Expiration date: 04/2025

Pharmacological action

Blocker of slow calcium channels (bmkk) generation II, a derivative of dihydropyridine. It has antianginal and hypotensive action, 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 narrowing of the coronary arteries (including those caused by Smoking).

When used in patients with stable angina in a daily dose of 1 time / day. increases tolerance to physical activity, increases the time before the attack of angina pectoris and ischemic depression of the ST segment, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long dose-dependent hypotensive effect. Hypotensive effect due to direct vasodilating effect on the smooth muscles of blood vessels. In hypertension, a single dose provides a clinically significant decrease in blood PRESSURE for 24 hours (in the patient's "lying" and "standing"). Orthostatic hypotension in the appointment of amlodipine is quite rare. Does not cause a decrease in the left ventricular ejection fraction. Reduces the degree of left ventricular hypertrophy. It has no effect on myocardial contractility and conductivity, 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 does not have any adverse effect on metabolism and plasma lipid concentrations and can be used in the treatment of patients with asthma, diabetes and gout. A significant decrease in blood PRESSURE is observed after 6-10 h, the duration of the effect is 24 h. 

In patients with diseases of the cardiovascular system (including coronary atherosclerosis with lesions of one vessel and to the stenosis of 3 or more arteries, atherosclerosis of the carotid arteries), who underwent myocardial infarction, percutaneous transluminal angioplasty (TLA) of the coronary arteries or patients with angina, the use of amlodipine prevents the development of thickening of intima-media of the carotid, reduces mortality from myocardial infarction, stroke, TLA, coronary artery bypass grafting, it reduces the frequency of unstable angina attacks and the progression of chronic heart failure (CHF), reduces the frequency of interventions aimed at the restoration of coronary blood flow.

Does not increase the risk of death or complications and death in patients with CHF (functional class III-IV according to NYHA classification) during therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (III-IV functional class NYHA classification) non-ischemic etiology when using amlodipine there is the likelihood of pulmonary edema.

Indications

• hypertension (in monotherapy or in combination with other antihypertensive agents), 
  
• stable tension angina and vasospastic angina (in monotherapy or in combination with other antianginal agents).
  

Contraindications

• severe hypotension (systolic blood PRESSURE less than 90 mm Hg.V.), 
  
• unstable angina (except prinzmetals angina), 
  
• clinically significant aortic stenosis, 
  
• under 18 years of age (efficacy and safety not established).
  
• hypersensitivity to the components Of the drug amlodipine Zentiva, 
  
• hypersensitivity to other dihydropyridine derivatives.
  

With caution, the drug should be used for violations of liver function, SSS (severe bradycardia, tachycardia), CHF of non-ischemic etiology of III-IV functional class according to the classification of NYHA, arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after myocardial infarction), in elderly patients.

Use during pregnancy and breast-feeding

The safety of amlodipine during pregnancy has not been established, so the use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

Amlodipine is excreted in breast milk, so if you need to prescribe the drug amlodipine Zentiva during lactation should stop breastfeeding.

Special instruction

During therapy with the drug Amlodipine Zentiva should monitor body weight and sodium intake.

It is necessary to maintain oral hygiene and supervision at the dentist (to prevent pain, bleeding and hyperplasia of the gums).

In patients of advanced age may increase T1/2 and decrease in clearance of amlodipine. Changes in doses are not required, but more careful monitoring of patients in this category is necessary.

Patients of low growth with low body weight and patients with severe liver dysfunction may require a smaller dose of the drug.

The effectiveness and safety of the drug amlodipine Zentiva in hypertensive crisis has not been established

Despite the absence of the bmcc "withdrawal syndrome", discontinuation of treatment with Amlodipine Zentiva is desirable, gradually reducing the dose of the drug.

Impact on the ability to drive and operate machinery:

Although there was no negative effect on the ability to manage transport or other complex mechanisms against the background of taking the drug Amlodipine Zentiva, due to the possible excessive decrease in blood PRESSURE, the development of dizziness, drowsiness and other adverse reactions, patients should be careful in these situations, especially at the beginning of treatment and with increasing dose.

Composition

1 tablet contains:

 is amlodipine besylate 6, 935 mg, that corresponds to the content of amlodipine 5 mg

Excipients: microcrystalline cellulose-71.356 mg, calcium hydrophosphate dihydrate-37.5 mg, sodium carboxymethyl starch (type A) - 2.4 mg, magnesium stearate-1.8 mg.

1 tablet contains:

- besylate amlodipine 13.87 mg, that corresponds to the content of amlodipine 10 mg

Excipients: microcrystalline cellulose-71.356 mg, calcium hydrophosphate dihydrate-37.5 mg, sodium carboxymethyl starch (type A) - 2.4 mg, magnesium stearate-1.8 mg.

Dosage and administration

Is inside, 1 time / day., drinking the necessary amount of water (100 ml).

In hypertension and angina the initial dose is 5 mg 1 time / day. If necessary, the daily dose can be increased to 10 mg in 1 dose.

In elderly patients, the drug amlodipine Zentiva is recommended for use in the medium therapeutic dose, dose adjustment is not required.

Although T1 / 2 amlodipine, like all bmcc, increases in patients with impaired liver function, dose adjustment is not usually required.

In patients with renal insufficiency, It is recommended to use the drug amlodipine Zentiva in normal doses, but it is necessary to take into account a possible slight increase in T1/2.

No dose adjustment is required while the use of thiazide diuretics, beta-blockers and ACE inhibitors.

Side effect

Determination of the frequency of adverse reactions (according to who): very often ( > , 1/10), often ( > , 1/100 to<, 1/10), infrequently (from>, 1/1000 to 1/10 000 to<, 1/1000), very rarely (from the nervous system: often - headache, dizziness, fatigue, drowsiness, infrequent-asthenia, General malaise, hypesthesia, 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, dry mouth, thirst, rarely - gum hyperplasia, increased appetite, very rarely - pancreatitis, gastritis, jaundice (due to cholestasis), hyperbilirubinemia, jaundice, increased activity of hepatic transaminases, hepatitis.

From the cardiovascular system: often-a feeling of heartbeat, peripheral edema (ankles and feet), "tides" of blood to the skin of the face, infrequently - excessive decrease in blood PRESSURE, very rarely - fainting, shortness of breath, vasculitis, orthostatic hypotension, development or worsening of CHF, heart rhythm disorders (including bradycardia, ventricular tachycardia and atrial flicker), myocardial infarction, chest pain.

On the part of the hemopoietic system: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the urinary system: infrequently-frequent urination, painful urination, nicturia, very rarely - dysuria, polyuria.

Part of the reproductive system: rarely - impotence, gynecomastia

From the respiratory system: infrequently-rhinitis, very rarely - cough.

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

On the part of the skin: rarely-dermatitis, very rarely-alopecia, xeroderma, sweating, cold sweat, skin pigmentation disorders.

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

From the sensory organs: rare - tinnitus, diplopia, violation ccomodation, xerophthalmia, conjunctivitis, eye pain, rarely - parosmia.

Other: rarely - fever, nasal bleeding, very rarely - hyperglycemia.

Drug interaction

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

Unlike other bmcc clinically significant interaction of amlodipine (II generation bmcc) was not detected in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin.

It is possible to increase the antianginal and hypotensive action of bmcc in combination with thiazide and" loop " diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as strengthening their hypotensive action in combination with alfa1-blockers, neuroleptics.

Although in the study of amlodipine negative inotropic action is not usually observed, however, some bmcc may increase the severity of negative inotropic effects of antiarrhythmic agents, causing prolongation of THE Qt interval (eg, amiodarone and quinidine).

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

Long-term use of amlodipine in a dose of 10 mg and atorvastatin in a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Amlodipine at a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiviral agents (ritonavir) increases plasma concentrations of bmcc, including amlodipine.

Calcium supplementation may reduce the effect of bmcc.

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

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

Amlodipine does not change the pharmacokinetics of cyclosporine.

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

Does not have a significant effect on the effect of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In in vitro studies, amlodipine does not affect plasma protein binding of digoxin, phenytoin, warfarin and indomethacin.

Simultaneous single reception of 240 ml of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a significant change in the pharmacokinetics of amlodipine.

In a single dose of aluminum or magnesium-containing antacids do not have a significant effect on the pharmacokinetics of amlodipine.

Overdose

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

Treatment: gastric lavage, taking activated charcoal (especially in the first 2 hours after overdose), maintaining the function of the cardiovascular system, the patient should take a horizontal position with an elevated position of the lower extremities, monitoring the performance of the heart and lungs, BCC and diuresis. To restore vascular tone-the use of vasoconstrictors (in the absence of contraindications to their use), to eliminate the effects of blockade of calcium channels - in/calcium gluconate. Hemodialysis is ineffective.