Expiration date: 04/2025

Form and composition:

Tablets white, round, flat-cylindrical shape with a chamfer.

1 tablet contains:

amlodipine (in the form of besylate) 2.5, 5 or 10 mg

Excipients: lactose, potato starch, povidone, crosspovidone, microcrystalline cellulose, calcium stearate, talc.

10 PCs. - packaging sells contoured (3) - packs cardboard.

Pharmacological action:

Blocker of slow calcium channels of the II generation, a derivative of dihydropyridine. It has antianginal and antihypertensive effect. Communicating with digidropiridinovmi receptors, does calzieve channels, lowers transmembranny transition of calcium ions into the cell (more in gladkomyshechne cells receptacles, than cardiomiotita).

Antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: with angina reduces the severity of myocardial ischemia expanding peripheral arterioles, reduces OPSS, reduces postnagruzku heart, reduces myocardial oxygen demand. Expanding the main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina) prevents the development of coronary artery constriction (incl.Smoking). In patients with angina pectoris, a single daily dose increases the time of physical activity, slows the development of angina and ischemic depression of the ST segment, reduces the frequency of angina attacks and nitroglycerin consumption.

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

In hypertension, a single dose provides a clinically significant decrease in blood PRESSURE for 24 hours (in the patient's lying and standing). Does not cause the sharp decline in AD, reduced tolerance to physical exertion, ejection fraction of the left ventricle.

Reduces the degree of myocardial hypertrophy of the left ventricle, exerts anti-atherosclerotic and cardioprotective action in coronary heart disease. It does not affect the contractility and conductivity of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy does not increase the severity of microalbuminuria. It has no adverse effects on metabolism and blood plasma lipids.

The time of the effect-2-4 hours, the duration of the effect 24 hours. 

Pharmacokinetics:

Suction

After oral amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-90%. Cmax in blood plasma is observed after 6-9 h. Css is achieved after 7 days of therapy. Food does not affect the absorption of amlodipine.

Distribution

The average Vd is 21 l / kg, which indicates that most of the drug is in the tissues, and relatively less - in the blood. Binding to plasma proteins-95%.

The drug penetrates the BBB. Stands out with breast milk.

Metabolism

Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, undergoes the effect of the first passage through the liver. Metabolites have no clinically significant pharmacological activity.

Breeding

After a single oral administration T1/2 varies from 31 to 48 h, with the re - appointment of T1 / 2 is approximately 45 h.About 60% of the dose taken orally is excreted in the urine mainly in the form of metabolites, 10% - unchanged, 20-25% - with feces. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h / kg).

Pharmacokinetics in special clinical cases

In elderly patients (over 65 years), the excretion of amlodipine is slowed (T1/2 - 65 h) compared with young patients, but this difference has no clinical significance. In patients with hepatic insufficiency, lengthening T1/2 is assumed, and with long - term administration of the drug in the body will be higher (T1/2-up to 60 h).

Renal failure does not have a significant effect on the pharmacokinetics of amlodipine.

When hemodialysis is not removed.

Indications:

• arterial hypertension (as monotherapy or in combination with other antihypertensive agents: diuretics, beta-blockers, ACE inhibitors)
  
• stable angina, vasospastic angina (Prinzmetal's angina) (as monotherapy or in combination with other antianginal drugs).
  

Dosage regimen:

The drug is prescribed inside.

In the treatment of hypertension and angina pectoris initial is 5 mg 1 time / day. If necessary, the dose can be increased to a maximum of 10 mg 1 time/day. In hypertension, the maintenance dose may be 5 mg / day.

When vasospastic angina (strokes Prinzmetala) - 5-10 mg /day 1 reception.

No dose changes are required while administration with thiazide diuretics, beta-blockers and ACE inhibitors.

No dose changes are required in patients with renal insufficiency.

In patients with hepatic insufficiency, elderly patients, the initial dose for hypertension may be 2.5 mg.

Side effect:

From the cardiovascular system: heartbeat, shortness of breath, marked decrease in blood PRESSURE, fainting, vasculitis, swelling (swelling of the ankles and feet), blood flow to the face rarely - rhythm disorders (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension in some cases - the development or worsening of heart failure, extrasystole, migraine.

From the Central and peripheral nervous system: headache, dizziness, fatigue, drowsiness, mood changes, convulsions rarely - loss of consciousness, hypesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams in some cases - ataxia, apathy, agitation, amnesia.

From the digestive system: nausea, vomiting, epigastric pain, rarely - increase in liver transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, hyperplasia of the gums, constipation or diarrhea in some cases - gastritis, increased appetite.

On the part of the urinary system: rarely-pollakiuria, painful urge to urinate, nicturia in some cases-dysuria, polyuria.

From the sexual system: rarely-violation of sexual function (including decreased potency), gynecomastia.

Dermatological reactions: in some cases - xeroderma, alopecia, dermatitis, purpura, skin color change.

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

From the side of musculoskeletal system: rare - artralgia, osteoarthritis, myalgia (with long-term use) in some cases, myasthenia gravis.

From the metabolic: rare - poliuretane, increase/decrease in body weight, hyperglycemia, increased sweating, thirst, in some cases, a cold clammy sweat.

From the hematopoietic system: rarely-thrombocytopenia, leukopenia.

From the sensory organs: rare - impaired vision, diplopia, conjunctivitis, eye pain, ringing in the ears, parosmia, a violation of taste sensations, violation ccomodation, xerophthalmia.

From the respiratory system: rarely-dyspnea, nose bleeding, cough, rhinitis.

Other: rarely - pain in the back.

Contraindications:

• severe arterial hypotension
  
• collapse
  
• cardiogenic shock
  
• unstable angina (except prinzmetals angina)
  
• pregnancy
  
• lactation
  
• age up to 18 years (efficacy and safety not established)
  
• increased sensitivity to amlodipine and other dihydropyridine derivatives.
  

With caution should use the drug in violation of the liver, SSSU (expressed aetiology, tachycardia), chronic heart failure being decompensation, if mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and during the 1 month after), diabetes, abnormalities of lipid profile in patients of advanced age.

Pregnancy and lactation:

The drug is contraindicated in pregnancy and lactation (breastfeeding).

Special instruction:

During the treatment it is necessary to control the body weight, sodium intake, it is necessary to appoint an appropriate diet.

It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent pain, bleeding and hyperplasia of the gums).

The dosage regimen for elderly patients is the same as for patients of other age groups.

When increasing the dose should be carefully monitored for elderly patients.

Despite the absence of slow calcium channel blocker withdrawal syndrome, before discontinuation of treatment is recommended gradual reduction of doses.

Amlodipine does not affect plasma concentrations of potassium, glucose, TG, total cholesterol, LDL, uric acid, creatinine and urea nitrogen.

Impact on the ability to drive and operate machinery

There are no reports on the impact of amlodipine on the ability to drive or work with mechanisms. However, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. When they occur, the patient should take special precautions in potentially hazardous activities.

Overdose:

Symptoms: marked decrease in blood PRESSURE, tachycardia, excessive peripheral vasodilation.

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, control of heart and lung function, elevated position of the limbs, control of BCC, diuresis. To restore vascular tone-the use of vasoconstrictive drugs (in the absence of contraindications to their use) to eliminate the effects of the blockade of calcium channels – in/in the introduction of calcium gluconate. Hemodialysis is ineffective.

Drug interaction:

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

Decrease the hypotensive effect of amlodipine cause NSAIDs, especially indometacin (delay sodium and blockade of the synthesis of prostaglandins by the kidneys), alpha-agonists, estrogens (delay sodium), simpatomimetiki.

Thiazide and loop diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates enhance antianginal and hypotensive effects.

Amiodarone, quinidine, alfa1-adrenoblokatory, antipsychotic drugs (neuroleptics) and slow calcium channel blockers can enhance the hypotensive effect of amlodipine.

It has no effect on the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

When combined with drugs lithium may increase the manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations can reduce the effect of slow calcium channel blockers.

Procainamide, quinidine, and other drugs that cause QT interval prolongation increase the negative inotropic effect and may increase the risk of a significant QT interval prolongation.

Grapefruit juice can reduce the concentration of amlodipine in the blood plasma, but this reduction is so small that it does not significantly change the effect of amlodipine.

Storage conditions and terms:

List B. the Drug should be stored out of reach of children, dry, protected from light at a temperature not exceeding 25°C. shelf life - 2 years.