Tenochek, tablets 28 pcs

Tenochek is a combined antihypertensive drug.

Pharmacodynamics

The effect is due to the action of two components – a beta1-adrenoblocker (atenolol) and a “slow” calcium channel blocker, (amlodipine).

The fixed combination of Atenolol and Amlodipine is considered the most effective combination when considered from the perspective of metabolic and hemodynamic interaction of drugs. Amlodipine administration leads to dilatation of arterioles, manifested by reflex tachycardia. This is one of the main side effects of Amlodipine.

The increase in heart rate leads to increased myocardial oxygen demand, which is undesirable for patients with coronary heart disease. As a selective blocker of β₁-adrenergic receptors, Atenolol levels out the reflex tachycardia caused by Amlodipine administration. Clinical studies in recent years have demonstrated a favorable effect of therapy with “slow” calcium channel blockers on the blood lipid spectrum, which helps to reduce the risk of cardiovascular outcomes. The complementary mechanism of action of Amlodipine which decreases general peripheral vascular resistance and Atenolol which reduces cardiac output results in more pronounced hypotensive effect and better tolerability in comparison with Amlodipine and Atenolol monotherapy, improving efficiency/side effect ratio.

Atenolol: has antianginal, hypotensive and antiarrhythmic effects. It does not have membrane stabilizing and intrinsic sympathomimetic activity. Reduces stimulation by catecholamines of cAMP and ATP formation, reduces intracellular Ca²⁺ flow. In the first 24 hours after oral administration, against a background of decreased cardiac output, there is a reactive increase in total peripheral vascular resistance, the severity of which gradually decreases over 1-3 days. Hypotensive effect is associated with decreased cardiac output, decreased activity of the renin-angiotensin system, barocereceptor sensitivity and influence 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 volumes. In medium therapeutic doses, it has no effect on peripheral arterial tone. The hypotensive effect lasts for 24 hours and with regular administration is stabilized by the end of 2 weeks of treatment.

The antianginal effect is determined by decreasing myocardial oxygen demand as a result of decreasing heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility and decreasing myocardial sensitivity to sympathetic innervation. It decreases the heart rate at rest and during physical activity. By increasing ventricular muscle fiber tension and left ventricular end diastolic pressure, it may increase myocardial oxygen demand, especially in patients with chronic insufficiency. Antiarrhythmic action is manifested by suppression of sinus tachycardia and is associated with the elimination of arrhythmogenic sympathetic effects on the cardiac conduction system, inhibition of heterogeneous automatism, reduction of the rate of excitation spread through the sinoauricular node and prolongation of the refractory period. Inhibits impulse conduction in antegrade and, to a lesser extent, in retrograde direction through the atrioventricular node and along accessory pathways.
Increases survival of patients who had myocardial infarction (reduces the frequency of ventricular arrhythmias and attacks of angina pectoris).

In therapeutic concentrations it has no effect on beta-2-adrenoreceptors; in contrast to non-selective beta-adrenoborcators it has less significant effect on the smooth muscle of the bronchi and peripheral arteries and on lipid metabolism. It slightly reduces the vital capacity of the lungs, practically does not weaken the bronchodilator effect of isoproterenol. When taken more than 100 mg per day it may have beta-2-adrenoblocking effect. The negative chronotropic effect appears 1 hour after intake, reaches a maximum after 2-4 hours and lasts up to 24 hours. Amlodipine: a dihydropyridine derivative. It has antihypertensive, atnyanginal, antispasmodic and vasodilator effects. It blocks entry of calcium ions through cell membranes into myocardial and vascular smooth muscle cells.

The mechanism of hypotensive action is caused by direct relaxant effect on smooth muscles of blood vessels.
Antiinflammatory effect of the drug is due to, firstly, its ability to dilate peripheral arterioles which leads to decrease of total peripheral vascular resistance. Decrease of heart load leads to decrease of myocardial oxygen demand. Secondly, under the action of the drug, due to the expansion of the coronary arteries, the flow of oxygen to the myocardium increases (especially in vasospastic angina pectoris). Amlodipine has no adverse effect on metabolism and blood plasma lipids, has antiatherosclerotic, antithrombotic activity, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria.

Pharmacokinetics

Athenololol: After oral administration the drug is quickly absorbed from the gastrointestinal tract – approximately 50% of the oral dose. Fat solubility is poor, bioavailability is 40-50%, time to reach maximum plasma concentration after oral administration – 2-4 hours. It penetrates poorly through the blood-brain barrier, passes in small amounts through the placental barrier and into breast milk. Binding with blood plasma proteins is 6-16%.

It is practically unmetabolized in the liver. The elimination half-life is 6-9 hours (it increases in elderly patients). Excreted by kidneys through glomerular filtration (85-100% unchanged). Impaired renal function is accompanied by prolongation of T_&frac; and cumulation, with creatinine clearance below 35 mg/min/1.73 m² , T_&frac; is 16-27 hours, with clearance below 15 mg/min over 27 hours (dose reduction required). It is excreted during hemodialysis.

Amlodipine: After oral administration amlodipine is rapidly absorbed from the gastrointestinal tract by 90%, the maximum concentration of the drug in blood is observed after 6-12 hours. The equilibrium concentration of the drug in blood plasma is reached after 7-8 days after its continuous administration.

The drug has high volume of distribution – about 20 l/kg; bioavailability is 60-65%, compliance with blood plasma proteins is high – more than 95%. T_½ of the drug is 35-45 hours. It is metabolized mainly in liver with formation of inactive metabolites. Less than 10% of the dose taken orally is excreted unchanged, about 60% is excreted by the kidneys as inactive metabolites; 20-25% is excreted as metabolites in the bile and intestine, as well as with the breast milk. It penetrates through the blood-brain barrier.

Indications

Arterial hypertension; prevention of angina attacks

Pharmacological effect

Tenochek is a combined antihypertensive drug.

Pharmacodynamics

The effect is due to the action of two components – a beta1-blocker (atenolol) and a blocker of “slow” calcium channels (amlodipine).

The fixed combination of Atenolol and Amlodipine is considered the most effective combination when considering it from the standpoint of metabolic and hemodynamic interaction of drugs. Taking Amlodipine leads to dilatation of arterioles, expressed as reflex tachycardia. This is one of the main side effects of Amlodipine.

An increase in heart rate leads to an increase in myocardial oxygen demand, which is undesirable for patients with coronary heart disease. Being a selective blocker of β1-adrenergic receptors, Atenolol neutralizes reflex tachycardia caused by taking Amlodipine. Clinical studies in recent years have demonstrated the beneficial effects of therapy with “slow” calcium channel blockers on the blood lipid spectrum, which helps reduce the risk of cardiovascular outcomes. The complementary mechanism of action of Amlodipine, which reduces total peripheral vascular resistance, and Atenolol, which reduces cardiac output, leads to a more pronounced hypotensive effect and better tolerability compared to monotherapy with Amlodipine and Atenolol, improving the efficacy/side effects ratio.

Atenolol: has antianginal, hypotensive and antiarrhythmic effects. It does not have membrane stabilizing or internal sympathomimetic activity. Reduces the stimulation by catecholamines of the formation of cAMP and ATP, reduces the intracellular Ca2+ current. In the first 24 hours after oral administration, against the background of a decrease in cardiac output, a reactive increase in total peripheral vascular resistance is observed, the severity of which gradually decreases over 1-3 days. The hypotensive effect is associated with a decrease in cardiac output, a decrease in the activity of the renin-angiotensin system, barocceptor 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 volumes. In average therapeutic doses it has no effect on the tone of peripheral arteries. The hypotensive effect lasts 24 hours, and with regular use it stabilizes by the end of 2 weeks 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 contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces heart rate at rest and during physical activity. By increasing the tension of the ventricular muscle fibers and end-diastolic pressure in the left ventricle, it can increase myocardial oxygen demand, especially in patients with chronic failure. The antiarrhythmic effect 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 propagation of excitation through the sinoauricular node and an extension of the refractory period. Inhibits the conduction of impulses in the antegrade and, to a lesser extent, in the retrograde directions through the atrioventricular node and along additional pathways.
Increases the survival rate of patients who have had myocardial infarction (reduces the frequency of ventricular arrhythmias and angina attacks).

In therapeutic concentrations it does not affect beta-2 adrenergic receptors; in contrast to non-selective beta-adrenergic antagonists, it has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries and on lipid metabolism. Slightly reduces the vital capacity of the lungs, practically does not weaken the bronchodilatory effect of isoproterenol. When taken more than 100 mg per day, it may have a beta-2 adrenergic blocking effect. The negative chronotropic effect appears 1 hour after administration, reaches a maximum after 2-4 hours and lasts up to 24 hours. Amlodipine: a dihydropyridine derivative. It has antihypertensive, atnianginal, antispasmodic and vasodilating effects. Blocks the entry of calcium ions through cell membranes into smooth muscle cells of the myocardium and blood vessels.

The mechanism of hypotensive action is due to a direct relaxing effect on vascular smooth muscles.
The antianginal effect of the drug is due, firstly, to its ability to dilate peripheral arterioles, which leads to a decrease in total peripheral vascular resistance. Reducing the load on the heart leads to a decrease in myocardial oxygen demand. Secondly, under the influence of the drug, due to the expansion of the coronary arteries, the supply of oxygen to the myocardium increases (especially with vasospastic angina). Amlodipine does not have an adverse effect on metabolism and plasma lipids, has antiatherosclerotic, antithrombotic activity, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria.

Pharmacokinetics

Atenolol: after oral administration, the drug is rapidly absorbed from the gastrointestinal tract – approximately 50% of the dose taken orally. Fat solubility is poor, bioavailability is 40-50%, time to reach maximum concentration in blood plasma after oral administration is 2-4 hours. It penetrates poorly through the blood-brain barrier and passes in small quantities through the placental barrier and into breast milk. Communication with blood plasma proteins – 6-16%.

Practically not metabolized in the liver. The half-life is 6-9 hours (increases in elderly patients). Excreted by the kidneys by glomerular filtration (85-100% unchanged). Renal dysfunction is accompanied by prolongation of T&frac; and cumulation, with creatinine clearance below 35 mg/min/1.73 m2, T&frac; is 16-27 hours, with clearance below 15 mg/min – more than 27 hours (dosage reduction is necessary). Excreted during hemodialysis.

Amlodipine: after oral administration, amlodipine is rapidly absorbed from the gastrointestinal tract by 90%, the maximum concentration of the drug in the blood is observed after 6-12 hours. The equilibrium concentration of the drug in the blood plasma is achieved 7-8 days after its continuous administration.

The drug has a high volume of distribution – about 20 l/kg; bioavailability is 60-65%, the connection with blood plasma proteins is high – more than 95%. T½ of the drug is 35-45 hours. Metabolized mainly in the liver with the formation of inactive metabolites. Less than 10% of the dose taken orally is excreted unchanged, about 60% is excreted by the kidneys in the form of inactive metabolites; 20-25% is excreted in the form of metabolites with bile and through the intestines, as well as with breast milk. Penetrates the blood-brain barrier.

Special instructions

Monitoring of patients should include monitoring heart rate and blood pressure (at the beginning of treatment – daily, then once every 3-4 months), monitoring blood glucose concentrations in patients with diabetes (once every 4-5 months). In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50/min. In case of thyrotoxicosis, the drug may mask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can increase symptoms. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal levels.

In patients with coronary heart disease (CHD), abrupt discontinuation of the drug may cause an increase in the frequency or severity of anginal attacks, so discontinuation of use in patients with CHD must be done gradually. Particular attention also requires dose selection in patients with decompensated heart failure (compensated).

Particular attention is required in cases where surgery under general anesthesia is required. The drug should be stopped 48 hours before surgery. As an anesthetic, a drug with a possible minimal negative inotropic effect should be selected. When used simultaneously with clonidine, Tenochek should be stopped several days before clonidine in order to avoid the withdrawal syndrome of the latter.

It is possible that the severity of the allergic reaction may increase and there will be no effect from normal doses of epinephrine against the background of a burdened allergic history. Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect a pronounced decrease in blood pressure or bradycardia. If severe bradycardia (less than 50 beats/min), a marked decrease in blood pressure (systolic blood pressure below 100 mm Hg, AV block, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction) occurs in elderly patients, it is necessary to reduce the dose or stop treatment. If depression caused by taking the drug develops, it is recommended to stop therapy.

If intravenous administration of verapamil is necessary, this should be done no less than 48 hours after taking Tenochek.
When using atenolol, it is possible to reduce the production of tear fluid, which is important for patients who use contact lenses. Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 3-4 days).

The drug should be discontinued before testing the concentration of catecholamines and vanillylmandelic acid in the blood and urine; antinuclear antibody titers. Beta blockers are less effective in smokers.

Tenochek should not be abruptly discontinued in patients suffering from coronary heart disease.

Impact on the ability to drive and operate machinery

Tenochek should be prescribed with caution to drivers of vehicles and persons working with machinery, due to a possible decrease in attention.

Active ingredient

Amlodipine, Atenolol

Composition

1 tablet contains active substances:

Active substances:
atenolol 50 mg, and amlodipine 5 mg.
Excipients:
corn starch,
calcium phosphate dibasic,
microcrystalline cellulose,
povidone-30,
sodium starch glycolate,
purified talc,
magnesium stearate,
colloidal silicon dioxide,
isopropyl alcohol,
purified water.

Pregnancy

Pregnant women should be prescribed Tenochek only in cases where the benefit to the mother outweighs the potential risk to the fetus.

Tenochek is excreted in breast milk, so during feeding it should be taken only in exceptional cases with great caution.

Contraindications

Hypersensitivity to the drug Tenochek.
Severe arterial hypotension, atrioventricular block II and III degrees,
sick sinus syndrome,
sinoauricular blockade,
acute heart failure,
chronic heart failure stage II B – stage III decompensated,
severe bradycardia,
metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease,
Prinzmetal’s angina,
cardiomegaly without signs of heart failure,
simultaneous use with MAO inhibitors,
age under 18 years (efficacy and safety have not been established).

Prescribe with caution when:

First degree atrioventricular block.
Liver dysfunction.
With stenosis of the aortic mouth.
Chronic heart failure (in the compensation stage).
Chronic renal failure.
Pheochromocytoma.
Diabetes mellitus.
Hypoglycemia.
Tereotoxicosis.
Obliterating diseases of peripheral vessels (“intermittent” claudication, Raynaud’s syndrome).
Myasthenia.
Depression (including history).
Psoriasis.
Old age.

Side Effects

Usually the drug is well tolerated by patients, however, in some cases the following side effects may occur:

cardiovascular system: the appearance of symptoms of heart failure, impaired atrioventricular conduction, bradycardia, a marked decrease in blood pressure, a feeling of coldness and paresthesia in the extremities, palpitations, shortness of breath, flushes of blood to the skin of the face;
digestive tract: dry mouth, nausea, vomiting, diarrhea, abdominal pain, constipation, rarely: increased activity of liver transaminases and jaundice (due to cholestasis), dyspepsia;
central nervous system: dizziness, sleep disturbance, decreased ability to concentrate, drowsiness, depression, hallucinations, lethargy, feeling tired, headache, rarely – mood changes, asthenia, blurred vision, paresthesia;
musculoskeletal system: muscle cramps, myalgia;
respiratory system: dyspnea, bronchospasm, apnea;
hematological reactions: thrombocytopenic purpura, anemia (aplastic), thrombosis;
endocrine system: gynecomastia, decreased potency, decreased libido, gynecomastia;
metabolic reactions: hyperlipidemia, hypoglycemia;
skin reactions: urticaria, dermatitis, itching, photosensitivity, rarely – exudative erythema multiforme;
other: increased urination, peripheral edema, gingival hyperplasia.

Interaction

When used simultaneously, atenolol and insulin (or other oral hypoglycemic agents) mask the symptoms of hypoglycemia. When used together with antihypertensive drugs of other groups, the hypotensive effect is enhanced. The hypotensive effect is weakened by estrogens (sodium retention).

With the simultaneous use of atenolol and cardiac glycosides, the risk of developing bradycardia and atrioventricular conduction disorders increases. When atenolol is prescribed simultaneously with reserpine, methyldopa, clonidine, verapamil, severe bradycardia may occur. For patients taking atenolol and clonidine simultaneously, clonidine should be discontinued only after several days have passed after stopping treatment with atenolol. When taking atenolol simultaneously with ergotamine and xanthine derivatives, its effectiveness is reduced.

Concomitant use with lidocaine may reduce its elimination and increase the risk of toxicity.

Use together with phenothiazine derivatives helps to increase the concentration of each drug in the blood serum.

Phenytoin, when administered intravenously, and agents for general anesthesia increase the severity of the cardiodepressive effect of atenolol. Concomitant use with MAO inhibitors is not recommended. Allergens used for immunotherapy or allergen extracts for skin testing and iodinated radiocontrast agents for intravenous administration increase the risk of severe systemic allergic reactions or anaphylaxis.

Agents for inhalation general anesthesia (hydrocarbon derivatives) increase the risk of suppression of myocardial function and a pronounced decrease in blood pressure. Amiodarone increases the risk of bradycardia and inhibits AV conduction. Cimetidine increases the concentration of atenolol in the blood plasma (inhibits metabolism).

Prolongs the effect of non-depolarizing muscle relaxants, the anticoagulation effect of coumarins.

Overdose

Symptoms: severe bradycardia, atrioventricular block II-III degree, increasing symptoms of heart failure, marked decrease in blood pressure, bronchospasm, hypoglycemia.

Treatment: for severe bradycardia, intravenous administration of 1 ml of 0.1% atropine sulfate solution is indicated. For AV blockade of the second and third degree, it is possible to prescribe isoprenaline in tablets of 5 mg sublingually (if necessary, repeated administration after 2-4 hours) or intravenous drip or slow jet administration of the drug in a dose of 0.5-1 mg. If bronchospasm occurs, beta2-agonists are indicated. To restore vascular tone, use vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade, intravenous administration of calcium gluconate.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

Ipka Laboratories Limited, India