Instructions for Tenoric film-coated tablets 100 mg + 25 mg No. 28
Composition
active ingredients: atenolol, chlortalidone;
1 tablet contains atenolol 100 mg and chlorthalidone 25 mg;
excipients: anhydrous lactose, corn starch, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, povidone, talc, magnesium stearate, hypromellose, titanium dioxide (E 171), light mineral oil, polyethylene glycol, carnauba wax;
shell: isopropyl alcohol, dichloromethane, hydroxypropylmethylcellulose, purified talc, titanium dioxide (E 171), light mineral oil, macrogol.
Dosage form
Film-coated tablets.
Main physicochemical properties: round, biconvex tablets, film-coated, white or almost white, with a breakline on one side.
Pharmacotherapeutic group
Selective β-adrenergic blockers in combination with diuretics. ATC code C07C B03.
Pharmacological properties
Pharmacodynamics
Combined antihypertensive drug. Atenolol is a cardioselective β1-adrenoblocker. It has no intrinsic sympathomimetic and membrane-stabilizing activity. It reduces heart rate, stroke volume and cardiac output. After oral administration, the maximum effect is achieved after 2-4 hours and lasts up to 24 hours.
Chlorthalidone is a thiazide-like diuretic that increases the excretion of sodium ions, chlorine, and an equivalent amount of water from the body. The onset of action is 2 hours, the peak effect is 2–6 hours. The duration of the effect when taken orally is from 24 to 72 hours.
Pharmacokinetics
Absorption: After oral administration, 50% of the dose of atenolol is absorbed from the gastrointestinal tract, and food intake does not significantly affect it. Maximum plasma concentration is reached after 2–4 hours.
Distribution: Atenolol is approximately 6-16% bound to plasma proteins. Chlorthalidone is 90% bound to plasma proteins and erythrocytes.
Metabolism and excretion. Atenolol is practically not metabolized in the liver. It is excreted mainly by the kidneys (90%). The half-life is 6–9 hours. Chlorthalidone is excreted in feces and urine. The half-life is 24–55 hours, and increases in the elderly and with renal failure.
Indication
Arterial hypertension.
Contraindication
Hypersensitivity to any component of the drug. Severe sinus bradycardia, arterial hypotension, metabolic acidosis, severe peripheral circulatory disorders, atrioventricular block II-III degree, sinoatrial block, sick sinus syndrome, cardiogenic shock, acute heart failure, decompensated chronic heart failure, untreated pheochromocytoma, anuria, renal and hepatic failure; precoma associated with Addison's disease; hypokalemia, intoxication with cardiac glycosides, bronchial asthma, broncho-obstructive syndrome. The drug is contraindicated in patients receiving verapamil for 48 hours. Hyponatremia, hypercalcemia, simultaneous use of lithium preparations, gout.
Interaction with other medicinal products and other types of interactions
Tenoric™ potentiates the effects of other antihypertensive agents when used concomitantly. In patients treated with Tenoric™ in combination with a catecholamine (e.g., reserpine), hypotension and/or bradycardia have been observed in studies, which may lead to dizziness, syncope, or orthostatic hypotension.
With simultaneous use with dihydropyridone (e.g. nifedipine), the risk of arterial hypotension and heart failure, which are observed in patients with chronic heart failure, may increase.
Calcium channel blockers also have an additive effect when used with Tenoric™.
Digitalis preparations and atenolol slow down the heart rate, worsen atrioventricular conduction. Simultaneous use with digitalis preparations increases the effect on the sinus node, intraventricular conduction. Simultaneous use with digitalis preparations increases the symptoms of hypokalemia, therefore monitoring of laboratory parameters is required. Caution should be exercised when prescribing the drug to patients who use digitalis preparations along with an inadequate diet (which does not meet the body's need for potassium), or to those who have gastrointestinal diseases.
Tenoriq™ enhances the antihypertensive effect of hydralazine and prazosin, their combination leads to a greater reduction in blood pressure than when taking only one drug.
Concomitant therapy with dihydropyridines, such as nifedipine, may increase the risk of arterial hypotension, and patients with latent heart failure may develop signs of circulatory disorders.
β-blockers may exacerbate rebound hypertension that may occur after clonidine withdrawal.
If Tenoric™ and clonidine are used simultaneously, clonidine can be discontinued only a few days after discontinuation of Tenoric™.
Atenolol may mask the clinical signs (manifestations) of hypoglycemia. When Tenoric™ is used simultaneously with insulin, antidiabetic agents for internal use, their hypoglycemic effect increases. Regular monitoring of blood glucose levels is necessary.
When Tenoric™ is used simultaneously with antihypertensive agents of different groups, tricyclic antidepressants, barbiturates, ethanol, diuretics, phenothiazines, nitrates, and peripheral vasodilators, their hypotensive effect increases.
With simultaneous use of Tenoric™ with reserpine, methyldopa, clonidine, verapamil, bradycardia may occur.
Caution should be exercised when prescribing β-blockers in combination with class I antiarrhythmics (desopyramide), as the cardiodepressive effect may be additive. When used with amiodarone, there is a risk of impaired automaticity, conduction, and contractility of the heart.
When using inhalation anesthetics (halothane, methoxyflurane) and Tenoric™, the risk of myocardial depression and the development of arterial hypotension increases, therefore, a few days before anesthesia, it is necessary to stop taking Tenoric™ or choose an anesthetic with minimal negative inotropic effect.
Concomitant use of Tenoric™ and nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), as well as estrogens, reduces the effectiveness of atenolol.
The interaction of atenolol, which is part of Tenoric™, with quinolones increases the bioavailability of atenolol, with adrenaline - enhances the vasopressor effect with subsequent bradycardia, with lidocaine - increases the level of lidocaine, with amiodarone - increases the risk of dysfunction of the sinus or atrioventricular node (should not be prescribed), with cimetidine - decreases the clearance of atenolol, which causes an increase in its level in the blood plasma and an increase in the therapeutic effect. When used simultaneously with euphylline or theophylline, mutual inhibition of therapeutic effects is possible.
Concomitant use of diuretics (chlorthalidone) with lithium preparations reduces renal clearance of lithium. Concomitant use with glucocorticosteroids, amphotericin, furosemide increases potassium excretion.
Quitting smoking increases the therapeutic effect of atenolol by reducing its metabolism and increasing the level of the drug in the blood.
Cimetidine may increase the level of the drug in the blood.
Alcohol potentiates the effect of the drug.
With propafenone - increased effect of atenolol, which is part of the drug;
with nicotine - increased effect of atenolol as a result of reduced metabolism and increased blood levels of the drug;
with MAO inhibitors - increased effect of chlorthalidone, which is part of the drug;
with cholestyramine - weakening of the effect of chlorthalidone, which is part of the drug;
with drugs containing potassium - weakening of the effect of the latter;
with drugs that depress the central nervous system (CNS) - increased sedative effect;
with lithium - increased effect of the latter;
with narcotic analgesics - increased narcotic effect; dangerous inhibition;
with oral hypoglycemic agents, insulin - increased effect of the latter;
with anticholinesterase agents, angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril) - increased potassium levels in the blood.
Application features
Hypersensitivity reactions may occur in patients with or a history of bronchial asthma who are receiving thiazides. Exacerbation of systemic lupus erythematosus has been reported. The hypotensive effects of thiazides may be increased in post-sympathectomy patients.
Heart failure. Sympathetic nervous system stimulation is necessary to maintain circulatory function in chronic heart failure. Blockade of β-receptors poses a potential risk of further depression of myocardial contractility and leads to more severe heart failure. Tenoric™ should be used with caution in patients with chronic heart failure controlled by digitalis and/or diuretics. Digitalis and atenolol slow atrioventricular conduction.
Renal or hepatic insufficiency: Since atenolol is excreted by the kidneys, in severe renal impairment the dose of the drug should be reduced. In case of impaired liver and/or kidney function, the dynamics of their functional state should be monitored. In patients with renal insufficiency, the drug may provoke the occurrence of azotemia. Given that a cumulative effect may develop with reduced renal insufficiency and, if renal function continues to deteriorate, treatment with Tenoric™ should be discontinued.
In patients with impaired liver function or progressive liver disease, a slight change in fluid and electrolyte balance may lead to hepatic coma. Therefore, Tenoric™ should be administered with caution to such patients.
Coronary heart disease. Angina pectoris and, in some cases, myocardial infarction may occur when therapy with some β-blockers is abruptly discontinued in patients with coronary heart disease. Therefore, in such patients, therapy with this drug should be discontinued with caution and only under medical supervision. Even in the absence of existing angina pectoris, when Tenoric™ is planned to be discontinued, the patient should be under medical supervision and physical activity should be minimized. Treatment with Tenoric™ should be resumed if withdrawal symptoms occur.
Because coronary artery disease is common and may be unrecognized, it is advisable not to discontinue Tenoric™ therapy abruptly, even in patients treated for hypertension.
Concomitant use of calcium channel blockers. Bradycardia, atrioventricular block, and left ventricular fatal outcome may occur, and diastolic pressure may increase if β-blockers are used with verapamil or diltiazem. Patients with pre-existing intraatrial conduction disorders or left ventricular dysfunction are particularly sensitive to the effects of the drug.
Bronchoobstructive syndrome: Patients with bronchoobstructive syndrome should not use β-blockers.
Since Tenoric™ is a relatively selective β1-adrenergic blocker, it may be used with caution in patients with bronchoobstructive syndrome who are unresponsive to or intolerant of other antihypertensive therapy. Since selective
β-blockers are not absolute, Tenoric™ should be used at the lowest possible dose and β2-adrenergic agonists should be available. If the dosage must be increased, the dose should be divided to achieve lower peak blood levels.
Anaesthesia and major surgery. As with other β-blockers, it may be necessary to discontinue the drug before surgery. In such cases, 48 hours should elapse between the last dose of the drug and anesthesia. If treatment is continued, caution should be exercised when using anesthetic agents. If vagal dominance occurs, it can be reversed with atropine (1–2 mg intravenously).
β-blockers are competitive inhibitors of β-receptor agonists, and their effects on the heart can be completely reversed when agents such as dobutamine or isoproterenol are administered.
Painkillers should be prescribed with caution together with Tenoric™.
The anesthesiologist should be careful to select an analgesic with as little negative inotropic activity as possible. The use of β-blockers with anesthetic drugs may attenuate tachycardia and increase the risk of hypotension. Analgesics that cause myocardial depression are best avoided.
Metabolic and endocrine disorders: Tenoric™ should be administered with caution to patients with diabetes mellitus. β-blockers may mask tachycardia that occurs with hypoglycemia or other manifestations such as dizziness and sweating.
At recommended doses, atenolol does not potentiate insulin-dependent hypoglycemia and, unlike non-selective β-blockers, does not delay the restoration of blood glucose to normal levels.
Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Latent diabetes mellitus may become apparent during treatment with chlorthalidone.
β-adrenergic blockers may mask some of the clinical symptoms (e.g. tachycardia) of hyperthyroidism. Abrupt discontinuation of β-blocker therapy may precipitate thyroid flares; therefore, in patients suspected of developing thyrotoxicosis, consideration should be given to discontinuing Tenoric™ therapy or to closely monitoring.
Since thiazides reduce calcium excretion, Tenoric should be discontinued before parathyroid function tests are performed. Pathological changes in the parathyroid gland, with hypercalcemia and hypophosphatemia, have been observed in patients on long-term thiazide therapy; however, the common complications of hyperparathyroidism such as nephrolithiasis, bone atrophy, and gastric ulcer have not been observed.
Some patients receiving thiazide therapy may experience hyperuricemia or acute gout.
Untreated pheochromocytoma: Tenoric™ should not be used in patients with untreated pheochromocytoma.
Water and electrolyte balance. Periodic determination of electrolyte levels to detect possible electrolyte imbalance should be done at appropriate intervals.
Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as hyponatremia, hypochloremic alkalosis, and hypokalemia.
Determination of urinary electrolyte levels is especially important in patients with excessive vomiting or receiving parenteral fluids.
Warning signs or symptoms of fluid and electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, nervousness, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
It is advisable to determine potassium levels, especially in elderly patients, in patients taking digitalis preparations for the treatment of heart failure, in patients with an unbalanced diet, or in patients with complaints of digestive tract disorders.
Hypokalemia may develop especially with rapid diuresis, in the presence of severe cirrhosis, or during concomitant use of corticosteroids or ACTH.
Oral electrolytes may also contribute to hypokalemia. Hypokalemia may increase the sensitivity or response of the heart to the toxic effects of digitalis drugs (e.g., increase ventricular irritability). Hypokalemia can be reversed or treated with potassium supplements or foods high in potassium.
Any chloride deficiency during thiazide therapy is usually minor and does not require specific treatment except in exceptional circumstances (e.g., liver or kidney disease).
Dilutional hyponatremia may occur in patients with edema in hot weather; appropriate therapy is fluid restriction rather than salt restriction, except rarely when hyponatremia is life-threatening.
In case of excessive salt excretion from the body, the alternative is the drug of choice.
Due to the presence of lactose in the excipients, the drug should be used with caution in patients with hereditary intolerance to galactose, lactose, glucose-galactose, and diabetes mellitus.
This medicinal product contains sodium lauryl sulfate. Caution should be exercised when used in patients on a controlled sodium diet.
Patients with bronchial diseases should not use β-blockers. However, Tenoric™, due to its relative selectivity, can be used with caution in patients with bronchospastic diseases if necessary.
When prescribing the drug to patients with pheochromocytoma, it is necessary to prescribe α-adrenoceptor blockers in advance (to prevent the development of hypertensive crisis).
Treatment with the drug should be carried out under the supervision of a physician. The drug is not prescribed for the treatment of angina attacks.
Hypersensitivity reactions may occur in patients with a history of bronchial asthma who are receiving thiazides.
Use with caution in patients with first-degree AV block, pulmonary emphysema, water and electrolyte imbalance, gastrointestinal diseases, and hypoglycemia.
The drug should not be used before conducting studies on parathyroid function, since thiazides reduce calcium excretion.
Creatinine levels should be measured periodically in patients with renal impairment.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given the possibility of dizziness when using the drug, you should refrain from driving vehicles and performing work that requires increased attention.
Use during pregnancy or breastfeeding
Contraindicated in women during pregnancy or breastfeeding, as atenolol crosses the placenta and enters breast milk.
Method of administration and doses
Tenoric™ tablets should be administered to adults orally, without chewing, with water, before meals, preferably at the same time.
The dosage of the drug and the duration of treatment should be set individually depending on the therapeutic effect obtained.
Tenoric™ is not intended for initial therapy of arterial hypertension. The drug should be prescribed in case of ineffectiveness of monotherapy.
Usually the initial dose is Tenorik™ 1 tablet 50 mg/12.5 mg 1 time per day. If the therapeutic effect is insufficient, prescribe Tenorik™ 1 tablet 100 mg/25 mg 1 time per day. In most patients with arterial hypertension, the use of 1 tablet Tenorik™ (atenolol 100 mg and chlorthalidone 25 mg) 1 time per day provides a sufficient therapeutic effect. With an increase in the dose, a further decrease in blood pressure either does not occur or is insignificant, but if necessary, another antihypertensive agent may be additionally prescribed.
Elderly patients need a lower dose of atenolol prescribed by a doctor.
Caution should be exercised when treating patients with severe renal impairment. In patients with creatinine clearance less than 35 ml/min/1.73 m2 (normal 100-150 ml/min/1.73 m2), the drug can be used only after dose adjustment of the individual components of the drug.
| Creatinine clearance (ml/min) | Atenolol half-life (hours) | Maximum dose |
| 15-35 | 16-27 | 50 mg daily |
| < 15 | <27 | 50 mg every other day |
Children
Do not use on children.
Overdose
Symptoms: bradycardia, atrioventricular block II-III degree, acute heart failure, arterial hypotension, respiratory disorders, arrhythmias, loss of consciousness, hypoglycemia, bronchospasm, convulsions, increased drowsiness, dizziness, nausea, hypovolemia, electrolyte disturbances with cardiac arrhythmias and muscle spasms.
Treatment: the drug should be discontinued. Monitor and correct vital functions of the body. In addition to gastric lavage and the use of adsorbents, the following measures are recommended if necessary: excessive bradycardia can be eliminated by intravenous administration of 1-2 mg of atropine and/or the installation of a pacemaker. If necessary, a bolus of 10 mg of glucagon can be administered intravenously. This procedure can be repeated if necessary or followed by intravenous administration of glucagon at a rate of 1-10 mg/hour depending on the response. In the absence of a response to glucagon or in the absence of glucagon itself, a β1-adrenomimetic - dobutamine - can be administered intravenously at a dose of 5-10 μg/kg/min. Dobutamine, due to its positive inotropic effect, can also be used to treat arterial hypotension and acute heart failure. These doses are unlikely to be sufficient to control the cardiac symptoms associated with β-blockade in cases of significant overdose. Therefore, if necessary, the dose of dobutamine may be increased to achieve the desired response according to the patient's clinical condition.
Maintain normal fluid and electrolyte balance in the body. In case of arterial hypotension - administration of blood plasma or plasma substitutes. Bronchospasm is stopped with bronchodilators.
Fluids and electrolytes should be administered if there is significant diuresis.
Adverse reactions
Cardiovascular system: bradycardia, feeling of coldness in the extremities, orthostatic hypotension, which may be associated with syncope, atrioventricular conduction disorders, symptoms of heart failure, palpitations, in patients with angina pectoris there may be an increase in attacks, arterial hypotension with intermittent claudication and may increase in patients with Raynaud's syndrome, necrotizing vasculitis, sick sinus syndrome, lupus erythematosus, arrhythmia.
From the blood system: purpura, thrombocytopenia, leukopenia, agranulocytosis, eosinophilia, aplastic anemia, neutropenia, pancytopenia, worsening of diabetes mellitus.
On the part of the psyche: mood changes, nightmares, confusion, loss of consciousness, agitation, aggressiveness, psychosis, disorientation, hallucinations, depression, sleep disturbances, impaired concentration.
From the nervous system: dizziness, paresthesia, headache, fatigue, lethargy, drowsiness, muscle cramps, weakness, short-term memory loss.
From the organs of vision: decreased tear secretion, conjunctivitis, dry eyes, visual impairment.
On the part of the respiratory system: bronchospasm in patients with bronchial asthma or in patients with a tendency to bronchial obstruction, shortness of breath, cough, stridor.
On the part of the digestive tract: dyspepsia, nausea, vomiting, constipation, diarrhea, dry mouth, anorexia, gastric irritation, spasms, thrombosis of mesenteric arterial vessels, ischemic colitis, abdominal pain.
Hepatobiliary system: hepatotoxicity, intrahepatic cholestasis, liver dysfunction, cholestatic jaundice, pancreatitis, increased liver enzymes.
On the part of the endocrine system: the development of a hypoglycemic state is possible, especially in patients with diabetes mellitus on the background of hypoglycemic therapy.
Skin: itching, alopecia, psoriasis-like rashes, exacerbation of psoriasis, skin rashes, erythema, photosensitivity, toxic epidermal necrolysis, purpura, urticaria, necrotizing vasculitis, Lyell's syndrome, erythematous rashes.
Allergic reactions: fever accompanied by pain and sore throat.
From the urinary system: interstitial nephritis.
Immune system disorders: Hypersensitivity reactions, including urticaria and angioedema.
From the reproductive system: impotence, Peyronie's disease.
Other: fatigue, muscle weakness, general weakness, fatigue, muscle spasms, gout, increased sweating, alopecia.
Laboratory indicators: hyperuricemia, hyponatremia, hypokalemia, hypomagnesemia, hypercalcemia, hypochloremic alkalosis, hyperglycemia, glucosuria, impaired glucose tolerance, increased serum transaminases, bilirubin, increased ANA (antinuclear antibodies), hypercholesterolemia, hypertriglyceridemia.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
14 tablets in a blister; 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Ipka Laboratories Limited.
Ipka Laboratories Ltd.
Location of the manufacturer and its business address
P.O. Sejavta, District Ratlam – 457002 (M.P.), India.
