Active substanceAmlodipineAmlodipine
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  • Dosage form: & nbsppills
    Composition:

    1 tablet contains:

    active substance: Amlodipine - 5,000 mg or 10,000 mg (in the form of amlodipine besylate - 6,934 mg or 13,869 mg);

    Excipients: salting out [microcrystalline cellulose 98%, silicon dioxide colloid 2%] 111.066 mg or 222.131 mg, pregelatinized starch 30,000 mg or 60,000 mg, magnesium stearate 2,000 mg or 4,000 mg.

    Description:

    Round, flat tablets from white to almost white with a bevel.

    Pharmacotherapeutic group:The blocker of "slow" calcium channels
    ATX: & nbsp

    C.08.C.A.01   Amlodipine

    Pharmacodynamics:

    The dihydropyridine derivative has an antianginal and hypotensive effect. Linking to the segment S6 III and IV domains of alpha1-subunit of the calcium channel L-type, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).Antianginal action is due to the expansion of peripheral and coronary arteries and arterioles. When angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance (reduces afterload on the heart), without causing a reflex increase in the heart rate, which helps reduce energy consumption; reduces myocardial oxygen demand. Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium with vasospastic angina; prevents development of coronary spasm (including those caused by smoking).

    In patients with angina, a single daily dose of amlodipine increases the time until the onset of the first ischemic episode during exercise, prevents the development of an attack of angina and the "ischemic" depression of the segment ST (by 1 mm) on the background of physical activity, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

    The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels.Has a long-term dose-dependent hypotensive effect.

    In arterial hypertension, a single daily dose of amlodipine provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing"). Does not cause a sharp decrease in blood pressure, the fraction of the ejection of the left ventricle. Does not affect the contractility and conductivity of the myocardium. Reduces the degree of myocardial hypertrophy of the left ventricle.

    In patients with ischemic heart disease (CHD) (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries and carotid artery atherosclerosis) who underwent myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (PTCA) or those suffering from angina, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, aorto-coronary bypass, leads to a reduction in the number of hospitalizations for unstable st. angina pectoris and progression of chronic heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow.

    Amlodipine does not increase the risk of death or development of complications leading to fatal outcomes in patients with chronic heart failure (CHF) (III-IV functional class by classification NYHA) on the background of therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors.

    In patients with CHF (III-IV functional class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

    Amlodipine does not have any adverse effect on the metabolism and concentration of plasma lipids. It inhibits platelet aggregation, increases the rate of glomerular filtration, and has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria.

    The time of onset of the effect is 2-4 hours, the duration of the effect is 24 hours.

    Pharmacokinetics:

    Suction. After oral administration amlodipine is well absorbed in the gastrointestinal tract. Food intake does not affect the absorption of amlodipine. The maximum concentration in the serum is achieved 6-12 hours after administration. Bioavailability is 60-65%.The average volume of distribution is 21 l / kg of body weight. The connection with plasma proteins is 90-97%. The drug penetrates the blood-brain barrier.

    Metabolism and excretion. Amlodipine is subjected to a slow, insignificant metabolism (90%) in the liver with the formation of inactive metabolites, has a low hepatic clearance (the effect of "primary passage" through the liver). Half-life is an average of 35 hours (varies from 35 to 50 hours), which corresponds to the appointment of the drug once a day. The total clearance is 500 ml / min. A stable equilibrium concentration in plasma is achieved after 7-8 days of therapy. It is excreted by the kidneys (10% unchanged, 60% in the form of metabolites), with bile and through the intestine - 20-25% in the form of metabolites. When hemodialysis is not removed.

    In elderly patients, patients with hepatic insufficiency and severe CHF, the elimination half-life increases to 60-65 hours; if the kidney function is not affected - does not change.

    Indications:

    Arterial hypertension (monotherapy or in combination with other antihypertensive drugs).

    Stable exertional angina and vasospastic angina (Prinzmetal angina) (monotherapy or in combination with other antianginal agents).

    Contraindications:

    Hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as to other components of the drug; marked hypotension (systolic blood pressure less than 90 mmHg) to collapse, cardiogenic shock, unstable angina (except Prinzmetal angina), acute myocardial infarction (first 28 days), clinically significant aortic stenosis; pregnancy, lactation, age under 18 years (efficacy and safety not established).

    Carefully:

    Dysfunction of the liver, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), chronic heart failure of non-ischemic etiology III-IV functional class by classification NYHA, hypotension (systolic blood pressure greater than 90 and less than 100 mm Hg), aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy (GOKMP), acute myocardial infarction (after 28 days), advanced age.

    Pregnancy and lactation:

    The efficacy and safety of amlodipine during pregnancy are not established. The drug is contraindicated for use in pregnancy.

    Data on excretion of amlodipine with breast milk are absent.If you need to use amlodipine during lactation, breast-feeding should be discontinued.

    Dosing and Administration:

    Inside, once a day, regardless of food intake, with enough water.

    The initial dose for arterial hypertension and angina is usually 5 mg. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 10 mg per day. It is recommended to increase the dose 7-14 days after the start of therapy (a faster increase in the dose requires careful monitoring of the patient).

    Patients with low body weight or low growth, as well as with severe hepatic insufficiency, may require smaller doses.

    In patients with renal insufficiency, dose adjustment is not required.

    Changes in the dosage regimen of amlodipine with simultaneous use with thiazide diuretics, beta adrenoblockers and angiotensin converting enzyme (ACE) inhibitors are not required.

    Side effects:

    Frequency of adverse reactions according to the WHO classification: very often (10%), often (≥1% and <10%), infrequently (≥0.1% and <1%), rarely (≥0.01% and <0.1%), very rarely (<0.01%), including individual reports.

    From the central and peripheral nervous system: often - increased fatigue, dizziness, headache, drowsiness; infrequent - malaise, fainting, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, depression, anxiety; rarely - apathy, agitation, loss of consciousness; very rarely - ataxia, amnesia, migraine.

    From the cardiovascular system: often - peripheral edema (ankles and feet), a feeling of palpitations, a feeling of heat and a "tide" of blood to the face; infrequently - excessive reduction of blood pressure, orthostatic hypotension, vasculitis; very rarely - development or aggravation of heart failure; heart rhythm disturbances (extrasystole, bradycardia, ventricular tachycardia and fibrillation or atrial flutter), myocardial infarction, chest pain.

    From the digestive system: often - abdominal pain, nausea; infrequent - vomiting, constipation, flatulence, indigestion, diarrhea, anorexia, dryness of the oral mucosa; rarely - gingival hyperplasia,increased appetite; very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of "hepatic" transaminases, hepatitis.

    From the genitourinary system: infrequent - frequent urination (pollakiuria), painful urge to urinate, nocturia, violation of sexual function (including decreased potency); very rarely - dysuria, polyuria.

    From the musculoskeletal system: infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely - myasthenia gravis.

    From the skin: infrequently - alopecia; rarely - dermatitis, very rarely - xeroderma, a violation of skin pigmentation.

    On the part of the hematopoiesis system: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

    From the respiratory system: infrequently - shortness of breath, rhinitis; very rarely - cough.

    Allergic reactions: infrequently - itchy skin, rash (including erythematous, maculopapular rash); very rarely - angioedema, erythema multiforme, urticaria.

    Other: infrequent - "ringing" in the ears, gynecomastia, weight gain / decrease, vision impairment, diplopia, accommodation disorder, xerophthalmia,conjunctivitis, pain in the eyes, a violation of taste sensations, chills, nosebleeds; very rarely - parosmia, "cold" sticky sweat, hyperglycemia, increased sweating, thirst.

    Overdose:

    Symptoms: a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of a pronounced and persistent reduction in blood pressure, including with the development of shock and death).

    Treatment: gastric lavage (especially in the first 2 hours after an overdose), reception of activated charcoal; the patient should take a horizontal position with an elevated position of the lower limbs; maintaining the function of the cardiovascular system, monitoring the performance of the heart and lungs, monitoring the volume of circulating blood and diuresis. To restore the vascular tone - the use of vasoconstrictive drugs (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

    Interaction:

    Inhibitors of microsomal oxidation may increase the concentration of amlodipine in the blood plasma,increasing the risk of side effects, and inductors of microsomal liver enzymes - reduce.

    Unlike other BCCI, there is no clinically significant interaction of amlodipine with non-steroidal anti-inflammatory drugs (NSAIDs), especially indomethacin.

    Thiazide and "loop" diuretics, beta-blockers, verapamil, alpha1-adrenoblockers, ACE inhibitors and nitrates increase the antianginal or antihypertensive effects of BCCC.

    Simultaneous reception of BCC with neuroleptics and isoflurane may increase the hypotensive effect.

    Cimetidine does not affect the pharmacokinetics of amlodipine.

    Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

    With the joint application of BCCC with lithium preparations, it is possible to intensify manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

    Amlodipine is not affected in vitro on the degree of binding to blood proteins of digoxin, phenytoin, warfarin and indomethacin.

    A single administration of antacids containing aluminum / magnesium does not significantly affect the pharmacokinetics of amlodipine.

    A single dose of sildenafil in a dose of 100 mg in patients with essential hypertension does not affect the pharmacokinetics parameters of amlodipine.The repeated simultaneous use of amlodipine in a dose of 10 mg and atorvastatin 80 mg does not significantly affect the pharmacokinetics of atorvastatin.

    With the simultaneous use of digoxin and amlodipine, the serum digoxin concentration and its renal clearance do not change.

    Amlodipine does not affect the change in prothrombin time caused by warfarin. Calcium preparations can reduce the effect of BCCC.

    Some BCCI can enhance the expressed negative inotropic effect of antiarrhythmic drugs that cause lengthening of the interval QT (amiodarone, quinidine), however, when the drug is used amlodipine negative inotropic action is usually not observed.

    Antiviral drugs (ritonavir) increase plasma concentrations of BCCC, including amlodipine.

    At a single and repeated application in a dose of 10 mg amlodipine has no significant effect on the pharmacokinetics of ethanol.

    Simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine by mouth is not accompanied by a significant change in the pharmacokinetics of amlodipine.

    Special instructions:

    In the treatment of hypertension amlodipine can be used in combination with thiazide diuretics, alpha and beta-adrenoblockers, ACE inhibitors, short and prolonged-action nitrates, NSAIDs, antibiotics and hypoglycemic agents for oral ingestion.

    In the treatment of angina pectoris amlodipine can be administered in the form of monotherapy or in combination with other antianginal drugs, including in patients refractory to treatment with nitrates and / or beta-adrenoblockers, in adequate doses. Amlodipine does not affect the potassium content and plasma concentrations of glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL), uric acid, creatinine and uric acid and can be used in patients with bronchial asthma, diabetes and gout.

    Amlodipine can be used in patients prone to vasospasm / vasoconstriction.

    During the treatment period it is necessary to control body weight and intake of table salt.

    It is necessary to maintain oral hygiene and regular visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).

    Dosage regimen in the elderly is the same as in patients of other age groups.When increasing the dose, careful monitoring of elderly patients is necessary.

    Despite the lack of "slow" calcium channels of the syndrome in blockers "cancellation", before the cessation of treatment, a gradual dose reduction is recommended (the risk of worsening of angina pectoris).

    Women of childbearing age during the treatment with amlodipine should use reliable methods of contraception.

    Amlodipine tablets are not recommended for hypertensive crisis.

    Effect on the ability to drive transp. cf. and fur:

    Reports of the adverse effects of amlodipine on the ability to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions were not. Nevertheless, in some patients, mainly at the beginning of treatment or with a change in the dosing regimen, drowsiness, dizziness, and the like may occur due to a possible pronounced decrease in blood pressure. side effects. When they occur, the patient must observe special precautions when driving the vehicle and working with the mechanisms.

    Form release / dosage:

    Tablets 5 mg or 10 mg.

    Packaging:For 10 tablets in a blister of PVC / PVDC film of white color and AL foil. 2 blisters together with instructions for use in a pack of cardboard.
    Storage conditions:

    At a temperature of no higher than 30 ° C in the original packaging in a dark place. Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-002623
    Date of registration:02.05.2012 / 24.02.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:Hemofarm ADHemofarm AD Serbia
    Manufacturer: & nbsp
    Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia
    Information update date: & nbsp10.08.2017
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