Atenolol (Tablets) Instructions for Use

ATC Code

C07AB03 (Atenolol)

Active Substance

Atenolol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

It has antianginal, antihypertensive, and antiarrhythmic effects. It does not possess membrane-stabilizing or intrinsic sympathomimetic activity. It reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and reduces the intracellular flow of Ca²⁺.

Within the first 24 hours after oral administration, against the background of reduced cardiac output, a reactive increase in total peripheral vascular resistance is noted, which gradually returns to the initial level within 1-3 days, and then gradually decreases. The hypotensive effect is associated with a decrease in minute volume of blood, a reduction in the activity of the renin-angiotensin system, baroreceptor sensitivity, and an influence on the central nervous system.

The hypotensive effect is manifested by a decrease in both systolic and diastolic blood pressure (BP), and a reduction in stroke and minute volume of blood. In medium therapeutic doses, it does not affect the tone of peripheral arteries. The hypotensive effect lasts for 24 hours and stabilizes by the end of the second week of regular use.

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

Due to an increase in 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 manifested by the suppression of sinus tachycardia and is associated with the elimination of arrhythmogenic sympathetic influences on the cardiac conduction system, a decrease in the speed of excitation propagation through the sinoatrial node, and a prolongation of the refractory period.

It inhibits impulse conduction in the antegrade and, to a lesser extent, retrograde directions through the AV (atrioventricular) node and along accessory pathways. The negative chronotropic effect appears 1 hour after administration, reaches a maximum after 2-4 hours, and lasts up to 24 hours.

It reduces the automaticity of the sinus node, slows HR, slows AV conduction, reduces myocardial contractility, and decreases myocardial oxygen demand. It reduces myocardial excitability. When used in medium therapeutic doses, it has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries than non-selective beta-blockers.

It increases the survival of patients who have had myocardial infarction (reduces the incidence of ventricular arrhythmias and angina attacks). It practically does not weaken the bronchodilating effect of isoproterenol.

Unlike non-selective beta-blockers, when prescribed in medium 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 bathmo-, chrono-, ino-, and dromotropic effect. When used in high doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors.

Pharmacokinetics

Absorption from the gastrointestinal tract is rapid, incomplete (50-60%), bioavailability is 40-50%, T_max in blood is 2-4 hours. It poorly penetrates the blood-brain barrier, passes in insignificant amounts through the placental barrier and into breast milk. Plasma protein binding is 6-16%.

It is practically not metabolized in the liver. T_1/2 is 6-9 hours (increases 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: with a creatinine clearance below 35 ml/min/1.73 m², T_1/2 is 16-27 hours, with a creatinine clearance below 15 ml/min/1.73 m² – more than 27 hours (dose reduction is necessary). It is removed during hemodialysis.

Indications

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

ICD codes

Dosage Regimen

Tablets

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

Arterial hypertension. Treatment begins with 50 mg of atenolol 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 clinical effect.

For ischemic heart disease, tachyarrhythmias – 50 mg once a day.

Angina. 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.

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 creatinine clearance. In patients with renal failure and creatinine clearance 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 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 BP may occur.

For elderly patients, the initial single dose is 25 mg (can be increased under the control of BP, HR). An increase in the daily dose above 100 mg is not recommended, as the therapeutic effect does not increase, but the likelihood of side effects increases.

Adverse Reactions

Cardiovascular system development (worsening) of symptoms of chronic heart failure (ankle and foot swelling; shortness of breath), atrioventricular conduction disturbance, arrhythmias, bradycardia, marked decrease in BP, palpitations, decreased myocardial contractility, orthostatic hypotension, manifestations of angiospasm (coldness of the lower extremities, Raynaud’s syndrome), vasculitis, chest pain.

CNS dizziness, decreased ability to concentrate, decreased reaction speed, drowsiness or insomnia, depression, hallucinations, increased fatigue, headache, weakness, “nightmare” dreams, anxiety, confusion or short-term memory loss, paresthesia in the extremities (in patients with “intermittent” claudication and Raynaud’s syndrome), muscle weakness, convulsions.

Gastrointestinal tract dry mouth, nausea, vomiting, diarrhea, abdominal pain, constipation or diarrhea, taste change.

Respiratory system dyspnea, bronchospasm, apnea, nasal congestion.

Hematological reactions thrombocytopenic purpura, (aplastic) anemia, thrombosis.

Endocrine system decreased potency, decreased libido, hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state.

Skin reactions urticaria, dermatitis, skin itching, photosensitivity, increased sweating, skin hyperemia, exacerbation of psoriasis, reversible alopecia.

Sensory organs visual impairment, decreased tear secretion, dry and painful eyes, conjunctivitis.

Effect on the fetus intrauterine growth retardation, hypoglycemia, bradycardia. Laboratory parameters: agranulocytosis, leukopenia, increased activity of “liver” enzymes, hyperbilirubinemia, thrombocytopenia (unusual bleeding and hemorrhage).

Other back pain, arthralgia, “withdrawal” syndrome (tachycardia, increased frequency of angina attacks, increased BP, etc.). The frequency of side effects increases with an increase in the drug dose.

Contraindications

• Cardiogenic shock;
• Atrioventricular (AV) block II-III degree;
• Severe bradycardia (HR less than 40 beats/min.);
• Sick sinus syndrome;
• Sinoauricular block;
• Acute or chronic heart failure in the stage of decompensation;
• Cardiomegaly without signs of heart failure;
• Prinzmetal’s angina;
• Arterial hypotension (in case of use in myocardial infarction;
• Systolic BP less than 100 mm Hg);
• Lactation period;
• Concomitant use of MAO inhibitors (MAO);
• Age under 18 years (efficacy and safety of the drug have not been established);
• Hypersensitivity to the drug.

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

Use in Pregnancy and Lactation

Atenolol crosses the placental barrier and is found in umbilical cord blood. Studies on the use of atenolol in the first trimester have not been conducted, and therefore, the possibility of a damaging effect on the fetus cannot be excluded. For the treatment of arterial hypertension in the third trimester of pregnancy, the drug is used under careful medical supervision. The use of atenolol during pregnancy may cause impaired fetal growth.

Atenolol should be prescribed to pregnant women or women planning pregnancy only in cases where the benefit to the mother outweighs the potential risk to the fetus, especially in the first and second trimester of pregnancy, since beta-blockers reduce the level of placental perfusion, which can lead to intrauterine fetal death or its immaturity and premature birth. In addition, side effects such as hypoglycemia and bradycardia can be observed in both the fetus and the newborn.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in chronic renal failure.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

Prescribe with caution to elderly patients.

Special Precautions

Monitoring of patients taking Atenolol should include observation of HR and BP (at the beginning of treatment – daily, then once every 3-4 months), blood glucose levels in patients with diabetes (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 HR and instructed about the need for medical consultation if HR is less than 50 beats/min. In thyrotoxicosis, Atenolol may mask certain clinical signs of thyrotoxicosis (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis 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 to normal concentration.

In patients with ischemic heart disease (IHD), abrupt withdrawal of beta-blockers can cause an increase in the frequency or severity of anginal attacks, therefore, discontinuation of atenolol in patients with IHD must be carried out gradually.

Compared to non-selective beta-blockers, cardioselective beta-blockers have less impact on lung function; nevertheless, in obstructive airway diseases, Atenolol is prescribed only in case of absolute indications. If 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 monitoring of the dosage is necessary. 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. 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 and clonidine, atenolol should be discontinued several days earlier than clonidine to avoid the withdrawal syndrome of the latter. It is possible to increase the severity of the hypersensitivity reaction and the lack of effect from usual doses of epinephrine 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 combinations of drugs should be under constant medical supervision for the detection of marked hypotension or bradycardia.

In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic BP below 100 mm Hg), atrioventricular block, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function in elderly patients, 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.

When using atenolol, 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 severe arrhythmias and myocardial infarction. Withdrawal should be carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 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. In smokers, the effectiveness of beta-blockers is lower. Pregnancy and breastfeeding period.

Atenolol 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, so if the drug is indicated during breastfeeding, it is better to stop breastfeeding for a while.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms severe bradycardia, AV block II-III degree, worsening of heart failure symptoms, excessive decrease in BP, difficulty breathing, bronchospasm, dizziness, fainting, arrhythmia, ventricular extrasystole, cyanosis of fingernails or palms, convulsions.

Treatment gastric lavage and administration of adsorbent drugs; in case of bronchospasm, inhalation or intravenous administration of the beta₂-adrenergic agonist salbutamol is indicated. For AV conduction disturbance, bradycardia – intravenous administration of 1-2 mg of atropine, epinephrine, or placement of a temporary pacemaker; for ventricular extrasystole – lidocaine (class IA drugs are not used); for decreased BP – 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. Dialysis is possible.

Drug Interactions

With simultaneous use of atenolol with insulin, oral hypoglycemic agents – their hypoglycemic effect is enhanced. When used together with antihypertensive agents of different groups or nitrates, the hypotensive effect is enhanced. Simultaneous use of atenolol and verapamil (or diltiazem) can cause mutual enhancement of the cardiodepressive effect.

The hypotensive effect is weakened by estrogens (sodium retention) and non-steroidal anti-inflammatory drugs, glucocorticosteroids. With simultaneous use of atenolol and cardiac glycosides, the risk of bradycardia and atrioventricular conduction impairment increases.

With simultaneous administration of atenolol with reserpine, methyldopa, clonidine, verapamil, the occurrence of marked bradycardia is possible.

Simultaneous intravenous administration of verapamil and diltiazem may provoke cardiac arrest; nifedipine may lead to a significant decrease in blood pressure. With simultaneous administration of atenolol with derivatives of ergotamine, xanthine, 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, drugs 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 treatment interval 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.

Inhalational 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 radiopaque agents for intravenous administration 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 central nervous system depression.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulation disorders.

Storage Conditions

List B. In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

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.