Anaprilin - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 64.0 mg, corn starch - 20.0 mg, gelatin - 2.5 mg, sodium carboxymethyl starch - 2.5 mg, magnesium stearate - 1.0 mg.

Composition per one tablet 40 mg:

Active substance: propranolol hydrochloride 40.0 mg.

Excipients: lactose monohydrate (sugar milk) - 256.0 mg, corn starch - 80.0 mg, gelatin - 10.0 mg, sodium carboxymethyl starch - 10.0 mg, magnesium stearate - 4.0 mg.

Description:Round flat cylindrical tablets of white or almost white color with a risk on one side and with a bevel.

Pharmacotherapeutic group:Beta-blocker

ATX: & nbsp

C.07.A.A Non-selective beta-blockers

C.07.A.A.05 Propranolol

Pharmacodynamics:

Non-selective beta-blocker. Has antianginal, antihypertensive and antiarrhythmic action. Unselectively blocking beta-adrenergic receptors (75% of beta1 and 25% of beta2-adrenoreceptors) reduces catecholamine-stimulated the formation of cAMP from adenosine triphosphate, which reduces the intracellular intake of calcium, has a negative chrono-, dromo-, batmo-, and inotropic action (urezhaet heart rate (heart rate), inhibits conduction and excitability, reduces myocardial contractility).

At the beginning of beta-blockers application, the total peripheral vascular resistance increases in the first 24 hours (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation of beta2-adrenoreceptors of the vessels of skeletal muscles), but after 1-3 days it returns to the initial, decreases.

The antihypertensive effect is associated with a decrease in the minute volume of the heart,sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (important in patients with initial renin hypersecretion), sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in blood pressure (BP)) and influence on the central nervous system ). The antihypertensive effect is stabilized by the end of the 2-week course.

The antianginal effect is due to a decrease in myocardial oxygen demand (due to a negative chronotropic and inotropic effect). The decrease in heart rate leads to diastole lengthening and improvement of myocardial perfusion. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers, the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

Antiarrhythmic effect is due to 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 conduction.Oppression of impulses is noted predominantly in the antegrade and to a lesser extent in the retrograde direction through the atrioventricular node and along additional pathways. According to the classification of Vaughan-Williams antiarrhythmic drugs propranolol refers to preparations of group II. Reducing the severity of myocardial ischemia - by reducing myocardial oxygen demand, postinfarct death rate may also decrease due to antiarrhythmic action.

The ability to prevent the development of headache of vascular genesis is due to a decrease in the expansion of cerebral arteries due to beta-adrenoblockade of vascular receptors, inhibition of catecholamines aggregation of platelets and lipolysis, decrease adhesiveness of platelets, prevention of activation of clotting factors during release adrenaline, stimulation of oxygen in the tissue and a decrease in renin secretion.

Reduction of tremor on the background of the use of propranolol may be due to blockade of beta2-adrenergic receptors. Increases atherogenic properties of blood.Strengthens uterine contractions (spontaneous and drug-induced, stimulating myometrium). Increases bronchial tone.

Pharmacokinetics:

Suction

Quickly and fairly fully (90%) is absorbed when ingested from the gastrointestinal tract and is relatively quickly eliminated from the body. Bioavailability after oral administration is 30-40% (the effect of "primary passage" through the liver, microsomal oxidation), with prolonged use - increases (metabolites that inhibit liver enzymes are formed), the bioavailability depends on the nature of food and the intensity of hepatic blood flow.

Bioavailability increases by 50% when taking food rich in protein. The maximum concentration in the blood plasma is achieved after 1-1.5 hours after ingestion.

Propranolol is a substrate of P-glycoprotein. It has been shown that P-glycoprotein has no effect on the metabolism of propranolol in the usual therapeutic dose range.

Distribution

The connection with blood plasma proteins (albumin and alpha 1 acid glycoprotein) is 90-95%. The volume of distribution is 3-5 l / kg.

Penetrates through the blood-brain and placental barrier, as well as into breast milk.

Metabolism

Propranolol is extensively metabolized in the liver in three main ways: aromatic hydroxylation (42%), N-dealkylation followed by oxidation (41%) and direct glucuronation (17%). The ratio of the pathways of metabolism of propranolol can vary significantly in some cases.

There were 4 main metabolites: propranolol glucuronide, naphthyloxy-milk acid, glucuronic acid and complex sulfate compounds of 4-hydroxypropranolol.

According to research in vitro, in the metabolism of propranolol are involved isoenzymes of the cytochrome P450 system, mainly isoenzyme CYP2D6 (aromatic hydroxylation), isoenzyme CYP1A2 (oxidation of chains) and, to a lesser extent, isoenzyme CYP2C19.

In healthy volunteers, "fast" and "slow" isoenzyme metabolizers CYP2D6, there were no significant differences in clearance and half-life of propranolol.

Excretion

Half-life - 3-6 hours, against the background of the course of use can be extended to 12 hours. It is excreted mainly by kidneys in the form of metabolites, in an unchanged form, less than 1% is excreted. It is not removed during hemodialysis.

Indications:

- Arterial hypertension;

- angina pectoris tension;

- unstable angina;

- sinus tachycardia (including hyperthyroidism);

- supraventricular tachycardia;

- tahisystolic form of atrial fibrillation (ciliary tachyarrhythmia);

- supraventricular and ventricular extrasystole;

- prevention of repeated myocardial infarction (systolic blood pressure more than 100 mm Hg);

- pheochromocytoma (with simultaneous use with alpha-blockers);

- essential tremor;

- migraine (prevention of seizures);

- as an aid in the therapy of thyrotoxicosis and thyrotoxic crisis (with intolerance of thyreostatic drugs);

- sympatoadrenal crises against the background of diencephalic syndrome.

Contraindications:

- Hypersensitivity to the active ingredient or other components of the drug

- atrioventricular (AV) blockade II-III degree

- syndrome of weakness of the sinus node (including sinoaurikulyarnuyu (sinoatrial) blockade)

- bradycardia (heart rate less than 60 beats / min)

- arterial hypotension (systolic blood pressure less than 100 mm Hg)

- uncontrolled chronic heart failure

- acute heart failure

- acute myocardial infarction

- cardiogenic shock

- pulmonary edema

- angina of Prinzmetal

- Cardiomegaly (no signs of heart failure)

- severe peripheral vascular disease (Raynaud's syndrome)

- metabolic acidosis (including diabetic ketoacidosis)

- bronchial asthma, propensity to bronchospastic reactions, chronic obstructive pulmonary disease (including in the anamnesis)

- pheochromocytoma (without simultaneous use of alpha-blockers)

- spastic colitis

- simultaneous use with antipsychotic drugs (neuroleptics), anxiolytics (chlorpromazine, trioxazine, etc.), monoamine oxidase (MAO) inhibitors, blockers of "slow" calcium channels (BCCC) (see "Interaction with other drugs")

- pregnancy

- Breastfeeding period

- age to 18 years (effectiveness and safety not established)

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption (the preparation contains lactose).

Carefully:

Hepatic and / or renal failure, hyperthyroidism, myasthenia gravis, heart failure, pheochromocytoma, psoriasis, weighed down allergic anamnesis, peripheral circulatory disturbances, elderly age, atrioventricular blockade of the 1st degree, respiratory diseases, diabetes mellitus.

Pregnancy and lactation:

Anaprilin is not recommended for use during pregnancy and during breastfeeding.

Therefore, before starting the drug in women of childbearing age, pregnancy should be excluded, and during treatment they must use reliable methods of contraception. In case of confirmation of the fact of pregnancy during treatment with the drug, it should be stopped as soon as possible and transferred to the patient for taking other drugs, in which application the risk for the child will be the least.

Pregnancy

In pregnancy, the drug is used only on strict indications if the intended benefit for the mother exceeds the potential risk to the fetus (due to the possibility of delayed fetal growth, fetal death, premature birth, and development of a newborn bradycardia, arterial hypotension, hypoglycemia and paralysis respiration).

If the use of beta-blockers during pregnancy is necessary, it is more preferable to use selective beta-1 blockers. Treatment should be interrupted for 48-72 hours before delivery. In cases where this is not possible, it is necessary to monitor uteroplacental blood flow and fetal growth, as well as to ensure strict observation of the newborn during the first 3 days after delivery.

Breastfeeding period

Propranolol excreted in breast milk. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Take the drug inside before eating.

When arterial hypertension - Inward, 40 mg twice a day. If the antihypertensive effect is insufficient, the dose is increased at a weekly interval up to 40 mg 3 times or up to 80 mg 2 times a day. The maximum daily dose is 320 mg.

When angina, heart rhythm disorders - in an initial dose of 20 mg (2 tablets of 10 mg or ½ tablets of 40 mg) 3 times a day, then the dose is increased with a weekly interval to 80-120 mg in 2-3 doses. The maximum daily dose is 240 mg.

Prevention of recurrent myocardial infarction - therapy should be started between the 5th and on the 21st day after myocardial infarction in a dose 40 mg 4 times a day in for 2-3 days, then in a dose of 80 mg 2 times a day.

Day of prevention of migraine attacks, at an essential tremor, simpatoadrenal crises against a background of a diencephalic syndrome - it is recommended to use in an initial dose of 40 mg 2-3 times a day, if necessary, the dose is gradually increased to 160 mg / day with a weekly interval.

With pheochromocytoma - Use only in combination with alpha-adrenoreceptor blockers. Before operation used in a dose of 60 mg per day for 3 days. With inoperable malignant pheochromocytoma, a dose of 30 mg per day is used.

As an aid in the therapy of thyrotoxicosis and thyrotoxic crisis - in a dose of 10-20 mg 3-4 times a day. If necessary, it is possible to increase the dose to 120-160 mg per day in 2-3 doses.

Special patient groups

Use in patients with impaired liver function

Bioavailability of propranolol may be increased in patients with impaired liver function, which may require dose adjustment.In patients with severe impairment of liver function, the initial dose of the drug should not exceed 20 mg 3 times daily under the control of heart rate.

Use in patients with impaired renal function

In case of violations of kidney function, it is necessary to reduce the initial dose of the drug or increase the interval between doses of the drug (possibly increasing the concentration of propranolol in the blood plasma).

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of their incidence in accordance with the classification of the World Health Organization: Often (≥ 1/10); often (from ≥ 1/100 to <1/10); infrequently (from ≥ 1/1000 to <1/100); rarely (from ≥ 1/10000 to <1/1000); rarely (<1/10000), the frequency is unknown: it is not possible to establish the frequency of occurrence from the available data.

Disorders from the heart: infrequently - atrioventricular block; rarely - bradycardia, heart failure, palpitations, conduction disturbance of the myocardium, arrhythmia, chest pain.

Vascular disorders: often - cold extremities; rarely - expressed reduction of blood pressure, orthostatic hypotension, angiospasm, mesenteric thrombosis, Raynaud's syndrome.

Disorders from the gastrointestinal tract: infrequently - nausea, vomiting, diarrhea, epigastric pain, taste change; frequency unknown - dryness of the oral mucosa, ischemic colitis, constipation.

Disorders from the liver and bile ducts: the frequency is unknown - abnormal liver function.

Disturbances from the nervous system: rarely - psychosis, emotional lability, confusion or short-term memory loss, paresthesia, dizziness; frequency unknown - headache.

Disorders from the psyche: very often - sleep disorders (insomnia, drowsiness); often - agitation (prolonged excitation accompanied by anxiety), nightmares, irritability; frequency unknown - depression, convulsions, catatonia, decreased speed of psychomotor reactions.

Disturbances from the respiratory system, chest and mediastinal organs: Often - bronchitis; often - bronchiolitis; rarely - rhinitis, nasal congestion, bronchospasm (sometimes with a lethal outcome), laryngospasm; frequency unknown - dyspnea.

Disorders from the metabolism and nutrition: often - decreased appetite; infrequently - hypoglycemia (in patients with type 1 diabetes mellitus), hyperglycemia (in patients with type 2 diabetes mellitus), an increase in the concentration of triglycerides and cholesterol.

Disorders from the side of the organ of vision: rarely - dryness of the mucous membrane of the eyes (a decrease in the secretion of tear fluid), impaired visual acuity; frequency unknown - keratoconjunctivitis.

Disorders from the reproductive system and mammary glands: frequency unknown - decreased libido, decreased potency, Peyronie's disease.

Disturbances from the skin and subcutaneous tissue: rarely - alopecia; frequency unknown - exacerbation of psoriasis, increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, skin rash, skin itching.

Disorders from the endocrine system: the frequency is unknown - reduced function thyroid gland.

Violations from the blood and lymphatic system: infrequently - neutropenia; rarely - thrombocytopenia; frequency unknown - agranulocytosis, and leukopenia.

Laboratory and instrumental data: frequency unknown - Increased activity of "liver" transaminases and bilirubin concentration, increase in the titer of antinuclear antibodies, hyperkalemia.

General disorders and reactions at the site of administration of the drug: the frequency is unknown - pain in the chest, withdrawal syndrome, asthenic syndrome (weakness), increased fatigue.

Disorders from the musculoskeletal system and connective tissue: the frequency is unknown - arthralgia, muscle weakness, back pain or joint pain.

Overdose:

Symptoms:

From the heart: bradycardia, lowering of blood pressure, atrioventricular blockade, slowing of intraventricular conduction, heart failure.

From the respiratory system: bronchospasm.

Laboratory indicators: hypoglycemia.

From the nervous system: cramps are possible, because propranolol penetrates the blood-brain barrier.

Treatment: connect the patient to a pacemaker. It is necessary to control the vital vital indicators: glucose concentration, psycho-emotional status; in the case of bradycardia apply atropine. If the patient does not have a corresponding reaction to the introduction of plasma-substituting solutions, the possibility of using glucagon or catecholamines should be considered. When bronhospazme introduction of aminophylline. Hemodialysis is ineffective.

Interaction:

The antihypertensive effect of propranolol is enhanced by simultaneous use with diuretics, reserpine, hydralazine and other antihypertensive agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, alpha-blockers).

When used simultaneously with antihypertensive agents of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of heart failure due to a decrease in sympathetic tone (decrease Heart rate and cardiac output, increased symptoms of vasodilation). In the case of abrupt withdrawal of these drugs, especially before the abolition of propranolol, it is possible to develop a "ricochet" arterial hypertension.

Simultaneous application with IMCK dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of developing arterial hypotension. It can not be ruled out that there is an increased risk of further reduction of myocardial contractility in patients with heart failure.

Propranolol should be discontinued several days before the termination of the use of clonidine (see section "Special instructions").

Medications that cause orthostatic hypotension (nitrates, phosphodiesterase 5 inhibitors, tricyclic antidepressants, neuroleptics, dopamine receptor agonists, levodopa, amifostine, baclofen and others) can enhance the action of beta-blockers.

Antihypertensive effect weaken nonsteroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys), estrogens (sodium retention), and MAO inhibitors.

Cimetidine increases the bioavailability of propranolol.

Increases concentration lidocaine in blood plasma, reduces clearance theophylline. Simultaneous application with phenothiazine derivatives increases the concentration of both drugs in the blood plasma.

Strengthens the action thyreostatic and uterotonizing means; reduces the effect of antihistamines.

Increases the likelihood of severe systemic reactions (anaphylaxis) on the background of administration allergens, used for immunotherapy or for skin tests.

Amiodarone, verapamil, diltiazem, bepridil - increased severity of negative chrono, foreign and dromotropic effects of propranolol.

Iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.

Phenytoin when in / in the introduction, drugs for inhalation of general anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of lowering blood pressure.

Changes the efficiency insulin and hypoglycemic agents for oral administration, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Propranolol reduces clearance xanthines (except for diphylline).

Antihypertensive effect weaken glucocorticosteroids.

Cardiac glycosides, methyldopa, reserpine and guanfacine, antiarrhythmics increase the risk of developing or worsening bradycardia, atrioventricular blockade, cardiac arrest and heart failure.

Lengthens the action Nondepolarizing muscle relaxants and anticoagulant effect coumarins.

Tri- and tetracyclic antidepressants, antipsychotics (antipsychotics), antipsychotics ethanol, sedatives and hypnotics increase the CNS depression. It is not recommended to use the MAO inhibitors due to a significant increase in antihypertensive action, a break in treatment between taking MAO inhibitors and propranolol should be at least 14 days. Simultaneous use with anxiolytics (chlorpromazine, trioxazine, etc.) enhances the antihypertensive effect of beta-blockers.

Unhydrated alkaloids of ergot increase the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of propranolol in the blood plasma (inhibits metabolism), rifampicin shortens the half-life.

Special instructions:

Beta-blockers should not be used in patients with untreated chronic heart failure, until the condition has stabilized.

Before using the drug for patients with heart failure (early stages), cardiac glycosides and / or diuretics should be used.

Control of patients taking the drug should include monitoring heart rate and blood pressure (at the beginning of treatment - every day, then once every 3-4 months), recording the electrocardiogram.

In elderly patients it is recommended to monitor kidney function (1 time in 4-5 months).

In the case of elderly patients with increasing bradycardia (less than 60 beats per minute), arterial hypotension (systolic blood pressure less than 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe violations of the liver and / or kidneys, it is necessary to reduce the dose of the drug or stop treatment.

With caution apply the drug in patients with atrioventricular blockade of the I degree.

It is necessary to teach the patient how to calculate the heart rate and instruct him about the need for medical consultation at a heart rate of less than 60 beats per minute.

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

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

Treatment of coronary heart disease and persistent hypertension should be long - taking the drug is possible for several years.

Termination of treatment is carried out gradually, under the supervision of a doctor: a sharp cancellation can dramatically increase myocardial ischemia, anginal syndrome, worsen tolerance to physical exertion. Cancellation is carried out gradually, reducing the dose by 25% every 3-4 days for 2 weeks or more.

When deciding on the use of the drug Anaprilin in patients with psoriasis should carefully compare the expected benefits and the possible risk of exacerbation of the course of psoriasis.

With thyrotoxicosis propranolol can mask certain clinical signs of hyperthyroidism (for example, tachycardia). Sharp abolition in patients with hyperthyroidism is contraindicated because it can enhance symptoms.

On the background of therapy with propranolol, some reports on the development of myasthenia gravis were recorded. If you have muscle weakness, you need to consult a doctor. In patients with diabetes, the use of the drug is controlled by the concentration of glucose in the blood (1 time in 4-5 months). With caution apply simultaneously with hypoglycemic agents, because during prolonged breaks in food intake, as well as against the background of insulin therapy, hypoglycemia may develop.And such her symptoms, like tachycardia or tremor, will be masked by the action of the drug. The patient should be instructed that the main symptom of hypoglycemia during treatment with the drug is increased sweating. Also there is a risk of hyperglycemia when taking hypoglycemic agents for oral administration.

With the simultaneous administration of clonidine, his admission may be terminated only a few days after the withdrawal of the drug.

Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Propranolol can be the cause of a severe reaction to a number of allergens when administered to patients who have a history of severe anaphylactic reaction to these allergens. Such patients may not respond to the usual doses of epinephrine (adrenaline) used to treat anaphylactic shock.

When pheochromocytoma is used only in combination with alpha-blockers. Contraindicated simultaneous use with antipsychotic drugs (neuroleptics) and tranquilizers.

Drugs that reduce catecholamine stocks (for example, reserpine) can enhance the action of propranolol.so patients taking the combination of drugs should be under the constant supervision of the doctor for the detection of arterial hypotension and bradycardia.

On the background of treatment, intravenous administration of verapamil, diltiazem should be avoided.

Use with caution together with psychotropic drugs, for example, MAO inhibitors, with their course use for more than 2 weeks.

A few days before the general anesthesia with chloroform or ether, it is necessary to stop taking the drug (increased risk of oppression of myocardial function and development of arterial hypotension). It is necessary to warn the anesthesia doctor that the patient is taking Anaprilin.

The effectiveness of beta-blockers in smokers is lower than in non-smoking patients. It is necessary to cancel the preparation Anaprilin before the study of blood and urine content of catecholamines, normetanephrine and vanillylmandelic acid, titers of antinuclear antibodies.

It is necessary to suspend therapy with the drug for respiratory infection of the lower respiratory tract, accompanied by shortness of breath. The use of beta2-agonists and inhaled glucocorticosteroids is acceptable.Renewal of the use of the drug is possible only after full recovery of the patient. When re-infection, as well as in the case of isolated bronchospasm, the drug should be discontinued altogether.

During treatment, it is not recommended to take alcohol.

Beta-adrenoblockers should be used with caution in patients with peripheral circulatory disorders, since it is possible to aggravate the data symptoms.

Avoid the use of natural licorice: food rich in protein, can increase the bioavailability of propranolol.

Propranolol can give a positive result in the doping test.

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

The effect of Anaprilin on the ability to drive vehicles and mechanisms has not been studied. Because of the possible occurrence of side effects such as dizziness, drowsiness, decreased speed of psychomotor reactions, during the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 10 mg and 40 mg.

Packaging:

By 10, 25, 30, 50 tablets in a contour cell package from the film polyvinylchloride and aluminum foil printed lacquered.

10, 20, 30, 50, 60 or 100 tablets in banks of PET for drugs sealed with lids screw-with the control of the first opening or the system "push-turn" of polypropylene or polyethylene or banks polypropylene for drugs sealed with lids tensioned control the first opening of polyethylene or polypropylene jars for drugs sealed with lids tensioned to control the first opening of the high-pressure polyethylene.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package.

Storage conditions:

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.

Terms of leave from pharmacies:On prescription

Registration number:LP-004424

Date of registration:21.08.2017

Expiration Date:21.08.2022

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp18.09.2017

Illustrated instructions

Instructions

Anaprilin (Anaprilin)