Estecor (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group hf. (Iceland)

Manufactured By

Emcure Pharmaceuticals, Inc. (USA)

ATC Code

C07AB11 (Esatenolol)

Active Substance

Esatenolol (Rec.INN registered by WHO)

Dosage Forms

	Estecor	Tablets 12.5 mg: 28 pcs.
		Tablets 25 mg: 28 pcs.
		Tablets 50 mg: 28 pcs.

Dosage Form, Packaging, and Composition

Tablets white, round, biconvex, with a beveled edge, smooth on both sides.

Excipients: microcrystalline cellulose – 100.5 mg, pregelatinized starch – 15 mg, colloidal silicon dioxide – 1 mg, sodium carboxymethyl starch – 9 mg, magnesium stearate – 2 mg.

14 pcs. – aluminum strips (2) – cardboard packs.

Tablets white, round, biconvex, with beveled edges and a score on one side.

Excipients: microcrystalline cellulose – 85.5 mg, pregelatinized starch – 15 mg, colloidal silicon dioxide – 3 mg, sodium carboxymethyl starch – 9 mg, magnesium stearate – 2.5 mg.

14 pcs. – aluminum strips (2) – cardboard packs.

Tablets light orange, round, with a score on one side.

Excipients: microcrystalline cellulose – 110.7 mg, pregelatinized starch – 90 mg, colloidal silicon dioxide – 2.5 mg, sodium carboxymethyl starch – 10 mg, magnesium stearate – 2.5 mg, sodium lauryl sulfate – 2.5 mg, starch – 1.5 mg, dye sunset yellow – 300 mcg.

14 pcs. – aluminum strips (2) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Atenolol is a racemic mixture of two optical isomers R(+) and S(-), the ratio of which in racemic atenolol is 1:1. S(-) atenolol is the chirally purified form of atenolol.

S(-) atenolol is a cardioselective β-adrenergic blocker. The effect of S(-) atenolol on the endocrine system and metabolism consists of reducing the activity of the renin-angiotensin system and the concentration of free fatty acids in blood plasma. S(-) atenolol is highly hydrophilic, unlike other β-adrenergic blockers that exhibit lipophilic properties. This may be the reason for the low incidence of central nervous system side effects. Furthermore, the selective β-adrenergic blocker S(-) atenolol causes less prolongation of insulin action, which is a cause of hypoglycemia, compared to non-selective β-blockers.

S(-) atenolol reduces heart rate (HR) and myocardial contractility, which helps reduce the occurrence of angina symptoms.

Results from clinical studies have shown that only the S(-) enantiomer is capable of blocking the β-receptor, while the R(+) enantiomer does not exhibit blocking activity against the receptors. It follows that the dose of S(-) atenolol (25 mg) is halved compared to racemic atenolol (50 mg).

A comparative study of racemic atenolol, S(-) atenolol, and R(+) atenolol showed that racemic atenolol and S(-) atenolol equally reduce systolic and diastolic blood pressure and HR, while R(+) atenolol did not cause any changes in these parameters.

The hemodynamic effect of racemic atenolol (100 mg) is similar in intensity to S(-) atenolol at a dose half as large (50 mg), while the R-isomer does not cause any changes in parameters at a dose of 50 mg.

The affinity of S(-) atenolol for β-adrenergic receptors is clearly higher than that of R(+) atenolol. It was also proven that only S(-) atenolol is responsible for the negative chronotropic and inotropic effects, and the R-isomer does not affect these parameters.

Pharmacokinetics

S(-) atenolol is well absorbed after oral administration and undergoes metabolism during the “first pass” through the liver. Since the drug is hydrophilic, oral absorption is incomplete but rapid. The C_max value is 781.81 mg/ml, which reaches its value after three hours (T_Cmax). AUC_0-∞ is 4513.88 ng*h/ml. T_1/2 is 4.02 h.

Indications

• Arterial hypertension;
• Prevention of angina attacks (except for Prinzmetal’s angina);
• Cardiac arrhythmias.

ICD codes

Dosage Regimen

Method of administration and dosage

Orally, before meals, without chewing and with a small amount of liquid.

Arterial hypertension. Treatment begins with 12.5 mg of Estecor once a day. It takes 1-2 weeks of administration to achieve a stable antihypertensive effect. If the antihypertensive effect is insufficient, the dose is increased to 25 or 50 mg once a day. Further dose increase is not recommended, as it is not accompanied by an enhancement of the clinical effect.

Cardiac arrhythmias and prevention of angina attacks. The initial dose is 12.5 mg/day. If the optimal therapeutic effect is not achieved within a week, the dose is increased to 25 or 50 mg per day. Elderly patients and patients with impaired renal excretory function require dosage regimen adjustment.

In elderly patients, the initial single dose is 12.5 mg (can be increased under the control of blood pressure and heart rate).

Increasing the daily dose above 50 mg is not recommended, as the therapeutic effect does not increase, but the likelihood of adverse reactions increases.

For patients on hemodialysis, Estecor is prescribed at 25 mg/day immediately after each dialysis, which should be performed in a hospital setting, as a decrease in blood pressure may occur.

Adverse Reactions

From the nervous system: asthenia, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, decreased ability to concentrate, decreased reaction speed, paresthesia in the extremities (in patients with “intermittent” claudication and Raynaud’s syndrome), vasculitis, chest pain.

From the digestive system: dry mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, taste changes.

From the respiratory system: nasal congestion, breathing difficulties when prescribed in high doses (loss of selectivity) and/or in predisposed patients- laryngo- and bronchospasm.

From the endocrine system: hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state.

Allergic reactions: itching, rash, urticaria.

From the skin: increased sweating, skin hyperemia, exacerbation of psoriasis symptoms, psoriasis-like skin rashes, reversible alopecia.

Laboratory parameters: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of “liver” enzymes, hyperbilirubinemia.

Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: back pain, arthralgia, decreased libido, impotence, withdrawal syndrome (increased angina attacks, increased blood pressure).

The frequency of adverse events increases with increasing drug dose.

Contraindications

• Hypersensitivity to S(-) Atenolol or racemic atenolol;
• Cardiogenic shock;
• Atrioventricular (AV) block II-III degree;
• Severe bradycardia (heart rate less than 40 beats/min.);
• Sick sinus syndrome;
• Sinoatrial block;
• Acute heart failure (HF) or chronic heart failure (CHF) in the stage of decompensation;
• Cardiomegaly without signs of CHF;
• Prinzmetal’s angina;
• Arterial hypotension (in case of use in myocardial infarction;
• Systolic blood pressure less than 100 mm Hg);
• Various peripheral arterial circulation disorders;
• Concomitant use of MAO inhibitors (MAO);
• Pregnancy and lactation period.

With caution: diabetes mellitus, metabolic acidosis, hypoglycemia; history of allergic reactions; chronic obstructive pulmonary disease (including bronchial asthma, pulmonary emphysema); CHF (compensated), obliterating peripheral vascular diseases (“intermittent” claudication, Raynaud’s syndrome); pheochromocytoma, hepatic insufficiency, chronic renal failure, myasthenia, thyrotoxicosis, depression (including in history), psoriasis, pregnancy, old age, age under 18 years (efficacy and safety not established).

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in chronic renal failure.

Pediatric Use

Use with caution in children under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Monitoring of patients taking Estecor should include observation of heart rate and blood pressure (at the beginning of treatment – daily, then – once every 3-4 months), blood glucose levels 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. Approximately 20% of patients with angina do not respond to β-adrenergic blockers. The main reasons are severe coronary atherosclerosis with a low ischemia threshold (heart rate less than 100 beats/min) and increased left ventricular end-diastolic volume (LVEDV), which impairs subendocardial blood flow.

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

Patients using contact lenses should take into account that treatment may reduce the production of tear fluid.

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

When clonidine is taken concomitantly, its administration can be discontinued only several days after discontinuation of Estecor.

There may be an increase in the severity of an allergic reaction and a lack of effect from usual doses of epinephrine in patients with a burdened allergic history.

Several days before general anesthesia with chloroform or ether, it is necessary to discontinue the drug. If the patient has taken the drug before surgery, a general anesthetic agent with minimal negative inotropic effect should be selected for him. Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Drugs that reduce catecholamine stores (e.g., reserpine) may enhance the effect of beta-adrenergic blockers, so patients taking such combinations should be under constant medical supervision for detection of marked hypotension or bradycardia.

The drug can be prescribed to patients with bronchospastic diseases in case of intolerance and/or ineffectiveness of other antihypertensive agents, but the dosage should be strictly monitored. Overdose is dangerous due to the development of bronchospasm.

In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV 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-adrenergic blockers develops. Treatment should not be abruptly interrupted due to the risk of severe arrhythmias and myocardial infarction. Discontinuation should be gradual, reducing the dose over 2 weeks or more (reduce the dose by 25% every 3-4 days).

It should be discontinued before testing the blood and urine for catecholamines, normetanephrine, and vanillylmandelic acid; titers of antinuclear antibodies.

During treatment, caution should be exercised when driving vehicles and engaging in activities requiring concentration and speed of psychomotor reactions.

The drug dose should be adjusted in renal disease.

Overdose

Symptoms: severe bradycardia, dizziness, excessive decrease in blood pressure, fainting, arrhythmia, ventricular extrasystole, AV block II-III degree, CHF, cyanosis of nails, fingers or palms, convulsions, difficulty breathing, bronchospasm.

Treatment: gastric lavage and administration of adsorbent drugs; in case of impaired AV conduction and/or 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 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 or hemoperfusion may be performed.

Drug Interactions

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

Iodine-containing X-ray contrast drugs for intravenous administration increase the risk of anaphylactic reactions.

Phenytoin for intravenous administration, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of decreased blood pressure.

When co-administered with insulin and oral hypoglycemic drugs, it masks the symptoms of developing hypoglycemia.

Reduces the clearance of lidocaine and xanthines (except diprophylline) and increases their plasma concentration, especially in patients with initially increased theophylline clearance due to smoking.

The hypotensive effect is weakened by non-steroidal anti-inflammatory drugs (Na+ retention and blockade of renal Pg synthesis), glucocorticosteroids and estrogens (Na+ retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, “slow” calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of development or worsening of heart failure, bradycardia, AV block, or cardiac arrest.

Diuretics, clonidine, sympatholytics, hydralazine, calcium channel blockers and other antihypertensive agents can lead to an excessive decrease in blood pressure.

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

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

Concomitant 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.

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

Storage Conditions

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.

Do not use after the expiration date.

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.