Amrorus - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 45.83 mg, 63.17 mg, 88.34 mg; cellulose microcrystalline - 45.7 mg, 62.9 mg, 87.8 mg; crospovidone 1.0 mg, 1.4 mg, 2.0 mg; silicon dioxide colloid (aerosil) - 0.5 mg, 0.7 mg, 1.0 mg; talc - 2.5 mg, 3.5 mg, 5.0 mg; calcium stearate (calcium stearic acid) 1.0 mg, 1.4 mg, 2.0 mg.

Description:

Tablets of white or almost white color of flat-cylindrical shape with a bevel, the presence of "marble" is allowed.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

The dihydropyridine derivative blocking the "slow" calcium channels, has an antihypertensive and antianginal effect.Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes).

Antihypertensive effect is due to direct vasodilating effect on smooth muscle vessels. Has a prolonged dose-dependent ₍antihypertensive effect.

Amlodipine reduces myocardial ischemia (has an antianginal effect) in two ways:

1) expands peripheral arterioles and thus reduces the overall peripheral resistance of blood vessels, reduces afterload on the heart, with the heart rate practically unchanged, which leads to a decrease in energy consumption and myocardial oxygen demand;

2) dilates coronary and peripheral arteries and arterioles in unchanged and ischemic. zones of the myocardium, which increases the flow of oxygen into the myocardium (especially with vasospastic angina), reduces the severity of myocardial ischemia and prevents the development of spasm of the coronary arteries (including those caused by smoking).

With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure over the course of ₍24 h (in the patient's position "lying" and "standing") Due to the slow onset of action amlodipine does not cause a sharp drop in blood pressure. Does not reduce exercise tolerance and the left ventricular ejection fraction.

In patients with angina, a single daily dose of amlodipine increases the time of exercise, slows the development of angina pectoris and the "ischemic" depression of the segment ST (by 1 mm), reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

Reduces the degree of myocardial hypertrophy of the left ventricle, has antiatherosclerotic and cardioprotective action in coronary heart disease (IHD).

In patients with ischemic heart disease (including coronary atherosclerosis with the lesion of one vessel and up to stenosis of three or more arteries and carotid artery atherosclerosis) who have suffered a heart attack myocardium, percutaneous transluminal angioplasty of the coronary arteries (PTCA) or suffering from angina pectoris, the use of amlodipine prevents the development of thickening ₍intima-media of carotid arteries, significantly reduces the mortality from cardiovascular causes, myocardial infarction, stroke, PTCA, coronary artery bypass grafting,leads to a reduction 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.

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

In patients with chronic heart failure (III-IV, functional class by classification NYHA) non-ischemic etiology, with the use of amlodipine, there is a likelihood of pulmonary edema.

Does not affect the contractility of the non-conductivity of the myocardium, does not cause a reflex increase in the heart rate (heart rate), inhibits, platelet aggregation, increases the rate of glomerularfiltration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria.It has no adverse effects on the metabolism and concentration of lipids in the blood plasma and can be used in the treatment of patients with bronchial asthma, diabetes and gout.

The time of onset of the effect of the drug is 2-4 hours, the duration of the effect is 24 hours. When long-term therapy, the maximum decrease in blood pressure occurs 6-12 hours after taking amlodipine inside. If after prolonged treatment amlodipine abolish, the effective reduction in blood pressure persists for 48 hours after the last dose. Then the blood pressure indicators gradually return to the baseline within 5-6 days.

Pharmacokinetics:

Absorption slow does not depend on food intake, is about 90 %.

Bioavailability is 60-90%, the maximum concentration in serum is observed 6-12 hours after admission.

The volume of distribution is approximately 21 liters / kg of body weight, indicating that most of the drug is in the tissues, and relatively less in the blood. GreatI part of the drug in the blood (95-97%), binds to blood plasma proteins. Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed. The equilibrium concentration of amlodipine in the blood plasma (Css) is achieved after 7-8 days of constant intake of the drug.

Amlodipine undergoes a slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites has the effect of a "primary" passage through the liver. Metabolites do not have significant pharmacological activity.

After a single oral intake, the half-life period (T1 / 2) varies from 31 to 48 hours, with the repeated appointment of T1 / 2 is approximately 45 hours, which corresponds to the prescription of the drug 1 time per day. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).

In elderly patients (over 65 years), amlodipine withdrawal is slowed (T1 / 2 increases to 65 hours) compared with younger patients. The elderly and young patients the time required to achieve the maximum concentration of amlodipine in blood plasma is almost the same.

In patients with hepatic insufficiency and with severe chronic cardiac insufficiency, T1 / 2 increases to 56-60 hours.

T1 / 2 from blood plasma in patients with renal insufficiency increases to 60 h.The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of impaired renal function.

About 60 % the dose taken internally is excreted by the kidneys mainly in the form of metabolites; 10% in unchanged form, with bile and through the intestine - 20-25% in the form of metabolites.

Indications:

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

Stable exertional angina, vasospastic angina (angina pectoris Prinzmetal) (monotherapy or in combination with other antianginal drugs).

Contraindications:

Hypersensitivity to amlodipine, other dihydropyridine derivatives and other components of the drug;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
cardiogenic shock;
acute myocardial infarction during the first 28 days;
unstable angina (with the exception of vasospastic);
obstruction, the outflow tract of the left ventricle (including clinically significant stenosis of the aorta);
age to 18 years;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

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, arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, elderly age.

Pregnancy and lactation:

The safety of the use of amlodipine in pregnancy is not established, so use in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

There is no evidence of excretion of amlodipine in breast milk. However, it is known that other blockers of "slow" calcium channels - dihydropyridine derivatives, excreted in breast milk. In this connection, if it is necessary to prescribe Amrorus® during lactation, the question of stopping breastfeeding should be solved.

Women of childbearing age should use reliable methods of contraception.

Dosing and Administration:

Tablets are taken once inside, washed down with the necessary volume of water (up to 100 ml).

For treatment arterial hypertension and angina pectoris the initial dose is 5 mg once a day. Depending on the individual reaction of the patient, if necessary, the dose can be increased to a maximum of 10 mg once a day.

With hypertension, the maintenance dose can be 5 mg per day. With vasospastic angina (Prinzmetal angina) - 5-10 mg per day, once.

Do not require dose changes with simultaneous administration with thiazide diuretics, beta-blockers and ACE inhibitors.

In patients with liver failure, elderly patients - can a dose change is required, the initial dose for arterial hypertension may be 2.5 mg.

When prescribing the drug, patients with renal insufficiency do not need to change the dosage regimen.

Side effects:

Under the frequency of adverse reactions is understood: very often ≥1/10; often ≥ 1/100, <1/10; infrequently ≥1/1000, <1/100; rarely ≥ 1/10000, <1/1000; very rarely <1/10000, including individual messages.

From the side of the cardiovascular system: often - peripheral edema (ankleand stop), a feeling of palpitation, a sensation of heat and "tides" of blood to the skin of the face; infrequently - excessive decrease in arterial pressure, orthostatic hypotension,vasculitis; rarely - development or aggravation of the course of chronic heart failure; rarely - heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

From the central nervous system: often - increased fatigue, dizziness, headache, drowsiness, migraine; infrequent - general malaise, syncope, increased sweating, asthenia, hypoesthesia, paresthesia, peripheral neuropathy; tremor, insomnia, mood lability; unusual dreams, nervousness, depression, anxiety; rarely - cramps, - apathy, agitation; very rarely - ataxia, amnesia.

From the sense organs: infrequent - ringing in the ears, visual disturbances, pain in the eyes, diplopia, xerophthalmia, conjunctivitis, disruption of accommodation, perversion of taste; very rarely - parosmia.

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

From the urinary system: infrequently - frequent urination, painful urination, nocturia, impotence; very rarely - dysuria; polyuria.

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

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

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

From the hematopoiesis: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the side of metabolism: very rarely - hyperglycemia.

Allergic reactions: infrequent cutaneous, itching, rash; very, rarely - angioedema, erythema multiforme, urticaria.

Other: infrequently - gynecomastia, increase / decrease in body weight, chills; rarely - cold sweat.

Overdose:

Symptoms: a marked decrease in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (there is the likelihood of a pronounced and persistent arterial hypotension, in,with the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, counteraboutheart and lung function, elevated position of the lower extremities, control of 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. Because the amlodipine is largely associated with serum proteins, hemodialysis is ineffective.

Interaction:

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.

Amlodipine has no effect on the pharmacokinetic parameters of digoxin and warfarin, does not affect the prothrombin time changes caused by warfarin. Cimetidine does not affect the pharmacokinetics of amlodipine.

Calcium preparations can reduce the effect of blockers of "slow" calcium channels (including amlodipine).

Unlike other blockers of "slow" calcium channels, significant interaction with joint use with non-steroidal anti-inflammatory drugs (including indomethacin) was not detected.

Thiazide and "loop" diuretics; beta-blockers, verapamil, ACE inhibitors and nitrates increase the anti-anginal and antihypertensive effects of amlodipine.

Alfa-1-adrenoblockers, antipsychotics, amiodarone and quinidine - can enhance the antihypertensive effect of amlodipine in a joint application.

Blocks of "slow" calcium channels (in, t.ch. amlodipine) can enhance the severity of the negative inotropic effect of antiarrhythmic drugs that cause lengthening of the interval QT (amiodarone, quinidine, procainamide).

When combined with lithium preparations, it is possible to intensify their manifestations neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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 use of amlodipine in a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Antiviral drugs (ritonavir) increase plasma concentrations of blockers of "slow" calcium channels (including amlodipine).

A single intake of aluminum and magnesium-containing antacids does not significantly affect the pharmacokinetics of amlodipine.

Grapefruit juice can reduce the concentration of amlodipine in the blood plasma, but the simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a significant change in the pharmacokinetics of amlodipine.

Special instructions:

In the treatment of arterial hypertension, Amrorus® can be used in combination with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers and ACE inhibitors.

For the treatment of angoras, Amrorus® can be combined with other antianginal agents, for example, with prolonged or short-acting nitrates, beta-blockers.

Amrorus® can be used also in those cases when the patient is predisposed to vascular spasm (vasoconstriction).

Amrorus® does not affect the plasma concentrations of potassium ions, glucose, triglycerides, total cholesterol, low density lipoproteins, uric acid, creatinine and urea nitrogen and can be used in the treatment of patients with bronchial asthma, diabetes and gout.

Patients with low body weight, low growth patients and patients with marked impairment of liver function as an antihypertensive agent Amrorus® are prescribed in an initial dose of 2.5 mg, as an antianginal agent - 5 mg.

During treatment, it is necessary to control body weight and sodium intake, the purpose of the appropriate diet, observation at the dentist (to prevent soreness, bleeding and gingival hyperplasia) is indicated.

Despite the absence of the "withdrawal" syndrome, before the cessation of treatment a gradual reduction of doses is recommended.

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

During the period of treatment, care should be taken when driving vehicles and engaging in potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 2.5 mg, 5 mg, 10 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2 or 3 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place, at a temperature of no higher than 25 ° C.

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:LS-001556

Date of registration:01.08.2011

Expiration Date:Unlimited

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp25.07.2017

Illustrated instructions

Instructions

Amrorus® (Amlorus®)