm of the heart (tachyarrhythmias, including supraventricular tachycardia).

Prevention of migraine attacks.

Contraindications:

- Hypersensitivity to metoprolol, other β-adrenoblockers, or other components of the drug;

- heart failure in the stage of decompensation;

- shock (including cardiogenic);

- syndrome of weakness of the sinus node;

- Sinoatrial blockade;

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

- pronounced bradycardia (heart rate less than 50 beats / min before treatment);

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- Acute myocardial infarction (heart rate less than 45 beats / min, interval PQ more than 0.24 s or systolic blood pressure less than 100 mm Hg);

metabolic acidosis;

- hyperreactivity of the bronchi;

- severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD);

- severe peripheral circulatory disturbances;

- permanent or intermittent therapy with ionotropic agents acting as β-adrenomimitics;

- pheochromocytoma (without simultaneous application of α-blockers);

- the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels (BCCC) such as verapamil and diltiazem, as well as other antiarrhythmic drugs (eg, disopyramide), except for intensive care;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Carefully:

Diabetes mellitus, prolonged severe fasting and heavy physical exertion; renal failure of severe severity (creatinine clearance (CK) less than 40 ml / min), atrioventricular blockade of the 1st degree; thyrotoxicosis (metoprolol can mask the symptoms of thyrotoxicosis); depression (including in the anamnesis); psoriasis; abnormal liver function; hypersensitivity reactions in the anamnesis (there is a possibility of increasing sensitivity to allergens and weighting of anaphylactic reactions, and in this connection, in patients with history of hypersensitivity reactions or passing desensitizing therapy, anaphylactic reactions may increase and the response to adrenaline administration decrease); elderly age,chronic obstructive pulmonary disease (COPD); violations of peripheral circulation; pheochromocytoma (apply metoprolol follows only after blockade of α-adrenergic receptors).

Pregnancy and lactation:

During pregnancy (especially in the first trimester), Corvitol® 50 should be given taking into account the ratio of expected benefit to the mother and the risk to the fetus, as currently data on the use of metoprolol during pregnancy are limited. In this case, careful monitoring of fetal development should be carried out. β-adrenoblockers reduce placental circulation, which can lead to premature birth or intrauterine fetal death. In newborns, prenatally exposed to metoprolol, the postpartum period increased the risk of complications from the heart and lungs.

In connection with the possible development of fetal bradycardia, arterial hypotension, hypoglycemia, the use of the drug Corvitol® 50 should be discontinued 48-72 hours before the calculated term of childbirth. Careful observation of the newborn is necessary within 2-3 days after delivery.

Metoprolol penetrates into breast milk.In breast milk, the concentration of metoprolol is three times higher than the concentration in the blood plasma. If it is necessary to take Corvitol® 50 during lactation Breastfeeding should be discontinued.

Dosing and Administration:

Tablets can be taken with or without food as well as on an empty stomach.

Arterial hypertension: the initial dose is 50-100 mg of the drug once in the morning or in two doses - in the morning and in the evening. With insufficient therapeutic effect, the daily dose can be increased to 200 mg or additionally used other antihypertensives. The maximum daily dose is 200 mg.

Functional disorders of cardiac activity, accompanied by tachycardia: 50-100 mg per day, in 2 divided doses (morning and evening), if necessary, the daily dose can be increased to 200 mg.

Myocardial infarction, secondary prevention: 200 mg per day, divided into two doses: morning and evening.

Prevention of angina attacks: 50-200 mg per day in two divided doses, morning and evening.

Heart rhythm disturbances (tachyarrhythmias, including supraventricular tachycardia): 100 mg per day in two divided doses, morning and evening.

Prevention of migraine attacks: 100-200 mg per day, divided into 2 doses in the morning and evening).

Elderly patients it is recommended to start treatment with 50 mg per day. Care should be taken when increasing the dose.

Renal insufficiency does not require dose adjustment.

With hepatic insufficiency a dose adjustment may be required depending on the clinical condition of the patient.

If there is a need to interrupt or stop treatment with the drug after prolonged therapy, the dosage of the drug should be gradually reduced by 2 times for a minimum of 2 weeks.

When there is a syndrome of "cancellation", the dose reduction should be slower. A sharp discontinuation of the drug may cause myocardial ischemia and may lead to an exacerbation of the course of angina pectoris or myocardial infarction, and also to increase arterial hypertension.

Side effects:

Possible side effects are given below in accordance with the classification of the World Health Organization (WHO) for the descending frequency of occurrence: very often ≥ 1/10); often (≥1 / 100 <1/10); infrequently ≥ 1/1000, < 1/100); rarely (≥ 1/10000, < 1/1000); Very rarely (<1/10000), including individual messages, is unknown (according to available data, the frequency can not be established).

From the side of the coryza and lymphatic system:

Rarely: thrombocytopenia, and leukopenia.

From the immune system:

Rarely: allergic rhinitis.

From the side of metabolism and nutrition:

Rarely: diabetes mellitus, worsening of diabetes mellitus, hyperglycemia, hypothyroidism;

Unknown: hypoglycemia *.

From the side of the psyche:

Infrequently: depression, nightmares, sleep disorders, hallucinations;

Rarely: changes in personality, mood swings, temporary memory loss.

From the nervous system:

Infrequently: dizziness, headache, confusion, excessive dreams, paresthesia, slowing of psychomotor reactions, anxiety;

Rarely: myasthenia gravis.

From the side of the organ of vision:

Rarely: conjunctivitis, dryness and soreness of the eyes, a decrease in the secretion of tear fluid;

Rarely: visual impairment.

From the side of the hearing organ and labyrinthine disorders:

Rarely: hearing impairment, tinnitus.

From the side of the cardiovascular system:

Infrequently: coldness of limbs;

Rarely: heart palpitations, bradycardia, disorders AV conduction, arrhythmias, worsening of heart failure, cardialgia, peripheral edema, hypotension (including orthostatic hypotension), syncope;

Rarely: worsening of the course of angina pectoris;

Unknown: worsening of the course of Raynaud's syndrome **.

On the part of the respiratory system, the organs of the thorax and the mediastinum:

Rarely: shortness of breath with physical effort;

Infrequently: bronchospasm;

Unknown: respiratory distress syndrome ***.

From the side of the digestive tract:

Infrequently: nausea, vomiting, abdominal pain, constipation, diarrhea;

Rarely: dryness of the oral mucosa, a change in taste sensitivity.

Co hand liver and gall bladder:

Rarely: hepatitis.

From the skin and subcutaneous tissues:

Infrequently: increased sweating, skin allergic reactions (hives, itching, rash);

Rarely: deterioration of the course of psoriasis, psoriasis-like skin reactions, alopecia, skin hyperemia.

From the side of the musculoskeletal system:

Rarely: muscle weakness, muscle cramps;

Rarely: monoarthritis, polyarthritis, arthralgia.

From the side of the kidneys and urinary tract:

Rarely: worsening of renal failure.

From the genitourinary system:

Rarely: violations of libido, erectile dysfunction, Peyronie's disease.

Common violations:

Infrequently: malaise, weakness.

Impact on the results of laboratory and instrumental studies:

Rarely: increase in body weight, increased activity of aspartate aminotransferase in blood plasma, increased activity of alanine aminotransferase in blood plasma;

Unknown: a decrease in the concentration of high-density lipoprotein in the blood plasma, an increase in the concentration of triglycerides in the blood plasma.

* After prolonged severe fasting or severe physical exertion, hypoglycemia may develop with the use of Corvitol® 50.

** Also applies to other forms of peripheral circulatory disorders.

*** As a result of a possible increase in airway resistance, respiratory failure may occur in patients prone to bronchospastic reactions (in particular, in pathology of the obstructive airways).

Overdose:

Symptoms: Depending on the degree of intoxication, the clinical picture is mainly characterized by symptoms from the cardiovascular system and the central nervous system.

The pronounced sinus bradycardia up to cardiac arrest, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole,bronchospasm, syncope, heart failure, cardiogenic shock, loss of consciousness, coma, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), cardialgia, hypoglycemia, hyperkalemia, convulsions, respiratory arrest.

The first signs of an overdose appear after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage and intake of absorbents; 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, severe bradycardia and heart failure - intravenously, with an interval of 2-5 min β-adrenomimetics (dobutamine) -to achieve the desired effect or intravenously 0.5-2 mg of atropine. In the absence of a positive effect, other sympathomimetics should be introduced (dopamine, dobutamine or norepinephrine (norepinephrine)). It is possible to use glucagon (1-10 mg intravenously, followed by infusion at a rate of 2-2.5 mg / h). In the case of stable bradycardia, a temporary setting of an artificial pacemaker is possible. With bronchospasm, the use of aerosols β₂-adrenomimetics.If the bronchodilator effect with inhalation is insufficient, intravenous administration of β₂adrenomimetics or aminophylline. With cramps, slow intravenous diazepam is recommended.

Hemodialysis is ineffective.

Interaction:

Metoprolol is almost completely metabolized in the liver with the participation of cytochrome P450 isoenzymes (mainly isoenzyme CYP2D6). Therefore, the concentration of metoprolol in the blood plasma can increase with simultaneous use of substances that inhibit the isoenzyme CYP2D6, and decrease with the simultaneous use of substances that induce isoenzyme CYP2D6. Care should be taken when using Corvitol® 50 with inhibitors / isoenzyme inducers CYP2D6.

To inhibitors of isoenzyme CYP2D6, applied in clinical practice, are:

- antidepressants (for example, fluoxetine, paroxetine or bupropion);

- antipsychotics (for example, thioridazine);

- antiarrhythmic drugs (for example, quinidine and propafenone);

- antiviral drugs (for example, ritonavir);

- antihistamines (for example, diphenylhydramine);

- antimalarial drugs (for example, hydroxychloroquine or quinine);

- antifungal agents (for example, terbinafine);

- blockers H₂receptors (e.g., cimetidine).

With simultaneous use with these drugs may increase the effect of metoprolol.

To inductors of isoenzyme CYP2D6 are:

- rifampicin;

- dexamethasone.

With simultaneous use with these drugs may weaken the effects of metoprolol.

Simultaneous use with MAO inhibitors is contraindicated due to the possible enhancement of antihypertensive action. A break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days.

Simultaneous intravenous administration of verapamil may provoke cardiac arrest.

With concomitant use of BCCC like verapamil and diltiazem or other antiarrhythmic drugs (such as disopyramide), care should be taken and careful monitoring of the development of arterial hypotension, bradycardia, or other rhythm disturbances should be performed.

With the simultaneous use of metoprolol and BCCC like nifedipine, a marked decrease in blood pressure and, in some cases, the development of heart failure, is possible.

With the simultaneous use of metoprolol and antiarrhythmic drugs (for example, amiodarone) mutual reinforcement of their action is possible.

Means for inhalation anesthesia (halogenated hydrocarbons) increase the risk of oppression of myocardial function and development of arterial hypotension.

The simultaneous use of metoprolol with cardiac glycosides, reserpine, methyldopa, clonidine and guanfacin can lead to a decrease in heart rate and depression AV conductivity.

Means that reduce catecholamine stocks (for example, reserpine), can strengthen the action β-adrenoconvertors, therefore patients taking such combinations of drugs should be under regular supervision of the doctor for the detection of excessive reduction in blood pressure or bradycardia.

If metoprolol and clonidine take simultaneously, then with the cancellation of metoprolol clonidine cancellation in a few days (in connection with the risk of the syndrome of "withdrawal", accompanied by a sharp increase in blood pressure).

With the simultaneous use of metoprolol and norepinephrine, epinephrine or other sympathomimetic substances (for example, contained in some preparations from cough, nasal and eye drops), a significant increase in blood pressure is possible.

When treating allergic reactions with epinephrine, a decrease in the response to epinephrine on the background of metoprolol therapy.

β-adrenomimetics, theophylline, cocaine, indomethacin and other non-steroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys) weaken the antihypertensive effect of metoprolol.

Arterial pressure jumps may occur with simultaneous use of metoprolol with tricyclic antidepressants, barbiturates, phenothiazines and nitroglycerin (as well as with diuretics, vasodilators and other antihypertensive drugs).

Simultaneous use with ergot alkaloids increases the risk of peripheral circulatory disorders.

With the simultaneous use of metoprolol with hypoglycemic agents for oral administration, a decrease in their effect is possible; with insulin - increased risk of developing hypoglycemia, increasing its severity and duration, masking some of the symptoms of hypoglycemia (tachycardia, excessive sweating, increased blood pressure). Regular monitoring of the concentration of glucose in the blood plasma is necessary.

With the simultaneous use of metoprolol with antihypertensive drugs, diuretics, nitroglycerin or blockers of "slow" calcium channels, ethanol can lower blood pressure, special caution is needed when using simultaneously with prazosin.

Allergens used for immunotherapy or extracts of allergens for skin tests with simultaneous application with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.

Metoprolol reduces the clearance of xanthines (except diprofilin), especially with the initially elevated clearance of theophylline under the influence of smoking.

Metoprolol lowers the clearance of lidocaine, increases the concentration of lidocaine in the blood plasma.

Neuromuscular blockade caused by peripheral muscle relaxants (eg, suksamethonium or tubocurarine) can be enhanced by blocking βreceptors with metoprolol.

The simultaneous use of metoprolol and narcotic analgesics can cause excessive reduction in blood pressure,can increase the negative inotropic effect of the above medicines.

Cimetidine can enhance the action of metoprolol.

Special instructions:

Careful monitoring of patients taking beta-blockers, including regular monitoring of heart rate and blood pressure, and the concentration of glucose in blood plasma in patients with diabetes should be carefully monitored. If necessary, for patients with diabetes, the dose of insulin or hypoglycemic agents (prescribed internally, should be selected individually.) Symptoms of hypoglycemia, in particular tachycardia and tremor, can be masked and expressed not explicitly.The patient should be taught the method of calculating heart rate and instructing about the need for medical advice at a heart rate of less than 50 beats per minute.

Especially careful monitoring is required for patients undergoing a course of prolonged severe fasting or undergoing severe physical exertion (due to the possible development of severe hypoglycemia).

It is possible to increase the severity of allergic reactions (against the background of a burdened allergic medical history) and the lack of the effect of the administration of usual doses of epinephrine (adrenaline).

In elderly patients, it is recommended that the kidney function is monitored (once every 4-5 months). With renal failure of severe severity, the use of the drug Corvitol® 50 is possible only with the regular observation of the kidney function.

When using Corvitol® 50, symptoms of peripheral arterial circulation may worsen.

Cancellation Corvitol® 50 is carried out gradually, reducing the dose for 1-2 weeks.

The drug Corvitol® 50 may mask some clinical manifestations of thyrotoxicosis (eg, tachycardia). Sharp abolition in patients with thyrotoxicosis is contraindicated, as it can strengthen symptoms.

When using pheochromocytoma, the preparation Corvitol® 50 should be used only after blockade αadrenoreceptors.

When, when It is impossible to abolish the use of Corvitol® 50 before applying general anesthesia or before using peripheral muscle relaxants, it is necessary to warn the anesthesia doctor about the use of the drug.

Reciprocal activation of the vagus (vagus nerve) can be eliminated by intravenous injection of atropine (0.5-2 mg).

In the case of an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure below 100 mmHg) AV blockade, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, it is necessary to reduce the dose or stop treatment.

It is recommended to stop therapy with the appearance of skin rashes and the development of depression caused by the admission of β-blockers.

With a sharp cessation of treatment, there may be a "cancellation" syndrome (increased angina attacks, increased blood pressure). Particular attention should be paid to patients with angina when the drug is withdrawn.

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

In some cases, β-blockers can provoke the onset of psoriasis, exacerbation of the disease, or the occurrence of psoriasis exanthema. Use of β-blockers in patients with cases of psoriasis in a family history is possible only after a thorough assessment of the benefit-risk relationship.

The use of the drug Corvitol® 50 can lead to a positive result of doping control.

It is impossible to predict the consequences of improper use of Corvitol® 50 as a dope; the possibility of danger to health is not ruled out.

The drug Corvitol® 50 contains lactose, therefore its use is contraindicated in patients with lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome.

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

When taking Corvitol® 50, drowsiness, dizziness, paresthesia and blurred vision may occur, and as a consequence, a decrease in the ability to concentrate, therefore, during the use of the preparation Corvitol® 50, care must be taken when driving vehicles and other potentially hazardous activities, requiring concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 50 mg.

Packaging:

For 10 tablets in a planar cell pack (blister) made of PVC / aluminum foil.

By 3, 5 or 10 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N012267 / 01

Date of registration:26.07.2010 / 28.09.2015

Expiration Date:Unlimited

Date of cancellation:2018-01-16

The owner of the registration certificate:Berlin-Chemie, AGBerlin-Chemie, AG Germany

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp03.02.2018

Illustrated instructions

Instructions

Corvitol® 50 (Corvitol® 50)