Atenolol - zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ATELOL-ZDOROVIYA

Composition:

Active ingredient: 1 tablet contains 50 mg of atenolol;

Excipients: potato starch, light magnesium carbonate, microcrystalline cellulose, povidone, calcium stearate, talc, sodium croscarmellose.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets are white or white with a creamy shade, flat cylindrical in shape with a bevel.

Pharmacotherapeutic group. Selective β-adrenoreceptor blockers. ATC code C07AB03.

Pharmacological properties.

Pharmacodynamics. Cardioselective β-adrenoceptor blocker. Has antianginal, antihypertensive, and antiarrhythmic effects. Has no intrinsic sympathomimetic or membrane-stabilizing activity. Reduces sinus node automaticity, slows atrioventricular conduction, decreases myocardial contractility and its oxygen demand. Exerts negative chronotropic, dromotropic, bathmotropic, and inotropic effects.

Pharmacokinetics. After oral administration, 50–60% of atenolol is absorbed in the gastrointestinal tract. Maximum plasma concentration (2 μg/mL) is reached within 2–4 hours. The elimination half-life is 6–7 hours.

Less than 5% of atenolol binds to plasma proteins. Atenolol is a hydrophilic agent, poorly penetrating the blood-brain and placental barriers, and passes into breast milk. Atenolol is minimally metabolized in the liver (less than 10%). The majority of atenolol (85%) is excreted unchanged in urine.

The elimination half-life may be prolonged in patients with renal insufficiency.

Removed by hemodialysis.

Clinical Characteristics.

Indications.

• Treatment of arterial hypertension;
• treatment and prevention of angina attacks (chronic stable and unstable angina, especially in combination 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 use 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 the 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 blood pressure less than 90 mm Hg);
• bronchial asthma;
• metabolic acidosis;
• advanced stages of peripheral circulatory disorders;
• concomitant use of monoamine oxidase inhibitors (MAOIs), except MAO-B inhibitors;
• untreated pheochromocytoma;
• renal insufficiency.

Interaction with other medicinal products and other types 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 addition, symptoms of hypoglycemia (especially tachycardia and tremor) may be masked or absent. Therefore, regular monitoring of blood glucose levels is necessary;
• tricyclic antidepressants, barbiturates, phenothiazines, nitroglycerin, diuretics, vasodilators, and other antihypertensive agents (e.g., prazosin), the hypotensive effect may be enhanced;
• calcium channel blockers (nifedipine), in addition to enhanced hypotensive effect, heart failure may develop;
• calcium channel blockers with negative inotropic effect (verapamil, diltiazem) may have their effects enhanced, 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 may cause significant slowing of heart rate;
• indomethacin may reduce the antihypertensive effect of atenolol;
• narcotic agents and antiseptics the antihypertensive effect is enhanced. An additive negative inotropic effect of both agents may occur;
• peripheral muscle relaxants (e.g., succinylcholine, tubocurarine) may lead to enhanced neuromuscular blockade; therefore, the anesthesiologist should be informed prior to surgery under anesthesia that the patient is taking atenolol;
• euphyllinum (aminophylline) and theophylline mutual inhibition of therapeutic effects may occur;
• lidocaine may result in reduced elimination and increased risk of lidocaine toxicity;
• sympathomimetic agents (adrenaline) may reduce the effectiveness of β-adrenergic blockers;
• nitrates, peripheral vasodilators, monoamine oxidase inhibitors (MAOIs) the hypotensive effect is increased;
• propafenone leads to enhancement of the effect of atenolol contained in the preparation;
• potassium-containing preparations leads to reduction of their effect;
• central nervous system depressants leads to enhancement of sedative effect;
• narcotic analgesics leads to enhancement of narcotic effect and potentially dangerous CNS depression;
• anticholinesterase agents, angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril) lead to increased potassium levels in blood.

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 results in greater reduction in blood pressure than with either drug 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.

An exception is made for patients undergoing treatment in intensive care units.

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

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 exceptionally manifest or the condition of patients with existing diabetes may worsen. Occasionally, lipid metabolism disturbances 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 treatment must not be made without consulting a physician. Abrupt discontinuation of the drug may lead to withdrawal syndrome. Therefore, discontinuation of the drug and dose reduction should be carried out gradually and slowly.

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

• in first-degree atrioventricular block;

• in diabetes mellitus with fluctuating blood glucose levels (due to the risk of developing severe hypoglycemia);

• in cases of prolonged fasting and heavy physical exertion (risk of severe hypoglycemic states);

• in pheochromocytoma (after prior administration of α₁-adrenoceptor 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 existing 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 thyrotoxicosis, atenolol may mask clinical signs of hyperthyroidism.

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

Atenolol should be used cautiously in patients with myasthenia gravis.

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.

In thyrotoxicosis, atenolol may mask symptoms of hypoglycemia, particularly tachycardia.

During atenolol treatment, changes in the results of certain laboratory tests are possible: increased serum potassium levels, increased levels of catecholamines and their metabolites in urine and blood. Although a definitive link between atenolol and depression has not been fully established, the drug should be used cautiously in such patients.

In elderly patients, treatment should be initiated with reduced doses (the dose may be increased under control of blood pressure and heart rate). If marked bradycardia, hypotension, rhythm or conduction disturbances, or other complications occur in these patients, the dose of atenolol should be reduced or discontinued.

Use during pregnancy or breastfeeding. Atenolol crosses the placental barrier and is excreted into breast milk. During pregnancy (especially in the first trimester), atenolol may be used only under strict medical indications with careful consideration of the benefit/risk ratio, as sufficient experience with its use in pregnant women, particularly in early stages, is still lacking. If women have 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 monitoring for 24–48 hours after delivery.

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. In individual cases, at the beginning of treatment, during dose escalation, when switching medications, or in combination with alcohol, reaction speed when driving a vehicle or operating machinery may be reduced.

Method of Administration and Dosage

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

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

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

Chronic stable and unstable angina pectoris: 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 respond adequately to 50 mg daily. The effect becomes apparent within 2 weeks. If ineffective, atenolol should be used in combination with diuretics.

Supraventricular and ventricular arrhythmias: The drug should be administered 1–2 times daily at doses of 50–100 mg.

Maximum daily dose – 200 mg.

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

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

Children. The drug is not recommended for use in children.

Overdose.

Symptoms: The clinical picture depends on the degree of intoxication and is primarily characterized by disturbances of the cardiovascular and central nervous systems.

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

Treatment: In case of overdose or when there is a risk of decreased heart rate and/or arterial pressure, atenolol therapy must be discontinued. Close monitoring of vital signs should be performed in intensive care units, with corrective measures as necessary.

If needed, administer:

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

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

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

For generalized seizures, administer diazepam slowly intravenously.

The drug can be removed by hemodialysis.

Side effects.

Cardiovascular system: arterial hypotension, bradycardia, atrioventricular conduction disturbances (up to cardiac arrest), orthostatic hypotension, onset of heart failure symptoms, cold sensation and paresthesia in extremities. In individual cases, exacerbation of angina attacks cannot be excluded in patients with angina pectoris.

Central nervous system: fatigue, dizziness, sleep disturbances, headache, increased sweating, depressive disorders, nightmares, insomnia, drowsiness, confusion, hallucinations, mood changes, psychoses.

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

Gastrointestinal tract: nausea, constipation, diarrhea, dry mouth, dyspepsia, elevated 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 susceptible patients – onset of bronchial obstruction symptoms, bronchospasm.

Hematopoietic system: purpura, thrombocytopenia.

Immune system: skin hyperemia, itching, skin rashes (psoriasis exacerbation), psoriasiform skin reactions, exanthema, alopecia, urticaria, increased levels of antinuclear antibodies, photosensitization, urticarial rash, hypersensitivity reactions (angioneurotic edema).

Other: muscle weakness, dry mouth, withdrawal syndrome.

Shelf life. 3 years.

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

Keep out of reach of children.

Packaging. 50 mg tablets, № 20 (10×2) in blisters in a box; № 10 in blisters.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's address and place of business. 22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.