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Active ingredients
Amlodipine
Release form
Pills
Composition
Amlodipine besylate 13.889 mg, which corresponds to the content of amlodipine 10 mg adjuvants: microcrystalline cellulose - 248.111 mg, calcium phosphate - 126 mg, sodium carboxymethyl starch - 8 mg, and 4 mg of magnesium stearate.
Pharmacological effect
Slow calcium channel blocker, a dihydropyridine derivative. Provides antihypertensive and antianginal effect. Blocks slow calcium channels, inhibits the transmembrane transfer of calcium ions into cells (to a greater extent in vascular smooth muscle cells than in cardiomyocytes). expanding peripheral arterioles, reduces the round focal disease, reduces the afterload on the heart, reduces the need for myocardium in oxygen. Expanding the coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic stenocardia); prevents 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 strokes and ischemic depression of the ST segment, reduces the frequency of strokes and consumption of nitroglycerin and other nitrates. dose-dependent antihypertensive effect, the mechanism of which is due to a direct relaxing effect on vascular smooth muscle. In patients with arterial hypertension, a single dose of Norvasc provides a clinically significant reduction in blood pressure for 24 hours both in the prone position and standing. Orthostatic hypotension with amlodipine is quite rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of hypertrophy of the left ventricular myocardium. Does not affect the contractility and conductivity of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases GFR, has a weak natriuretic effect. In diabetic nephropathy 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 duration of the effect is 24 hours. In patients with cardio -vascular diseases (including coronary atherosclerosis with damage to one vessel and up to stenosis of 3 or more arteries and atherosclerosis of the carotid arteries) that have had a myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (TLP) or suffering from angina pectoris, the use of Norvaska prevents the development of carotid intima media thickening, reduces mortality from myocardial infarction, stroke, TLP, coronary artery bypass surgery, reduces the number of hospitalizations for unstable stenocardia and the progression of chronic heart failure, reduces the number of hospitalizations for unstable angina, and reduces the heart rate; blood flow.Norvask does not increase the risk of death or the development of complications leading to death in patients with chronic heart patients with chronic heart failure (III-IV functional class according to NYHA classification) of non-ischemic etiology with amlodipine, there is a likelihood of pulmonary edema.
Pharmacokinetics
Absorption and distribution After oral administration, amlodipine is well absorbed, Cmax in the blood is reached 6-12 hours after administration. Absolute bioavailability is 64-80%. Meal does not affect the absorption of amlodipine. The average Vd is about 21 l / kg of body weight, which indicates that most of the drug is in the tissues, and the smaller part is in the blood. Plasma protein binding is approximately 97.5%. Amlodipine penetrates through BBB.Css in plasma is reached after 7-8 days of therapy. Metabolism and elimination Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant effect of first passage through the liver. Metabolites do not have significant pharmacological activity. After a single dose, T1 / 2 varies from 35 to 50 hours, with repeated administration of T1 / 2 is approximately 45 hours.The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg). About 60% of the ingested dose is excreted in the urine mainly as metabolites, 10% in unchanged form, and 20 25% - through the intestine with bile. Amlodipine is not removed during hemodialysis. Pharmacokinetics in special clinical situations In elderly patients (over 65 years of age) amlodipine excretion is delayed (T1 / 2 - 65 h) compared with young patients, but this difference has no clinical values. The T1 / 2 extension in patients with hepatic insufficiency suggests that for Tel'nykh application drug accumulation in the body is higher (T1 / 2 - 60 h) .Pochechnaya failure does not significantly affect the kinetics of amlodipine.
Indications
- arterial hypertension (both as monotherapy and in combination with other antihypertensive drugs); - stable angina and angiospastic angina (Prinzmetal stenocardia) (both as monotherapy, and in combination with other antianginal drugs).
Contraindications
- severe hypotension (systolic blood pressure less than 90 mm Hg); obstruction of the outgoing tract of the left ventricle (including severe aortic stenosis); - hemodynamically unstable heart failure after myocardial infarction; - children and adolescents under 18 years of age (efficacy and safety not established); - hypersensitivity to amlodipine and other derivatives of dihydropyridine, as well as excipients that are part of the drug. The drug should be used with caution in patients with hepatic impairment malformation, chronic heart failure of non-ischemic etiology of III-IV functional class according to NYHA classification, unstable stenocardia, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and for 1 month after it), SSS (severe myocardial infarction (and within 1 month after it), SSS (severe myocardial infarction (and within 1 month after it), SSS (severe myocardial infarction (and within 1 month after it) arterial hypotension, with simultaneous use with inhibitors or inducers of CYP3A4 isoenzyme.
Precautionary measures
In the course of treatment, exacerbation of psoriasis is possible. During pheochromocytoma, propranolol can be used only after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually,under the supervision of a doctor. Against the background of treatment with propranolol, it is necessary to avoid intravenous injection of verapamil, diltiazem. For several days before undergoing anesthesia, it is necessary to stop taking propranolol or to choose a remedy for anesthesia with minimal negative inotropic effect. 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 safety of the use of the drug Norvasc during pregnancy has not been established, therefore, use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. There are no data indicating the elimination of amlodipine in breast milk. However, it is known that other blockers of slow calcium channels (dihydropyridine derivatives) are excreted in breast milk. In this regard, if necessary, the use of the drug Norvasc during lactation should decide on the termination of breastfeeding.
Dosage and administration
The drug is taken orally 1 time / day, with a necessary amount of water (100 ml). In hypertension and angina, the initial dose is 5 mg, depending on the patient’s individual response, it can be increased to a maximum dose of 10 mg. Norvasc with simultaneous use of thiazide diuretics, beta-blockers or ACE inhibitors. In elderly patients it is recommended to use the drug in an average therapeutic dose, changing the dose of the drug is not required. Not Although T1 / 2 amlodipine, like all calcium channel blockers, increases in patients with impaired liver function, dose adjustment for this category of patients is usually not required. In patients with impaired renal function, it is recommended to use Norvasc in usual doses, however Consideration should be given to a possible slight increase in T1 / 2.
Side effects
The frequency of adverse reactions listed below was determined in accordance with the WHO classification: very often (more than 1/10), often (from more than 1/100 to less than 1/10),infrequently (from greater than 1/1000 to less than 1/100), rarely (from greater than 1/10 000 to less than 1/1000), very rarely (from less than 1/10 000), including individual messages. From the side of the cardiovascular system: often - a feeling of heartbeat , peripheral edema (ankles and feet), flushing of the face; infrequently - excessive decrease in blood pressure; very rarely - fainting, shortness of breath, vasculitis, orthostatic hypotension, development or aggravation of chronic heart failure, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain. On the part of the musculoskeletal system: infrequent - arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely - myasthenia. From the nervous system: often - headaches, dizziness, fatigue, drowsiness; infrequently - asthenia, general malaise, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, irritability, depression, anxiety, ringing in the ears, taste perversion; very rarely - migraine, increased sweating, apathy, agitation, ataxia, amnesia. On the part of the digestive system: often - abdominal pain, nausea; infrequently - vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dry mouth, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis. From the hematopoietic system: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia. ; very rarely - cough. For the organ of vision: infrequently - diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain, visual disturbances. Of urinary system: infrequent - frequent urination, painful urination, nocturia; very rarely - dysuria, polyuria. From the reproductive system: infrequently - a violation of erectile function, gynecomastia. From the skin: rarely - dermatitis; very rarely - alopecia, xeroderma, cold sweat, impaired skin pigmentation. On the metabolic side: infrequently - an increase / decrease in body weight; very rarely - hyperglycemia. Allergic reactions: infrequently - pruritus, rash (including erythematous, maculo-papular rash, urticaria); very rarely - angioedema, erythema multiforme. Others: infrequently - chills; very rarely - parosmia.
Overdose
Symptoms: marked reduction in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (there is a likelihood of severe and persistent arterial hypotension, including with the development of shock and death). Treatment: gastric lavage, the appointment of activated carbon (especially in the first 2 h after overdose), a horizontal position with a low head, active maintenance of the function of the cardiovascular system, monitoring of the performance of the heart and lungs, monitoring of BCC and diuresis. To restore vascular tone - the use of vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - on / in the introduction of calcium gluconate. Hemodialysis is ineffective.
Interaction with other drugs
Amlodipine can be safely used for the treatment of arterial hypertension along with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, with prolonged or short-acting nitrates, beta-blockers. Unlike other slow calcium channel blockers, clinically significant interaction of amlodipine (III generation slow calcium channel blockers) was not found with combined use with NSAIDs incl. and indometatsinom.Vozmozhno amplification antianginal and antihypertensive action of calcium channel blockers slow when used together with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhancing their antihypertensive action when combined with alpha 1-blockers, neyroleptikami.Hotya in the study of amlodipine, a negative inotropic effect was usually not observed, however, some blockers of slow calcium channels may enhance the pronounced A host of negative inotropic effects of antiarrhythmic drugs that prolong the QT interval (for example, amiodarone and quinidine). Amlodipine can also be safely used simultaneously with antibiotics and hypoglycemic agents for oral administration. A single dose of sildenafil 100 mg in patients with essential hypertension is notaffects 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. Simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in simvastatin exposure . In such cases, the dose of simvastatin should be limited to 20 mg. Amlodipine, when administered once and at a dose of 10 mg, does not affect ethanol pharmacokinetics. Anti-viral drugs (for example, ritonavir) increase plasma concentrations of calcium channel blockers that are slow, including amlodipine. Neuroleptics and isoflurane increase the antihypertensive effect of dihydropyridine derivatives. Calcium preparations can reduce the effect of slow calcium channel blockers. When combined with slow calcium channel blockers with lithium preparations (for amlodipine, there are no data), they may increase their neurotoxicity (nausea, vomiting, and vomiting of the latter (nausea, vomiting). ataxia, tremor, tinnitus). Studies on the simultaneous use of amlodipine and cyclosporine in healthy volunteers and all groups of patients for lawsuit Patients after kidney transplantation were not performed. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees to 40%. These data should be taken into account and the concentration of cyclosporine in this group of patients should be monitored with simultaneous use of cyclosporine and amlodipine. Amlodipine does not affect the serum concentration of digoxin and its renal clearance. Norvusc 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 plasma proteins digoxin, phenytoin, warfarin and indomethacin. Simultaneously th single dose of 240 ml grapefruit juice, and 10 mg amlodipine inwardly not accompanied by a significant change in the pharmacokinetics of amlodipine.However, it is not recommended to use grapefruit juice and amlodipine at the same time, since in genetic polymorphism of the CYP3A4 isoenzyme, the bioavailability of amlodipine is possible and, consequently, an increase in the hypotensive effect. Taking aluminum / magnesium-containing antacids at once does not significantly affect the pharmacokinetics of amlodipine. mg in elderly patients (from 69 to 87 years old) with arterial hypertension increases the systemic exposure of amlodipine by 57%. The simultaneous use of amlodipine and erythromycin in healthy volunteers (from 18 to 43 years old) does not lead to significant changes in the exposure to amlodipine (an increase in AUC by 22%). Although the clinical significance of these effects is not completely clear, they may be more pronounced in older patients. Potent inhibitors of the isoenzyme CYP3A4 (for example, ketoconazole, itraconazole) can lead to an increase in the concentration of amlodipine in the blood plasma to a greater extent than diltiazem. Amlodipine and CYP3A4 isoenzyme inhibitors should be used with caution. There is no data on the effect of CYP3A4 isoenzyme inducers on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored with simultaneous use of amlodipine and CYP3A4 isoenzyme inducers.
special instructions
During drug treatment, it is necessary to maintain oral hygiene and observation at the dentist (to prevent pain, bleeding and gingival hyperplasia). In elderly patients T1 / 2 may increase and clearance of the drug may decrease. Changes in doses are not required, but more careful monitoring of patients in this category is necessary. Efficacy and safety of using Norvasc during a hypertensive crisis has not been established. Despite the fact that the calcium channel blockers do not have withdrawal syndrome, it is advisable to stop treatment with Norvasc by gradually reducing the dose. Against the background of the use of amlodipine in patients with chronic heart failure (NYHA class III and IV), non-ischemic genesis was noted to be higher the decrease in the frequency of pulmonary edema, despite the absence of signs of deterioration of heart failure. Effect on the ability to drive vehicles and control mechanismsAlthough taking the drug Norvasc, there was no negative effect on the ability to drive a car or other technical means,however, due to the possible excessive decrease in blood pressure, the development of dizziness, drowsiness and other side effects, one should carefully consider the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.