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Active ingredients
Amlodipine
Release form
Pills
Composition
Active ingredient: Amlodipine (Amlodipine) Active ingredient concentration (mg): 5
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 myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (TLP) or those suffering from angina pectoris coronary artery bypass surgery, leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow. Norvus does not increase the risk of death or the development of complications leading to death in patients with chronic heart failure (III Functional class IV (NYHA classification) with therapy with digoxin, diuretics and ACE inhibitors. In patients with chronic heart failure Acidity (III-IV functional class according to the NYHA classification) of non-ischemic etiology when using amlodipine there is a possibility 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), the release of amlodipine is delayed (T1 / 2 - 65 h) compared with young patients, but this difference It has no clinical significance. The extension of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged use, the cumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours). Renal failure does not have a significant effect on the kinetics of amlodipine.
Indications
Arterial hypertension (both in monotherapy and in combination with other antihypertensive drugs). Stable angina and vasospastic angina (Prinzmetal's angina) (in monotherapy as well as in combination with other antianginal drugs).
Contraindications
Hypersensitivity to amlodipine and other derivatives of dihydropyridipa, as well as to the excipients that make up the drug. Severe arterial hypotension
Precautionary measures
Do not exceed the recommended dose. With caution, the drug should be used in patients with liver failure, chronic heart failure, non-ischemic etiology of functional class III-IV according to NYHA classification, unstable angina, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and 1 month after it), SSSU (severe tachycardia, bradycardia), arterial hypotension, with simultaneous use with inhibitors or inducers and zoenzyme CYP3A4.
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
Inside, once a day, drinking down the required volume of water (100 ml). In hypertension and angina, the usual initial dose is 5 mg, depending on the individual patient's response, it can be increased to a maximum of 10 mg. It is used in the elderly. It is recommended to use in usual doses, changing the dose of the drug is not required. Use in patients with impaired liver function. Despite the fact that T1 / 2, Norvaska, as well as all BMCC, increases in patients with this pathology, any changes in the dosage of the drug in patients with impaired liver function are usually not required (see the section "Special Instructions"). renal failure. It is recommended to use in usual doses, however it is necessary to consider possible insignificant increase in T1 / 2. Changing the dosing regimen of Norvasc with simultaneous use of thiazide diuretics, beta-blockers or ACE inhibitors is not required.
Side effects
Further, the frequency of adverse reactions is understood: frequent (> 1%), infrequent (<1%), rare (<0.1%), very rare (<0.01%). Cardiovascular system: peripheral edema (ankles and stop), palpitations, not often - excessive decrease in blood pressure, orthostatic hypotension, vasculitis; rarely, development or worsening of heart failure; very rarely - cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, migraine. From the musculoskeletal system: not often - arthralgia, muscle cramps, myalgia, back pain, arthrosis, rarely - myasthenia. Central and peripheral nervous system: sensation of heat and flushing to the skin of the face, increased fatigue, dizziness, headache, drowsiness, not often - indisposition, fainting, increased sweating, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, anxiety; rarely - convulsions, apathy, agitation; very rarely - ataxia, amnesia. Digestive tract: abdominal pain, nausea, not often - vomiting, changes in bowel movements (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry mouth, thirst, rarely - gum hyperplasia, rising appetite, very rarely - gastritis, pancreatitis, hyperbilirubinemia,jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis. Hematopoietic system: very rare carp - thrombocytopenic purpura, leukopenia, thrombocytopenia. Metabolic disorders: very rarely - hyperglycemia. Respiratory system: not often - dyspnea, rhinitis, very rarely - carp. system: not often - frequent urination, painful urination, nocturia, impotence, very rarely - dysuria, polyuria. Allergic reactions: not often - pruritus, rash, very rarely - angioedema, multiforme item, urticaria. Others: not often - alopecia, tinnitus, gynecomastia, weight gain / loss, visual impairment, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, taste perversion, chills, nasal bleeding, rarely - dermatitis ; very rarely - parosmia, xerodermia, cold sweat, violation of skin pigmentation.
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 does not affect the parameters pharmacokinetics 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 pharmacokin levels. tics atorvastatina.Odnovremennoe repeated application of amlodipine 10 mg of simvastatin and 80 mg resulting in increased exposure of simvastatin by 77%. 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 decrease in the incidence 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, but , development of dizziness, drowsiness and other side effects should be attentive to the individual action of the drug in the indicated x situations, especially at the beginning of treatment and when changing the dose regimen.