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

Excipients: calcium phosphate dihydrate, potato starch, microcrystalline cellulose, carboxymethyl starch sodium (sodium starch glycolate, primogel), silicon dioxide colloid (aerosil), magnesium stearate.

Description:

Tablets are white or almost white in color, flat-cylindrical.

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.Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes).

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 afterload on the heart, reduces the need for myocardium in oxygen. Expanding 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 spasm of the coronary arteries (including 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 decrease in blood pressure (BP) for 24 hours (in the patient's position "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. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in 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.

In patients with diseases of the cardiovascular system (CCC) (including coronary atherosclerosis with the defeat of one vessel and up to stenosis of 3 or more arteries, carotid atherosclerosis), after myocardial infarction,percutaneous transluminal angioplasty (TLD) of coronary arteries or patients with angina, the use of amlodipine prevents the development of thickening of the intima-media of carotid arteries, reduces the mortality from myocardial infarction, stroke, TI, coronary artery bypass graft; 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 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.

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.The equilibrium 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 the smaller - 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 administration, the elimination half-life (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 intestines with bile. 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.

Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

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

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

Contraindications:

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

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

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

- clinically significant aortic stenosis;

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

Carefully:

At narteries of liver function, syndrome of sinus node weakness (pronounced bradycardia, tachycardia), CHF of non-ischemic etiology III-IV functional class by classification NYHA, arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after myocardial infarction), in old 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 BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, if it is necessary to prescribe Amlodipine during the lactation period, the question of stopping breastfeeding should be solved.

Dosing and Administration:

Inside, once a day, washing down with the necessary amount of water (100 ml).

With arterial hypertension and angina, the initial dose is 5 mg once a day. If necessary, the daily dose can be increased to 10 mg, at one time.

Have elderly patients

Amlodipine is recommended for use in an average therapeutic dose, dose adjustment is not required.

Have patients with impaired liver function

Although T_1/2 Amlodipine, like all BCCC,increases in patients with impaired liver function, dose adjustment is usually not required (see section "Special instructions"),

Have patients with renal insufficiency

It is recommended that Amlodipine in normal doses, but it is necessary to take into account the possible slight increase T_1/2.

No dosage adjustment is required for simultaneous administration with thiazide diuretics, beta-blockers and ACE inhibitors.

Side effects:

The frequency of adverse reactions listed below was determined according to the following (World Health Organization classification): very often more than 1/10, often from more than 1/100 to less than 1/10, infrequently from more than 1/1000 to less than 1/100 , rarely from more than 1/10000 to less than 1/1000, very rarely from less than 1/10000, including individual messages.

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

From the digestive system: often - nausea, abdominal pain; infrequent - vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity of "liver" transaminases, hepatitis.

From the cardiovascular system: often - palpitations, peripheral edema (ankles and feet), "hot flashes" of blood to the skin of the face; infrequent reduction of blood pressure; very rarely - fainting, shortness of breath, vasculitis, orthostatic hypotension, development or exacerbation of CHF, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

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

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

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

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

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

Allergic reactions: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema, erythema multiforme.

Other: infrequent - ringing in the ears, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, chills, nosebleeds, gynecomastia; very rarely - parosmia, hyperglycemia.

Overdose:

Symptoms: a 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 cardiovascular function, sublime the position of the lower extremities, the monitoring of heart and lung function, the control of the volume of circulating blood (BCC) and diuresis.To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

Interaction:

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

Unlike other BCCI, clinically significant interaction of amlodipine (III generation of BCCI) was not detected when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin.

It is possible to strengthen the anti-anginal and hypotensive action of BCCC when combined with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when combined with alpha1-adrenoblockers, 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 is not has an effect on 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

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 plasma concentrations of BCCC, including 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 manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, 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 of blood proteins to 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.

Aluminum- or magnesium-containing antacids: their single administration does not have a significant effect on the pharmacokinetics of amlodipine.

Special instructions:

During the period of Amlodipine therapy, it is necessary to control body weight and sodium intake, and the purpose of the appropriate diet is indicated.

It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

In elderly patients may increase T_1/2 and decrease the clearance of the drug.Dose changes are not required, but more careful monitoring of patients of this category is necessary.

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

The efficacy and safety of the use of amlodipine in hypertensive crisis is not established.

Despite the absence of the "cancellation" syndrome in BCC, it is desirable to stop amlodipine treatment, gradually reducing the dose of the drug.

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

Although amlodipine was not adversely affected by the ability to drive vehicles or other complex mechanisms, however, due to possible excessive BP reduction, dizziness, drowsiness, and other adverse reactions, caution should be taken in these situations, especially at the start of treatment and with increasing dose.

Form release / dosage:

Tablets of 5 and 10 mg.

Packaging:

10 tablets per contour cell package; for 1 or 3 contour mesh packages together with the instruction for use are placed in a cardboard pack.

For 30 or 100 tablets in a jar or a bottle of polymer materials. Each jar or bottle together with the instruction for use is placed in a cardboard pack.

Storage conditions:

List B. In a dry, 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 the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002800/10

Date of registration:02.04.2010

Expiration Date:Unlimited

The owner of the registration certificate:Berezovsky Pharmaceutical Plant, ZAO Berezovsky Pharmaceutical Plant, ZAO Russia

Manufacturer: & nbsp

Berezovsky Pharmaceutical Plant, ZAO Russia

Information update date: & nbsp10.08.2017

Illustrated instructions

Instructions

Amlodipine (Amlodipine)