Atenolol Nycomed (Tablets) Instructions for Use

Marketing Authorization Holder

Takeda Pharma A/S (Denmark)

ATC Code

C07AB03 (Atenolol)

Active Substance

Atenolol (Rec.INN registered by WHO)

Dosage Forms

	Atenolol Nycomed	Film-coated tablets, 50 mg: 30 pcs.
		Film-coated tablets, 100 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, capsule-shaped, biconvex, with a break line and the imprint “AB55”.

Excipients: gelatin – 2.1 mg, sodium lauryl sulfate – 3.3 mg, magnesium stearate – 5 mg, corn starch – 60 mg, magnesium carbonate – 87.5 mg.

Coating composition propylene glycol – about 400 mcg, titanium dioxide – about 800 mcg, talc – about 800 mcg, hypromellose E15 – about 2.1 mg.

30 pcs. – plastic bottles.

Film-coated tablets white, capsule-shaped, biconvex, with a break line and the imprint “AB57”.

Excipients: gelatin – 4.2 mg, sodium lauryl sulfate – 6.6 mg, magnesium stearate – 10 mg, corn starch – 120 mg, magnesium carbonate – 175 mg.

Coating composition propylene glycol – about 800 mcg, titanium dioxide – about 1.7 mg, talc – about 1.7 mg, hypromellose E15 – about 4.2 mg.

30 pcs. – plastic bottles.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Cardioselective beta₁-adrenergic blocker, does not possess membrane-stabilizing or intrinsic sympathomimetic activity. It has antihypertensive, antianginal, and antiarrhythmic effects.

By blocking beta₁-adrenergic receptors of the heart in low doses, it reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular flow of calcium ions, and exerts negative chronotropic, dromotropic, bathmotropic, and inotropic effects (slows heart rate), inhibits conduction and excitability, and reduces myocardial contractility.

The total peripheral vascular resistance increases at the beginning of beta-blocker use (in the first 24 hours after oral administration) as a result of a reciprocal increase in alpha-adrenergic receptor activity and elimination of beta₂-adrenergic receptor stimulation), which returns to the initial level after 1-3 days and decreases with long-term administration.

The antihypertensive effect is associated with a decrease in cardiac output, a reduction in the activity of the renin-angiotensin-aldosterone system (more important for patients with initial hypersecretion of renin), sensitivity of the aortic arch baroreceptors (their activity does not increase in response to decreased blood pressure), and an effect on the central nervous system.

The antihypertensive action is manifested by a decrease in both systolic and diastolic blood pressure, and a reduction in stroke volume and cardiac output. In average therapeutic doses, it does not affect the tone of peripheral arteries. The antihypertensive effect lasts for 24 hours and stabilizes by the end of the 2nd week of regular administration.

The antianginal effect is determined by a decrease in myocardial oxygen demand due to a reduction in heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to sympathetic stimulation. It slows the heart rate at rest and during physical exertion.

Due to an increase in the end-diastolic pressure in the left ventricle and increased stretching of the ventricular muscle fibers, it may 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 levels, arterial hypertension), a decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers, and slowing of atrioventricular conduction.

Inhibition of impulse conduction is noted mainly in the antegrade and to a lesser extent in the retrograde direction through the atrioventricular (AV) node and via accessory pathways.

It practically does not weaken the bronchodilatory effect of isoprenaline.

Unlike non-selective beta-blockers, when prescribed 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.

It has a less pronounced negative bathmotropic, chronotropic, inotropic, and dromotropic effect. When used in high doses (more than 100 mg/day), it exerts a blocking effect on both subtypes of beta-adrenergic receptors.

The negative chronotropic effect appears 1 hour after administration, reaches a maximum after 2-4 hours, and lasts up to 24 hours.

Pharmacokinetics

Absorption from the gastrointestinal tract is rapid, incomplete (45-60%), bioavailability is 40-50%, time to reach C_max in blood plasma is 2-4 hours. It penetrates poorly through the blood-brain barrier, passes in insignificant amounts through the placental barrier and into breast milk. Binding to blood plasma proteins is relatively low and amounts to less than 5%.

It is practically not metabolized in the liver. T_1/2 from blood plasma is 6-8 hours (increased in elderly patients). It is excreted by the kidneys through glomerular filtration (85-100% unchanged).

Impaired renal function is accompanied by a prolongation of T_1/2 and accumulation (dose reduction is necessary): with creatinine clearance (CrCl) below 35 ml/min/1.73 m², T_1/2 is 16-27 hours, with CrCl below 15 ml/min – more than 27 hours, with anuria it is prolonged to 144 hours. It is removed during hemodialysis.

Indications

• Arterial hypertension;
• Prevention of attacks of stable angina pectoris (except for Prinzmetal’s angina);
• Heart rhythm disorders: sinus tachycardia, prevention of supraventricular tachyarrhythmias.

ICD codes

Dosage Regimen

It is prescribed orally before meals, without chewing, with a small amount of liquid.

Arterial hypertension. Treatment begins with 50 mg of Atenolol Nycomed once a day. It takes 1-2 weeks of administration to achieve a stable hypotensive effect. If the hypotensive effect is insufficient, the dose is increased to 100 mg in a single dose. Further increase in dose is not recommended, as it is not accompanied by an enhancement of the hypotensive action.

Angina pectoris. The initial dose is 50 mg per day. If the optimal therapeutic effect is not achieved within a week, the dose is increased to 100 mg per day. Sometimes it is possible to increase the dose to 200 mg once a day. Elderly patients and patients with impaired renal excretory function require adjustment of the dosage regimen. In the presence of renal failure, dose adjustment is recommended depending on CrCl. In patients with renal failure with CrCl values above 35 ml/min/1.73 m²(normal values are 100-150 ml/min/1.73 m² ) significant accumulation of atenolol does not occur.

The following maximum doses are recommended for patients with renal failure

For patients on hemodialysis, Atenolol Nycomed is prescribed at 25 or 50 mg/day immediately after each dialysis, which should be carried out in a hospital setting, as a decrease in blood pressure may occur. In elderly patients, the initial single dose is 25 mg (can be increased under the control of blood pressure and heart rate). Increasing the daily dose above 100 mg is not recommended, as the therapeutic effect does not increase, and the likelihood of developing adverse reactions increases.

Adverse Reactions

Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1,000); very rare (<1/10,000).

From the cardiovascular system common – bradycardia, cold extremities, hypotension; rare – development or worsening of chronic heart failure, AV block, arrhythmias, syncope, peripheral edema, chest pain, cardiac conduction disorders, orthostatic hypotension and syncope, Raynaud’s syndrome.

From the central nervous system common – asthenia, muscle weakness; uncommon – sleep disorders (drowsiness or insomnia); rare – “nightmare” dreams, hallucinations, psychoses, depression, confusion or short-term memory loss, anxiety, dizziness, headache, paresthesia of the extremities (in patients with intermittent claudication and Raynaud’s syndrome), convulsions, taste changes; very rare – myasthenia.

From the sensory organs visual impairment, decreased tear secretion, dry and sore eyes, conjunctivitis.

From the endocrine system uncommon – may mask symptoms of hyperthyroidism. Hypoglycemia (in patients receiving insulin) or hyperglycemia (in patients with type 2 diabetes mellitus).

From the respiratory system rare – bronchospasm, wheezing, shortness of breath in predisposed patients and/or when taken in high doses (loss of selectivity), nasal congestion.

From the digestive system common – nausea, vomiting. Abdominal pain, constipation or diarrhea; rare – dry oral mucosa, cholestasis.

Laboratory parameters uncommon – increased activity of liver transaminases; rare – thrombocytopenia, agranulocytosis, leukopenia, hyperbilirubinemia; very rare – positive test results for antinuclear antibodies.

From the skin rare – skin rash, reversible alopecia, purpura, exacerbation of psoriasis and skin itching; very rare – lupus-like syndrome. Psoriasis-like skin rash, hypersensitivity reactions, including angioedema and urticaria.

Other rare – decreased potency; very rare – decreased libido.

Contraindications

• Shock (including cardiogenic and hypovolemic);
• AV block II-III degree;
• Acute heart failure or decompensated chronic heart failure;
• Severe bradycardia (heart rate less than 40 beats/min.);
• Sick sinus syndrome;
• Sinoatrial (SA) block;
• Cardiomegaly without signs of chronic heart failure;
• Prinzmetal’s angina;
• Severe arterial hypotension (in case of use in myocardial infarction, systolic blood pressure less than 100 mm Hg);
• Concomitant use of MAO inhibitors (MAO);
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Pheochromocytoma, except for concomitant therapy with alpha-blockers;
• Hypersensitivity to the drug.

With caution diabetes mellitus type 1 and 2, metabolic acidosis, hypoglycemia, history of allergic reactions, chronic obstructive pulmonary disease, bronchial asthma, pulmonary emphysema, AV block I degree, chronic heart failure (compensated), obliterating peripheral vascular diseases (“intermittent” claudication, Raynaud’s syndrome), pheochromocytoma (with simultaneous use of alpha-blockers), hepatic insufficiency, chronic renal failure, myasthenia gravis, thyrotoxicosis, depression (including in history), psoriasis, pregnancy, old age.

Use in Pregnancy and Lactation

Atenolol Nycomed should be prescribed to pregnant women only in cases where the benefit to the mother outweighs the potential risk to the fetus. Atenolol is excreted in breast milk, therefore, during lactation, if it is necessary to use the drug Atenolol Nycomed, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution: hepatic insufficiency.

Use in Renal Impairment

With caution: chronic renal failure.

Pediatric Use

Contraindicated: age under 18 years (efficacy and safety not established).

Geriatric Use

With caution: old age. In elderly patients, it is recommended to monitor renal function (once every 4-5 months). If elderly patients develop increasing bradycardia (less than 40 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, it is necessary to reduce the dose or discontinue treatment.

Special Precautions

Monitoring of patients taking Atenolol Nycomed should include observation of heart rate and blood pressure (at the beginning of treatment – daily, then once every 3-4 months), blood glucose concentration in patients with diabetes mellitus (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months).

The patient should be taught the method of counting heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

In thyrotoxicosis, Atenolol Nycomed may mask certain clinical signs of thyrotoxicosis (e.g., tachycardia). Abrupt withdrawal of the drug is contraindicated, as it can exacerbate symptoms. In diabetes mellitus, it may mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal values.

In patients with coronary artery disease, abrupt withdrawal of beta-blockers can cause an increase in the frequency or severity of angina attacks, therefore, discontinuation of Atenolol Nycomed in patients with coronary artery disease should be carried out gradually. The dose is reduced over two weeks or more. Compared to non-selective beta-blockers, cardioselective beta-blockers have less impact on lung function, nevertheless, in obstructive airway diseases, Atenolol Nycomed is used only in case of absolute indications. If their prescription is necessary, in some cases the use of beta₂-adrenergic agonists can be recommended.

Patients with bronchospastic diseases can be prescribed cardioselective adrenergic blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs, but strict dosage control should be observed. Overdose is dangerous due to the development of bronchospasm.

Special attention is required in cases where surgical intervention under anesthesia is required in patients taking Atenolol Nycomed. The drug should be discontinued 48 hours before the intervention. An anesthetic with the least possible negative inotropic effect should be chosen.

With simultaneous use of Atenolol Nycomed and clonidine, Atenolol Nycomed should be discontinued several days earlier than clonidine to avoid “withdrawal” syndrome.

An increase in the severity of hypersensitivity reactions and a lack of effect from usual doses of epinephrine may occur against the background of a burdened allergic history.

Drugs that reduce catecholamine reserves (e.g., reserpine) may enhance the effect of beta-blockers, so patients taking such drug combinations should be under constant medical supervision for the detection of a pronounced decrease in blood pressure or bradycardia.

If elderly patients develop increasing bradycardia (less than 40 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, it is necessary to reduce the dose or discontinue treatment.

It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

If intravenous administration of verapamil is necessary, it should be done no less than 48 hours after taking Atenolol Nycomed.

When using Atenolol Nycomed, a decrease in tear production is possible, which is important for patients using contact lenses.

Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmias and myocardial infarction. Discontinuation should be carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% every 3-4 days).

It should be discontinued before testing the content of catecholamines, normetanephrine and vanillylmandelic acid in blood and urine; titers of antinuclear antibodies (1-2 days before).

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

Effect on the ability to drive vehicles and perform work requiring increased concentration and speed of psychomotor reactions

During the treatment period, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms pronounced bradycardia, dizziness, marked decrease in blood pressure, fainting, arrhythmia, ventricular extrasystole, second- or third-degree AV block, chronic heart failure, cyanosis of fingernails or palms, convulsions, difficulty breathing, bronchospasm.

Treatment In case of impaired AV conduction and/or bradycardia – intravenous administration of 1-2 mg of atropine, epinephrine (adrenaline), or placement of a temporary pacemaker; for ventricular extrasystole – lidocaine (class IA antiarrhythmics are not used); for a marked decrease in blood pressure – the patient should be in the Trendelenburg position.

If there are no signs of pulmonary edema – intravenous plasma-substituting solutions; if ineffective – administration of epinephrine, dopamine, dobutamine; for chronic heart failure – cardiac glycosides, diuretics, glucagon; for convulsions – intravenous diazepam; for bronchospasm – inhaled or parenteral beta-adrenergic agonists. Hemodialysis is possible.

Drug Interactions

With the simultaneous use of atenolol with insulin and oral hypoglycemic agents, the hypoglycemic effect of the latter is enhanced.

When used concomitantly with antihypertensive agents of different groups or nitrates, the antihypertensive effect is enhanced.

The simultaneous use of atenolol and verapamil (or diltiazem) may cause a mutual enhancement of the effects of these drugs.

The antihypertensive effect is weakened by estrogens (sodium retention) and non-steroidal anti-inflammatory drugs, glucocorticosteroids.

With the simultaneous use of atenolol and cardiac glycosides, the risk of bradycardia and impaired AV conduction increases.

With the simultaneous administration of atenolol with reserpine, methyldopa, clonidine, verapamil, pronounced bradycardia may occur.

Simultaneous intravenous administration of verapamil and diltiazem can provoke cardiac arrest; nifedipine can lead to a significant decrease in blood pressure.

With the simultaneous use of atenolol with ergotamine derivatives and xanthines, its effectiveness decreases.

When discontinuing the combined use of atenolol and clonidine, treatment with clonidine should be continued for several more days after the withdrawal of atenolol.

Simultaneous use with lidocaine may reduce its excretion and increase the risk of lidocaine toxicity.

Concomitant use with phenothiazine derivatives contributes to an increase in the concentration of each of the drugs in the blood serum.

Phenytoin with intravenous administration, agents for general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressant effect and the likelihood of a decrease in blood pressure.

With concomitant use with aminophylline and theophylline, mutual suppression of therapeutic effects is possible.

Simultaneous use with MAO inhibitors is not recommended due to a significant enhancement of the hypotensive effect; the break in treatment between taking MAO inhibitors and atenolol should be at least 14 days.

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

Inhalation anesthetics (hydrocarbon derivatives) increase the risk of myocardial depression and the development of arterial hypertension.

Amiodarone increases the risk of bradycardia and AV conduction depression.

Cimetidine increases plasma concentration (inhibits metabolism).

Iodinated intravenous radiocontrast agents increase the risk of anaphylactic reactions.

It prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tricyclic and tetracyclic antidepressants, antipsychotic agents (neuroleptics), ethanol, sedatives and hypnotics enhance CNS depression.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C (77°F).

Keep out of reach of children.

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

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.