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

Excipients: sucrose (refined sugar) 78.7 mg or 110.0 mg, potato starch 27.0 mg or 44.0 mg, talc 3.3 mg or 4.6 mg, calcium stearate 1.0 mg or 1.4 mg .

Description:

Round tablets of white or almost white color of flat-cylindrical shape 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 anti-hypertensive, antiarrhythmic and antianginal effects.Not selectively blocks beta-adrenergic receptors (75% beta₁- and 25% beta₂-adrenoreceptors), reduces catecholamine-stimulated formation of cyclic adenosine monophosphate from adenosine triphosphate, resulting in decreased intracellular current of Ca²⁺, has a negative chrono-, dromo-, batmo- and inotropic effect (it cuts the heart rate, inhibits conduction and excitability, reduces myocardial contractility).

The total peripheral vascular resistance at the beginning of beta-blockers in the first 24 hours increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), after 1-3 days it returns to the initial, and with prolonged use decreases.

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

Antianginal action is caused by a decrease in myocardial oxygen demand (due to a negative chronotropic and inotropic effect). Reducing the heart rate leads to diastole lengthening and improvement of myocardial perfusion.

Antiarrhythmic effect is caused by elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of cyclic adenosine monophosphate, arterial hypertension), decreased speed and spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular conduction. The suppression of the impulse is noted mainly in the antegrade, and, to a lesser extent, in the retrograde direction through the atrioventricular node and along additional paths. According to the classification of antiarrhythmic drugs refers to drugs class II.

The severity of myocardial ischemia and postmyocardial lethality can also be reduced due to antiarrhythmic action.

Prevention of headache of vascular genesis is due to the prevention of the expansion of cerebral arteries due to beta adrenoblockade of vascular receptors,inhibition of catecholamine-induced platelet aggregation and lipolysis, decreased adhesion of platelets, prevention of activation of clotting factors during the release of adrenaline, stimulation of oxygen supply to the tissue, and a decrease in renin secretion.

Reduction of tremor on the background of the use of propranolol may be due to blockade beta₂adreporeceptors.

Increases atherogenic properties of blood.

It increases uterine contractions (spontaneous and caused by means stimulating the myometrium), which helps to reduce bleeding during labor and during the postoperative period.

Increases bronchial tone.

Pharmacokinetics:

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

Metabolized in the liver 3 ways - aromatic hydroxylation, n-dealkylation, glucuronation, including with the participation of cytochrome P450 isoenzymes CYP2D6, CYP1A2, CYP2C19. It falls into the intestines with bile, deglycuronizes and reabsorbs, as a result, the half-life period against the background of the course use may extend to 12 hours. The half-life period is 3-5 hours. It is excreted by the kidneys - 90%, unchanged - less than 1%. It is not removed during hemodialysis.

In elderly patients, patients with impaired renal and hepatic function, the concentration of the drug in the blood plasma increases and the half-life is prolonged.

Indications:

Arterial hypertension, angina pectoris, unstable angina, sinus tachycardia (including hyperthyroidism), supraventricular and ciliary tachyarrhythmias, supraventricular and ventricular extrasystole, myocardial infarction (to reduce cardiovascular mortality after myocardial infarction in patients with stable hemodynamic parameters), essential tremor,pheochromocytoma (together with alpha-adrenergic blockers), migraine (prophylaxis of attacks), as an aid in the therapy of thyrotoxicosis and thyrotoxic crisis (with intolerance of thyreostatic drugs).

Contraindications:

Hypersensitivity to the drug components, acute heart failure, decompensated heart failure (NYHA III and IV FC), cardiogenic shock, atrioventricular block II-III (less than 50 beats per minute), prinzmetal angina, cardiomegaly (without signs of heart failure), arterial hypotension (systolic blood pressure less than 90 mm Hg .st., especially with myocardial infarction); propensity to bronchospastic reactions, severe forms of bronchial asthma and chronic obstructive pulmonary disease; severe violations of peripheral circulation (complicated by gangrene, intermittent claudication or pain at rest), vasomotor rhinitis, decompensated diabetes mellitus, metabolic acidosis,simultaneous administration of monoamine oxidase inhibitors; pheochromocytoma (without simultaneous use of alpha-blockers); simultaneous intravenous administration of verapamil or diltiazem; deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption; lactation period, children under 18 years.

Carefully:

Allergic history, chronic heart failure I-II functional class for NYHA, Pheochromocytoma (while the use of alpha blockers), liver and / or renal failure, peripheral circulatory disorders, thyrotoxicosis, myasthenia gravis, depression (including history), psoriasis, chronic bronchitis, emphysema, diabetes, hypoglycemia, spastic colitis, old age, pregnancy.

Pregnancy and lactation:

Pregnancy is possible if the expected therapeutic effect for the mother outweighs the potential risk to the fetus. When applied during pregnancy necessary observation fruit, and for 48-72 hours before the expected date of delivery, interrupt propranolol therapy to prevent bradycardia, hypotension, respiratory depression hypoglycemia (neonatal asphyxia) newborn.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Take inside for 10-30 minutes before eating, squeezed with a sufficient amount of liquid. Dosing regimen is individual, the dose and duration of treatment is determined by the doctor.

With arterial hypertension the initial dose is 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 (in exceptional cases - 640 mg).

With angina and heart rhythm disorders the initial dose is 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.

After acute myocardial infarction use in the period from 5 to 21 days after a heart attack 40 mg 4 times a day for 2-3 days, then - 80 mg twice a day.

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

With pheochromocytoma after taking an alpha-blocker, 30-60 mg / day is used for 3 days (before surgery).

With thyrotoxicosis therapy (with intolerance of thyreostatic agents) 40 mg 3-4 times a day are used, with thyrotoxic crisis - 20-120 mg every 4-6 hours. The maximum daily dose is 320 mg (in exceptional cases - 640 mg).

If there is a violation of the liver, but not with a violation of the kidneys, you need to reduce the dose of the drug.

Side effects:

From the nervous system: increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenic syndrome, muscle weakness, paresthesia, tremor, decreased speed of psychomotor reactions, catatonia, emotional lability.

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

From the side of the cardiovascular system: sinus bradycardia, palpitations, conduction disturbance of myocardium, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, weakening of myocardial contractility,development (aggravation) of chronic heart failure (swelling of the ankles, feet, shortness of breath), lowering of arterial pressure, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disturbance, cooling of limbs, Raynaud's syndrome), chest pain, mesenteric thrombosis.

From the digestive system: dryness of the oral cavity mucosa, nausea, vomiting, epigastric pain, flatulence, diarrhea or constipation, impaired liver function (dark urine, icteric sclera or skin, cholestasis), taste change, ischemic colitis.

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

From the endocrine system: hyperglycemia (in patients with type 2 diabetes mellitus), hypoglycemia (in patients with type 1 diabetes mellitus), decreased thyroid function.

Allergic reactions: skin rash, itching, hives.

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

Laboratory indicators: agranulocytosis, thrombocytopenia (unusual bleeding and hemorrhage), leukopenia, increased activity of "hepatic" transaminases and bilirubin concentrations, an increase in the titer of antinuclear antibodies.

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

Other: back pain, arthralgia, weakening of libido, decreased potency, withdrawal syndrome (increased angina attacks, increased blood pressure), Peyronie's disease.

Overdose:

Symptoms: severe bradycardia, dizziness, marked decrease in arterial pressure, atrioventricular blockade, fainting, arrhythmia, ventricular extrasystole, worsening of chronic heart failure, cyanosis of fingernails or palms, convulsions, difficulty breathing, hypokalemia, bronchospasm.

Treatment: gastric lavage, the use of activated charcoal. If there is a violation of atrioventricular conduction - 1-2 mg of atropine intravenously, epinephrine, at a low efficiency, a temporary pacemaker is performed; with ventricular extrasystole - lidocaine (antiarrhythmic drugs IA class do not apply); with arterial hypotension - the patient should be in the Trendelenburg position. With bradycardia, 1-2 mg of atropine is administered intravenously, if necessary, the pacemaker is staged. With hypokalemia, prescribe potassium preparations.

If there are no signs of pulmonary edema, intravenously injected plasma-substituting solutions, with inefficiency - epinephrine, dopamine, dobutamine; with heart failure - cardiac glycosides, diuretics; with convulsions - diazepam, intravenously; at bronhospazme - beta-adrenomimetiki, inhalation or parenteral.

Interaction:

Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis.

Means for inhalation anesthesia (halothane, cyclopropane, methoxyflurane) increase the risk of oppression of myocardial function and development of arterial hypotension.

Amiodarone increases the risk of developing bradycardia and suppressing atrioventricular conduction.

Propranolol increases the concentration of lidocaine in the blood plasma.

Antihypertensive effect weaken non-steroidal anti-inflammatory drugs (sodium retention and blocking of synthesis Pg kidneys), estrogens (sodium retention).

Blocks of "slow" calcium channels (verapamil, diltiazem), cardiac glycosides and antiarrhythmic drugs increase the risk of developing or worsening atrioventricular blockade and heart failure. Simultaneous intravenous use of verapamil or diltiazem can provoke cardiac arrest; nifedinin - can lead to a significant decrease in blood pressure.

Phenytoin with intravenous administration, means for general anesthesia increase the severity of cardiodepressive action.

The antihypertensive effect of propranolol is enhanced when combined with hydrochlorothiazide, reserpine, hydralazine and other antihypertensive drugs.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs, as well as ethanol, can lead to an excessive decrease in blood pressure.

Hydralazine and ethanol increase the bioavailability of propranolol.

Methyldopa, reserpine and guanfacine increase the risk of developing arterial hypotension and bradycardia.

Cimetidine increases the concentration of propranolol in the blood plasma (inhibits metabolism).

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

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

Iodine-containing radiopaque substances with intravenous use increase the risk of anaphylactic reactions.

Reduces the clearance of xanthines, especially in patients with initially elevated clearance of theophylline under the influence of smoking. Xanthines and sympathomimetics reduce the activity of propranolol.

Lengthens the effect of nondepolarizing muscle relaxants, anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotics, ethanol, sedative and hypnotic drugs increase oppression of the central nervous system. Incompatible with antipsychotic drugs and anxiolytics.

Ergotamine increases the risk of peripheral circulatory disorders; sulfasalazine increases the concentration of propranolol in the blood plasma; rifampicin shortens the half-life.

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.

Increases the effect of insulin and reduces the effect of hypoglycemic agents for oral administration.

Fluvoxamine increases the concentration of propranolol in the blood plasma.

Special instructions:

Monitoring of patients taking propranolol, should include monitoring the heart rate and blood pressure (at the beginning of treatment - every day, then once in 3-4 months), an electrocardiogram, the concentration of blood glucose in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended to monitor kidney function (1 every 4 to 5 months).

The patient should be taught how to calculate the heart rate and instructed about the need for medical advice at a heart rate of less than 50 beats per minute.

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

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

Patients using contact lenses should take into account,that against the background of treatment may reduce the production of tear fluid.

Patients with pheochromocytoma propranolol appoint only after taking an alpha-blocker.

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

When using 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 use of clonidine, its administration can be stopped 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 anesthetized with chloroform or ether, it is necessary to stop taking the drug. If the patient has taken the drug before the operation, he should choose an anesthetic with minimal negative inotropic effect.

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

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

If elderly patients develop an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure less than 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe liver and / or kidney function impairment dose of the drug or discontinue treatment. It is recommended to stop therapy with the development of depression caused by the use of beta-blockers.

The interruption in the treatment between taking monoamine oxidase inhibitors and propranolol should be at least 14 days.

It is necessary to cancel the drug before examining the blood and urine content of catecholamines, normetanephrine and vanillylmandelic acid, antinuclear antibody titers.

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. When the drug is withdrawn, the dose is gradually reduced within 2 weeks or more (by 25% every 3-4 days).

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

During the treatment period, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 10 mg and 40 mg.

Packaging:

For 10 or 50 tablets in a contour mesh package. Five 5-cell contiguous packs of 10 tablets or one out-of-the-box cell pack of 50 tablets, along with instructions for medical use, are put in a pack.

For 50 tablets in a plastic container for medicines, equipped with a lid with a control of the first opening. The container, together with instructions for medical use, is put in a pack.

Storage conditions:

Keep in dry the dark place 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 expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015657 / 01

Date of registration:20.03.2009 / 18.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:HEALTH PHARMACEUTICAL COMPANY, LTD. HEALTH PHARMACEUTICAL COMPANY, LTD. Ukraine

Manufacturer: & nbsp

HEALTH PHARMACEUTICAL COMPANY, LTD. Ukraine

Information update date: & nbsp28.08.2017

Illustrated instructions

Instructions

Anaprilin (Anaprilin)