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

Excipients: microcrystalline cellulose 280.0 mg, potato starch - 10.0 mg, lactose monohydrate - 100.0 mg, calcium hydrophosphate dihydrate 86.1 mg, magnesium stearate 4.0 mg, silicon dioxide colloid (aerosil) 2.0 mg, crospovidone - 4.0 mg.

Description:Round, flat-cylindrical tablets white or white with a creamy shade of color with a facet and a risk on one side.

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 antianginal and antihypertensive effect. Linking to the segment S6 III and IV domains of alpha1-subunit of the calcium channel Ltype, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels, rather than in cardiomyocytes).

The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on the smooth muscle of the vessels.

Amlodipine reduces myocardial ischemia by expanding coronary and peripheral arteries and arterioles in unchanged and ischemic zones of the myocardium, reducing the overall peripheral vascular resistance, decreasing afterload, the need for myocardium in oxygen. Increases oxygen supply to the myocardium in patients with vasospastic angina (Prinzmetal angina); prevents the development of coronary spasm caused by smoking. In patients with angina, a single daily dose increases the time of exercise, delays the development of another attack of angina and depression of the segment ST (by 1 mm) with physical activity, reduces the incidence of angina attacks and the consumption of nitroglycerin and other nitrates.

Has a long-term dose-dependent antihypertensive effect.With arterial hypertension, a single daily dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's "lying" and "standing"). Due to the slow start of action amlodipine does not cause a sharp decrease in blood pressure.

In patients with cardiovascular diseases, systems (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries, carotid atherosclerosis), myocardial infarction (MI), percutaneous transluminal angioplasty of the coronary arteries or patients with angina, the use of amlodipine prevents thickening of intima-media of carotid arteries, reduces lethality from myocardial infarction, stroke, transluminal angioplasty, coronary artery bypass grafting; leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

Does not increase the risk of death or development of complications and deaths in patients with CHF (III-IV class according to the classification of the New York Heart Association (NYHA)) on the background of therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In patients with CHF (III-IV class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

Does not cause a decrease in exercise tolerance, the left ventricular ejection fraction (LV). Reduces the degree of myocardial hypertrophy of the LV.

Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate, inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have adverse effects on the concentration of plasma lipids.

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

Pharmacokinetics:

After oral administration at therapeutic doses amlodipine is well absorbed from the gastrointestinal tract, absorption is about 90%, bioavailability is 60-65%. Time to reach the maximum concentration (TC_m_Oh) for oral administration

6-9 hours.Food intake does not affect the absorption of amlodipine. With constant intake, the equilibrium concentration is created after 7-8 days. The volume of distribution is 21 l / kg. The connection with plasma proteins is 90-97%. Penetrates through the blood-brain barrier. Extensively (90%) is metabolized in the liver with the formation of inactive metabolites, does not have a significant "first pass" effect through the liver. The half-life (T1 / 2) is 35 hours on the average. The total clearance is 0.116 ml / s / kg (7ml / min / kg, 0.42 l / h / kg).

T1 / 2 in patients with arterial hypertension - 48 hours, in elderly patients is increased to 65 hours, with liver failure - up to 60 hours, similar parameters of T1 / 2 increase are observed and in severe CHF, with renal dysfunction - does not change. When hemodialysis is not removed.

It is excreted by the kidneys - 60% in the form of metabolites, 10% in unchanged form; with bile and through the intestine - 20-25% in the form of metabolites, as well as with breast milk.

Indications:

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

- Stable angina and vasospastic angina pectoris (monotherapy or in combination with other antianginal drugs).

Contraindications:

- Hypersensitivity to the components of the drug (including amlodipine and other dihydropyridines);

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- unstable angina (with the exception of Prinzmetal angina), clinically significant aortic stenosis;

- pregnancy;

- lactation period;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- age to 18 years (safety and efficacy not established).

Carefully:

With caution should be used in patients with arterial hypotension, aortic stenosis, mitral stenosis, CHF of non-ischemic etiology (III-IV classification class NYHA), a violation of liver function, acute myocardial infarction (and within 1 month after it), hypertrophic obstructive cardiomyopathy, weakness syndrome of the sinus node, in old age.

Pregnancy and lactation:

Contraindicated in pregnancy and lactation (breastfeeding). If pregnancy occurs during the treatment period, the drug should be discontinued. If it is necessary to use the drug during breastfeeding, breastfeeding should be stopped.

Dosing and Administration:

Inside, once.

The initial dose for arterial hypertension, angina is 5 mg / day, which if necessary increase to 10 mg / day for 2-4 weeks. The maximum dose is 10 mg / day.

Despite the fact that the half-life of amlodipine, like all blockers of "slow" calcium channels, increases in patients with impaired liver function, dose adjustment is usually not required; in patients with impaired renal function it is recommended to use the drug in usual doses; dose adjustment in the elderly is not required.

When used as a combination therapy with thiazide diuretics, beta-blockers and ACE inhibitors, dose adjustment is not required.

Side effects:

Adverse reactions are presented in accordance with the following gradation of their occurrence frequency: very often more than 1/10, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1 / 10,000 and less than 1/1000, very rarely, including single messages - less than 1/10000; the frequency is unknown (the available data do not allow you to determine the frequency).

From the cardiovascular system: often - peripheral edema (ankles and feet), a feeling of palpitations; infrequent - marked decrease in blood pressure, orthostatic hypotension,vasculitis; rarely - development or exacerbation of heart failure; very rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, chest pain.

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

From the digestive system: often - nausea, abdominal pain; infrequent - vomiting, constipation, flatulence, dyspepsia, diarrhea, anorexia, dry mucous membrane oral cavity, thirst; rarely hyperplasia of the gums, increased appetite; very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of alanine aminotransferase and aspartate aminotransferase, hepatitis.

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

From the urogenital: infrequently - pollakiuria, painful urge to urinate, nocturia, impotence; very rarely - dysuria, polyuria.

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

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

Allergic reactions: infrequently - itchy skin, rash; very rarely - angioedema, erythema multiforme, urticaria.

From the side skin integument: infrequently - alopecia, xerophthalmia, increased sweating; rarely - dermatitis; very rarely - a cold sticky sweat, a violation of skin pigmentation.

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

Other: infrequently - gynecomastia, increase / decrease in body weight, chills, nosebleeds; very rarely - hyperglycemia.

Overdose:

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

Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose), maintenance of function, cardiovascular system, monitoring of heart and lung function parameters, elevated position of lower extremities, control of circulating blood volume 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 not effective.

Interaction:

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

Unlike other blockers of "slow" calcium channels (BCC), there is no clinically significant - interaction of amlodipine with non-steroidal anti-inflammatory drugs, especially indomethacin.

Thiazide and "loop" diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase the antianginal or antihypertensive effects of amlodipine. Amlodipine does not affect the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

Calcium preparations can reduce the effect of BCCC.

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

Amiodarone, quinidine, alpha1-adrenoblockers (prazozin, alfuzosin, doxazosin, tamsulosin, terazosin) antipsychotics and isoflurane strengthen antihypertensive the effect of amlodipine and increase the risk of orthostatic hypotension. 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.

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

When amlodipine is used together with lithium preparations, it is possible to intensify manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). A single intake of antacids containing aluminum and magnesium does not significantly affect the pharmacokinetics of amlodipine.

Amlodipine does not significantly affect the pharmacokinetic parameters of cyclosporine.

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.

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

Special instructions:

During treatment it is necessary to control body weight and sodium intake.

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

Amlodipine does not affect plasma concentrations of potassium, glucose, triglycerides, total cholesterol, low-density lipoproteins, uric acid, creatinine and urea nitrogen.

It should be avoided abrupt discontinuation of the drug because of the risk of worsening of the course of angina pectoris. The efficacy and safety of amlodipine in hypertensive crisis is not established. Women of childbearing age in the period of treatment should use reliable methods of contraception.

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

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

In patients with impaired T1 / 2 liver function, amlodipine is increased. When prescribing the drug, such patients should be careful and regularly monitor the activity of liver enzymes.

Patients with a reduced body weight or low growth may require a smaller dose of the drug.

Effect on the ability to drive transp. cf. and fur:As a result of a possible pronounced reduction BP, development of dizziness, drowsiness during treatment with amlodipine, caution should be exercised during work for people whose profession is associated with the performance of potentially dangerous activities requiring increased concentration and speed of psychomotor reactions (driving and other vehicles, working with moving mechanisms, work dispatcher and operator).

Form release / dosage:

Tablets 10 mg.

Packaging:

For 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

3 contour mesh packages together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:LS-002220

Date of registration:21.07.2011

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp10.08.2017

Illustrated instructions

Instructions

Amlodipine (Amlodipine)