Pharmacological properties of the drug Tenox
Selective blocker of slow calcium channels with a predominant effect on blood vessels, a dihydropyridine derivative. Amlodipine is used as an antianginal and antihypertensive agent. The drug blocks calcium channels and reduces the transmembrane transition of calcium ions into arterial smooth muscle cells and cardiomyocytes. Amlodipine has a more pronounced selectivity for vascular muscle cells compared to myocardial cells. As a result, the main hemodynamic effect of the drug is systemic peripheral vasodilation, which leads to a decrease in peripheral vascular resistance and determines its antihypertensive effect. The antianginal effect of amlodipine is realized through two mechanisms: a decrease in myocardial oxygen demand due to a decrease in afterload (a decrease in peripheral resistance without reflex tachycardia); improving oxygen delivery to the myocardium due to the direct effect of the drug on the coronary vessels. After oral administration, amlodipine is slowly and completely absorbed from the digestive tract. The average absolute bioavailability is 64%, the maximum concentration in the blood plasma is achieved 6–9 hours after oral administration. Stable plasma concentrations are achieved after 7 days from the start of treatment. The mean volume of distribution is 21 L/kg body weight, indicating that most of the drug is found in body tissues and a relatively small portion in the blood. 95% of the drug binds to blood plasma proteins. The plasma half-life after a single dose of the drug ranges from 31 to 48 hours, and after multiple doses - approximately 45 hours. About 60% of an orally administered dose is excreted in the urine, mainly in the form of metabolites, and 20-25% is excreted in the feces. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). Elderly patients (over 65 years of age) eliminate amlodipine more slowly than younger patients, although this difference is not clinically significant. An increase in half-life in patients with liver failure indicates that with long-term use of the drug there may be an increase in its accumulation in the body. The presence of renal failure does not significantly affect the kinetics of amlodipine.
Instructions for use TENOX
Calcium channel blocker. Antianginal and antihypertensive drug. Amlodipine inhibits the flow of calcium ions through L-type calcium channels of the cell membranes of the smooth muscles of the heart and blood vessels, which leads to a decrease in vascular muscle tone.
The antihypertensive effect of amlodipine is due to a direct relaxing effect on the arteries and arterioles, which leads to a decrease in peripheral vascular resistance. The direct effect of the drug on the heart muscle is insignificant. Amlodipine selectively acts on blood vessels, approximately 80 times stronger than on the heart muscle.
In patients with angina pectoris, the antianginal effect of amlodipine is due to a decrease in oxygen consumption by the myocardium, a decrease in its oxygen demand as a result of a decrease in peripheral vascular resistance (without the development of reflex tachycardia), and an improvement in oxygen delivery to the myocardium due to the expansion of the coronary arteries and arterioles.
The use of the drug promotes regression of myocardial and vascular hypertrophy.
When using Tenox, there is no effect on the sinoatrial or atrioventricular nodes.
The drug increases renal blood flow and glomerular filtration, reduces renovascular resistance, causes moderate natriuresis, and reduces urinary albumin excretion.
Tenox has a protective effect on the myocardium by reducing the accumulation of calcium in cells, maintaining the normal structure and function of myocyte membranes, and maintaining normal mitochondrial function.
Tenox has an anti-atherosclerotic effect by modulating lipid metabolism, reducing cell migration into smooth muscle, inhibiting smooth muscle cell proliferation, reducing the expression and adhesion of molecules, and reducing the activity of proteolytic enzymes.
Reduces platelet aggregation. Does not change insulin sensitivity, does not affect carbohydrate or lipid metabolism.
Use of the drug once a day provides a prolonged and gradual antihypertensive effect. Maintains normal blood pressure for 24 hours while maintaining rhythm without reflex sympathetic activation.
After oral administration, a significant decrease in blood pressure is observed after 6–10 hours or more. With long-term treatment, the maximum reduction in blood pressure is observed after 6-12 hours.
When amlodipine is discontinued after long-term treatment, the effective reduction in blood pressure persists for 48 hours after the last dose. Blood pressure gradually returns to baseline levels over 5–6 days.
In patients with angina pectoris, a single dose of amlodipine significantly improves exercise tolerance, reduces the frequency of angina attacks and the consumption of short-acting nitrates.
The results of controlled clinical trials show that in patients with heart failure, amlodipine does not have a negative effect on symptoms, morbidity and mortality.
In placebo-controlled clinical trials in patients with heart failure (NYHA functional class II–IV) receiving standard therapy (ACE inhibitors, diuretics and digoxin), the risk of neither cardiovascular nor all-cause mortality was increased.
Side effects of the drug Tenox
Most often - headache, peripheral edema, palpitations, dizziness, drowsiness, fatigue, abdominal pain, nausea. Some side effects, such as asthenia, malaise, fainting, dyspepsia, bowel disorders, pancreatitis, gingival hyperplasia, dry mouth, increased sweating, alopecia, shortness of breath, cramps, muscle pain, joint pain, back pain, peripheral neuropathy, mood lability , thrombocytopenia, leukopenia, vasculitis, impotence, gynecomastia, hyperglycemia, increased frequency of urination and visual disturbances were sometimes noted in patients during treatment with amlodipine, but in most cases the relationship with the drug was not established. Isolated undesirable effects include increased liver enzymes, hepatitis and jaundice. Some patients have experienced allergic reactions such as skin rash, itching, angioedema and erythema multiforme. Some undesirable effects noted in individual patients could not be distinguished from symptoms characteristic of the course of the underlying disease; this applies to myocardial infarction, arrhythmias (including ventricular tachycardia and atrial fibrillation) and chest pain.
Special instructions for the use of Tenox
Amlodipine is primarily metabolized in the liver, so the half-life of the drug may be prolonged in patients with hepatic impairment. The drug should be prescribed to such patients with caution. For elderly patients, no dosage adjustment is required, however, increased sensitivity to amlodipine used in normal doses may occur, so treatment should be carried out under medical supervision. There is insufficient data on the use of amlodipine in acute myocardial infarction or within 1 month after it. It is not recommended to prescribe the drug to children under 18 years of age. During pregnancy and breastfeeding. Amlodipine is not recommended for use during pregnancy and breastfeeding. When planning pregnancy, you must stop taking the drug at least 1 month in advance. Impact on the ability to drive vehicles and operate other machinery . Amlodipine does not affect the ability to drive vehicles or operate other machinery. However, this drug may cause drowsiness and dizziness in some patients, especially at the beginning of treatment. In such cases, patients are advised to be especially careful when driving vehicles and operating other mechanisms.
Tenox tablets 10 mg No. 30
Compound
1 tablet contains the active substance amlodipine maleate in terms of amlodipine 10 mg.
Excipients: microcrystalline cellulose, pregelatinized starch, sodium starch glycolate,
colloidal silicon dioxide anhydrous, magnesium stearate.
Pharmacokinetics
After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is 64%, the maximum concentration in the blood serum is observed after 6-9 hours. A stable equilibrium concentration is achieved after 7 days of therapy. Food does not affect the absorption of amlodipine. The mean volume of distribution is 21 L/kg body weight, indicating that most of the drug is in the tissues and a relatively smaller portion is in the blood. Most of the drug in the blood (95%) binds to blood plasma proteins. Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites and has a “first pass” effect through the liver. Metabolites do not have significant pharmacological activity. After a single oral dose, the half-life (T1/2) varies from 31 to 48 hours; with repeated administration, T1/2 is approximately 45 hours. About 60% of the dose taken orally is excreted in the urine mainly in the form of metabolites, 10% unchanged, and 20-25% in feces and breast milk. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).
In elderly patients (over 65 years of age), the elimination of amlodipine is slower (T1/2 65 hours) compared to young patients, but this difference is not clinically significant. Prolongation of T1/2 in patients with liver failure suggests that with long-term administration, the accumulation of the drug in the body will be higher (T1/2 up to 60 hours).
Renal failure does not significantly affect the kinetics of amlodipine. The drug penetrates the blood-brain barrier. It is not removed by hemodialysis.
Indications for use
Arterial hypertension (monotherapy or in combination with other antihypertensive drugs)
Stable and vasospastic angina (Prinzmetal angina)
With caution: impaired liver function, sick sinus syndrome (severe bradycardia, tachycardia), decompensated chronic heart failure, mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after) , diabetes mellitus, lipid profile disorders, old age.
Contraindications
Hypersensitivity to amlodipine and other dihydropyridine derivatives;
severe arterial hypotension, collapse, cardiogenic shock,
pregnancy and lactation period up to 18 years of age (efficacy and safety have not been established).
Directions for use and doses
Orally, the initial dose for the treatment of arterial hypertension and angina is 5 mg of the drug once a day. The maximum dose can be increased to 10 mg once a day. For arterial hypertension, the maintenance dose can be 2.5-5 mg per day.
For angina pectoris and vasospastic angina - 5-10 mg per day, once. To prevent angina attacks - 10 mg/day.
For thin patients, short patients, elderly patients, patients with impaired liver function, Tenox is prescribed as an antihypertensive agent at an initial dose of 2.5 mg, and as an antianginal agent - 5 mg.
No dose change is required when administered concomitantly with thiazide diuretics, beta blockers and angiotensin-converting enzyme (ACE) inhibitors. No dose changes are required in patients with renal failure.
Storage conditions
List B. At a temperature not exceeding 30°C and out of the reach of children.
Best before date
2 years
special instructions
During treatment with Tenox, it is necessary to monitor body weight and sodium intake, and prescribe an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum overgrowth).
In elderly patients, the half-life and clearance of the drug may be prolonged.
The dosage regimen for the elderly is the same as for patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary. Despite the absence of withdrawal syndrome with slow calcium channel blockers, a gradual dose reduction is recommended before stopping treatment.
Description
Round, biconvex white tablets with a beveled edge and a score on one side.
Conditions for dispensing from pharmacies
On prescription
Dosage form
Pills
Manufacturer and organization accepting consumer complaints
Manufacturer KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia.
Representative office in the Russian Federation 123022, Moscow, st. 2nd Zvenigorodskaya, 13, building 41
Action
Blocker of “slow” calcium channels.
Pharmacodynamics
The dihydropyridine derivative is a second-generation blocker of “slow” calcium channels, has an antianginal and hypotensive effect. By binding to dihydropyridine receptors, it blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (more into vascular smooth muscle cells than into cardiomyocytes). The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in case of angina pectoris, it reduces the severity of myocardial ischemia; by expanding peripheral arterioles, it reduces total peripheral vascular resistance, reduces preload on the heart, and reduces myocardial oxygen demand. Expands the main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents the development of constriction of the coronary arteries (including those caused by smoking). In patients with angina pectoris, a single daily dose increases the time of physical activity, slows down the development of angina and “ischemic” depression of the ST segment, reduces the frequency of angina attacks and nitroglycerin consumption. It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on vascular smooth muscle. For arterial hypertension, a single dose provides a clinically significant reduction in blood pressure (BP) over 24 hours (in the patient’s “lying” and “standing” position). Does not cause a sharp decrease in blood pressure, exercise tolerance, or left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy, has an antiatherosclerotic and cardioprotective effect in ischemic heart disease. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. Does not have adverse effects on metabolism and plasma lipids. The onset of the effect is 2-4 hours, the duration of the effect is 24 hours.
Side effects
From the cardiovascular system: palpitations, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, edema (swelling of the ankles and feet), flushing of the face, rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial flutter), pain in the chest, orthostatic hypotension, very rarely - development or worsening of heart failure, extrasystole, migraine.
From the central nervous system: headache, dizziness, fatigue, drowsiness, mood changes, convulsions; rarely - loss of consciousness, hypoesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams; very rarely - ataxia, apathy, agitation, amnesia.
From the digestive system: nausea, vomiting, epigastric pain, rarely - increased levels of “liver” transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gum hyperplasia, constipation or diarrhea, very rarely - gastritis, increased appetite.
From the genitourinary system: rarely - pollakiuria, painful urge to urinate, nocturia, sexual dysfunction (including decreased potency), very rarely - dysuria, polyuria.
From the skin: very rarely - xeroderma, alopecia, dermatitis, purpura, skin discoloration.
Allergic reactions: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema. From the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia with long-term use, very rarely - myasthenia gravis.
Others: rarely - gynecomastia, polyuricemia, weight gain/loss, thrombocytopenia, leukopenia, hyperglycemia, blurred vision, conjunctivitis, diplopia, eye pain, tinnitus, back pain, dyspnea, nosebleeds, increased sweating, thirst; very rarely - cold sticky sweat, cough, rhinitis, parosmia, impaired taste, impaired accommodation, xerophthalmia.
Interaction
Inhibitors of microsomal oxidation increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes reduce it.
The hypotensive effect is weakened by nonsteroidal anti-inflammatory drugs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha adrenergic agonists, estrogens (sodium retention), and sympathomimetics.
Thiazide and loop diuretics, alpha, beta-blockers, veropamil, angiotensin-converting enzyme (ACE) inhibitors and nitrates enhance the antianginal and hypotensive effects. Amiodarone, quinidine, alpha 1-blockers, antipsychotic drugs (neuroleptics) and slow calcium channel blockers may enhance the hypotensive effect.
Does not affect the pharmacokinetic parameters of digoxin and warfarin. Cimetidine does not affect the pharmacokinetics of amlodipine. When used together with lithium drugs, their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Calcium supplements may reduce the effect of slow calcium channel blockers.
Procainamide, quinidine, and other drugs known to prolong the QT interval enhance the negative inotropic effect and may increase the risk of significant QT prolongation.
The pharmacokinetics of amlodipine does not change when administered simultaneously with cimetidine.
Grapefruit juice may reduce the plasma concentration of amlodipine, but this decrease is so small that it does not significantly alter the effect of amlodipine.
Overdose
Symptoms: marked decrease in blood pressure, tachycardia, excessive peripheral vasodilation, tachycardia.
Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring indicators of heart and lung function, elevated position of the extremities, monitoring the volume of circulating blood and diuresis. To restore vascular tone, use vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the effects of blockade of calcium channels - intravenous administration of calcium gluconate. Hemodialysis is not effective.
Release form
Package
Impact on the ability to drive vehicles and operate machinery
There have been no reports of Tenox affecting driving or operating machinery. However, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, the patient must take special precautions when driving and operating machinery.
Drug interactions Tenox
When treating patients with hypertension (arterial hypertension), amlodipine can be safely used simultaneously with thiazide diuretics, α- and β-adrenergic receptor blockers or ACE inhibitors. For patients with stable angina, this drug can be combined with other antianginal agents, such as long-acting nitrates, beta-blockers, or sublingual nitroglycerin. Amlodipine can be safely used concomitantly with NSAIDs, antibiotics and oral hypoglycemic agents. The results of pharmacokinetic studies with cyclosporine indicate that amlodipine does not significantly alter the pharmacokinetics of cyclosporine. In healthy people, simultaneous use of amlodipine and digoxin did not lead to changes in plasma digoxin concentrations or renal clearance of digoxin. The pharmacokinetics of amlodipine does not change with the combined use of cimetidine. When taken concomitantly, amlodipine does not significantly change the effect of warfarin on prothrombin time. In vitro experiments using human plasma showed that amlodipine does not affect the protein binding of digoxin, phenytoin, warfarin or indomethacin. Grapefruit juice may increase plasma concentrations of amlodipine, but the increase is very small to significantly alter the effect of amlodipine.
TENOX
Interaction
In the treatment of arterial hypertension, it is possible to use amlodipine simultaneously with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors.
In patients with stable angina, the drug can be combined with other antianginal agents, for example, long-acting nitrates, beta-blockers or sublingual nitrates. Amlodipine can be used concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs) (especially indomethacin), antibacterial agents and oral hypoglycemic agents.
It is possible to enhance the antianginal and hypotensive effect of slow calcium channel blockers (SCBC) when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when used together with alpha1 - adrenergic blockers, neuroleptics.
Although negative inotropic effects have generally not been observed in amlodipine studies, some CBMCs may enhance the negative inotropic effects of antiarrhythmic drugs that prolong the QT interval (eg, amiodarone and quinidine).
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Ethanol (ethanol-containing drinks): amlodipine with single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Antiviral agents (ritonavir) increase plasma concentrations of BMCC, incl. amlodipine.
Isoflurane - enhances the hypotensive effect of dihydropyridine derivatives. Calcium supplements may reduce the effect of BMCC.
When amlodipine is used together with lithium preparations, it is possible to increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine does not change the pharmacokinetics of cyclosporine.
Does not affect the serum concentration of digoxin and its renal clearance.
Does not significantly affect the effect of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.
In in vitro studies, amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to blood proteins.
Grapefruit juice: simultaneous single administration of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine.
Tenox drug overdose, symptoms and treatment
Data on overdose cases in humans are limited. Overdose can cause pronounced peripheral vasodilation with further severe and possibly prolonged systemic hypotension. Cardiovascular collapse and shock may also occur. Treatment. Emergency measures should primarily be aimed at removing the drug from the body and stabilizing hemodynamics. In patients, it is necessary to constantly monitor the functions of the cardiovascular and respiratory systems, levels of glucose and electrolytes (potassium, calcium) in the blood plasma, daily diuresis and blood volume. It is possible to administer calcium supplements. To maintain vascular tone, the administration of vasoconstrictors can be effective and beneficial. Since amlodipine is characterized by a high degree of binding to plasma proteins, hemodialysis is ineffective.
