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

Excipients: lactose monohydrate 78.7 mg, potato starch -24.8 mg, povidone (polyvinylpyrrolidone medium molecular weight) 3.0 mg, talc 2.3 mg, calcium stearate 1.2 mg.

1 tablet of 40 mg contains:

active substance: propranolol hydrochloride 40.0 mg;

Excipients: lactose monohydrate 110.0 mg, potato starch 40.0 mg, povidone (medium-molecular-weight polyvinylpyrrolidone) 4.2 mg, talc 3.9 mg, calcium stearate 1.9 mg.

Description:

Tablets are white, round, flat-cylindrical with a facet without any risks.

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, anti-hypertensive and anti-arrhythmic action. Not selectively blocking beta-adrenoceptors (75% beta₁ and 25% beta₂-adrenoceptors), reduces the catecholamines-stimulated formation of cyclic adenosine monophosphate from adenosine triphosphate, which reduces the intracellular intake of calcium, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces the number of cardiac contractions, inhibits conduction and excitability, and 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 the elimination of beta stimulation2adrenoreceptors vessels of skeletal muscles), but after 1-3 days, returns to the original, and with prolonged use decreases.

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

The antianginal effect is due to a decrease in myocardial oxygen demand (due to a negative chronotropic and inotropic effect). Reducing the number of cardiac contractions 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 of the heart 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 content of cyclic adenosine monophosphate, 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 antiarrhythmic drugs belongs to the drugs of group II.

Reducing the severity of myocardial ischemia - due to the reduction in myocardial oxygen demand, postmyocardial lethality - due to antiarrhythmic action.

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

Reduction of tremor on the background of the use of propranolol is due primarily to blockade of peripheral beta₂adrenoreceptors.

Increases atherogenic properties of blood.

Strengthens uterine contractions (spontaneous and caused by drugs, stimulating the myometrium).

Increases bronchial tone.

Pharmacokinetics:

Quickly and fairly fully (90%) is absorbed when taken orally and is relatively quickly eliminated from the body. Bioavailability after oral administration - 30-40% (the effect of "primary" passage through the liver, microsomal oxidation), with prolonged admission increases (metabolites that inhibit liver enzymes are formed), its magnitude depends on the nature of food and the intensity of hepatic blood flow. The maximum concentration in blood plasma is reached after 1-1.5 hours. It has high lipophilicity, accumulates in lung tissue, brain, kidneys, heart. Penetrates through the blood-brain barrier, placental barrier, into breast milk. The volume of distribution is 3-5 l / kg. The connection with plasma proteins is 90-95%.

It is metabolized in 3 ways - aromatic hydroxylation, n-dealkylation, glucuronation in the liver (including with the participation of cytochrome isoenzymes cyp2d6, cyp1a2, sur 2s19) - getting bile into the intestine, deglukuroniruetsya and reabsorbiruetsya, as a result, the half-life period against the background of the course of administration may extend to 12 hours, also in elderly patients and patients with impaired renal and hepatic function, the concentration of the drug in the blood plasma increases and the half-life extends. The half-life is 3-5 hours. It is excreted by the kidneys - 90%, unchanged - less than 1%. It is not removed during hemodialysis.

Indications:

Arterial hypertension, angina pectoris, unstable angina, sinus tachycardia (including thyrotoxicosis), supraventricular tachycardia, ciliary tachyarrhythmia, supraventricular and ventricular extrasystole, myocardial infarction (to reduce cardiovascular mortality after myocardial infarction in patients with stable hemodynamics , systolic blood pressure more than 100 mm Hg), pheochromocytoma (with simultaneous use of alpha-adrenoblockers), essential tremor, migraine (prophylaxis attacks), diffuse toxic goiter and thyrotoxic crisis (as an auxiliary drug, including intolerance thyreostatics medicaments), sympatoadrenal crises against the background of diencephalic syndrome.

Contraindications:Hypersensitivity to the drug components, acute and chronic heart failure in the stage of decompensation, cardiogenic shock, atrioventricular block II-III severe sinus bradycardia (the number of heartbeats is less than 50 (strokes) per minute), sinoatrial blockade, sinus node weakness syndrome, prinzmetal angina, cardiomegaly, severe peripheral circulation disorders, metabolic acidosis, bronchial asthma, propensity to bronchial obstruction, chronic obstructive pulmonary disease , simultaneous administration of monoamine oxidase inhibitors, antipsychotic anxiolytic agents, lactation period; chronic heart failure with the indication of the functional class, pulmonary edema, diabetes mellitus, sugar / isomaltase deficiency, fructose intolerance, tk. the preparation contains sucrose, the age of 18 years, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), acute myocardial infarction (systolic blood pressure less than 100 mm Hg), simultaneous intravenous injection, verapamil and diltiazem, pheochromocytoma (without simultaneous use of alpha-blockers).

Carefully:

Renal and / or hepatic insufficiency, hyperthyroidism, depression; myasthenia gravis, pheochromocytoma (with simultaneous use of alpha-blockers), psoriasis, peripheral circulatory disorders, allergic anamnesis, atrioventricular blockade of I degree, chronic cardiac insufficiency of I-II functional class according to nyha, pregnancy, elderly age.

Pregnancy and lactation:

Use during pregnancy is possible if the benefit to the mother exceeds the risk of side effects in the fetus and the baby. If you need to take during pregnancy - careful monitoring of the fetus, for 48-72 h before delivery should be canceled.

The use of the drug is contraindicated in the period of breastfeeding.

Dosing and Administration:

With arterial hypertension taken inside, 40 mg 2 times a day. If the antihypertensive effect is insufficient, the dose is increased to 40 mg three times or 80 mg twice a day. The maximum daily dose is 320 mg.

With angina pectoris, heart rhythm disturbances - in an initial dose of 20 mg 3 times a day, then the dose is gradually increased to 80-120 mg for 2-3 doses. The maximum daily dose is 240 mg.

For the prevention of migraine, as well as with essential tremor - in an initial dose of 40 mg 2-3 times a day, if necessary, the dose is gradually increased to 160 mg / day.

If the liver function is impaired, lower doses are necessary. Dysregulation of renal dosing does not require correction.

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

With pheochromocytoma - use only with alpha-adrenoreceptor blockers.

Before operation prescribe 60 mg per day, for 3 days.

With hyperthyroidism (adjuvant) - 40 mg 3-4 times a day, if necessary, it is possible to increase the dose to 120-160 mg per day.

Side effects:

From the nervous system: increased fatigue, weakness, dizziness, migraine, drowsiness or insomnia, bright dreams, depression, anxiety, confusion, hallucinations, tremor, paresthesia, nervousness, decreased speed of psychomotor reactions, increased fatigue, short-term memory loss, emotional lability, catatonia.

From the sense organs: decrease in secretion of tear fluid (dryness and soreness of the eyes), visual acuity, keratoconjunctivitis.

From the cardiovascular system: sinus bradycardia, atrioventricular blockade (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, development of chronic heart failure, marked decrease in arterial pressure, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disturbance, coldness of the lower limbs, Raynaud's syndrome) , chest pain, palpitations, mesenteric thrombosis.

From the digestive system: nausea, vomiting, discomfort in the epigastric region, constipation or diarrhea, impaired liver function (dark urine, icteric sclera or skin, cholestasis), changes in taste, dryness of the oral mucosa, ischemic colitis.

From the respiratory system: nasal congestion, bronchospasm, rhinitis, dyspnea, laryngospasm.

From the endocrine system: change in the concentration of blood glucose (hypo- or hyperglycemia).

Allergic reactions: skin itching, skin rash, hives, Stevens-Johnson syndrome.

From the skin: increased sweating, psoriasis-like skin reactions,exacerbation of psoriasis symptoms, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, alopecia, exanthema.

Laboratory indicators: thrombocytopenia (unusual bleeding and hemorrhage), leukopenia, increased activity of "hepatic" transaminases, lactate dehydrogenase, agranulocytosis, increase of antinuclear antibody titers, hyperbilirubinemia.

Influence on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: pain in the back, arthralgia, decreased potency, withdrawal syndrome (increased angina attacks, myocardial infarction, increased blood pressure), Peyronie's disease.

Overdose:

Symptoms: severe bradycardia, dizziness, atrioventricular block, marked decrease in blood pressure, fainting, arrhythmia, ventricular extrasystole, heart failure - acute or worsening of the course of chronic heart failure, cyanosis of fingernails or palms, convulsions, difficulty breathing, bronchospasm.

Treatment: gastric lavage, the use of activated charcoal,with violation of atrioventricular conduction - intravenously injected with 1-2 mg of atropine, at a low efficiency, a temporary pacemaker is performed; with ventricular extrasystole - lidocaine (preparations IA class do not apply); with a decrease in blood pressure - the patient should be in the Trendelenburg position; with bradycardia - 1-2 mg of atropine intravenously, if necessary staging the pacemaker; with atrioventricular blockade - epinephrine, staging the pacemaker. If there are no signs of pulmonary edema, intravenously injected plasma-substituting solutions, with inefficiency - epinephrine, dopamine, dobutamine; with heart failure - cardiac glycosides, diuretics, glucagon; with convulsions - intravenously diazepam; with bronhospazme - inhalation or parenteral beta-adrenomimetiki.

Interaction:

Allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving propranolol.

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

Phenytoin with intravenous administration, drugs for inhalation of general anesthesia (derivatives of hydrocarbons) increase the severity of cardio-depressive action and the likelihood of lowering blood pressure.

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

Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in the plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Antihypertensive effect weaken non-steroidal anti-inflammatory drugs (sodium retention and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers of "slow" calcium channels (verapamil and diltiazem with their simultaneous intravenous administration with beta-blockers), amiodarone and other antiarrhythmic drugs increase the risk of developing or exacerbating bradycardia, atrioventricular blockade, cardiac arrest and heart failure.The simultaneous use of propranolol and nifedipine can lead to a significant reduction in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to excessive lowering of blood pressure.

Lengthens the effect of nondepolarizing muscle relaxants and anticoagulant effect of warfarin.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase the inhibition of the central nervous system.

Fluvoxamine increases the concentration of propranolol in the blood plasma.

Contraindicated the joint use of propranolol with antipsychotic and anxiolytic drugs.

It is not recommended simultaneous use with monoamine oxidase inhibitors due to a significant increase in antihypertensive action, a break in the treatment between taking monoamine oxidase inhibitors and propranolol should be at least 14 days.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

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

Simultaneous use with phenothiazine derivatives increases the concentrations of both drugs in plasma.

Sulfasalazine and cimetidine; increase the concentration of propranolol in the plasma (inhibit metabolism), rifampicin shortens the half-life.

Special instructions:

Control of patients receiving propranololShould include monitoring the heart rate nd blood pressure (at the beginning of treatment every day, then 1 every 3-4 months), electrocardiogram, the concentration of plasma glucose in patients with diabetes mellitus (1 every 4-5 months). In elderly patients it is recommended to monitor the kidney function (1 time in 4-5 months).

It should teach the patient the method of counting the number of cardiac contractions and pro-instruct the need medical advice when the number of heart rate less than 50 beats / min.

Before using propranolol, patients with chronic heart failure (early stages) should use cardiac glycosides and / or diuretics.

In "smokers" the effectiveness of beta-blockers is lower.

Patients who use contact lenses should take into account that a reduction in tear fluid production is possible against the background of treatment.

Patients with pheochromocytoma are prescribed only in combination with the use of alpha-blockers.

With thyrotoxicosis propranolol can mask certain clinical signs of thyrotoxicosis (eg, tachycardia). Sharp abolition in patients with thyrotoxicosis is contraindicated, as it can strengthen symptoms.

When prescribing beta-blockers, patients receiving hypoglycemic drugs should be careful, because during prolonged interruptions in eating can develop hypoglycemia. And such her symptoms, like tachycardia or tremor, will be masked by the action of the drug. Patients should be instructed that the main symptom of hypoglycemia during treatment with beta-blockers is increased sweating.

With the simultaneous administration of clonidine, his reception may be discontinued only a few days after the withdrawal of propranolol.

It is possible to increase the severity of the hypersensitivity reaction and the lack of effect from the usual doses of epinephrine against the background of a burdened allergic anamnesis.

A few days before the general anesthesia should stop taking the drug. If the patient has taken the drug before surgery, he should choose a medicine for general anesthesia with a minimum negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Drugs that reduce catecholamine stores (for example, reserpine), can enhance the action of beta-blockers, so patients who take such combinations of drugs should be under constant medical supervision for the diagnosis of arterial hypotension or bradycardia.

It can not be used simultaneously with antipsychotic drugs (neuroleptics) and anxiolytic drugs (tranquilizers).

Carefully apply together with psychoactive drugs, for example, monoamine oxidase inhibitors, with their course use for more than 2 weeks.

Avoid intravenous administration of verapamil and diltiazem against the background of therapy with Anaprilin.

If elderly patients develop an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure below 100 mmHg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe violations of the liver and kidneys, it is necessary to reduce the dose or stop treatment. It is recommended to stop therapy with the development of depression caused by the use of beta-blockers.

Do not abruptly interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose for 2 weeks or more (by 25% in 3-4 days).

It should be canceled before testing in the blood plasma and urine catecholamines, normetanefrin and vanillylmandelic acid; titers of antinuclear antibodies.

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

During the treatment period, care must be taken when driving vehicles and other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 10 mg or 40 mg.

Packaging:

For 10 or 25 tablets in a contour mesh package.

5 contour cell packs of 10 tablets, 2 or 4 contour packs of 25 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002039

Date of registration:30.08.2011 / 09.04.2014

Expiration Date:Unlimited

The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia

Manufacturer: & nbsp

TATHIMFARMPREPARATY, JSC Russia

Representation: & nbspTATHIMFARM PREPARATIONS OJSC TATHIMFARM PREPARATIONS OJSC Russia

Information update date: & nbsp27.08.2017

Illustrated instructions

Instructions

Anaprilin (Anaprilin)