Tenorox (Tablets) Instructions for Use

Marketing Authorization Holder

Oxford Laboratories, Pvt. Ltd. (India)

Contact Information

Oxford Laboratories Pvt. Ltd. (India)

ATC Code

C07CB03 (Atenolol and other diuretics)

Active Substances

Atenolol (Rec.INN registered by WHO)

Chlorthalidone (USAN adopted for use in the USA)

Dosage Forms

	Tenorox	Film-coated tablets, 50 mg+12.5 mg: 10 or 28 pcs.
		Forte film-coated tablets 100 mg+25 mg: 10 or 28 pcs.

Dosage Form, Packaging, and Composition

Forte film-coated tablets white or almost white, round, biconvex, with a score line on one side; on the fracture – a uniform core of almost white color and a white coating layer.

Excipients: corn starch – 148.5 mg, lactose – 92.5 mg, sodium lauryl sulfate – 2.5 mg, purified talc – 10 mg, povidone – 6 mg, colloidal silicon dioxide – 8 mg, magnesium stearate – 4 mg, hypromellose – 5 mg, titanium dioxide – 3 mg, light liquid paraffin – 0.5 mg, polyethylene glycol-400 – 2 mg, white beeswax – 0.166 mg, carnauba wax – 0.333 mg.

10 pcs. – strips made of aluminum foil (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex, with a score line on one side; on the fracture – a uniform core of almost white color and a white coating layer.

Excipients: corn starch – 74.25 mg, lactose – 46.25 mg, sodium lauryl sulfate – 1.25 mg, purified talc – 5 mg, povidone – 3 mg, colloidal silicon dioxide – 4 mg, magnesium stearate – 2 mg, hypromellose – 2.5 mg, titanium dioxide – 1.5 mg, light liquid paraffin – 0.25 mg, polyethylene glycol-400 – 1 mg, white beeswax – 0.083 mg, carnauba wax – 0.1666 mg.

10 pcs. – strips made of aluminum foil (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive combination agent (beta1-adrenergic blocker + diuretic)

Pharmacological Action

A combined antihypertensive drug that has a long-lasting hypotensive effect. The effect is due to the action of two components – a beta1-adrenergic blocker (Atenolol) and a diuretic (Chlortalidone).

Atenolol: a cardioselective beta-1-adrenergic blocker acting primarily on the beta-1-adrenergic receptors of the heart. Selectivity decreases with increasing dose.

Atenolol does not have intrinsic sympathomimetic and membrane-stabilizing effects. Like other beta-blockers, it has a negative inotropic effect and reduces heart rate, which is why it is not recommended for use in heart failure.

Chlortalidone: a non-thiazide sulfonamide diuretic that enhances the excretion of sodium and chloride. Increases the excretion of potassium, magnesium, and bicarbonate. The combination of atenolol with diuretics is possible and, as a rule, more effective than the use of each component separately.

Pharmacodynamics

The combination of atenolol and chlortalidone provides an additive antihypertensive effect. The maximum effect is achieved after 2-4 weeks of therapy.

During treatment, the following may occur:

• Impaired glucose tolerance. Use with caution in patients with a known predisposition to diabetes mellitus;
• Hyperuricemia may occur. An increase in serum uric acid levels may, in some cases, require the use of agents that promote uric acid excretion.

In most patients with arterial hypertension, taking one forte 100 mg Tenorox tablet per day gives satisfactory results. With an increase in dose, a further decrease in blood pressure either does not occur or is insignificant, but, if necessary, another antihypertensive agent may be additionally prescribed.

Pharmacokinetics

After oral administration, Atenolol is absorbed from the gastrointestinal tract by 50%. C_max in blood plasma is reached 2-4 hours after oral administration. Atenolol does not undergo significant hepatic metabolism and more than 90% of the absorbed drug is excreted unchanged. T_1/2 is 6-9 hours, but may increase in cases of severe renal failure, since the excretion of this drug occurs mainly through the kidneys. Plasma protein binding is approximately 6-16%.

After oral administration, Chlortalidone is absorbed from the gastrointestinal tract by 60%. C_max in blood plasma is noted approximately 12 hours after oral administration. T_1/2 is approximately 50 hours, and excretion occurs mainly through the kidneys. Chlortalidone binds to blood plasma proteins by approximately 75%.

The simultaneous use of chlortalidone and atenolol has a slight effect on the pharmacokinetics of each of them.

Tenorox is effective for at least 24 hours after a single oral dose of the daily dose.

Indications

Arterial hypertension.

ICD codes

Dosage Regimen

For adults

Take orally, without chewing, 1 tablet per day.

For arterial hypertension, the initial dose is 50 mg of atenolol once a day; if the therapeutic effect is insufficient, Tenorox is prescribed as one forte tablet containing 100 mg of atenolol per day.

For elderly people

This age group often requires a lower dose of the drug (1/2 tablet of atenolol 50 mg).

For renal impairment

Caution should be exercised when treating patients with impaired renal function. Discontinuation of the drug after prolonged treatment should be carried out gradually, if possible.

Adverse Reactions

Tenorox is usually well tolerated.

Laboratory parameters: hyperuricemia; hyponatremia (associated with chlortalidone); hypokalemia: impaired glucose tolerance.

Side effects associated with its use are rare, in most cases they are mild and temporary.

Discontinuation of treatment with beta-blockers should be carried out gradually.

There have been reports of nausea and dizziness associated with the use of Chlortalidone and rarely reported idiosyncratic reactions to the drug, such as thrombocytopenia and leukopenia.

From the cardiovascular system: bradycardia; increased symptoms of heart failure; orthostatic hypotension, which may be accompanied by fainting; cold extremities. The appearance of cardiac arrhythmias, including atrioventricular block; manifestation of intermittent claudication, occurrence of Raynaud’s syndrome is possible.

From the central nervous system: confusion; dizziness; headache, emotional lability; acute psychosis, hallucinations; paresthesia; sleep disorders, increased fatigue, apathy; disorientation.

From the gastrointestinal tract: dry mouth; rarely – increased levels of “liver” transaminases in the blood serum, rarely – hepatotoxicity with signs of intrahepatic cholestasis; nausea (associated with chlortalidone), constipation, diarrhea, pancreatitis, anorexia.

Hematological reactions: leukopenia; purpura; thrombocytopenia; agranulocytosis, eosinophilia.

From the skin: alopecia; psoriasis-like skin reactions; exacerbation of psoriasis, skin rash.

From the respiratory system: bronchospasm may occur in patients suffering from bronchial asthma or with a history of bronchospasm.

From the sensory organs: visual disturbances.

Other: increased number of antinuclear antibodies, although the clinical significance of this fact is unclear, decreased potency.

Contraindications

• Hypersensitivity to any component of the drug;
• Severe bradycardia;
• Cardiogenic shock;
• Severe arterial hypotension,
• Metabolic acidosis;
• Severe peripheral circulatory disorders,
• Atrioventricular block II and III degree;
• Sick sinus syndrome;
• Pheochromocytoma,
• Acute heart failure;
• Chronic heart failure;
• Prinzmetal’s angina;
• Bronchial asthma, obstructive bronchitis;
• Diabetes mellitus;
• Hypokalemia;
• Gout;
• Myasthenia gravis;
• Acute hepatitis;
• Acute renal failure;
• Children under 18 years of age.

With caution prescribe to patients with atrioventricular block I degree, patients with bronchial obstruction syndrome, in case of deterioration of bronchial patency due to taking Tenorox, therapy with beta-adrenergic agonists (for example, salbutamol) is prescribed.

Use in Pregnancy and Lactation

The use of Tenorox during pregnancy and breastfeeding is contraindicated.

Use in Renal Impairment

Caution should be exercised when treating patients with impaired renal function. Discontinuation of the drug after prolonged treatment should be carried out gradually, if possible.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

For elderly people, a lower dose of the drug is often required (1/2 tablet of atenolol 50 mg).

Special Precautions

Due to the beta-blocker (Atenolol) included in Tenorox

• May mask the symptoms of thyrotoxicosis and hypoglycemia;
• If bradycardia develops during therapy (heart rate slowing to 50 beats per minute) with clinical symptoms, the dose should be reduced or the drug discontinued;
• Tenorox should not be abruptly discontinued in patients suffering from coronary artery disease;
• Smokers may experience a decrease in the therapeutic effect of the drug;
• Special attention is required in cases where general anesthesia surgery is needed in patients taking Atenolol. The drug should be discontinued 48 hours before surgery. An anesthetic with the least possible negative inotropic effect should be chosen;
• May increase sensitivity to allergens and cause severe anaphylactic reactions, therefore patients undergoing desensitization therapy should take the drug with great caution. These patients may not respond to the usual doses of epinephrine used to treat allergic reactions;
• When using atenolol, a decrease in the production of tear fluid is possible, which is important for patients using contact lenses.

Due to the action of chlortalidone included in Tenorox

• Hypokalemia may occur. It is necessary to regularly monitor potassium levels, especially in elderly patients, in patients taking cardiac glycosides for the treatment of heart failure, in patients with an unbalanced diet (low in potassium) or in patients with complaints of gastrointestinal dysfunction. In patients taking cardiac glycosides, hypokalemia may predispose to cardiac arrhythmias;
• Caution should be exercised when prescribing to patients with severe renal failure.

Influence on driving and operating machinery

The use of the drug is unlikely to lead to any impairment of the ability of patients to drive a car or operate machinery. However, it should be taken into account that dizziness and increased fatigue may occur. This effect is enhanced by the simultaneous use of alcohol.

Drug Interactions

Concomitant therapy with dihydropyridines, for example, nifedipine, may increase the risk of a pronounced decrease in blood pressure in patients with latent heart failure, and signs of circulatory disorders may appear.

Cardiac glycosides in combination with beta-blockers may increase atrioventricular conduction time.

Beta-blockers may exacerbate “rebound” hypertension, which may occur after discontinuation of clonidine. If both drugs are prescribed, the beta-blocker should be discontinued several days before stopping clonidine. If it is necessary to replace clonidine with a beta-blocker, the latter should be prescribed several days after discontinuation of clonidine treatment. Beta-blocker should be prescribed with caution in combination with class I antiarrhythmic drugs, such as disopyramide (cardiodepressive effects may be additive).

Concomitant use of sympathomimetic agents, for example, epinephrine, norepinephrine may neutralize the effect of beta-blockers (significant increase in blood pressure).

Salicylates and non-steroidal anti-inflammatory drugs (e.g., ibuprofen, indomethacin), estrogens may reduce the hypotensive effect of beta-blockers, and with high doses of salicylates, an increase in the toxic effect of salicylates on the central nervous system may be observed.

Lithium-containing drugs should not be used with diuretics, as they may reduce its renal clearance.

Caution should be exercised when using general anesthetics in combination with Tenorox. The anesthesiologist must be informed about the use of Tenorox and a general anesthetic with the least possible negative inotropic effect should be chosen. The use of beta-blockers together with anesthetics may lead to an increased risk of arterial hypotension. The use of general anesthetics that reduce myocardial contractility should be avoided. In addition, the effect of curare-like muscle relaxants is enhanced.

The drug should not be used with monoamine oxidase inhibitors (possible increase in blood pressure).

Caution should be exercised when using the drug with angiotensin-converting enzyme inhibitors (captopril, enalapril), since at the beginning of therapy a sharp increase in the antihypertensive effect of Tenorox is possible. When used concomitantly with glucocorticoids, carbenoxolone, amphotericin B, furosemide, increased potassium excretion is possible.

General anesthetics: enhancement of the hypotensive effect and summation of the negative inotropic effect of both agents.

Insulin and oral antidiabetic agents: the effect of the latter may be enhanced.

Signs of hypoglycemia: tachycardia, tremor, increased sweating, general weakness, decreased eyeball tone. It is necessary to regularly monitor blood glucose levels.

Tricyclic antidepressants, barbiturates, phenothiazines, diuretics, vasodilators and other antihypertensive agents, alcohol – possible enhancement of the antihypertensive effect of Tenorox.

The use of beta-blockers in combination with calcium channel blockers that have a negative inotropic effect, for example, verapamil, diltiazem, may lead to an enhancement of this effect, especially in patients with reduced myocardial contractility and/or with impaired sinoatrial or atrioventricular conduction. This can cause a pronounced decrease in blood pressure, severe bradycardia and heart failure. Calcium channel blockers should not be administered intravenously within 48 hours after discontinuation of the beta-blocker.

With simultaneous administration of Tenorox with reserpine, clonidine, guanfacine, severe bradycardia may occur.

Overdose

Symptoms of overdose may include: severe bradycardia, severe decrease in blood pressure, acute heart failure and bronchospasm, convulsions, increased drowsiness.

Treatment: Close monitoring; treatment in the intensive care unit; gastric lavage, use of activated charcoal and laxatives to prevent absorption of the drug still present in the gastrointestinal tract; use of plasma or plasma substitutes to treat low blood pressure and shock. Hemodialysis or hemoperfusion may be used. Bronchospasm is usually relieved with bronchodilators. With significant diuresis – administration of fluids and electrolytes.

Storage Conditions

In a dry place, protected from light, at a temperature below 25°C (77°F). The drug should be stored out of the reach of children.

Shelf Life

Shelf life – 3 years. The drug should not be used after the expiration date indicated on the packaging.

Dispensing Status

The drug is dispensed 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.