Prinorm (Tablets) Instructions for Use

Marketing Authorization Holder

Galenika, a.d. (Serbia)

ATC Code

C07AB03 (Atenolol)

Active Substance

Atenolol (Rec.INN registered by WHO)

Dosage Form

Prinorm

Tablets 100 mg: 14 pcs.

Dosage Form, Packaging, and Composition

7 pcs. – blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Cardioselective beta₁-adrenergic blocker without intrinsic sympathomimetic activity. It has antihypertensive, antianginal, and antiarrhythmic effects.

It reduces the stimulating effect on the heart of sympathetic innervation and circulating catecholamines. It has negative chronotropic, dromotropic, bathmotropic, and inotropic effects: it reduces heart rate, inhibits conduction and excitability, and reduces myocardial contractility. Total peripheral vascular resistance at the beginning of the use of beta-blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta₂-adrenergic receptors), returns to the initial level after 1-3 days, and decreases with long-term use.

The hypotensive effect is associated with a decrease in cardiac output, a decrease in the activity of the renin-angiotensin system (more important for patients with initial hypersecretion of renin), the sensitivity of the aortic arch baroreceptors (their activity does not increase in response to a decrease in blood pressure), and the effect on the central nervous system; it is manifested by a decrease in both systolic and diastolic blood pressure, stroke volume and cardiac output. In average therapeutic doses, it does not affect the tone of peripheral arteries.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. The decrease in heart rate occurs at rest and during physical exertion. Due to an increase in the end-diastolic pressure in the left ventricle and an increase in the stretching of the muscle fibers of the ventricles, it can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and a slowdown in AV conduction. Inhibition of impulse conduction is noted mainly in the antegrade and to a lesser extent in the retrograde directions through the AV node and along additional pathways.

Unlike non-selective beta-blockers, when used in average therapeutic doses, it has a less pronounced effect on organs containing beta₂-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism; the severity of the atherogenic effect does not differ from that of propranolol. The negative bathmotropic, chronotropic, inotropic and dromotropic effects are less pronounced. When used in high doses (more than 100 mg/day), it causes blockade of both subtypes of beta-adrenergic receptors.

The hypotensive effect lasts for 24 hours, and stabilizes by the end of the 2nd week of regular use. The negative chronotropic effect appears 1 hour after administration, reaches a maximum after 2-4 hours and lasts up to 24 hours.

Pharmacokinetics

After oral administration, absorption from the gastrointestinal tract is 50-60%, bioavailability is 40-50%. It is practically not metabolized in the body. It penetrates poorly through the blood-brain barrier. Plasma protein binding is 6-16%.

The half-life (T_1/2) is 6-9 hours. It is excreted mainly by the kidneys unchanged. Impaired renal function is accompanied mainly by an increase in T_1/2 and accumulation: with a creatinine clearance of less than 35 ml/min, T_1/2 is 16-27 hours, with a creatinine clearance of less than 15 ml/min – more than 27 hours, with anuria it increases to 144 hours. It is removed during hemodialysis.

In elderly patients, T_1/2 increases.

Indications

Arterial hypertension, hypertensive crisis, mitral valve prolapse, hyperkinetic cardiac syndrome of functional origin, neurocirculatory dystonia of the hypertensive type.

Treatment: coronary artery disease, angina pectoris (exertional, rest and unstable).

Treatment and prevention: myocardial infarction (acute phase with stable hemodynamic parameters, secondary prevention).

Arrhythmias (including during general anesthesia, congenital long QT syndrome, myocardial infarction without signs of chronic heart failure, thyrotoxicosis), sinus tachycardia, paroxysmal atrial tachycardia, supraventricular and ventricular extrasystole, supraventricular and ventricular tachycardia, atrial tachyarrhythmia, atrial flutter.

Essential and senile tremor, agitation and tremor in withdrawal syndrome.

As part of complex therapy: hypertrophic obstructive cardiomyopathy, pheochromocytoma (only together with alpha-blockers), thyrotoxicosis; migraine (prevention).

ICD codes

Dosage Regimen

The dose is set individually. The usual dose for adults is orally, at the beginning of treatment, 25-50 mg once a day. If necessary, the dose is gradually increased. In case of impaired renal function in patients with a creatinine clearance of 15-35 ml/min – 50 mg/day; with a creatinine clearance of less than 15 ml/min – 50 mg every other day.

Maximum dose for adults when taken orally is 200 mg/day in 1 or 2 doses.

Adverse Reactions

From the cardiovascular system in some cases – bradycardia, arterial hypotension, AV conduction disorders, appearance of symptoms of heart failure.

From the digestive system at the beginning of therapy, nausea, constipation, diarrhea, dry mouth are possible.

From the nervous system at the beginning of therapy, fatigue, dizziness, depression, mild headache, sleep disturbances, feeling of cold and paresthesia in the extremities, decreased patient reactivity are possible.

From the organ of vision decreased secretion of tear fluid, conjunctivitis.

From the endocrine system decreased potency, hypoglycemic conditions in patients with diabetes mellitus.

From the respiratory system in predisposed patients – the appearance of symptoms of bronchial obstruction.

Allergic reactions skin itching.

Other increased sweating, skin redness.

Contraindications

AV block of II and III degree, sinoatrial block, sick sinus syndrome, bradycardia (heart rate less than 40 beats/min), arterial hypotension (in case of use in myocardial infarction, systolic blood pressure less than 100 mm Hg), cardiogenic shock, chronic heart failure stage IIB-III, acute heart failure, Prinzmetal’s angina, lactation period, simultaneous use of MAO inhibitors, hypersensitivity to atenolol.

Use in Pregnancy and Lactation

Atenolol crosses the placental barrier, so use during pregnancy is possible only if the intended benefit to the mother outweighs the possible risk to the fetus.

Atenolol is excreted in breast milk, so if it is necessary to use it during lactation, it is recommended to stop breastfeeding.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in chronic renal failure. In case of impaired renal function in patients with a creatinine clearance of 15-35 ml/min – 50 mg/day; with a creatinine clearance of less than 15 ml/min – 50 mg every other day.

Pediatric Use

Use with caution in pediatrics (efficacy and safety have not been established).

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in diabetes mellitus, COPD (including bronchial asthma, pulmonary emphysema), metabolic acidosis, hypoglycemia; history of allergic reactions, chronic heart failure (compensated), obliterating diseases of peripheral arteries (intermittent claudication, Raynaud’s syndrome), pheochromocytoma, hepatic insufficiency, chronic renal failure, myasthenia gravis, thyrotoxicosis, depression (including history), psoriasis, during pregnancy, in elderly patients, in pediatrics (efficacy and safety have not been established).

When using atenolol, a decrease in the production of tear fluid is possible, which is important for patients using contact lenses.

Discontinuation of atenolol after a long course of treatment should be carried out gradually under medical supervision.

When discontinuing the combined use of atenolol and clonidine, treatment with clonidine should be continued for several more days after discontinuation of atenolol, otherwise severe arterial hypertension may occur.

If inhalation anesthesia is necessary in patients receiving Atenolol, it is necessary to stop taking atenolol several days before anesthesia or to select an anesthetic agent with minimal negative inotropic effect.

Effect on ability to drive vehicles and mechanisms

In patients whose activities require increased concentration, the issue of outpatient use of atenolol should be decided only after assessing the individual reaction.

Drug Interactions

With simultaneous use of diuretics, the antihypertensive effect is enhanced.

With simultaneous use of inhalation anesthetics, the risk of increased cardiodepressive effect and the development of arterial hypotension increases.

There are reports of the development of bradycardia and arterial hypotension with simultaneous use of alcuronium chloride.

With simultaneous use of verapamil, the negative inotropic effect is enhanced, bradycardia, bradyarrhythmia, and severe conduction disturbances develop; cases of postural hypotension, dizziness, left ventricular failure, and lethargy have been described. Under the influence of verapamil, the pharmacokinetic parameters of atenolol do not change significantly, although a case of an increase in the AUC of atenolol has been described.

With simultaneous use of disopyramide, the C_ss increases, the clearance of disopyramide decreases, and conduction disturbances are possible.

With simultaneous use of dipyridamole, a case of bradycardia and then asystole was described (during an ECG test with dipyridamole in a patient receiving Atenolol).

With simultaneous use of indomethacin, naproxen and other NSAIDs, a decrease in the antihypertensive effect of atenolol is possible, which is partly due to a violation (under the influence of NSAIDs) of the synthesis in the kidneys and release into the bloodstream of prostaglandins PGA and PGE, which have a strong vasodilating effect on peripheral arterioles.

With simultaneous use of insulin, an increase in blood pressure is possible.

With simultaneous use of clonidine, an additive hypotensive effect, sedative effect, and dry mouth are possible.

With simultaneous use of caffeine, a decrease in the effectiveness of atenolol is possible.

With simultaneous use of nizatidine, a case of increased cardiodepressive effect was described.

With simultaneous use of nifedipine, cases of severe arterial hypotension and heart failure have been described, which may be due to an increase in the inhibitory effect of nifedipine on the myocardium.

With simultaneous use of orlistat, the antihypertensive effect of atenolol decreases, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

With simultaneous use of prenylamine, an increase in the QT interval is possible.

With simultaneous use of chlorthalidone, the antihypertensive effect is enhanced.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.