Amlodipine-CRCA pills 5mg, 30pcs

Composition

1 tablet of 5 mg / 10 mg contains:

Active ingredient:

Amlodipine Maleate 6.42 mg / 12.84 mg, equivalent to Amlodipine 5.00 mg/10.00 mg

Auxiliary substances:

Microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate

Pharmacological action

slow calcium channel blocker

Clinical Pharmacology

Pharmacodynamics

A dihydropyridine derivative-a slow calcium channel blocker (BMCC), has an antianginal and antihypertensive effect. By binding to dihydropyridine receptors, it blocks “slow” calcium channels, reduces the transmembrane transfer of calcium ions into the cell (more to vascular smooth muscle cells than to cardiomyocytes).

The antianginal effect is caused by dilation of the coronary and peripheral arteries and arterioles:

• when angina reduces the severity of myocardial ischemia, dilating peripheral arterioles, reduces the total peripheral vascular resistance (SVR), reduces afterload on the heart, reduces the need for myocardium in oxygen;
• dilating coronary arteries and arterioles in the intact and ischemic zones of the myocardium, increases the supply of oxygen to the myocardium (especially when 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 attacks and “ischemic” ST-segment depression, reduces the frequency of angina attacks and the use of nitroglycerin and other nitrates.

It has a long-term dose-dependent antihypertensive effect. This effect is due to the direct vasodilating effect on vascular smooth muscles. In patients with arterial hypertension, a single dose provides a clinically significant reduction in blood pressure (BP) over 24 hours (in the patient’s “lying” and “standing”positions).

Orthostatic hypotension with the use of amlodipine is quite rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. 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 (GFR), and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It 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 mellitus and gout. A significant decrease 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 (including coronary atherosclerosis with damage to one vessel and before stenosis of 3 or more arteries, carotid artery atherosclerosis), who have suffered a myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina, the use of amlodipine prevents the development of thickening of the intima-media complex (CIM) of the carotid arteries, reduces mortality from heart attack myocardial infarction, stroke, PTCA, aorto-coronary bypass surgery, 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.

It does not increase the mortality rate or the development of complications and deaths in patients with CHF (NYHA functional class III-IV) during therapy with digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In patients with CHF (NYHA functional class III-IV) of non-ischemic etiology, amlodipine is likely to cause pulmonary edema.

Pharmacokinetics

After oral use, amlodipine is slowly absorbed from the gastrointestinal tract (GI). The average absolute bioavailability is 64-80%, the maximum concentration (cmax) in the blood serum is determined after 6-12 hours. Steady-state serum concentrations (Sss) are reached after 7-8 days of therapy.

Simultaneous food intake does not affect the absorption of amlodipine.

The average volume of distribution is 21 l / kg of body weight, which indicates that most of the drug is in the tissues, and less in the blood. Most of the drug in the blood (97.5%) binds to plasma proteins.

Amlodipine undergoes slow but active metabolism in the liver with no significant effect of “primary passage” through the liver. The metabolites do not have significant pharmacological activity.

After a single oral dose, the half-life (T_1/2) varies from 35 to 50 hours, with repeated use, T_1/2 is approximately 45 hours. About 60% of the oral dose 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).

Elderly patients

In elderly patients (over 65 years of age), the elimination of amlodipine is delayed (T_1/2-65 hours) compared to younger patients, however, this difference is not clinically significant.

Patients with hepatic insufficiency

Prolongation of T_1/2 in patients with hepatic insufficiency suggests that with prolonged use, the accumulation of the drug in the body will be higher (T_1/2 – up to 60 hours).

Patients with renal insufficiency

Renal failure does not significantly affect the kinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. It is not removed during hemodialysis.

Indications

• Arterial hypertension (both in monotherapy and in combination with other antihypertensive agents).
• Stable exertional angina and vasospastic angina (Prinzmetal angina) (both in monotherapy and in combination with other antianginal agents).

Use during pregnancy and lactation

The safety of using Amlodipine-KRKA during pregnancy and lactation has not been established, so use during pregnancy and lactation is possible only if the expected benefit to the mother exceeds the possible risk to the fetus and newborn.

Experience shows that amlodipine is excreted in human breast milk. The average milk / plasma ratio was 0.85 among 31 lactating women with pregnancy-related hypertension and receiving amlodipine at an initial dosage of 5 mg per day. The dosage of the drug was adjusted if necessary (depending on the average daily dose and weight: 6 mg and 98.7 mcg / kg, respectively). The estimated daily dose of amlodipine received by an children through breast milk is 4.17 mcg/kg.

In some patients, reversible biochemical changes in the sperm head were observed when using calcium channel blockers. There is insufficient clinical data on the potential effect of amlodipine on fertility. In a rat study, undesirable effects on male fertility were identified.

Contraindications

• Hypersensitivity to amlodipine, dihydropyridine derivatives and other components of the drug.
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).
• Shock (including cardiogenic shock).
• Obstruction of the left ventricular outflow tract (for example, severe aortic stenosis).
• Hemodynamically unstable heart failure after myocardial infarction.
• Age up to 18 years (efficacy and safety have not been studied).

Side effects

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

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

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:

infrequently: unusual dreams, anxiety, depression, depersonalization, insomnia, mood changes.

Nervous system disorders:

often: headache, dizziness, increased fatigue, drowsiness;

infrequently: asthenia, hyperesthesia, paresthesia, peripheral neuropathy, tremor, mood lability, increased excitability, dysgeusia (taste distortion);

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

frequency unknown: extrapyramidal disorders.

Visual disturbances:

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

Hearing disorders and labyrinth disorders:

infrequently: tinnitus, vertigo.

Cardiac disorders:

common: palpitation;

very rare: cardiac arrhythmia (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.

Disorders of the gastrointestinal tract:

often: abdominal pain, nausea;

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

rarely: gum hyperplasia, increased appetite;

very rarely: pancreatitis, gastritis.

Liver and biliary tract disorders:

frequency unknown: hepatitis, jaundice (due to cholestasis), hyperbilirubinemia, increased activity of “hepatic” transaminases in blood plasma.

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.

Kidney and urinary tract disorders:

infrequently: painful urination, nocturia, frequent urination;

very rarely: 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

Amlodipine can be safely used for the treatment of hypertension together with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, with prolonged or short-acting nitrates, beta-blockers.

Unlike other BMCs, no clinically significant interaction of amlodipine was found when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDs), including Indometacin.

It is possible to enhance the antianginal and antihypertensive effects of BMCC when used simultaneously with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as to enhance their antihypertensive effect when used simultaneously with alpha-1-blockers, neuroleptics.

In laboratory animals, cases of ventricular fibrillation with collapse and death were noted against the background of verapamil and intravenous dantrolene use, accompanied by hyperkalemia. Due to the risk of hyperkalemia, concomitant use of BMCC, including amlodipine, and dantrolene should be avoided in patients with malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

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).

Amlodipine can also be safely administered concomitantly with antibiotics and oral hypoglycemic agents.

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

Repeated 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 pharmacokinetics of atorvastatin.

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.

Ethanol (beverages containing alcohol): amlodipine with a single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiviral agents (ritonavir): increased plasma concentrations of BMCC, including amlodipine.

Antipsychotics and isoflurane: increased antihypertensive effect of dihydropyridine derivatives.

Calcium supplements: they can reduce the effect of BMCC.

Concomitant use of BMCC with lithium preparations (no data available for amlodipine) may increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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 either 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.

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

It does not significantly affect the effect of warfarin (prothrombin time indicator).

Cimetidine: It does not affect the pharmacokinetics of amlodipine.

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

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 CYP3A4 isoenzyme may increase the bioavailability of amlodipine and, consequently, increase the antihypertensive effect.

Aluminum-or magnesium-containing antacids: their single use does not significantly affect the pharmacokinetics of amlodipine.

Inhibitors of the isoenzyme WithUR 3 and 4: when diltiazem is co-administered at a dose of 180 mg and amlodipine at a dose of 5 mg in patients aged 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 significantly alter amlodipine exposure (22% increase in the area under the concentration-time curve (AUC)). Although the clinical significance of these effects is not fully understood, they may be more pronounced in elderly patients.

Powerful inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole) can lead to an increase in the concentration of amlodipine in blood plasma to a greater extent than diltiazem. Amlodipine and CYP3A4 inhibitors should be used with caution.

Clarithromycin: patients taking clarithromycin (an inhibitor of the CYP3A4 isoenzyme) 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: with simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in blood plasma may change. Therefore, it is necessary to monitor blood pressure and adjust the dose of medications taken both during and after their simultaneous use (including rifampicin, St. John’s wort preparations).

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 tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus adjusted if necessary.

Mammalian mechanistic target inhibitors of rapamycin(mTOR): mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.

How to take it, course of use and dosage

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

Arterial hypertension, stable angina and vasospastic angina

For hypertension and angina, the usual starting 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 ACE 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.

Special patient groups

Elderly patients

It is recommended to use the drug in normal doses, no changes in the dose of amlodipine are required.

Patients with impaired liver function

Despite the fact that the T_1/2 of amlodipine, like all BMCC, is increased 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

It is recommended to use amlodipine in normal doses.

Overdose

Symptoms: excessive peripheral vasodilation with a marked and possibly prolonged decrease in blood pressure, collapse, shock.

Treatment: gastric lavage, use of activated charcoal, maintenance of the cardiovascular system, monitoring of heart and lung function, elevated (above head level) position of the lower extremities, control of the volume of circulating blood (BCC) and diuresis. To restore vascular tone – the use of vasoconstrictors (in the absence of contraindications to their use), in order to eliminate the consequences of calcium channel blockade – intravenous use of calcium gluconate. Hemodialysis is ineffective.

Description

Round, biconvex tablets of white or almost white color with a chamfer and a risk on one side.

Special instructions

Hepatic impairment, sinus node weakness syndrome (severe bradycardia, tachycardia), non-ischemic heart failure of NYHA functional class III-IV, mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), acute myocardial infarction (and within 1 month after myocardial infarction), use in elderly patients, pregnancy and lactation breast-feeding (see section “Use during pregnancy and lactation”), concomitant use with inhibitors or inducers of the CYP3A4 isoenzyme.

Contraindicated in children under 18 years of age (efficacy and safety have not been studied).

Elderly patients

It is recommended to use the drug in normal doses, no changes in the dose of amlodipine are required.

Patients with impaired liver function

Despite the fact that the T_1/2 of amlodipine, like all BMCC, is increased 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

It is recommended to use amlodipine in normal doses.

Cardiovascular diseases

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

In acute myocardial infarction, the use of amlodipine is possible only after stabilization of hemodynamic parameters.

In rare cases, patients with coronary artery disease (especially those with severe obstructive coronary artery disease) have experienced an increase in the frequency, duration, and/or severity of angina attacks after starting BMCC or after increasing their dosage.

Although BMCC should generally be used with caution in patients with CHF, amlodipine has not been shown to increase mortality or cardiovascular events in patients with CHF in short – and long-term clinical trials. In patients with non-ischemic CHF (NYHA functional class III and IV), there was an increase in the incidence of pulmonary edema, despite the absence of signs of heart failure progression, when amlodipine was used.

Aortic stenosis, mitral stenosis, HOCMP

As with all vasodilating drugs, amlodipine should be used with caution in patients with aortic stenosis, mitral stenosis, or HOCMP. In patients with obstruction of the left ventricular outflow tract (for example, with severe aortic stenosis), the use of the drug is contraindicated.

Withdrawal syndrome

Despite the absence of “withdrawal” syndrome in BMCC, it is advisable to stop treatment with amlodipine by gradually reducing the dose of the drug. Amlodipine does not prevent the development of “withdrawal” syndrome when abruptly stopping taking beta-blockers.

Peripheral edema

Mild to moderate peripheral edema was the most common adverse event reported with amlodipine in clinical trials. The frequency of peripheral edema increases with increasing dose (when using amlodipine at a dose of 2.5 mg,5 mg and 10 mg per day, edema occurred in 1.8%,3% and 10.8% of patients, respectively). Peripheral edema associated with the use of amlodipine should be carefully differentiated from symptoms of progressive left ventricular heart failure.

Impaired liver function

No controlled studies have been conducted in patients with hepatic impairment. In a small number of patients with mild to moderate hepatic insufficiency, an increase in T_1/2 of amlodipine was noted. Patients with hepatic insufficiency should be monitored by a doctor if necessary for the use of amlodipine. In some cases (for example, in moderate hepatic insufficiency), a lower initial dose of amlodipine (2.5 mg per day) is recommended.

Elderly patients

In elderly patients, T_{1/2 may increase} and clearance of amlodipine may decrease. In clinical trials, the incidence of adverse events in patients aged >> 65 years was approximately 6% higher than in younger patients. There is no need to change the dose of amlodipine, but more careful monitoring of patients in this category is necessary.

Other things

During therapy with amlodipine, it is necessary to monitor body weight and consumption of table salt, and the appointment of an appropriate diet is indicated.

It is necessary to maintain dental hygiene and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

There have been no reports of the effect of Amlodipine – KRKA on driving or working with mechanisms. However, some patients may experience drowsiness and dizziness, especially at the beginning of treatment. If they occur, the patient should be careful when driving a car and working with complex mechanisms.

Form of production

Tablets 5 mg,10 mg.

During production at JSC “KRKA, D. D., Novo Mesto”, Slovenia:

10 tablets in a blister made of a combined material OPA / Al / PVC-aluminum foil.

3 or 9 blisters together with the instructions for use are placed in a cardboard pack.

During production at KRKA-RUS LLC, Russia:

10 tablets in a contour cell package made of combined OPA/Al/PVC material and aluminum foil.

3 or 9 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Storage conditions

Store at a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 4 years.

Do not use the drug after the expiration date.

Active ingredient

Amlodipine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets