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

as active ingredient: amlodipine besylate - 6.9 mg or 13.8 mg, corresponding to 5 mg or 10 mg of amlodipine; Excipients: lactose monohydrate - 85.7 / 171.4 mg, povidone - 3.2 / 6.4 mg, crospovidone - 3.2 / 6.4 mg, calcium stearate - 1.0 / 2.0 mg.

Description:

Tablets are white or white with a cream shade of color, flat-cylindrical with a risk and a facet.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Derivative of dihydropyridine - blocker of "slow" calcium channels (BCCI) of the second generation, has an antianginal and hypotensive effect. Linking with dihydropyridine receptors, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in smooth muscle cells of blood vessels, rather than in cardiomyocytes).

Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance (OPSS), reduces preload on the heart, reduces the need for myocardium in oxygen. Expands the main coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents the development of spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina pectoris and the "ischemic" depression of the segment ST, reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant reduction in blood pressure (BP) for 24 hours (in the patient's "lying" and"standing"). Orthostatic hypotension in the appointment of amlodipine is rare. Does not cause a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle, has antiatherosclerotic and cardioprotective effects in ischemic heart disease (IHD). Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate (HR), 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 any adverse effect on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours. With prolonged therapy, the maximum decrease in blood pressure occurs within 6-12 hours after taking amlodipine by mouth. If after a long treatment with amlodipine, cancel,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:

After oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT). The average absolute bioavailability is 64%, the maximum concentration (Cmah) in the serum is observed after 6-9 hours. Equilibrium serum concentrations (Css) are achieved after 7-8 days of therapy. Food intake does not affect the absorption of amlodipine.

The average volume of distribution is 21 l / kg body weight, indicating that most of the drug is in the tissues, and relatively less in the blood. Most of the drug in the blood (95%), binds to blood plasma proteins. Amlodipine is subjected to a slow but active metabolism in the liver in the absence of a significant "first passage" effect. Metabolites do not have significant pharmacological activity.

After a single oral intake, the half-life period (T_1/2) varies from 31 to 48 hours, with a reappointment T_1/2 is approximately 45 hours.About 60% of the dose taken internally is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - through the intestine, as well as breast milk. 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 of age), the excretion of amlodipine is slowed (T_1/2 - 65 hours) compared with young patients, but this difference has no clinical significance. Elongation T_1/2 in patients with hepatic insufficiency suggests that with prolonged administration, the cumulation of the drug in the body will be higher (T_1/2 up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. The drug penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

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

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

Contraindications:

- Hypersensitivity to amlodipine, dihydropyridine derivatives and other components of the drug;

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

- collapse, cardiogenic shock;

- unstable angina (with the exception of Prinzmetal's stenocardia);

- clinically significant aortic stenosis;

- pregnancy and lactation;

- age under 18 years (effectiveness and safety not studied);

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Use with caution when: violations of liver function, syndrome of weakness of the sinus node (SSSU) (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 (GOKMP), acute myocardial infarction (and within 1 month after myocardial infarction), in old age.

Pregnancy and lactation:

There was no evidence of teratogenicity of amlodipine in the study on animals, but there is no clinical experience of its use in pregnancy and lactation. therefore amlodipine should not be prescribed to pregnant women and during lactation, as well as to women of childbearing age,if they do not use reliable methods of contraception.

Dosing and Administration:

Inside, the initial dose for treatment arterial hypertension and angina pectoris is 5 mg once a day. The maximum daily dose is 10 mg once.

With hypertension, the maintenance dose may be 2.5 to 5 mg (1/2 tablets of 5 mg - 1 tablet of 5 mg) per day.

With angina pectoris and vasospastic angina pectoris, 5-10 mg per day, once. In order to prevent attacks of angina pectoris - 10 mg / day.

Patients with impaired liver function as an antihypertensive drug Amlodipine appoint with caution, at an initial dose of 2.5 mg (1/2 tablet of 5 mg), as an antianginal agent - 5 mg.

In elderly patients may increase T_1/2 Amlodipine and decrease the clearance of creatinine (QA). Dose changes are not required, but more careful monitoring of patients is necessary.

There is no need for dose changes with simultaneous administration with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. Do not require dose changes in patients with renal insufficiency.

Side effects:

Classification of the frequency of development of side effects of the World Organization Health (WHO):

very often> 1/10

often from> 1/100 to <1/10

sometimes from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

From the cardiovascular system: often - palpitations, peripheral edema (edema of the ankles and feet), "hot flashes" of blood to the skin of the face; sometimes - excessive decrease in blood pressure; very rarely - syncope, dyspnea, vasculitis, orthostatic hypotension, development or aggravation of heart failure, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

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

From the digestive system: often - nausea, pain in the abdomen; sometimes - vomiting, constipation or diarrhea, flatulence, indigestion, anorexia, dry mouth, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity of "liver" transaminases, hepatitis.

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

From the genitourinary system: sometimes - frequent urination, painful urination, nocturia, impotence, very rarely - dysuria, polyuria, gynecomastia. From the respiratory system: sometimes - shortness of breath, rhinitis, very rarely - cough.

From the skin: rarely - dermatitis, very rarely - alopecia, xeroderma, "cold" sweat, a violation of skin pigmentation.

Allergic reactions: itching, rash (including erythematous, maculopapular rash, urticaria), angioneurotic edema, erythema multiforme.

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

Other: sometimes - tinnitus, diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain, fever, epistaxis, very rarely - parosmiya, hyperglycemia.

Overdose:

Symptoms: excessive peripheral vasodilation with a pronounced and possibly long-term decline in blood pressure, collapse, shock.

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, control of heart and lung function, elevated, above the level of the head, the position of the lower extremities, control of the volume of circulating blood and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); with the purpose of elimination of consequences of blockade of calcium channels - intravenous introduction of calcium gluconate. Hemodialysis is ineffective.

Interaction:

Amlodipine can safely be used to treat hypertension along with thiazide diuretics, alpha-adrenoblockers, beta-blockers, or ACE inhibitors. In patients with stable angina, the drug can be combined with other antianginal agents, for example, with long-acting nitrates, beta-blockers or short-acting nitrates.

Amlodipine can be used simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (especially indomethacin),antibacterial agents and hypoglycemic agents for oral administration.

It is possible to increase the anti-anginal and hypotensive action of BCCC when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when combined with alpha 1-blockers and neuroleptics.

Although no negative inotropic effects were usually observed in the study of amlodipine, nevertheless, some BCCCs can increase the severity of the negative inotropic effect of antiarrhythmic agents that cause lengthening of the interval QT (eg, amiodarone and quinidine).

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics 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. Ethanol (drinks containing alcohol): amlodipine at a single and repeated application in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiviral drugs (ritonavir) increases the plasma concentrations of BCCI, incl. amlodipine.

Neuroleptics and isoflurane - Increased hypotensive effect of dihydropyridine derivatives.

Calcium preparations can reduce the effect of BCCC.

When amlodipine is used together with lithium preparations, it is possible to intensify the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, and tinnitus). Amlodipine does not change the pharmacokinetics of cyclosporine.

Does not affect the concentration of serum digoxin and its renal clearance.

Has no significant effect on the effect of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.

In studies in vitro Amlodipine does not affect the binding to blood proteins of digoxin, phenytoin, warfarin and indomethacin.

Grapefruit juice: simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine inwards is not accompanied by a significant change in the pharmacokinetics of amlodipine.

Special instructions:

During the period of Amlodipine treatment, it is necessary to control the body weight and sodium intake, the purpose of the appropriate diet. It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Patients with low body weight, low growth patients and patients with severe liver function impairment may need a smaller dose.

Elderly patients may be lengthened T_1/2 and clearance of the drug. Dosage changes for elderly patients are not required; with increasing the dose, more careful monitoring of patients is necessary.

If the liver function is also impaired T_1/2 preparation. Therefore, such patients Amlodipine must be administered with caution.

Despite the fact that stopping the use of amlodipine is not accompanied by the development of the "withdrawal" syndrome, it is desirable to stop the treatment, gradually reducing the dose of the drug.

The effectiveness and safety of the drug in hypertensive crisis is not established.

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

There was no report on the influence of Amlodipine on driving or working with machinery. However, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. When they occur, the patient must observe special precautions when driving and working with complex mechanisms.

Form release / dosage:

Tablets of 5 mg or 10 mg.

Packaging:

For 10 tablets in a planar cell package. 1, 2, 3, 4 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

For 100 tablets per can of polymer, each bank along with the instructions for use are placed 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:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009349/09

Date of registration:19.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:ALSI Pharma, ZAO ALSI Pharma, ZAO Russia

Manufacturer: & nbsp

ALSI Pharma, ZAO Russia

Information update date: & nbsp10.08.2017

Illustrated instructions

Instructions

Amlodipine (Amlodipine)