Corvitol 100 - instructions for use, dose, side effects, contraindications

Metoprolol refers to cardioselective blockers β₁-adrenoceptor weakly expressed and has a membrane stabilizing action and has no intrinsic sympathomimetic activity. Has antihypertensive, antianginal and antiarrhythmic action.

Blocking in low doses (less than 100 mg / day) β₁-adrenoceptors heart stimulated by catecholamines reduces the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces intracellular calcium ion current has a negative chronotropic, dromo-, BATM and inotropic effects (heart rate slows, inhibits conduction and excitability and reduces contractility of the myocardium).

The total peripheral resistance at the beginning of application of β₁adrenoblokatorov (in the first 24 hours after oral administration) - increases (as a result of reciprocal increase in the activity of α-adrenoceptor stimulation and removal of β₂-adrenoreceptors), which after 1-3 days returns to the original, and with a long-term appointment - decreases.

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

Antianginal action is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (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 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, it decreases the heart rate, or even can lead to the restoration of sinus rhythm. Prevents the development of migraine.

When used at average therapeutic doses, in contrast to non-selective β-blockers, it exerts 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 of β-adrenoreceptors.

Pharmacokinetics:

After oral administration metoprolol almost completely (95%) absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is achieved after 1.5-2 hours after administration.The half-life is 3-5 hours on average. It is subjected to intensive presystemic metabolism, bioavailability is 50% at the first admission. The connection with blood plasma proteins is 12%, the apparent volume of distribution is 5.6 l / kg.

Metoprolol is almost completely metabolized in the liver. In the metabolism of the drug takes part isoenzyme cytochrome P450 (CYP 2D6). Approximately 95% of metoprolol and its metabolites are excreted through the kidneys, unchanged approximately 10%. Penetrates through the blood-brain and placental barrier. Excreted in breast milk in small amounts. It is not removed during hemodialysis.

Indications:

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

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

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

- functional disorders of cardiac activity, accompanied by tachycardia;

- hyperthyroidism (complex therapy);

- prevention of migraine attacks.

Contraindications:

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

- chronic heart failure in the stage of decompensation; cardiogenic shock;

- syndrome of weakness of the sinus node;

- Sinoatrial blockade;

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

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

- angina of Prinzmetal;

- arterial hypotension (in the case of secondary prevention of myocardial infarction - systolic blood pressure less than 100 mm Hg);

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

- pheochromocytoma (without simultaneous application αadrenoblockers);

- lactation period;

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

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous use of blockers of "slow" calcium channels (BCCC) such as verapamil (see section "Interaction with other drugs");

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

Carefully:

Diabetes mellitus, metabolic acidosis, impaired renal function (creatinine clearance (CK) less than 40 ml / min), myasthenia gravis, AV blockade of I degree, thyrotoxicosis, depression (including history), psoriasis, impaired liver function, allergic reactions in the anamnesis (possibly increased sensitivity to allergens, weighty arterial hypertension and decreased therapeutic response to epinephrine (adrenaline), advanced age, chronic obstructive pulmonary disease, bronchial asthma, peripheral circulation disorders, pheochromocytoma (with simultaneous use of α-blockers).

Pregnancy and lactation:

During pregnancy (especially in the first trimester), the preparation of Corvitol® 100 should be taken in consideration of the ratio of expected benefits to the mother and the risk to the fetus. In this case, careful monitoring of fetal development is carried out. In connection with the possible development of fetal bradycardia, arterial hypotension, hypoglycemia, therapy with the drug Corvitod® 100 should be discontinued 48-72 hours before the calculated term of labor. Careful observation of the newborn is necessary within 2-3 days after delivery.

Metoprolol penetrates into breast milk in small amounts. If you need to take Corvitol® 100 during lactation Breastfeeding should be discontinued.

Dosing and Administration:

Tablets are taken orally, without chewing, squeezed with enough liquid, after eating. The duration of the course of therapy is determined by the doctor individually and depends on the features of the course of the disease.

Arterial hypertension

The initial daily dose is 50-100 mg of Corvitol® 100 in 1-2 doses (morning and evening). If necessary, the daily dose can be gradually increased to 100-200 mg in 2 divided doses (morning and evening).

The maximum daily dose is 200 mg.

Secondary prevention of myocardial infarction

At the end of the acute stage of myocardial infarction, the drug Corvitol® 100 is prescribed at 200 mg per day, in 2 divided doses (morning and evening). In case of severe bradycardia (heart rate less than 50 beats per minute) and / or lowering blood pressure, or other side effects associated with taking the drug, taking Corvitol 100 should be stopped immediately.

Angina pectoris, arrhythmias, prevention of migraine attacks

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

Functional disorders of cardiac activity, accompanied by tachycardia

For 50 mg of Corvitol® 100 2 times a day in the morning and evening.

With hyperthyroidism

For 50 mg of the drug Corvitol® 100 4 times a day.

In elderly patients with impaired renal function (CC less than 40 ml / min), and if hemodialysis is necessary, the dose is not changed.

When expressed violations of liver function the dose should be reduced.

Side effects:

Frequency of side effects: Often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), rarely (less than 0.01%), including individual reports.

From the central nervous system (CNS): often - increased fatigue, weakness, headache; infrequently - slowing down the speed of mental and motor reactions; rarely paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), depression, anxiety, decreased concentration, drowsiness, insomnia, nightmarish dreams, confusion or short-term memory impairment, myasthenia gravis, hallucinations, asthenia.

From the sense organs: rarely - dry and painful eyes, conjunctivitis, decreased secretion of tear fluid, decreased vision; rarely - Hearing impairment and noise in the ears.

From the side of the cardiovascular system: often - Sinus bradycardia, palpitations, marked decrease in blood pressure, orthostatic hypotension (dizziness, in rare cases, loss of consciousness); infrequent - a decrease in contractility of the myocardium, a temporary worsening of the symptoms of chronic heart failure; rarely - arrhythmias, manifestation of angiospasm (increased peripheral circulatory disturbance, cooling of the lower extremities), cardialgia; very rarely - aggravation of pre-existing AV conduction disorders.

From the digestive system: often - nausea, abdominal pain, diarrhea, constipation; infrequently - vomiting; rarely - dryness of the oral mucosa, change in taste; rarely - hepatitis.

From the skin: infrequently - urticaria, itchy skin, rash, increased sweating; rarely - exacerbation of psoriasis, psoriasis-like skin reactions, skin hyperemia, photosensitivity, reversible alopecia.

From the respiratory system: often - shortness of breath with physical effort; infrequently - bronchospasm; rarely - Rhinitis.

From the endocrine system: infrequently - hypoglycemia; rarely - hyperglycemia, hypothyroidism.

Other: in some cases can cause a slight increase in body weight; rarely - pain in the back or joints, decreased libido and / or potency.

Overdose:

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

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

In case of an overdose or a threatening reduction in heart rate and / or blood pressure, treatment with Corvitol® 100 should be discontinued immediately.

Treatment: gastric lavage and intake of adsorbing agents; 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 minutes. β-adrenomimetics (dobutamine) - until the desired effect is achieved or intravenously 0.5-2 mg of atropine. In the absence of a positive effect - dopamine or norepinephrine (norepinephrine). As a follow-up, it is possible to stage an artificial pacemaker.

When bronchospasm should be administered intravenously, β₂-adrenomimetic.

With convulsions, intravenous slow diazepam is recommended. Hemodialysis is ineffective.

Interaction:

It is not recommended simultaneous use with MAO due to a significant increase in hypotensive effect. A break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days.

Simultaneous iv injection of verapamil may provoke cardiac arrest. Means for inhalation anesthesia (halogenated hydrocarbons) increase the risk of oppression of myocardial function and development of arterial hypotension.

The combined use of metoprolol with verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, methyldopa, clonidine, guanfacin, general anesthetic agents and cardiac glycosides leads to a decrease in heart rate and depression AV conductivity.

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

Simultaneous reception of metoprolol and tri- and tetracyclic antidepressants, antipsychotics (antipsychotics), sedatives and hypnotics, ethanol increases CNS depression.

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

When combined 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, sweating, increased blood pressure).

When combined with antihypertensive drugs, diuretics, nitroglycerin or blockers of "slow" calcium channels, ethanol can lower blood pressure, special caution is necessary when combined with prazosin.

If metoprolol and clonidine take simultaneously, then with the cancellation of metoprolol clonidine cancellation after a few days (due to the risk of the syndrome of "withdrawal").

Inductors of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, a decrease in the concentration of metoprolol in the blood plasma and a decrease in the effect. Inhibitors of microsomal liver enzymes (cimetidine, oral contraceptives, phenothiazines) - increase the concentration of metoprolol in the blood plasma.

Allergens used for immunotherapy or allergen extracts for skin tests when combined 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.

Metoprolol enhances and prolongs the action of nondepolarizing muscle relaxants; prolongs the anticoagulant effect of coumarin derivatives.

Means that reduce catecholamine stocks (for example, reserpine), can increase the action of β-blockers, so patients taking such combinations of drugs should be under constant medical supervision for the detection of excessive reduction in blood pressure or bradycardia.

Special instructions:

Control of patients receiving β-adrenoconverters, includes regular monitoring of heart rate and blood pressure, the concentration of glucose in the blood in patients with diabetes mellitus. If necessary, for patients with diabetes mellitus, a dose of insulin or hypoglycemic drugs prescribed inside, should be selected individually. It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 50 beats per minute.

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). It can intensify the symptoms of peripheral arterial circulation.

Abolition of the drug Corvitol® 100 is carried out gradually, reducing the dose for 10 days.

With arterial hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months.

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 β-blockers is lower.

Corvitol® 100 may mask certain clinical manifestations of thyrotoxicosis (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

With diabetes, Corvitol® 100 can mask tachycardia caused by hypoglycemia.

In contrast to non-selective β-adrenoblockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

If it is necessary to use patients with bronchial asthma as a concomitant therapy, β₂-adrenomimetics; with pheochromocytoma - α-adrenoblockers.

If a surgical procedure is necessary, an anesthesiologist must be warned about taking Corvitol® 100 (choice of a general anesthetic agent with minimal negative inotropic effect), the drug cancellation is not recommended.

Reciprocal activation of the vagus (vagus nerve) can be eliminated by intravenous injection of atropine (1-2 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). 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 β-adrenoblockers, a decrease in the production of tear fluid is possible.

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

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

Form release / dosage:Tablets, 100 mg.

Packaging:

For 10 tablets in a contour squeeze box (blister), made of transparent PVC film and aluminum foil.

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

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 N012268 / 01

Date of registration:27.07.2010 / 05.10.2015

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® 100 (Corvitol® 100)