BETALOK ARC

Active material: Metoprolol
When ATH: C07AB02
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): G43, I10, i20, I21, I47.1, i48, I49.4, I50.0
When CSF: 01.01.01.02
Manufacturer: ASTRAZENECA AB (Sweden)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

With a slow-release tablets, coated white or nearly white, Oval, lenticular, with a notch on both sides and engraved “A/b” on one side.

Excipients: ethyl cellulose, gipromelloza, giproloza, microcrystalline cellulose, paraffin, macrogol, silicon dioxide, sodium fumarate, Titanium dioxide.

14 PC. – blisters (1) – packs cardboard.

With a slow-release tablets, coated white or nearly white, round, lenticular, with a notch on one side and engraving “A/mo” – another.

Excipients: ethyl cellulose, gipromelloza, giproloza, microcrystalline cellulose, paraffin, macrogol, silicon dioxide, sodium fumarate, Titanium dioxide.

30 PC. – plastic bottles (1) – packs cardboard.

With a slow-release tablets, coated white or nearly white, round, lenticular, with a notch on one side and engraving “A/ms” – another.

Excipients: ethyl cellulose, gipromelloza, giproloza, microcrystalline cellulose, paraffin, macrogol, silicon dioxide, sodium fumarate, Titanium dioxide.

30 PC. – plastic bottles (1) – packs cardboard.

Pharmacological action

Cardioselective beta₁-blocker without intrinsic sympathomimetic activity. Has a little membrane stabilizing effect. Provides antihypertensive, antianginalnoe and antiaritmicescoe action. Suppresses the stimulating effect of Catecholamines on the heart during physical and psychoemotional exertion: prevents an increase in HEART RATE, raise HELL, reduces cardiac output and reduces airway diseases.

Due to the peculiarities of the pharmaceutical form of constant concentration metoprolola plasma and clinical effect of steady medication for 24 no. Due to the lack of plasma concentration peaks clinically Betalok^® ZOCH is characterized by better beta₁-selectivity compared with traditionally used tablets forms of metoprolol. Besides, greatly reduces the potential risk of side effects, observed peak concentration of the drug in plasma (eg, aetiology or weakness in the legs when walking).

When used in therapeutic doses, medium Betalok^® ARC has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries, than selective beta-adrenoblokatora. If necessary, Betalok^® ZOCH in combination with beta₂-adrainomimetikami you can assign patients with symptoms of obstruction light.

Betalok^® ZOCH, to a lesser extent, affect insulin and carbohydrate metabolism and the activity of the cardiovascular system in conditions of hypoglycemia compared with unselective beta-adrenoblokatorami.

Application of Betalok^® ZOCH when hypertension leads to a significant reduction in AD for more than 24 no (in the supine position, Standing, under load). At the beginning of therapy metoprolol increasing CSO. With long-term use may decline ad by reducing ROUND while cardiac release.

IN THE MERIT-HF – study on survival in chronic heart failure (II-IV functional class NYHA classification) with reduced ejection fraction (≤ 40%), which included 3991 patient, Betalok^® ZOCH showed improved survival and reduced the frequency of hospitalization. In the long-term treatment of patients achieved an overall improvement in well-being, the easing of symptoms (functional NYHA classes). Also, therapy with Betaloka^® Increase in ejection fraction revealed the CARTEL left ventricle, reduction of end systolic and end-diastolic volume of left ventricle.

Quality of life during treatment with Betalok^® ZOCH not worsens or improves. Improving the quality of life when treated with Betalok^® ZOCH was observed in patients after myocardial infarction.

Pharmacokinetics

Absorption and distribution

After intake of metoprolol completely absorbed from the digestive tract.

Speed release of the active substance depends on acidity Wednesday. After taking the pill Betalok^® ZOCH (dosage form with a slow-release metoprolol) duration of therapeutic effect is more 24 no, When this is achieved by constant speed release of the active substance for 20 no.

Bioavailability after single administration of a single dose is approximately 30-40%. Linking blood plasma low metoprolol – about 5-10%.

Metabolism

Metoprolol biotransformiroetsa in the liver by oxidation. Three major metabolite metoprolol showed no clinically significant beta blocking effect.

Deduction

T_1/2 averages 3.5 no. About 5% oral dose of the drug excreted in the urine in an unmodified form, the rest of the drug appears in the form of metabolites.

Testimony

- Arterial hypertension;

- Angina;

— stable symptomatic chronic heart failure with impaired left ventricular systolic function (as an adjuvant therapy to the primary treatment of heart failure);

-maintenance treatment after the acute phase of myocardial infarction (to reduce mortality and frequency of re-infarction);

-cardiac arrhythmias (incl. supraventricular tachycardia), as well as to reduce the frequency of contractions of the ventricles in atrial fibrillation and ventricular jekstrasistolah;

-functional disorders of the heart, accompanied by tachycardia;

-Prevention of migraine attacks.

Dosage regimen

When selecting a dose, it is necessary to avoid the development of bradycardia.

At hypertension starting dose is 50-100 mg 1 time / day. In the absence of clinical effect can be increased dose to 100 mg 1 times/day or use Betalok^® ZOCH in combination with other antigipertenzivei drugs (preferably diuretic and calcium channel blocker derived digidropiridina).

At angina average therapeutic dose is 100-200 mg 1 time / day. If necessary, Betalok^® ARC can be used in combination with other drugs antianginalnami.

At stable symptomatic chronic heart failure with impaired left ventricular systolic function assign Betalok^® ZOCH you can patients, have in the past 6 weeks did not have episodes of exacerbation and during the last 2 weeks there was no change in the basic therapy. Therapy of cardiac insufficiency beta-adrenoblokatorami sometimes can lead to temporary impairment of symptomatic picture. In some cases, continued therapy or dose reduction, and in some – There may be a need for preparation.

At stable chronic congestive heart failure functional class II the recommended initial dose first 2 the week is 25 mg 1 time / day. Through 2 weeks the dose can be increased to 50 mg 1 times/day and can double every 2 of the week. Maintenance dose for long-term care is 200 mg 1 time / day.

At stable chronic heart failure III and IV functional classes the recommended initial dose first 2 the week is 12.5 mg 1 time / day. Dose selected individually. At a time of increased doses of the patient should be under the supervision of, tk. in some patients the symptoms of heart failure can get worse. Through 1-2 weeks the dose can be increased to 25 mg 1 time / day, then after another 2 of the week – to 50 mg 1 time / day. With good endurance can double the dose every 2 weeks until the maximum dose 200 mg 1 time / day.

In the case of arterial hypotension and/or bradycardia might need reducing concomitant therapy or dose reduction Betaloka^® ZOCH. Arterial gipotenzia, at the beginning of therapy does not necessarily indicate, that this dose Betaloka^® ARC will not be wrapped when the future long-term care. However, the dose should not increase until the, While the condition is not stabilized. You may also want to monitor kidney function.

To maintenance treatment after myocardial infarction the drug is prescribed for 200 mg 1 time / day.

At cardiac arrhythmias the drug is prescribed for 100-200 mg 1 time / day.

At functional disorders of cardiac activity, accompanied by tachycardia, dose of 100 mg 1 time / day, if necessary, the dose can be increased to 200 mg / day.

To Prevention of migraines appoint 100-200 mg 1 time / day.

Betalok^® ARC is designed for daily reception 1 time / day (preferably in the morning). Tablet Betaloka^® ZOCH should swallow, with some liquid. Tablets can be split in half, but you should not chew or crush.

In appointing the drug patients with impaired renal function or the elderly no need to adjust the dosage.

In appointing the drug patients with acute human liver (eg, in patients with severe cirrhosis or Porto-kavalnym anastomosis) may require dose reduction.

Side effect

To assess the incidence, the following criteria were used: Often – > 10%, often – 1-9.9%, sometimes – 0.1-0.9%, rarely – 0.01-0.09%, rarely – < 0.01%.

Cardio-vascular system: often – bradycardia, orthostatic hypotension (very rarely accompanied by fainting), cold extremities, palpitations; sometimes – temporary increased symptoms of heart failure, AV block I degrees, cardiogenic shock in patients with acute myocardial infarction; rarely – other violations conductivity, Arrhythmia; rarely – gangrene (in patients with severe disorders peripheral blood circulation).

From the central and peripheral nervous system: Often – fatiguability; often – dizziness, headache; sometimes – paresthesia, muscle cramps, depression, decreased ability to concentrate, drowsiness or insomnia, nightmares; rarely – nervousness, anxiety; rarely – memory impairment, amnesia, oppression, hallucinations.

From the digestive system: often – nausea, abdominal pains, diarrhea, constipation; sometimes – vomiting; rarely – dry mouth, abnormal liver function; rarely – hepatitis.

From the hematopoietic system: rarely – thrombocytopenia.

The respiratory system: often – shortness of breath on exertion; sometimes – bronchospasm; rarely – rhinitis.

On the part of the musculoskeletal system: rarely – arthralgia.

From the senses: rarely – dryness and/or eye irritation, conjunctivitis, blurred vision; rarely – tinnitus, dysgeusia.

Dermatological reactions: sometimes – rash (in the form of urticaria), increased sweating; rarely – hair loss; rarely – photosensitivity, exacerbation of psoriasis.

Other: sometimes – weight gain; rarely – impotence, sexual dysfunction.

Betalok^® ZOCH is well tolerated by patients, side effects, primarily, are mild and reversible.

Contraindications

— AV-blockade II and III degrees;

- Chronic heart failure decompensation (pulmonary edema, hypoperfusion syndrome or hypotension);

-prolonged or intermittent therapy inotropnami means, aimed at stimulation of β-adrenoreceptor;

-clinically significant sinusova aetiology;

- SSS;

- Cardiogenic shock;

- Hypotension;

— expressed by human peripheral blood circulation (incl. with the threat of gangrene);

-patients with suspected acute myocardial infarction with HEART RATE less than 45 u. / min, PQ interval more 0.24 with or systolic HELL less 100 mmHg.;

- Patients, assigned in/with the introduction of blocking slow calcium channels (incl. verapamil);

- Childhood and adolescence up 18 years (the efficacy and safety of the drug is not installed);

-hypersensitivity to the drug or to other beta-adrenoblokatoram.

FROM caution apply when AV blockade degree I, Angina Princmetalla, asthma, COPD, diabetes, severe renal insufficiency, metabolic acidosis, joint appointment with cardiac glycosides.

Pregnancy and lactation

Like most drugs Betalok^® ZOCH should not be appointed during pregnancy and breastfeeding, except, When the expected benefits to the mother outweighs the potential risk to the fetus and/or child.

Like other antihypertensives, Beta-adrenoblokatora may cause side effects, eg, Fetal bradycardia, infants or children, breastfed. Number of metoprolol, striking the breast milk, and beta blocking action in a child, breastfed (When taking the mother of metoprolol in therapeutic doses), are minor.

Cautions

Patients with obstructive lung disease is not recommended to appoint beta-adrenoblokatora. At bad portability or inefficiency of other antigipertenziveh funds you can assign metoprolol, because it is a selective drug. You should assign the minimum effective dose, If necessary it is possible to appoint beta₂-adrenomimetika.

Not recommended to appoint selective beta-adrenoblokatora patients with angina pectoris Prinzmetala. This group of patients, selective beta-adrenoblokatora should be administered with caution.

When using beta₁-adrenoblokatorov risk impact on carbohydrate metabolism, or the ability to mask symptoms gipoglikemii significantly less, than using the nonselective beta-adrenoblokatorov.

Patients with chronic heart failure should be in the stage of compensation and receive the primary therapy as to, and during treatment with Betalok^® ZOCH.

Very rare while therapy Betalokom^® ZOCH in patients with impaired conduction can occur until degradation AV-blockade. If a treatment developed bradycardia, It is necessary to reduce the dose or stop the drug should be gradually.

During the period of use of the drug may increase symptoms of human peripheral blood circulation, mainly because of lower HELL.

If necessary, the appointment of Betaloka^® ZOCH patients with feohromotsytoma simultaneously assign Alpha-adrenoreceptor antagonists.

Clinical studies on efficacy and safety in patients with severe stable heart failure (IV functional class NYHA classification) limited. Treatment of such patients should be conducted by doctors, with specialized knowledge and experience.

Patients with heart failure combined with acute myocardial infarction and unstable angina were excluded from studies, on the basis of which identified evidence for assignment. Efficacy and safety of the drug for this group of patients is not described. Application of unstable and decompensirovanna heart failure is contraindicated.

Avoid sudden discontinuation. Lifting drug should be gradually, during 2 weeks. The dose is gradually, in divided doses, to achieve the ultimate dose – 25 mg 1 time / day.

If you want to perform surgical intervention should notify anesthesiologist about therapy, to find a means to narcosis with minimal negative inotropic effect, However, the Elimination of the drug before surgery is not recommended.

It will be appreciated, that patients, taking beta-blockers, anaphylactic shock is more difficult.

Use in Pediatrics

Experience of applying Betaloka^® ZOCH in children is limited. Use of the drug in this category is contraindicated in patients.

Effects on ability to drive vehicles and management mechanisms

With regard to the likelihood of dizziness or fatigue question about the possibility of activities potentially hazardous activities, require increased attention and psychomotor speed reactions, should be dealt with after evaluating the patient's individual reactions to the drug.

Overdose

Metoprolol dose 7.5 g adult caused fatal intoxication. The child 5 years, accepting 100 mg metoprolol, after gastric lavage were observed signs of intoxication. Reception 450 mg metoprolol teenager 12 years resulted in moderate intoxication. Reception 1.4 and g 2.5 g metoprolol adults caused moderate and severe intoxication, respectively. Reception 7.5 g for adults has led to extremely severe intoxication.

Symptoms: the most serious are symptoms of cardiovascular system, Sometimes, however,, especially in children and adolescents, may prevail symptoms of the central nervous system and the Suppression of lung function, bradycardia, AV blockade III extent, asistolija, marked reduction in blood pressure, poor peripheral perfusion, heart failure, cardiogenic shock, inhibition of lung function, apnea, increased fatigue, the disruption and loss of consciousness, tremor, convulsions, increased perspiration, paresthesia, bronchospasm, nausea, vomiting, jezofagealnyj spasm, gipoglikemiâ (especially in children) or hyperglycemia, hyperkalemia; effect on kidneys; tranzitornyi miasteniceski syndrome.

The accompanying admission alcohol, antihypertensive agents, hinidina or barbiturates can worsen the condition of the patient. The first signs of an overdose can occur through 20 min-2 h after administration of the drug.

Treatment: administration of activated charcoal, if necessary – gastric lavage.

Atropine dose 0.25-0.5 mg in/in for adults and 10-20 µg/kg for children must be assigned to gastric lavage (because of the risk of stimulating the vagus nerve).

If necessary the maintenance of road respiratory tract is performed AV. For cupping the bronchoconstriction injection or inhalation terbutaline can be applied.

You must fill in the BCC, hold the infusion of glucose. Atropyn 1.0-2.0 mg / in, If necessary, repeat the introduction (especially when vagusnyh symptoms). ECG Monitoring.

In the case of myocardial depression shown or dobutamine infusion of dopamine. You can use glucagon 50-150 mcg/kg/in every 1 m. In some cases, can be effectively adding to the therapy of epinephrine.

When arrhythmia and advanced zheludochkovom (QRS) complex infuzionno injected sodium solutions (chloride or bicarbonate). It is possible to install artificial driver rhythm.

When cardiac arrest due to an overdose may need resuscitation for several hours.

Symptomatic treatment.

Drug Interactions

Metoprolol is a substrate of CYP2D6, in this connection, preparations, inhibiting CYP2D6, (quinidine, terʙinafin, paroxetine, fluoxetine, sertraline, celecoxib, propafepon and diphenhydramine) may affect plasma concentration metoprolola.

Combinations, which should be avoided

Barbituric acid derivatives: barbiturates increase metabolism of metoprolol, as a result of the induction of enzymes (the study was conducted with phenobarbital).

Propafenone: When assigning propafenon 4 patients, receiving metoprolol, There was an increase in concentration metoprolola plasma 2-5 time, at the same time 2 patients experienced side effects, characteristic of metoprolol. This interaction has been confirmed in the course of research on the 8 Volunteers. Probably, interaction is due to inhibition of propafenonom, like hinidinu, metabolism of metoprolol through izofermenta CYP2D6. Taking into account the fact, that propafenone has the properties of beta-adrenoblocker, the joint appointment of metoprolol and propafenon did not seem appropriate.

Verapamil: the combination of beta-adrenoblokatorov (atenolola, propranolol and pindolola) and verapamil can cause bradycardia and lead to lower HELL. Verapamil and beta-adrenoblokatora have complementary ingibiruty effect on AV conductivity and sinus node function.

Combinations, in the application that may require dose adjustment Betalok^® ZOCH

Class I antiarrhythmics: in combination with beta-adrenoblokatorami possibly summation of negative effect inotropnogo, as a consequence, develop severe haemodynamic side effects in patients with impaired left ventricular function. Such combinations should also be avoided in patients with SSSU and violation of AV conduction. Interaction described in example dizopiramida.

Amiodarone: joint application with metoprolol may lead to pronounced sinus bradycardia. Taking into consideration the extremely long T_1/2 amiodarona (50 days), should take into account possible interaction after long time after the cancellation of amiodarone.

Diltiazem: diltiazem and beta-adrenoblokatora reinforce ingibirutee to AV conductivity and sinus node function. In combination with metoprolol diltiazem cases of bradycardia.

NSAIDs: Npvs weaken antihypertensive action of beta-adrenoblokatorov. This interaction is registered in combination with indomethacin and were observed in combination with sulindakom. In studies with diclofenac this effect not noted.

Difengidramin: Diphenhydramine decreases biotransformatia metoprolol to α–gidroksimetoprolola in 2.5 times. At the same time there has been a strengthening of metoprolol.

Epinephrine (adrenaline): reported on 10 cases expressed arterial hypertension and bradycardia in patients, taking selective beta-adrenoblokatora (including pindolol and propranolol) and treated with epinephrine. Interaction observed in a group of healthy volunteers and. Expected, that such reactions can also occur when applying of epinephrine with local anaesthetics in the event of accidental ingestion in vascular track. Apparently, This risk is far lower when applying cardioselective beta blockers.

Phenylpropanolamine: phenylpropanolamine (norephedrine) single dose 50 mg may improve diastolic HELL to pathological values in healthy volunteers. Propranolol basically lets raise HELL, calling fenilpropanolaminom. However, beta-adrenoblokatora may cause reactions ironic hypertension patients, receiving high doses of phenylpropanolamine. It was reported on several cases development gipertoniceski kriza against the backdrop of the admission of phenylpropanolamine.

Quinidine: quinidine inhibits the metabolism of metoprolol from a specific group of patients with rapid gidroksilirovaniem (in Sweden, about 90% the population), calling, mainly, a significant increase in plasma concentration of metoprolol and increased β-adrenoceptor blockade. It is believed, that such interaction is characteristic for other beta-adrenoblokatorov, in the metabolism of CYP2D6 CYP.

Klonidin: hypertensive reactions in an abrupt cancellation of clonidine may be aggravated while receiving beta-adrenoblokatorov. In a joint application, in case of necessity to cancel clonidine, stopping beta-adrenoblokatorov should begin a few days before the lifting of clonidine.

Rifampicin: rifampin may increase metabolism of metoprolol, decreasing its concentration in blood plasma. Patients, at the same time taking metoprolol and other beta-adrenoblokatora (eye drops) or MAO inhibitors, should be under close supervision.

In the face of the reception beta-adrenoblokatorov 73.21 anaesthetics increase cardiodepressivne effect.

In the face of the reception beta-adrenoblokatorov patients, receiving oral gipoglikemicakie means, may require dose adjustment the past.

Plasma concentration of metoprolol may increase when taking cimetidine or gidralazina.

Heart glycosides in a joint application with beta-adrenoblokatorami can increase time AV conductivity and cause bradycardia.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be kept out of the reach of children at a temperature above 30° c. Shelf life - 3 year.