Active substanceAmlodipineAmlodipine
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  • Dosage form: & nbsppills
    Composition:

    Active substance: each tablet contains 2.5 mg, 5 mg or 10 mg of amlodipine (respectively as 3,475 mg, 6.95 mg or 13.9 amlodipine besylate).

    Excipients: microcrystalline cellulose, sodium carboxymethyl starch (type A), magnesium stearate, silicon dioxide colloidal anhydrous.

    Description:

    Tablets 2.5 mg: Round flat tablets with bevel, with an engraved "E" on one side and "251" on the other side, white, almost white or yellowish white.

    Tablets 5 mg: Round flat tablets with bevel, with an engraved "E" on one side and "252" on the other side, white, almost white or yellowish white.

    Tablets 10 mg: Round flat tablets with bevel, with engraving "E" on one side and "253" on the other side, white, almost white or yellowish white.

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

    C.08.C.A.01   Amlodipine

    Pharmacodynamics:

    Mechanism of action:

    Amlodipine suppresses the transmembrane incoming current of calcium ions into the smooth muscle cells of the heart and vessels (it blocks slow calcium channels, ie, it is a calcium antagonist).

    The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in the resistance of peripheral vessels.

    The mechanism of antianginal action is not completely understandable, however, it is most likely associated with the following two effects:

    1 Expansion of peripheral arterioles reduces the overall peripheral resistance, i.e., afterload. Because the amlodipine does not cause reflex tachycardia, energy consumption and oxygen myocardium decreases.

    2 Expansion of large coronary arteries and coronary arterioles improves the supply of oxygen to both normal and ischemic zones of the myocardium. Due to these effects, the supply of oxygen to the myocardium improves, even with spasm of the coronary arteries (Prinzmetal angina or unstable angina).

    Pharmacodynamics

    In patients with hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the supine position and standing during the entire 24-hour interval between doses of the drug. Due to the slow development of the effect of amlodipine, it does not cause acute arterial hypotension.

    In patients with angina pectoris, taking the drug once a day increases the total time of exercise possible physical exertion before the onset of an attack of angina pectoris, as well as the time to a significant decrease in the interval ST, and also reduces the frequency of angina attacks and the need for sublingual administration of nitroglycerin.

    There was no negative effect of amlodipine on the metabolism. The drug does not affect blood plasma lipid levels, blood glucose and uric acid serum levels. It is safe for patients with bronchial asthma.

    Pharmacokinetics:

    Suction:

    Amlodipine is well absorbed after ingestion. The maximum concentration in the blood plasma is observed after 6-12 hours. Taking the drug along with the food does not affect its absorption. Absolute bioavailability is 64 - 80%.

    Distribution:

    The apparent volume of distribution is 21 l / kg. Equilibrium concentration in blood plasma (5-15 ng / ml) is achieved 7-8 days after the start of the drug. Research in vitro showed that circulating amlodipine approximately 93 - 98% is associated with blood plasma proteins.

    Biotransformation and excretion:

    Amlodipine is subjected to intensive metabolism in the liver. Approximately 90% of the accepted dose is converted to inactive pyridine derivatives. Approximately 10% of the dose is excreted unchanged in the urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestine. The concentration-time curve in blood plasma has a two-phase character. The final half-life is approximately 35-50 hours, which allows the administration of the drug once a day. The clearance of the drug and the whole organism is 7 ml / min / kg (25 l / h in a patient weighing 60 kg). In elderly patients the clearance of the drug from the whole body is 19 l / h.

    The pharmacokinetics of amlodipine does not change with renal failure or in elderly patients.

    Due to lower clearance, patients with hepatic insufficiency should be given a lower initial dose.

    Indications:
    • Treatment of hypertension as a monotherapy or (if necessary) in combination with other antihypertensive drugs.
    • Stable angina and vasospastic angina (Prinzmetal) - as monotherapy or in combination with other antianginal agents.
    Contraindications:
    • Hypersensitivity to amlodipine and / or any other component of the drug.
    • Children under 18 years of age (due to lack of clinical experience).
    • Unstable angina (with the exception of Prinzmetal angina).
    • Clinically significant aortic stenosis.
    • Severe arterial hypotension.
    • Pregnancy and lactation (see "Pregnancy and lactation period").
    Carefully:

    Dysfunction of the liver, syndrome of weakness of the sinus node (severe bradycardia, tachycardia), chronic heart failure in the stage of decompensation, mild or moderate degree of arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes, elderly.

    Pregnancy and lactation:

    Given the limited clinical experience of the use of amlodipine in pregnancy and lactation, it should not be given to pregnant women, nor to women of reproductive age who do not use effective methods of contraception, except when the beneficial effects of the drug justify the possible risk.

    Amlodipine should not be taken during pregnancy, except in cases of absolute necessity or when the therapeutic benefit of the drug justifies the possible risk. If a nursing woman takes amlodipine because of the lack of other drugs, it is recommended to stop breastfeeding.

    Dosing and Administration:

    Inside. With arterial hypertension and angina, the initial dose is 5 mg once a day, preferably always at the same time of day. Depending on the reaction to the drug, the initial dose can be increased to 10 mg per day (maximum daily dose).

    There is no need for dose adjustment in the case of simultaneous administration of thiazide diuretics, beta-blockers or angiotensin-converting enzyme blockers.

    Elderly patients and with kidney failure can be administered the usual dose.

    If liver function is impaired, the dose (up to 2.5 mg per day) should be reduced because of the elongation of the half-life of the drug.

    Side effects:

    From the nervous system: headache, dizziness, excessive fatigue, drowsiness, mood changes, convulsions; rarely - loss of consciousness, hypoesthesia, paresthesia, tremor, asthenia, malaise, insomnia, nervousness, depression, unusual dreams, anxiety; very rarely - ataxia, apathy, agitation, amnesia.

    From the digestive system: nausea, abdominal pain; rarely hyperbilirubinemia, jaundice, increased activity of "liver" transaminases, dry mouth, anorexia, vomiting, constipation or diarrhea, dyspepsia, flatulence, gingival hyperplasia; very rarely - gastritis, increased appetite, pancreatitis.

    From the cardiovascular system: heart palpitations, edema of the ankles and feet, shortness of breath, blood flushes to the face, rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial flutter), chest pain, excessive blood pressure lowering, orthostatic hypotension; very rarely - the development or aggravation of heart failure, extrasystole, migraine.

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

    From the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use); very rarely - myasthenia gravis.

    From the skin: very rarely - xeroderma, alopecia, dermatitis, purpura. Allergic reactions: skin itch, rash (including erythematous, maculopapular rash, urticaria).

    Other: rarely - visual impairment, conjunctivitis, diplopia, eye pain, accommodation disorder, xerophthalmia, ringing in the ears, gynecomastia, back pain, fever, chills, weight gain, dyspnoea, epistaxis, increased sweating, thirst; very rarely - cold sticky sweat, cough, rhinitis, parosmia, taste perversion, hyperglycemia.

    Overdose:

    Symptoms: a marked decrease in blood pressure, tachycardia, excessive peripheral vasodilation.

    Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, monitoring of heart and lung function,elevated position of limbs, control of the volume of circulating blood and diuresis. Intensive symptomatic therapy. 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 not effective.

    Interaction:

    The use of amlodipine was found to be safe in combination with thiazide diuretics, beta-adrenoblockers, long-acting nitrates, sublingual preparations nitroglycerin, non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic agents.

    Thiazide and "loop" diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effects.

    Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotic drugs (antipsychotics) and blockers of "slow" calcium channels can intensify the hypotensive effect.

    Calcium preparations can reduce the effect of blockers of "slow" calcium channels.Inhibitors of microsomal oxidation increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inductors of microsomal liver enzymes reduce.

    Hypotensive effect weakens non-steroidal anti-inflammatory drugs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha-adrenostimulants, estrogens (sodium retention), sympathomimetics.

    Procainamide, quinidine and other drugs that cause lengthening of the interval QT, reinforce the negative inotropic effect and may increase risk of significant lengthening of the interval QT.

    Cimetidine does not affect the pharmacokinetics of amlodipine.

    Does not affect the pharmacokinetic parameters of digoxin and warfarin. Grapefruit juice can slightly increase the level of amlodipine in the blood serum, but this does not lead to significant changes in blood pressure.

    Special instructions:

    Studies in patients with heart failure II-III stages by classification NYHA when receiving amlodipine, there was no evidence of a decrease in exercise tolerance, a function of ejection of the left ventricle or worsening of clinical symptoms.Results of clinical trials involving patients with heart failure III-IV stages by classification NYHA (“PRAISE”) showed that amlodipine does not increase the incidence of cardiovascular disorders or mortality when combined with ACE inhibitors, diuretics or digoxin.

    During the treatment, it is necessary to maintain dental hygiene and visit the dentist (to prevent soreness, bleeding and gingival hyperplasia).

    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. The vasodilator effect of amlodipine develops gradually. Therefore, acute arterial hypotension after its use is very rare, however, before the cessation of treatment is recommended a gradual decrease in doses.

    Amlodipine does not affect plasma concentrations of K+, glucose, triglycerides, total cholesterol, LDL, uric acid, creatinine and uric acid nitrogen.

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

    There were no reports of the effects of amlodipine on driving or working with machinery.However, some patients may experience drowsiness and dizziness at the beginning of treatment. When they occur, the patient must observe special precautions when driving and working with machinery.

    Form release / dosage:

    Tablets 2.5 mg, 5 mg, 10 mg.

    Packaging:For 10 tablets in a blister of PVC / PVDC / al.foil. 1, 2 or 3 blisters in a cardboard box together with instructions for medical use.
    Storage conditions:

    Store at a temperature of 15 to 25 ° C, in a place protected from light. Keep out of the reach of children.

    Shelf life:

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

    Terms of leave from pharmacies:On prescription
    Registration number:П N014354 / 01
    Date of registration:08.07.2008 / 01.11.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary
    Manufacturer: & nbsp
    Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Information update date: & nbsp10.12.2017
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