ATENOLOL

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Atenolol (ATENOLOL)

Composition:

Active substance: atenolol;

1 tablet contains atenolol 50 mg (0.05 g);

Excipients: potato starch, calcium stearate, magnesium carbonate, microcrystalline cellulose, povidone.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets are white or white with a greyish tint, with a flat surface and beveled edges.

Pharmacotherapeutic group. Selective β-adrenoreceptor blockers.

ATC code C07AB03.

Pharmacological properties.

Pharmacodynamics.

Atenolol belongs to the group of cardioselective β1-adrenoblockers. The drug has antianginal, antihypertensive, and antiarrhythmic effects. It reduces the automaticity of the sinoatrial node, heart rate (HR), slows atrioventricular conduction, decreases myocardial contractility and its oxygen demand. When used in medium therapeutic doses, it does not cause adverse effects (such as bronchospasm, heart failure, etc.) typical for non-selective β-adrenoblockers.

Pharmacokinetics.

After oral administration, approximately 50 % is absorbed (food does not affect bioavailability), slightly more in elderly individuals. It is slowly absorbed in the gastrointestinal tract. Maximum drug concentration in blood plasma is observed within 2–4 hours. Plasma protein binding is insignificant (6–16 %). It does not penetrate the blood-brain barrier, but crosses the placental barrier. 85 % is excreted by the kidneys, and it is also secreted into breast milk. The elimination half-life after oral administration is 6–9 hours; in patients with renal insufficiency, this period may be prolonged. Atenolol undergoes minimal biotransformation in the liver (less than 10 %).

Clinical characteristics.

Indications.

• Treatment of arterial hypertension;
• treatment and prevention of angina attacks (chronic stable and unstable angina, especially in cases associated with tachycardia and arterial hypertension);
• cardiac rhythm disorders (arrhythmia, sinus tachycardia, prevention of supraventricular tachycardia, paroxysmal supraventricular tachycardia, atrial fibrillation and flutter; ventricular arrhythmias, including those caused by increased physical exertion or intake of sympathomimetic agents; prevention of ventricular tachycardia and ventricular fibrillation);
• myocardial infarction (treatment and prevention to reduce mortality and decrease the risk of recurrent infarction).

Contraindications.

• Hypersensitivity to components of the drug or to other β-adrenergic blockers;
• acute heart failure;
• cardiogenic shock;
• second- and third-degree atrioventricular block;
• sick sinus syndrome;
• sinoatrial block;
• sinus bradycardia (heart rate less than 45 beats per minute);
• arterial hypotension (systolic pressure less than 90 mm Hg);
• bronchial asthma;
• metabolic acidosis;
• severe peripheral circulatory disorders;
• concomitant use of monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors);
• untreated pheochromocytoma;
• renal failure.

Interaction with other medicinal products and other forms of interactions.

When atenolol is used concomitantly with:

• oral antidiabetic agents, such as insulin, the effect of these agents may be enhanced or prolonged. In this case, symptoms of hypoglycemia (especially tachycardia and tremor) may be masked or absent. Therefore, regular blood glucose monitoring is necessary;
• tricyclic antidepressants, barbiturates, phenothiazines, nitroglycerin, diuretics, vasodilators, and other antihypertensive agents (e.g., prazosin), a potentiation of the hypotensive effect may occur;
• calcium channel blockers (nifedipine), in addition to enhanced hypotensive effect, may lead to development of heart failure;
• calcium channel blockers with negative inotropic effect (verapamil, diltiazem), an enhanced effect is possible, especially in patients with impaired ventricular function and/or atrioventricular conduction, increasing the risk of arterial hypotension and bradycardia. If intravenous verapamil is required, it should be administered no sooner than 48 hours after discontinuation of atenolol;
• cardiac glycosides, reserpine, α-methyldopa, guanfacine, and clonidine, a significant reduction in heart rate may occur;
• indomethacin may reduce the antihypertensive effect of atenolol;
• narcotic agents and antiseptics may enhance the antihypertensive effect. An additive negative inotropic effect of both agents may manifest;
• peripheral muscle relaxants (e.g., succinylcholine, tubocurarine), enhanced neuromuscular blockade may occur; therefore, the anesthesiologist should be informed prior to surgery under anesthesia that the patient is taking atenolol;
• theophylline and ephedrine may mutually suppress their therapeutic effects;
• lidocaine may have reduced elimination and increased risk of lidocaine toxicity;
• sympathomimetic agents (epinephrine), the effect of β-blockers may be reduced;
• nitrates, peripheral vasodilators, monoamine oxidase inhibitors (MAOIs), their hypotensive effects are increased;
• propafenone, the effect of atenolol contained in the drug is enhanced;
• potassium-containing preparations, the effect of the latter is diminished;
• central nervous system depressants, the sedative effect is enhanced;
• narcotic analgesics, the narcotic effect is enhanced, leading to dangerous sedation;
• anticholinesterase agents, angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril, lisinopril), serum potassium levels may increase.

In patients receiving both atenolol and clonidine, clonidine should be discontinued only several days after stopping atenolol.

Atenolol enhances the antihypertensive effect of prazosin; their combination leads to a greater reduction in blood pressure than with administration of either agent alone.

During treatment with atenolol, intravenous administration of calcium channel blockers such as verapamil and diltiazem, or other antiarrhythmic agents (e.g., disopyramide), should not be used.

Special precautions for use.

If thrombocytopenic or non-thrombocytopenic purpura has occurred in patients during treatment with other β-blockers, the possibility of this adverse effect should be considered also during atenolol therapy.

It should be remembered that during atenolol treatment, latent diabetes mellitus may rarely manifest or the condition of patients with existing diabetes may worsen. Occasionally, disturbances in lipid metabolism may occur: while total cholesterol levels remain within normal limits, levels of high-density lipoproteins decrease and plasma triglyceride levels increase.

Dosage adjustments or discontinuation of atenolol therapy must not be made without consulting a physician. In patients with ischemic heart disease or arterial hypertension, abrupt discontinuation of the drug may lead to withdrawal syndrome, including increased frequency or severity of angina attacks and elevated blood pressure; therefore, discontinuation or dose reduction should be carried out gradually and slowly over a period of 10–14 days.

If the pulse rate decreases below 50–55 beats per minute at rest and patients develop symptoms related to bradycardia, the dose should be reduced.

Atenolol may increase both sensitivity to allergens and the severity of anaphylactic reactions. Such patients may be unresponsive to usual doses of adrenaline (epinephrine) used in the treatment of allergic reactions.

Since atenolol is eliminated by the kidneys, the dose should be reduced in patients with a creatinine clearance below 35 mL/min/1.73 m².

Atenolol should be used with particular caution and only under strict medical supervision in the following cases:

• in patients with first-degree atrioventricular block;
• in diabetes mellitus with fluctuating blood glucose levels (due to the risk of severe hypoglycemia);
• during prolonged fasting or heavy physical exertion (risk of severe hypoglycemia);
• in pheochromocytoma (only after prior administration of α1-adrenoreceptor blockers);
• in hepatic and/or renal dysfunction (when prescribing atenolol to these patients, continuous monitoring of liver and/or kidney function is required);
• in patients with psoriasis or a personal or family history of psoriasis;
• in patients with peripheral circulatory disorders, including Raynaud's syndrome;
• in patients undergoing desensitization therapy or with a history of severe allergic reactions;
• in patients with a history of thrombocytopenic or non-thrombocytopenic purpura;
• in hyperthyroidism (the drug may mask tachycardia);
• in patients with myasthenia gravis.

In thyrotoxicosis, atenolol may mask clinical signs of hyperthyroidism and hypoglycemia (particularly tachycardia and tremor).

β-blockers are not recommended for use in vasospastic angina (Prinzmetal's angina).

If surgical intervention is required, atenolol therapy should be discontinued 24 hours before surgery, or an anesthetic agent with minimal negative inotropic effect should be selected.

During atenolol treatment, changes in certain laboratory test results may occur: increased levels of lipoproteins, cholesterol, and potassium in serum, as well as increased levels of catecholamines and their metabolites in urine and blood.

Although the association between atenolol and depression has not been fully established, the drug should be used cautiously in such patients.

Elderly patients should start treatment with reduced doses, particularly if renal function is impaired (the dose may be increased under control of blood pressure and heart rate). If pronounced bradycardia, hypotension, arrhythmias, conduction disturbances, or other complications occur in these patients, the dose of atenolol should be reduced or the drug discontinued.

If atenolol must be prescribed to patients with bronchial obstruction, concomitant use of β2-adrenergic agonists may be considered.

Alcohol consumption should be avoided during atenolol therapy.

In all the above-mentioned cases, the physician must carefully weigh the benefit-risk ratio before prescribing atenolol.

Use during pregnancy or breastfeeding.

Atenolol crosses the placental barrier and is excreted in breast milk. During pregnancy (especially in the first trimester), atenolol should be used only in exceptional cases, after careful assessment of the benefit-risk ratio, as sufficient experience with its use in pregnant women, particularly in early stages, is still lacking. If a woman has been taking atenolol, treatment should be discontinued at least 24–48 hours before delivery due to the risk of bradycardia, hypoglycemia, and respiratory depression in the newborn. If discontinuation is not possible, the newborn must be under close and careful observation for 24–48 hours after birth.

Atenolol is excreted in breast milk; therefore, breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

During treatment, patients should refrain from driving vehicles or operating complex machinery, considering that adverse reactions of the nervous system such as dizziness, headache, confusion, hallucinations, and depressive disorders may occur during atenolol therapy.

Dosage and Administration.

Tablets should be swallowed whole with a small amount of liquid, without chewing, before meals, preferably at the same time each day.

The dosage and duration of treatment are determined individually by the physician, depending on the therapeutic effect achieved.

Myocardial infarction: 12 hours after intravenous administration, 50 mg of atenolol should be administered orally, followed by 100 mg another 12 hours later.

Chronic stable and unstable angina: usually 100 mg of atenolol once daily or 50 mg twice daily is prescribed.

Arterial hypertension: treatment is generally initiated with 100 mg of the drug once daily. Some patients may require only 50 mg daily. The effect becomes apparent after 2 weeks. If ineffective, atenolol should be used in combination with diuretics.

Supraventricular and ventricular arrhythmias: the drug is prescribed 1–2 times daily at 50–100 mg doses.

Maximum daily dose – 200 mg.

Dosage for patients with significantly impaired renal function depends on creatinine clearance (CC): when CC is 10–30 mL/min, doses should be reduced by half (50 mg daily or every other day); when CC is less than 10 mL/min, doses should be reduced fourfold compared to standard doses.

For patients undergoing hemodialysis, 50 mg of the drug should be administered after each dialysis session. This should be performed under hospital conditions, as a significant drop in arterial blood pressure may occur.

Children.

The medicinal product should not be used in children.

Overdose.

Symptoms: the clinical picture depends on the degree of intoxication and is mainly manifested by disturbances of the cardiovascular and central nervous systems.

Overdose may lead to bradycardia, decreased arterial blood pressure, heart failure, and cardiogenic shock. In severe cases, impaired consciousness and/or respiratory depression, bronchospasm, and vomiting may occur; generalized seizures are extremely rare.

Treatment: gastric lavage, administration of activated charcoal. In cases of overdose or when there is a risk of decreased heart rate and/or arterial blood pressure, atenolol treatment must be discontinued. Close monitoring of vital signs should be performed in intensive care units, with appropriate corrective measures as needed.

If necessary, administer:

• atropine (0.5–2 mg intravenously as a bolus), epinephrine;
• glucagon: initial dose 1–10 mg intravenously (as a bolus), followed by 2–2.5 mg/hour as a continuous infusion;
• sympathomimetics according to body weight and response (dopamine, dobutamine, isoprenaline, oxyprenaline, or adrenaline).

If bradycardia is refractory to therapy, temporary cardiac pacing may be considered.

In cases of bronchospasm, administer β2-sympathomimetics as an aerosol (and, if insufficient response, also intravenously) or intravenous aminophylline.

For generalized seizures, administer diazepam slowly intravenously.

The drug can be removed by hemodialysis.

Adverse reactions.

Cardiovascular system: arterial hypotension, bradycardia, atrioventricular conduction disturbances (up to cardiac arrest), orthostatic hypotension which may result in syncope, intermittent claudication more pronounced in patients with Raynaud's syndrome, onset of heart failure symptoms, sensation of cold and paresthesia in extremities. In individual cases, exacerbation of angina attacks may occur in patients with angina pectoris.

Nervous system: fatigue, dizziness, sleep disturbances, headache, increased sweating, depressive disorders, night terrors, insomnia, somnolence, confusion, hallucinations, mood changes, psychoses.

Eye disorders: visual disturbances, decreased lacrimal gland secretion, conjunctivitis, sensation of dry eyes.

Gastrointestinal tract: nausea, constipation, diarrhea, dry mouth, dyspepsia, disturbances in transaminase levels, intrahepatic cholestasis, hepatotoxicity.

Endocrine system: hypoglycemia (in patients with diabetes mellitus).

Urinary and reproductive system: libido and potency disturbances, impotence, gynecomastia, difficulty in urination.

Respiratory system: in predisposed patients – onset of bronchial obstruction symptoms, bronchospasm.

Hematopoietic system: purpura, thrombocytopenia, leukopenia.

Immune system: skin hyperemia, pruritus, skin rashes (psoriasis exacerbation), psoriasiform skin reactions, exanthema, alopecia, urticaria, increased levels of antinuclear antibodies, photosensitization, hypersensitivity reactions (angioneurotic edema), lupus-like syndrome.

Other: muscle weakness, withdrawal syndrome: increased frequency or severity of anginal attacks, elevated blood pressure.

Shelf life.

2 years.

Storage conditions.

Store in original packaging at temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 2 blisters per cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

JSC "Monfarm".

Manufacturer's address and location of business activity.

8, Zavodska St., Avramivka village, Uman district, Cherkasy region, 19161, Ukraine.