Metoprolol

General characteristics. Structure:

Active ingredient: 25 mg, 50 mg and 100 mg of a metoprolol.

Excipients: cellulose microcrystallic, sodium of starch glikolit, talc, magnesium stearate, lactose.

The cardiological drug having anti-anginal, anti-hypertensive and antiarrhytmic effect.

Pharmacological properties:

Pharmacodynamics. Metoprolol is beta adrenoblocker. Has no internal sympathomimetic activity. The increased arterial pressure reduces both in a standing position, and in a prone position. Does not cause orthostatic hypotension and does not influence electrolytic composition of blood. Has anti-anginal, anti-hypertensive and antiarrhytmic effect. Reduces a promoting effect of catecholamines by heart at exercise and psychoemotional stress, leads to reduction of ChSS, contractility of a myocardium, cordial emission. In the first days of use drug increases OPSS which at prolonged use is normalized or even decreases.

Reduces the need of a myocardium for oxygen (at the expense of an urezheniye of ChSS and decrease in contractility of a myocardium), reduces number and weight of attacks of stenocardia and increases tolerance to an exercise stress. At supraventricular tachycardia, atrial fibrillation, sinus tachycardia, functional heart diseases and a hyperthyroidism urezhat ChSS and can lead to recovery of a sinoatrial rate. Antiarrhytmic action is caused by reduction of speed of spontaneous excitement of a sinus and ectopic pacemaker and delay of AV of conductivity. Prevents development of a headache of vascular genesis. To a lesser extent, than non-selective beta adrenoblockers, influences release of insulin and carbohydrate metabolism, masks hypoglycemia symptoms at patients with a diabetes mellitus, increases the content in blood of triglycerides, reduces the content of free fatty acids and lipoproteins of high density.

Pharmacokinetics. Absorption and distribution. After administration of drug inside метопролол almost completely (about 95%) it is absorbed from a GIT. The maximum concentration in a blood plasma is reached in 1,5-2 h. Bioavailability of a metoprolol makes about 50% at single and about 70% at multiple dose. The concomitant use of food can increase bioavailability of a metoprolol for 30 — 40%. Linkng with proteins of plasma - 10%. Gets through GEB and a placental barrier, it is allocated with breast milk. Metoprolol is widely distributed in fabrics and has the large volume of distribution (5,6 l/kg).

Metabolism and removal. Metoprolol biotransformirutsya intensively in a liver with formation of inactive metabolites. Plasma elimination half-life makes from 1 to 9 hours (on average - 3,5 hours). The general clearance of drug makes about 1 l/min. About 5% - in not changed look, the rest - in the form of metabolites are removed generally by kidneys (95%).

Separate groups of patients. Essential differences of pharmacokinetics of a metoprolol at elderly patients are not revealed.

At a renal failure removal of metabolites decreases and practically removal of not changed metoprolol does not change. At a heavy renal failure (SKF of 5 ml/min.) considerable accumulation of metabolites is observed, however extent of beta and adrenergic blockade at the same time amplifies.

The abnormal liver function slightly influences pharmacokinetics of a metoprolol. However at heavy cirrhosis and/or after imposing of the porto-caval shunt bioavailability can increase, and the general clearance - to decrease. After porto-caval shunting the general clearance of drug makes about 0,3 l/min, and the area under a curve of concentration time increases approximately by 6 times in comparison with healthy faces.

Indications to use:

- Arterial hypertension.

- Stenocardia.

- Stable symptomatic chronic heart failure with disturbance of systolic function of a left ventricle (as auxiliary therapy to the main treatment of chronic heart failure).

- Decline in mortality and frequencies of a repeated heart attack after an acute phase of a myocardial infarction.

- As supportive application at hyperfunction of a thyroid gland.

- Disturbances of a cordial rhythm, including supraventricular tachycardia, decrease in frequency of reduction of ventricles at fibrillation of auricles and ventricular extrasystoles.

- The functional disturbances of cordial activity which are followed by tachycardia.

- Prevention of attacks of migraine.

Route of administration and doses:

The dosage is selected individually according to disease symptomatology.

Pill is taken inside in time or after food, without chewing and washing down with enough drinking water. During selection of a dose it is necessary to control heart rate for the prevention of bradycardia. Duration of a course of therapy is established by the doctor individually and depends on features of a course of a disease. If after prolonged use of drug the treatment termination is required, then it is necessary to do it gradually and slowly as sudden drug withdrawal can lead to sharp increase in arterial pressure. Arterial hypertension. At arterial hypertension moderate and the moderately severe initial dose makes 25 — 50 mg two times a day (in the morning and in the evening). If necessary it is possible to raise a daily dose gradually to 200 mg (on 100 mg in the morning and in the evening) or to add other antihypertensive.

Stenocardia. An initial dose of 25-50 mg two-three times a day. Depending on effect this dose can be raised gradually to 200 mg a day in two steps or to add other anti-anginal drug.

Secondary prevention of a myocardial infarction. The usual dose makes 50-100 mg two times a day (in the morning and in the evening).

Arrhythmias. The initial dose makes 25-50 mg two-three times a day. If necessary the daily dose can be raised gradually to 200 mg or to add other antiarrhythmic means. Hyperthyroidism. The dose should be established individually. Recommendations about use: in an initiation of treatment on 50 mg 3-4 times a day; it is possible to increase a dose to 100 mg 3-4 times a day if ChSS is higher than the 75th blows/minute 3-4 days of treatment later an initial dose of drug. At a hyperthyroidism biotransformation of a metoprolol is raised therefore use of the highest dose of drug can be necessary. Drug is usually used during cancellation of other medicine. The functional disorders of heart which are followed by tachycardia. The usual dose makes 50 mg two times a day (in the morning and in the evening); if necessary the single dose can be raised to 100 mg, keeping the former mode of reception.

Prevention of attacks of migraine. The usual dose makes 50 mg two times a day (in the morning and in the evening); in need of it it is possible to raise to 100 mg a day.

Special groups of patients. Renal failures. Change of dosing of medicine at renal failures is not required.

Abnormal liver functions. To the patients having liver diseases метопролол appoint in the same doses, as to patients at whom function of a liver is not broken. However in case of a considerable abnormal liver function (for example, after shunting operation) there can be a need for a dose decline of a metoprolol.

Patients of advanced age. Correction of a dose is not required.

Children. Clinical experience of use of a metoprolol for children is limited.

Features of use:

At AV to blockade of the I degree drug is appointed with care, considering the dromotropic effect rendered to them. At Printsmetal's stenocardia beta adrenoblockers can increase number and duration of attacks. At patients with diseases of peripheral arteries purpose of beta adrenoblockers can lead to an aggravation of a course of these diseases.

To elderly people drug is appointed with care in low doses and under constant medical observation with regular control of indicators of function of kidneys. At patients with a non-insulin-dependent diabetes mellitus it is necessary to control the content of glucose in a blood plasma. In need of Metoprolol's appointment patients with a pheochromocytoma at the same time should appoint alpha adrenoblockers.

At patients with psoriasis against the background of Metoprolol's reception the exacerbation of a disease is possible. At predisposition to heavy anaphylactic reactions irrespective of their origin (especially after purpose of yodokontrastny drugs or during the desensibilizing treatment) use of beta adrenoblockers can lead to strengthening of allergic reactions and to lack of effect of use of adrenaline in average doses.

Before carrying out a radiological research with yodosoderzhashchy contrast agents treatment by Metoprolol has to be beforehand stopped. In cases when use of a metoprolol is absolutely necessary and it it is impossible to cancel, it is necessary to appoint the corresponding treatment. When carrying out the general anesthesia against the background of reception of beta adrenoblockers the risk of development of arterial hypotension increases.

In need of carrying out surgical intervention it is necessary to warn the anesthesiologist about the carried-out therapy to pick up anesthetic with the minimum negative inotropic effect, however drug withdrawal before operation at patients with an ischemic heart disease is not recommended. At purpose of drug periodic control of ChSS is necessary for patients with renal failures.

Use of drug can mask symptoms of a hypoglycemia and a thyrotoxicosis. The patients using contact lenses have to consider that against the background of treatment by beta adrenoblockers reduction of products of the lacrimal liquid is possible.

Influence on driving of the car and work with mechanisms. With care to apply in operating time to drivers of vehicles and people whose profession is connected with the increased concentration of attention.

Side effects:

From a nervous system and sense bodys: not less than 10% weakness; 1-9.9% - dizziness and a headache; 0.1-0.9% - decrease in concentration of attention, drowsiness/sleeplessness, nightmares, a depression, muscular spasms, paresthesia; 0.01-0.09% - nervousness, alarm, easing a libido, a vision disorder, a xerophthalmia, conjunctivitis; less than 0.01% - slackness, increased fatigue, concern, confusion of consciousness, amnesia / short-term loss of memory, a hallucination, a sonitus, disturbance of flavoring feelings.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): 1-9.9% - bradycardia, heartbeat, hypotension, a cold snap of extremities; in 0.1-0.9% - heart failure, AV blockade, an edematous syndrome, a stethalgia; in 0.01-0.09% - decrease in contractility of a myocardium, arrhythmia, less than 0.01% - gangrene (at patients with heavy disturbance of peripheric circulation); disturbance of conductivity of a myocardium, syncope, thrombocytopenia, leukopenia, agranulocytosis.

From bodies of a GIT: 1-9.9% - nausea, an abdominal pain, diarrhea or a lock, 0.1-0.9% - vomiting; 0.01-0.09% - dryness in oral cavities, abnormal liver functions; meteorism, dyspepsia, heartburn, hepatitis.

From respiratory system: asthma (1-9.9%), bronchospasm (0.1-0.9%), vasculomotor rhinitis (0.01-0.09%), диспноэ.

From integuments: 0.1-0.9% - rash, dystrophic changes of skin; 0.01-0.09% - a reversible alopecia; less than 0.01% - a photosensitization, an exacerbation of psoriasis; itch, erythema, small tortoiseshell, hyperhidrosis.

Others: body degrowth (0.1-0.9%), arthralgia, arthritis, mialgiya, muscular weakness, Peyroni's disease.

Interaction with other medicines:

Combined use of Metoprolol with Amiodaronum can lead to disturbance of a cordial rhythm (the combination is not recommended).

At combined use with blockers of calcium channels (including bepridit, diltiazem, verapamil), cardiac glycosides, Reserpinum, nitrates, a clonidine, antiarrhytmic means increase in expressiveness of bradycardia, oppression of conductivity, arterial hypotension is possible (such combination demands care, treatment is carried out under medical observation with monitoring of an ECG, especially at elderly patients and at the beginning of therapy).

Can lead use of means for an inhalation anesthesia against the background of Metoprolol's reception to oppression of sokratitelny function of a myocardium and provoke development of arterial hypotension.

At combined use Baclofenum strengthens anti-hypertensive effect of Metoprolol (control of the ABP and, perhaps, dose adjustment of a metoprolol is required).

At simultaneous use with Metoprolol Cimetidinum increases concentration of a metoprolol in a blood plasma (use of this combination demands implementation of medical observation; in case of need Metoprolol's dose has to be lowered for the period of treatment by Cimetidinum and is raised after its cancellation).

Antiacid drugs (derivatives of aluminum, magnesium, calcium) reduce Metoprolol's absorbability therefore the period between Metoprolol's reception and antiacid drugs has to make not less than 2 h.

At combined use of NPVS, are oestrogenic, beta адреностимуляторы, theophylline, cocaine weaken hypotensive effect of Metoprolol.

Simultaneous use of Metoprolol with tricyclic imipraminovy antidepressants and with antipsychotic drugs increases risk of development of arterial and heavy orthostatic hypotension.

At combined use of GKS reduce anti-hypertensive effect of drug.

At simultaneous use with Metoprolol phenobarbital and rifampicin reduce its concentration in a blood plasma, reducing, thus, effect of its use.

Contraindications:

• Hypersensitivity to a metoprolol to tartrate, other beta and adrenolytic means or to any other excipients.
• Blockade of an atrioventricular node of the second or third degree.
• Heart failure in a decompensation stage (a fluid lungs, disturbances of blood circulation or hypotonia) and constant or periodic use of the drugs increasing sokratitelny function of a myocardium (agonists of beta and adrenergic receptors).
• Symptomatic and clinical sinus bradycardia (heart rate <50/mines).
• Sick sinus syndrome.
• Cardiogenic shock.
• Printsmetal's stenocardia.
• Heavy disturbances of peripheric arterial circulation.
• Hypotonia (systolic pressure <90 mm Hg).
• Metabolic acidosis.
• Heavy bronchial asthma or chronic obstructive disease of lungs.
• Simultaneous use of inhibitors of a monoaminooxidase (except for MAO-B inhibitors).
• Serious illness of peripheral vessels with threat of gangrene.
• Age up to 18 years (efficiency and safety are not established).
• Metoprolol patients cannot appoint with suspicion of an acute myocardial infarction and with a heart rate less than 45 blows/min., PQ interval> 0,24 seconds or systolic pressure <100 mm Hg.
• Metoprolol patients cannot apply with heart failure and with a repeating systolic pressure less than 100 mm Hg (inspection before an initiation of treatment is shown). Contraindicated (except for intensive care unit) co-administration intravenously the drugs blocking calcium channels such as verapamil or diltiazem, or other drugs of antiarrhytmic action (as Disopyramidum).

Overdose:

Symptoms: nausea, vomiting, cyanosis, decrease in the ABP, sinus bradycardia, AV blockade, heart failure, cardiogenic shock, bronchospasm, loss of consciousness, coma.

Treatment: in case of heavy arterial hypotension, bradycardia, heart failure - in/in a beta adrenostimulyatory at an interval of 2-5 min. before achievement of desirable effect. In the absence of a beta adrenostimulyatorov - in/in 0.5-2 mg of Atropini sulfas; in the absence of positive effect - introduction of a dopamine, Dobutaminum or Norepinephrinum. Then purpose of a glucagon (1-10 mg) is possible. Installation of an electrocardiostimulator can be required. At a bronchospasm recommend in/in introduction of beta2-adrenostimulyator; at ventricular premature ventricular contraction - lidocaine (the drugs IA of a class are not used); at spasms - in/in administration of diazepam.

Storage conditions:

To store drug in the place protected from moisture at a temperature not above 25 °C. Period of validity 2 years.

Issue conditions:

Without recipe

Packaging:

On 10 tablets dosage of 25 mg, 50 mg and 100 mg; on 15 tablets a dosage of 50 mg; on 20 tablets a dosage of 25 mg at blister strip packagings. On the 3rd blister strip packagings on 10 and 20 tablets in a cardboard pack together with the application instruction. On 6 planimetric yacheykoy packagings on 10 tablets in a cardboard pack together with the application instruction. On 2 or 4 blister strip packagings on 15 tablets in a cardboard pack together in the application instruction.