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Active ingredients
Amlodipine
Release form
Pills
Composition
amlodipine maleate 6.42 mg, which corresponds to the content of amlodipine 5 mg Supplementary substances: microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, anhydrous colloidal silicon dioxide, magnesium stearate.
Pharmacological effect
Slow calcium channel blocker II generation, a derivative of dihydropyridine. It has antianginal and hypotensive effects. By binding to dihydropyridine receptors, it blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes). The anti-anginal effect is due to the expansion of the coronary and peripheral arteries and arterioles. When angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces the round focal disease, reduces the preload on the heart, reduces the need for myocardium in oxygen. Expands the main coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents the development of spasm of the coronary arteries (including caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of another attack of angina and ischemic depression of the ST segment, reduces the incidence of angina attacks and nitroglycerin consumption. It has a long dose-dependent hypotensive effect. The hypotensive effect is due to the direct vasodilating effect on vascular smooth muscle. In case of arterial hypertension, a single dose provides a clinically significant decrease in blood pressure for 24 hours (in the position of the patient lying and standing). Decreases the degree of left ventricular myocardial hypertrophy, has anti-atherosclerotic and cardioprotective effect in IHD. Does not affect the contractility and conductivity of the myocardium, does not cause a reflex increase in heart rate. It inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria.It does not have any adverse effect on the metabolism and plasma lipid concentration and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. A significant decrease in blood pressure is observed after 6-10 hours, the effect lasts 24 hours. With long-term therapy, the maximum decrease in blood pressure comes 6-12 hours after taking amlodipine inside. If, after prolonged treatment, amlodipine is withdrawn, an effective reduction in blood pressure persists for 48 hours after the last dose. Then the blood pressure indicators gradually return to the initial level within 5-6 days.
Pharmacokinetics
AbsorptionAfter oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is 64%, Cmax is observed after 6-9 hours. The distribution of Css is achieved after 7-8 days of regular use. Meal does not affect the absorption of amlodipine. The average Vd is 21 l / kg body weight. This indicates that most of the drug is in the tissues, and relatively smaller - in the blood. Most of the drug in the blood (95%) binds to plasma proteins. It penetrates through BBB. Metabolism Amlodipine undergoes a slow, but active metabolism in the liver in the absence of a significant first-pass effect. Metabolites do not have significant pharmacological activity. Withdrawal after single intake T1 / 2 varies from 31 to 48 hours, with repeated administration of T1 / 2 is approximately 45 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites (10% - in unchanged form), 20-25% - through the intestines, as well as with breast milk. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg). Pharmacokinetics in special clinical situations in elderly patients (over 65 years of age) depletion of amlodipine is delayed (T1 / 2 is 65 h) compared with younger patients, however, this difference has no clinical significance. With prolonged use in patients with liver failure, T1 / 2 increases to 60 hours and there will be an increase in drug cumulation. Renal failure does not have a significant effect on the amlodipine kinetics. Amlodipine is not removed by hemodialysis.
Indications
- Arterial hypertension (as monotherapy or in combination with other antihypertensive agents); - Stable exertional angina and vasospastic stenocardia (Prinzmetal's angina) (as monotherapy or in combination with other antianginal agents).
Contraindications
- severe arterial hypotension (systolic blood pressure less than 90 mm Hg); - collapse; - cardiogenic shock; - unstable angina (with the exception of Prinzmetal stenocardia; - clinically significant aortic stenosis; - pregnancy; - lactation (breastfeeding); - children's age up to 18 years (efficacy and safety have not been established); - hypersensitivity to the components of the drug; - hypersensitivity to other dihydropyridine derivatives. With caution, you should use the drug for liver dysfunction, SSS (severe brady cardia, tachycardia), chronic heart failure of non-ischemic etiology of III-IV functional class according to NYHA classification, mild or moderate arterial hypotension, with aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, with acute myocardial infarction (and within 1 month after heart attack) ), in elderly patients.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
The teratogenicity of amlodipine was not detected in animal studies, however, there is no clinical experience with its use during pregnancy and lactation. Therefore, Tenox should not be prescribed during pregnancy and lactation, as well as women of childbearing age, if they do not use reliable methods of contraception.
Dosage and administration
The drug is prescribed inside. The initial dose for hypertension and angina is 5 mg 1 time / day. The maximum dose is 10 mg 1 time / day.Maintenance dose may be 2.5-5 mg / day. In case of stable angina of tension and vasospastic angina, the drug is prescribed in a dose of 5-10 mg 1 time / day. In order to prevent attacks of stenocardia - 10 mg / day. Patients with impaired liver function as a hypotensive agent Tenox is prescribed with caution in an initial dose of 2.5 mg, as an antianginal agent - 5 mg. Patients with renal insufficiency do not need to change the dosage regimen. elderly patients may increase T1 / 2 and reduce the clearance of amlodipine; a dose change is not required, but more careful clinical monitoring is required. It is not necessary to change the dose when administered concurrently with thiazide diuretics, beta-blockers and ACE inhibitors.
Side effects
Determination of the incidence of side effects (WHO): very often (more than 1/10), often (from more than 1/100 to less than 1/10), sometimes (from more than 1/1000, to less than 1/100), rarely (from more than 1/10 000, to less than 1/1000), very rarely (from less than 1/10 000, including individual messages). On the part of the cardiovascular system: often - heartbeat, marked decrease in blood pressure, orthostatic hypotension, peripheral edema (swelling of ankles and feet), flushing to facial skin; sometimes - an excessive decrease in blood pressure, orthostatic hypotension, vasculitis, shortness of breath; rarely, development or worsening of heart failure; very rarely - migraine, syncope. Some adverse effects noted in individual patients cannot be differentiated from symptoms of the natural course of the underlying disease: myocardial infarction, arrhythmias (very rarely bradycardia, ventricular tachycardia and atrial fibrillation), chest pain. From the CNS and peripheral nervous system: often - headache, dizziness, drowsiness, fatigue; sometimes - tremor, insomnia, emotional lability, unusual dreams, nervousness, depression, anxiety, paresthesia; rarely - convulsions, apathy, agitation; very rarely - ataxia, amnesia, asthenia, general malaise, peripheral neuropathy. On the digestive system: often - nausea, abdominal pain; sometimes - vomiting, change of the mode of defecation (including constipation), flatulence, anorexia, thirst; rarely, increased appetite; very rarely - dyspepsia, diarrhea, gastritis, pancreatitis,hyperbilirubinemia, gingival hyperplasia, dry mouth, increased activity of hepatic transaminases, hepatitis, jaundice (due to cholestasis). From the urinary system: sometimes gynecomastia, pollakiuria, painful urination, nocturia; very rarely - impotence, dysuria, polyuria. Dermatological reactions: sometimes - alopecia; rarely - dermatitis; very rarely - a violation of skin pigmentation. Allergic reactions: sometimes - pruritus, rash (including erythematous, maculo-papular rash); very rarely - urticaria, angioedema, erythema multiforme. On the part of the musculoskeletal system: sometimes - arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely - myasthenia gravis; very rarely - muscle cramps. From the sense organs: sometimes - ringing in the ears, diplopia, accommodation disturbance, xerophthalmia, conjunctivitis, eye pain, taste perversion; very rarely - parosmia. Others: sometimes - increase / decrease in body weight, chills, nosebleeds, rhinitis, increased sweating; very rarely - thrombocytopenic purpura, thrombocytopenia, leukopenia, hyperglycemia, increased sweating, cold sticky sweat (against the background of arterial hypotension), cough.
Overdose
Symptoms: excessive peripheral vasodilation with a pronounced and possibly prolonged decrease in blood pressure, collapse, shock. Treatment: gastric lavage, administration of activated carbon, maintenance of cardiovascular function, monitoring of heart and lung function, elevated (above the head) position of the lower limbs, control bcc and diuresis. To restore vascular tone - the use of vasoconstrictor agents (in the absence of contraindications to their use); in order to eliminate the effects of calcium channel blockade - in / in the introduction of calcium gluconate. Hemodialysis is not effective.
Interaction with other drugs
In the treatment of arterial hypertension, it is possible to use amlodipine with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, the drug can be combined with other antianginal drugs, for example, with long-acting nitrates, beta-blockers or nitrates for subcutaneous administration. Amlodipine can be used simultaneously with NSAIDs (especially with indomethacin),antibacterial and hypoglycemic agents for oral administration. It is possible to enhance the antianginal and hypotensive action of calcium channel blockers when used in combination with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-adrenergic blockers and nitrates, as well as enhancing their hypotensive action when used together with alpha1 adrenergic blockers, neuroleptics. Although in the study of amlodipine negative inotropic action is usually not observed, however, some blocker Calcium channels may increase the severity of the negative inotropic effect of antiarrhythmic agents causing prolongation of the QT interval (eg, amiodarone and quinidine). Taking Sildenafil 100 mg once a day has no effect on the pharmacokinetics of amlodipine in patients with essential hypertension. Repeated use of amlodipine in dose 10 mg atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin. Amlodipine with a single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol. Antivirals (ritonavir) increases plasma concentrations of calcium channel blockers, incl. amlodipine. Isoflurane enhances the hypotensive effect of dihydropyridine derivatives. Calcium preparations can reduce the effect of calcium channel blockers. With the combined use of amlodipine with lithium, it is possible to increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine doesn’t change the effect of neurotoxicity. Amlodipine does not affect the serum concentration of digoxin and its renal clearance. It 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 blood proteins to digoxin, phenytoin, warfarin, and indomethacin. A simultaneous single dose of 240 mg of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a pharmacy.
special instructions
On the background of the use of the drug, it is necessary to control the patient’s body weight, the appointment of an appropriate diet (control sodium consumption)as well as maintaining dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum overgrowth). For patients with underweight or short stature, patients with severely impaired liver function may require a smaller dose. T1 / 2 amlodipine. Therefore, patients with impaired function of the liver Tenoks should be prescribed with caution. The efficacy and safety of the drug in a hypertensive crisis has not been established. Impact on the ability to drive vehicles and control mechanisms There were no reports of the effect of the drug Tenoks on the ability to drive vehicles and work with mechanisms. However, in some patients, mainly at the beginning of treatment, drowsiness and dizziness may occur. When they occur, the patient must be careful when driving and working with complex mechanisms.