Tenochek (Tablets) Instructions for Use

Marketing Authorization Holder

Ipca Laboratories Ltd. (India)

ATC Code

C07EB (Selective beta-adrenergic blocking agents in combination with vasodilators)

Active Substances

Atenolol (Rec.INN registered by WHO)

Amlodipine (Rec.INN registered by WHO)

Dosage Form

Tenochek

Tablets 50 mg+5 mg: 10, 14, 20, 28, 30, or 42 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat, with bevelled edges and an imprint “TC” on one side and a score line on the other side of the tablet.

Excipients: isopropanol, calcium hydrogen phosphate (dibasic calcium phosphate), sodium starch glycolate, corn starch, colloidal silicon dioxide, magnesium stearate, povidone-30, purified talc, microcrystalline cellulose.

10 pcs. – blisters (1) – carton packs.
10 pcs. – blisters (2) – carton packs.
10 pcs. – blisters (3) – carton packs.
14 pcs. – blisters (1) – carton packs.
14 pcs. – blisters (2) – carton packs.
14 pcs. – blisters (3) – carton packs

Clinical-Pharmacological Group

Drug with antihypertensive and antianginal action

Pharmacotherapeutic Group

Antihypertensive combination agent (beta-adrenoblocker+CCB)

Pharmacological Action

A combined drug, the action of which is determined by the properties of its components.

Atenolol is a cardioselective beta₁-adrenergic blocker, it has antianginal, antihypertensive and antiarrhythmic action. It does not have membrane-stabilizing or intrinsic sympathomimetic activity. It reduces the formation of cAMP and ATP stimulated by catecholamines, and reduces the intracellular flow of calcium ions. Within the first 24 hours after oral administration of the drug, against the background of a decrease in cardiac output, a reactive increase in total peripheral vascular resistance is noted, the severity of which gradually decreases over 1-3 days.

The antihypertensive effect is associated with a decrease in cardiac output, a decrease in the activity of the renin-angiotensin system, baroreceptor sensitivity and an effect on the central nervous system. The hypotensive effect is manifested by a decrease in systolic and diastolic blood pressure, a decrease in stroke and minute volume. When used in average recommended doses, it does not affect the tone of peripheral arteries. The hypotensive effect lasts for 24 hours; with regular use, blood pressure stabilizes by the end of the 2nd week of treatment.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and a decrease in myocardial contractility, as well as a decrease in myocardial sensitivity to the effects of sympathetic innervation. It reduces heart rate at rest and during physical exertion. Due to an increase in the tension of the muscle fibers of the ventricles and the end-diastolic pressure in the left ventricle, it can increase the myocardial oxygen demand, especially in patients with chronic heart failure.

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

The antiarrhythmic action is manifested by the suppression of sinus tachycardia and is associated with the elimination of arrhythmogenic sympathetic influences on the conduction system of the heart, inhibition of heterogeneous automatism, a decrease in the speed of excitation propagation through the sinoatrial node and prolongation of the refractory period. It inhibits the conduction of impulses in the antegrade and, to a lesser extent, retrograde directions through the AV node and along additional pathways.

It increases the survival of patients who have had myocardial infarction (reduces the frequency of ventricular arrhythmias and angina attacks).

In therapeutic concentrations, it does not affect β₂-adrenergic receptors; unlike non-selective beta-blockers, it has a less pronounced effect on the smooth muscles of the bronchi, peripheral arteries and on lipid metabolism. It slightly reduces vital lung capacity and practically does not weaken the bronchodilating effect of isoproterenol. When taken in doses of more than 100 mg/day, it may affect β₂-adrenergic receptors.

Amlodipine is a slow calcium channel blocker, a dihydropyridine derivative. It has antihypertensive, antianginal, antispasmodic and vasodilating effects. It blocks the entry of calcium ions through cell membranes into the smooth muscle cells of blood vessels and myocardium. The mechanism of the antihypertensive action is due to a direct effect on the vascular smooth muscle.

The antianginal effect of amlodipine is due to its dilating effect on peripheral arterioles, which leads to a decrease in total peripheral vascular resistance. At the same time, the reduction in cardiac load leads to a decrease in myocardial oxygen demand, and simultaneously increases oxygen supply to the myocardium due to the expansion of the coronary arteries (which is especially important in vasospastic angina).

Amlodipine does not have an adverse effect on metabolism and on the lipid composition of blood plasma, has antiatherosclerotic, antithrombotic activity, increases the glomerular filtration rate, and has a weakly pronounced natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria.

Pharmacokinetics

Amlodipine

After oral administration, Amlodipine is rapidly and almost completely (90%) absorbed from the gastrointestinal tract, C_max is reached in 6-12 hours. Bioavailability is 60-65%. Steady-state concentration is established after 7-8 days of continuous use of the drug. The volume of distribution is 20 L/kg. Plasma protein binding is more than 95%. It penetrates the blood-brain barrier. It is biotransformed mainly in the liver with the formation of inactive metabolites. Less than 10% is excreted unchanged, about 60% is excreted by the kidneys as inactive metabolites, 20-25% is excreted as metabolites with bile and through the intestines, and also with breast milk.

Atenolol

After oral administration, Atenolol is rapidly absorbed from the gastrointestinal tract (approximately 50% of the administered dose). Bioavailability is 40-50%. C_max is reached 2-4 hours after oral administration. It penetrates poorly through the blood-brain barrier and the placental barrier, and is excreted in small amounts in breast milk. Plasma protein binding is 6-16%. It is practically not biotransformed in the liver. It is excreted by the kidneys by glomerular filtration, with 85-100% excreted unchanged. The elimination half-life is 6-9 hours.

Indications

Arterial hypertension; prevention of angina attacks.

ICD codes

Dosage Regimen

Take Tenochek tablets orally once daily. Swallow the tablet whole with water, with or without food.

Initiate therapy with one tablet (50 mg atenolol + 5 mg amlodipine) per day. The dosage must be individualized based on the patient’s therapeutic response and tolerability.

For patients not adequately controlled on a single antihypertensive agent, this fixed-dose combination may be suitable. Titrate the dose gradually, with dose adjustments occurring at 1- to 2-week intervals.

Do not exceed the maximum recommended daily dose of one tablet. The tablet is scored and can be broken in half for dose titration, but the fixed-dose combination should not be used for initial titration of individual components.

For patients with severe hepatic impairment, use is not recommended. In patients with renal impairment (creatinine clearance less than 35 mL/min), use with caution and monitor renal function.

In elderly patients, initiate therapy at the standard dose. Monitor blood pressure and heart rate closely due to a potential for increased sensitivity.

Do not abruptly discontinue therapy, as this may lead to a rebound exacerbation of angina or hypertension. Gradually reduce the dose over 1-2 weeks under medical supervision.

Regularly monitor blood pressure, heart rate, and clinical status. Assess efficacy and tolerability periodically to ensure the continued appropriateness of the regimen.

Adverse Reactions

From the cardiovascular system appearance or worsening of symptoms of heart failure, AV conduction disturbance, bradycardia, marked decrease in blood pressure, palpitations, dyspnea, flushing, peripheral edema.

From the digestive system dry mouth, nausea, vomiting, diarrhea, abdominal pain, constipation, gingival hyperplasia; rarely – increased activity of liver transaminases, cholestatic jaundice, dyspepsia.

From the nervous system dizziness, sleep disturbance, decreased ability to concentrate, drowsiness, depression, hallucinations, lethargy, feeling of fatigue, headache; rarely – mood changes, asthenia, visual impairment, paresthesia.

From the musculoskeletal system muscle cramps, myalgia.

From the respiratory system dyspnea, bronchospasm, apnea.

From the hematopoietic system thrombocytopenic purpura, aplastic anemia, thrombosis.

From the endocrine system decreased potency, decreased libido, gynecomastia, hyperlipidemia, hypoglycemia.

From the skin urticaria, dermatitis, itching, photosensitivity; rarely – multiform exudative erythema.

Other increased frequency of urination.

Contraindications

Severe arterial hypotension; AV block II and III degree; sick sinus syndrome; sinoatrial block; acute heart failure; chronic heart failure stage IIB – III in the decompensation phase; severe bradycardia; metabolic acidosis; bronchial asthma, chronic obstructive pulmonary disease; Prinzmetal’s angina; cardiomegaly without signs of heart failure; simultaneous use of MAO inhibitors; children and adolescents under 18 years of age; hypersensitivity to the components of the combination.

With caution

In AV block I degree, impaired liver function, aortic stenosis, chronic heart failure (in the compensation phase), chronic renal failure, pheochromocytoma, diabetes mellitus, hypoglycemia, thyrotoxicosis, obliterating peripheral vascular diseases (intermittent claudication, Raynaud’s syndrome), myasthenia gravis, depression (including in history), psoriasis, as well as in elderly patients.

Use in Pregnancy and Lactation

During pregnancy, use only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

During lactation (breastfeeding), the drug should be used only in exceptional cases with great caution.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with chronic renal failure.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

In thyrotoxicosis, the combination may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, as it may exacerbate symptoms.

It slightly enhances insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal levels.

Dose selection of this combination in patients with chronic heart failure (compensated) should be done with caution.

If surgery under general anesthesia is necessary, the drug should be discontinued 48 hours before surgery. An anesthetic with the least possible negative inotropic effect should be chosen.

When used concomitantly with clonidine, the combination should be discontinued several days before clonidine to avoid withdrawal syndrome of the latter.

It is possible to increase the severity of allergic reactions and lack of effect from usual doses of epinephrine in patients with a burdened allergic history.

Drugs that reduce catecholamine stores (e.g., reserpine) may enhance the effect of beta-blockers, so patients receiving such a combination of drugs should be under constant supervision to detect a marked decrease in blood pressure or bradycardia.

If elderly patients develop severe bradycardia (heart rate less than 50/min), a significant decrease in blood pressure (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 this combination.

If depression develops during the use of the drug, it is recommended to discontinue therapy.

If intravenous administration of verapamil is necessary, this administration should be done no less than 48 hours after the last dose of this combination.

When using atenolol, a decrease in the production of tear fluid is possible, which is important for patients using contact lenses.

This combination should be discontinued before testing the concentration of catecholamines, vanillylmandelic acid in blood and urine; titers of antinuclear antibodies.

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

It is necessary to monitor 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 persons, it is recommended to assess renal function (once every 4-5 months).

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

Effect on ability to drive vehicles and operate machinery

It should be used with caution in patients engaged in potentially hazardous activities due to a possible decrease in concentration.

Drug Interactions

When used concomitantly with insulin (or oral hypoglycemic agents), the symptoms of hypoglycemia are masked (due to the action of atenolol).

When used concomitantly with antihypertensive agents of other groups, mutual enhancement of the hypotensive effect occurs.

The hypotensive effect of the drug is weakened by estrogens, glucocorticosteroids, mineralocorticoids, NSAIDs (due to sodium retention).

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

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

When taken concomitantly with ergotamine and xanthine derivatives, the effectiveness of atenolol decreases.

Simultaneous use with lidocaine may slow down the excretion of atenolol and amlodipine from the body and increase the risk of toxic effects of the drug.

Use together with phenothiazine derivatives contributes to an increase in the concentration of active substances in the blood serum.

Phenytoin (with intravenous administration) and agents for intravenous anesthesia enhance the severity of the cardiodepressive effect of atenolol.

Allergens used for immunotherapy, or allergen extracts for skin tests and iodine-containing radiopaque agents for intravenous administration increase the risk of severe systemic allergic reactions or anaphylaxis.

Agents for inhalational general anesthesia (hydrocarbon derivatives) increase the risk of myocardial function depression and a marked decrease in blood pressure.

With concomitant use, amiodarone increases the risk of bradycardia and slowing of AV conduction.

Cimetidine increases the concentration of atenolol in plasma (due to inhibition of its metabolism).

With concomitant use, it prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.