Amlodivel pills 5mg, 30pcs

Composition

Per tablet:

Active ingredient: amlodipine besylate (in terms of amlodipine) – 5 mg.

Excipients: lactose monohydrate (milk sugar), microcrystalline cellulose, crospovidone (collidone CL, collidone CL-M), colloidal silicon dioxide (aerosil), talc, calcium stearate.

Pharmacological action

Pharmacotherapeutic group: slow calcium channel blocker (BMCC).

ATX code: [C 08 CA 01]

Pharmacological properties

Pharmacodynamics

Dihydropyridine derivative-a blocker of “slow” calcium channels, has antihypertensive and antianginal effects. Blocks calcium channels, reduces the transmembrane transfer of calcium ions into the cell (more to vascular smooth muscle cells than to cardiomyocytes).

The antihypertensive effect is due to the direct vasodilating effect on vascular smooth muscles. It has a long-term dose-dependent antihypertensive effect.

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

1) dilates peripheral arterioles and thus, reduces the total peripheral resistance of blood vessels, reduces afterload on the heart, while the heart rate is almost constant, which leads to lower energy consumption and demand of myocardial oxygen;

2) dilates coronary and peripheral arteries and arterioles in the unaltered and in ischemic areas of the myocardium, which increases the flow of oxygen to the myocardium (especially when vasospastic angina), reduces the severity of myocardial ischemia and prevents the development of koronarospazm (including caused by Smoking).

In patients with arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient’s “lying” and “standing” positions). Due to the slow onset of action, amlodipine does not cause a sharp decrease in blood pressure. It does not reduce exercise tolerance and left ventricular ejection fraction.

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

Reduces the degree of left ventricular myocardial hypertrophy, has anti-atherosclerotic and cardioprotective effects in coronary heart disease (CHD).

In patients with coronary artery disease (including coronary atherosclerosis with damage to one vessel and before stenosis of three or more arteries and carotid artery atherosclerosis), who have suffered a myocardial infarction, percutaneous transluminal angioplast of the coronary arteries (TLAP) or suffering from angina pectoris, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, significantly reduces mortality from cardiovascular causes, myocardial infarction stroke, TLAP, and coronary artery bypass grafting, leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure, and reduces the frequency of interventions aimed at restoring coronary blood flow.

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

Patients with chronic heart failure (NYHA functional class III-IV) of non-ischemic etiology may develop pulmonary edema when using amlodipine.

It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase

the severity of microalbuminuria. It has no adverse effects on the metabolism and concentration of lipids in blood plasma and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.

The time of onset of the amlodipine effect is 2-4 hours, the duration of the effect is 24 hours. With long-term therapy, the maximum decrease in blood pressure (BP) occurs 6-12 hours after oral use of amlodipine. If amlodipine is discontinued after prolonged treatment, an effective reduction in blood pressure is maintained for 48 hours after the last dose. Then the blood pressure values gradually return to the initial level within 5-6 days.

Pharmacokinetics

Absorption is slow, does not depend on food intake, is about 90%. Bioavailability is 60-90%, the maximum concentration in the blood serum is observed 6-12 hours after use.

The volume of distribution is approximately 21 l / kg of body weight, which indicates that most of the amlodipine is in the tissues, and relatively less in the blood. Most of the amlodipine in the blood (95-97%) binds to plasma proteins. Amlodipine penetrates the blood-brain barrier. It is not removed during hemodialysis. Steady-state plasma concentration of amlodipine (Css) is reached after 7-8 days of continuous use of the drug.

Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, has a “first pass” effect through the liver. The metabolites do not have significant pharmacological activity.

After a single oral dose, the half-life (T1/2) varies from 35 to 50 hours, with repeated use, T1 / 2 is approximately 45 hours-which corresponds to the appointment 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 of age), the elimination of amlodipine is slowed (T1 / 2 increases to 65 hours) compared to younger patients. In elderly and younger patients, the time required to reach the maximum concentration of amlodipine in blood plasma is almost the same.

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

T1 / 2 from blood plasma in patients with renal insufficiency increases to 60 hours. Changes in the concentration of amlodipine in blood plasma do not correlate with the degree of impaired renal function.

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

Indications

Arterial hypertension both in monotherapy and in combination with other antihypertensive agents.

Stable angina and vasospastic angina (Prinzmetal angina or variant angina) both in monotherapy and in combination with other antianginal agents.

Use during pregnancy and lactation

Pregnancy

The safety of using amlodipine during pregnancy has not been established. In preclinical studies, the fetotoxic and embryotoxic effects of amlodipine were not detected. In rats, amlodipine increased the duration of gestational age and labor. Some other BMCs have a teratogenic effect.

The use of amlodipine during pregnancy is possible only if the benefit to the mother exceeds the risk to the fetus and newborn.

Breast-feeding period

Amlodipine is excreted in breast milk. According to the data of a clinical study in 31 nursing women, when using amlodipine at an average daily dose of 6 mg (98.7 mcg/kg body weight), the median ratio of “amlodipine concentration in milk/blood plasma concentration” is 0.85. The estimated intake of amlodipine in the body of a child with breast milk is 4.17 mcg/kg of body weight per day.

The use of amlodipine during breastfeeding is contraindicated. If it is necessary to use the drug during lactation, stop breastfeeding.

Fertility

Studies in rats have reported undesirable effects of amlodipine on male fertility. Reversible biochemical changes in sperm heads have been observed in some patients treated with BMCC. Clinical data regarding the potential effects of amlodipine on fertility are insufficient.

Contraindications

– hypersensitivity to amlodipine, other derivatives of dihydropyridine and other components of the drug;

– severe hypotension (systolic blood pressure less than 90 mm Hg. St. )

– cardiogenic shock;

– hemodynamically unstable heart failure after myocardial infarction;

– obstruction of the outflow tract of the left ventricle (including clinically significant aortic stenosis);

– age under 18 years;

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

With caution

Hepatic insufficiency; chronic heart failure of non-ischemic etiology of NYHA functional class III-IV; ischemic heart disease with severe obstructive coronary artery disease; acute myocardial infarction (and the period within 1 month after it); unstable angina; aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy; arterial hypotension; sinus node weakness syndrome (pronounced tachycardia, bradycardia); concomitant use with inhibitors or inducers of the CYP3A4 isoenzyme; pregnancy; elderly age.

Side effects

Disorders of the blood and lymphatic system

very rare: thrombocytopenic purpura, leukopenia, thrombocytopenia.

Immune system disorders infrequently: urticaria, allergic reactions; very rarely: angioedema.

Metabolic and nutritional disorders infrequently: weight gain/loss;

very rarely: hyperglycemia.

Mental disorders

are uncommon: unusual dreams, anxiety, depression, depersonalization, insomnia, mood changes.

Nervous system disorders

common: headache, dizziness, increased fatigue, drowsiness;

uncommon: asthenia, hypersthesia, paresthesia, peripheral neuropathy, tremor, mood lability, increased excitability, taste distortion;

very rare: migraine, apathy, agitation, ataxia, amnesia;

frequency unknown: extrapyramidal disorders.

Disorders of the visual organ

infrequently: diplopia, accommodation disorders, xerophthalmia, conjunctivitis, eye pain, visual impairment.

Hearing disorders and labyrinth disorders infrequently: tinnitus, vertigo.

Cardiac disorders

common: palpitation sensation;

very rare: cardiac arrhythmias (including bradycardia, ventricular tachycardia, and atrial fibrillation), development or worsening of CHF, myocardial infarction, chest pain, and pulmonary edema.

Vascular disorders

very often: peripheral edema (ankles and feet);

often: “hot flashes” of blood to the skin of the face;

infrequently: excessive decrease in blood pressure, orthostatic hypotension;

very rarely: vasculitis.

Respiratory, thoracic and mediastinal disorders infrequently: shortness of breath, rhinitis, nosebleeds;

very rarely: cough.

Gastrointestinal disorders common: nausea, abdominal pain;

uncommon: vomiting, constipation, diarrhea, flatulence, dyspepsia, anorexia, dry oral mucosa, dyspepsia, bloating;

rare: gum hyperplasia, increased appetite;

very rare: pancreatitis, gastritis.

Liver and biliary tract disorders

frequency unknown:  jaundice (due to cholestasis), hyperbilirubinemia, increased activity of “liver” transaminases, hepatitis.

Skin and subcutaneous tissue disorders

infrequently: pruritus, skin rash (including erythematous, maculopapular rash), increased sweating;

rarely: dermatitis;

very rarely: erythema multiforme, alopecia, xeroderma, skin pigmentation disorder.

Musculoskeletal and connective tissue disorders infrequently: arthralgia, muscle cramps, myalgia, back pain, osteoarthritis;

rarely: myasthenia gravis, muscle weakness.

Renal and urinary tract

disorders uncommon: frequent urination, painful urination, nocturia;

very rare: dysuria, polyuria.

Genital and breast disorders

infrequently: gynecomastia, erectile dysfunction, sexual dysfunction (in men and women).

General disorders and disorders at the injection site infrequently: chills, thirst, general malaise, asthenia; very rarely: fainting, parosmia.

Interaction

Pharmacodynamic interactions

Other antihypertensive and antianginal medications

Amlodipine can be safely used for the treatment of hypertension together with thiazide diuretics, beta-blockers or ACE inhibitors.

In patients with stable angina, amlodipine can be used in combination with other antianginal agents, such as long-acting or short-acting nitrates and beta-blockers.

It is possible to enhance the antianginal and antihypertensive effects of BMCC when combined with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates.

Ethanol, barbiturates, antipsychotics, antidepressants, narcotic analgesics, general anesthesia

It is possible to increase the antihypertensive effect of dihydropyridine derivatives and increase the risk of orthostatic hypotension.

Other drugs that can lower blood pressure

It can be expected that some drugs (for example, baclofen and amifostine), due to their pharmacological properties, will enhance the antihypertensive effect of amlodipine. It is necessary to monitor blood pressure and renal function, as well as adjust the dose of amlodipine if necessary.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide

Reduced antihypertensive effect of amlodipine (due to fluid retention and sodium ions as a result of corticosteroids).

Calcium supplements

Calcium supplements can reduce the effect of BMCC.

Dantrolene (for intravenous use)

In animal experiments, cases of fatal ventricular fibrillation and cardiovascular failure associated with hyperkalemia were observed after use of verapamil and dantrolene (intravenously). Given the risk of hyperkalemia, concomitant use of BMCC (including amlodipine) and dantrolene should be avoided in patients with malignant hyperthermia.

Pharmacokinetic interactions

Effect of other drugs on the pharmacokinetics of amlodipine Inhibitors of the CYP3A4 isoenzyme

With the simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (69 to 87 years) with arterial hypertension, there is an increase in systemic exposure to amlodipine by 57%. Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years of age) did not result in significant changes in amlodipine exposure (22% increase in the area of the concentration-time curve (AUC)). The clinical significance of these effects is unclear.

Ritonavir (a potent inhibitor of the CYP3A4 isoenzyme) increases plasma concentrations of BMCC, including amlodipine.

It is possible that powerful inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole, ritonavir) may increase the concentration of amlodipine in blood plasma to a greater extent than diltiazem. Caution should be exercised when using amlodipine concomitantly with CYP3A4 inhibitors (especially in elderly patients).

Clarithromycin

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. Patients taking clarithromycin and amlodipine at the same time have an increased risk of lowering blood pressure. Patients taking this combination are advised to be under close medical supervision.

Inducers of the CYP3A4 isoenzyme

There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine.

Caution should be exercised when using amlodipine concomitantly with inducers of the CYP3A4 isoenzyme (phenobarbital, phenytoin, carbamazepine, primidone, rifampicin, St. John’s wort), blood pressure should be carefully monitored when used simultaneously (the antihypertensive effect of amlodipine may be weakened).

Grapefruit juice

Simultaneous single use of 240 mg grapefruit juice and 10 mg amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. However, it is not recommended to use grapefruit juice and amlodipine simultaneously, since the genetic polymorphism of the cytochrome P 450 isoenzyme may increase the bioavailability of amlodipine and, consequently, increase its antihypertensive effect.

Aluminum-or magnesium-containing antacids

With a single co-use, they do not significantly affect the pharmacokinetics of amlodipine.

Sildenafil

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

Cimetidine

Cimetidine does not affect the pharmacokinetics of amlodipine.

Effect of amlodipine on the pharmacokinetics of other drugs Simvastatin

Simultaneous multiple use of 10 mg amlodipine and 80 mg simvastatin resulted in a 77% increase in simvastatin exposure. In such cases, the dose of simvastatin should be limited to 20 mg.

Atorvastatin

Repeated co-use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetic parameters of AUC (an average increase of 18%) Cmax and TSmax of atorvastatin.

Cyclosporine

Studies on the concomitant use of amlodipine and cyclosporine in healthy volunteers and all groups of patients, with the exception of patients after kidney transplantation, have not been conducted. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect or increase the minimum concentration of cyclosporine to varying degrees up to 40%. These data should be taken into account and the concentration of cyclosporine should be monitored in this group of patients with concomitant use of cyclosporine and amlodipine.

Tacrolimus

When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in blood plasma. In order to avoid toxicity of this drug when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma should be monitored and the dose of tacrolimus adjusted if necessary.

mTOR inhibitors (mammalion Target of Rapamycin – target of rapamycin in mammalian cells)

mTOR inhibitors (e. g., temsirolimus, sirolimus, everolimus) are substrates of CYP3A4. Since amlodipine is a weak inhibitor of CYP3A4, co-use may increase exposure to mTOR inhibitors.

Ethanol

Amlodipine with a single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Lithium preparations

When BMCC is co-administered with lithium (no data available for amlodipine), their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Digoxin

Amlodipine has no effect on serum digoxin concentrations and renal clearance in healthy volunteers. In vitro studies, amlodipine did not affect the binding of digoxin to plasma proteins.

Warfarin

Amlodipine does not significantly affect the effect of warfarin (prothrombin time). In vitro studies, amlodipine did not affect the binding of warfarin to plasma proteins.

Phenytoin

In vitro studies, amlodipine did not affect the binding of phenytoin to plasma proteins.

Other interactions

Amlodipine can be safely administered concomitantly with antibiotics and oral hypoglycemic agents. Unlike other BMCs, there was no clinically significant interaction of amlodipine when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDs), including Indometacin. In vitro studies, amlodipine did not affect the binding of Indometacin to plasma proteins.

Although no negative inotropic effects have usually been observed in studies of amlodipine, however, some BMCs may increase the severity of the negative inotropic effects of antiarrhythmic agents that cause prolongation of the QT interval (for example, amiodarone and quinidine).

How to take, course of use and dosage

Inside,1 time a day, with the required amount of water (100 ml).

Arterial hypertension, stable angina and vasospastic angina With arterial hypertension and angina, the usual initial dose is 5 mg per day. Depending on the therapeutic response, the dose can be increased to a maximum daily dose of 10 mg. Usually, the dose of amlodipine is recommended to be increased no earlier than after 7-14 days of treatment. However, if necessary, a more rapid increase in the dose of amlodipine is possible, provided that the patient’s condition is regularly monitored.

In patients with low body weight, short stature, or moderate hepatic insufficiency, the recommended initial dose of amlodipine is 2.5 mg per day.

Concomitant use with other antihypertensive and antianginal drugs No dose adjustment of amlodipine is required when used concomitantly with thiazide diuretics, beta-blockers and angiotensin-converting enzyme inhibitors.

In cases where amlodipine is prescribed as adjunctive therapy to patients receiving other antihypertensive drugs, the recommended starting dose is 2.5 mg per day.

Use in special patient groups Elderly patients

It is recommended to use the drug in normal doses, changing the dose of amlodipine is not required.

Patients with impaired liver function

Despite the fact that T 1/2 of amlodipine, like all BMCC, increases in patients with mild hepatic impairment, dose adjustment of the drug is usually not required. In patients with moderate hepatic insufficiency, the recommended starting dose of amlodipine is 2.5 mg per day.

Patients with impaired renal function are recommended to use amlodipine in normal doses.

Overdose

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

Treatment: gastric lavage, use of activated charcoal (especially in the first 2 hours after overdose), maintenance of the cardiovascular system, monitoring of heart and lung function, elevated position of the lower extremities, control of the volume of circulating blood and diuresis. To restore vascular tone – the use of vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade – intravenous use of calcium gluconate. Since amlodipine is largely bound to serum proteins, hemodialysis is ineffective.

Description

Round flat-cylindrical tablets of white or almost white color with a chamfer, the presence of “marbling” is allowed.

Special instructions

In the treatment of arterial hypertension, amlodipine can be used in combination with thiazide diuretics, alpha – and beta-blockers, and ACE inhibitors.

For the treatment of angina pectoris, amlodipine can be combined with other antianginal agents, for example, with prolonged or short – acting nitrates, beta-blockers.

Amlodipine can also be used in cases where the patient is predisposed to vascular spasm (vasoconstriction).

Against the background of the use of the drug in patients with chronic heart failure class III and IV functional class according to the NYHA classification of non-ischemic origin, an increase in the incidence of pulmonary edema was noted, despite the absence of signs of worsening heart failure.

Amlodipine does not affect the plasma concentrations of potassium, 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 mellitus and gout.

In elderly patients, T 1/2 may increase and drug clearance may decrease. Dose changes are not required, but more careful monitoring of patients in this category is necessary.

The efficacy and safety of amlodipine in hypertensive crisis has not been established.

During treatment, it is necessary to monitor body weight and sodium intake, prescribe an appropriate diet, and follow up with a dentist (to prevent soreness, bleeding, and gum hyperplasia).

Despite the absence of withdrawal symptoms, a gradual dose reduction is recommended before discontinuing treatment.

Influence on the ability to drive vehicles and mechanisms

Against the background of the use of the drug amlodipine, no negative effect on the ability to drive a car or other complex mechanisms was observed, however, due to a possible excessive decrease in blood pressure, dizziness, drowsiness and other adverse reactions, caution should be exercised in these situations, especially at the beginning of treatment and when increasing the dose.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Amlodipine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets