Expiration date: 02/2025

Composition and form of issue:

Tablets, 1 tablet contains:

amlodipine besilate 6.935 or 13.870 mg (equivalent to 5 and 10 mg amlodipine, respectively) 

auxiliary substances: microcrystalline cellulose calcium hydrogen phosphate anhydrous sodium starch glycolate type a magnesium stearate 

in packing contour cell 10 PCs in a carton 3 carton packing or packing contour cell 14 PCs. in cardboard box 1 packaging.

Description of dosage form:

Tablets 5 mg — white or almost white, in the form of emerald (octahedron with uneven sides) with the logo "Pfizer" on one side and "AML-5" — on the other.

Tablets 10 mg-white or almost white tablets in the form of emerald (octahedron with uneven sides) with the logo "Pfizer" on one side and "AML-10" — on the other.

Characteristic:

Amlodipine is a dihydropyridine derivative.

Pharmacokinetics:

Suction. After ingestion in therapeutic doses amlodipine is well absorbed, reaching Cmax in the blood through 6-12 no. Absolute bioavailability leaves 64-80%. Vd is approximately 21 l / kg plasma protein Binding is approximately 97, 5%. Eating does not affect the absorption of amlodipine, penetrates through the BBB.

Biotransformation / excretion. T1 / 2 of the plasma is about 35-50 hours, which corresponds to the appointment of the drug once a day. In patients with hepatic insufficiency and severe chronic heart failure T1/2 increased to 56-60 no. total clearance-0, 43 l / h / kg. 

Stable CSS in plasma is achieved through 7-8 days of constant intake of amlodipine, it is metabolized in the liver to form inactive metabolites 10% of the original drug and 60% of metabolites excreted in the urine. Excretion of breast milk is unknown. During hemodialysis is not removed.

Use in patients with renal insufficiency. T1/2 from blood plasma in patients with renal insufficiency is increased to 60 h. the Change in the concentration of amlodipine in plasma does not correlate with the degree of renal dysfunction.

Application in the elderly. In elderly Tmax and Mahalaadimine do not differ from those in younger people. In elderly people suffering from chronic heart failure, there is a tendency to reduce the clearance of amlodipine, which leads to an increase in AUC and T1/2 to 65 hours.

Description of pharmacological action:

When binding to dihydropyridine receptors, blocks calcium channels, inhibits transmembrane transition of calcium inside the smooth muscle cells of blood vessels and cardiomyocytes (to a greater extent — in smooth muscle cells of blood vessels than in cardiomyocytes). It has a hypotensive and antianginal effect.

The mechanism of the hypotensive action of amlodipine is due to the direct relaxing effect on the smooth muscles of the vessels.

Amlodipine reduces myocardial ischemia in the following two ways:

1. Dilates peripheral arterioles and thus reduces peripheral vascular resistance (afterload), while heart rate remains practically unchanged, which leads to lower energy consumption and need of myocardium in oxygen.

2. Dilates coronary and peripheral arteries and arterioles in both normal and ischemic areas of the myocardium, which increases the flow of oxygen to the myocardium in patients with vasospastic angina (princmetal angina) and prevents the development of coronary spasm caused by Smoking.

In patients with hypertension, a single daily dose of Norvasca provides a decrease in blood PRESSURE for 24 hours (both in the supine and standing). Due to the slow onset of action, amlodipine does not cause a sharp decrease in blood PRESSURE.

In patients with angina pectoris, a single daily dose of the drug increases the time of exercise, delays the development of another attack of angina and depression of the ST segment (by 1 mm) against the background of physical activity, reduces the frequency of angina attacks and the need for nitroglycerin.

The use in patients with coronary artery disease

In patients with cardiovascular diseases (including coronary atherosclerosis with the defeat of one vessel and to the stenosis of 3 or more arteries and atherosclerosis of the carotid arteries), who underwent myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (TLP) or suffering from angina, the use of Norvask prevents the development of thickening of intima-media of the carotid, significantly reduces mortality from cardiovascular causes, heart attack myocardium, stroke, TLP, coronary artery bypass grafting, leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow.

Use in patients with heart failure. Norvasc not increase the risk of death or development of complications and lethal outcomes in patients with chronic heart failure III–IV functional class (NYHA) during therapy with digoxin, diuretics and ACE inhibitors. In patients with chronic heart failure III–IV functional class NYHA nonischemic etiology in the application Norvasca there is the likelihood of pulmonary edema.

Norvask does not have any adverse effect on metabolism and plasma lipid concentration.

Indications:

• arterial hypertension (both in monotherapy and in combination with other antihypertensive agents)
  
• stable angina and vasospastic angina (Prinzmetal's angina) (as a monotherapy and in combination with other antianginal drugs).
  

Contraindications:

• increased sensitivity to amlodipine and other derivatives of dihydropyridine, as well as auxiliary substances included in the drug
  
• severe hypotension.
  

With caution:

• liver failure
  
• chronic heart failure of class III–IV non-ischemic etiology
  
• aortic stenosis
  
• acute myocardial infarction (and period within 1 month after it)
  
• age up to 18 years (efficacy and safety are not exactly established).
  

As with the appointment of other BCC, caution should be exercised against the background of taking amlodipine in patients with sinus node weakness syndrome, mitral stenosis, hypertrophic obstructive cardiomyopathy, hypotension.

Use during pregnancy and breast-feeding:

The safety of Norvasca during pregnancy and lactation is not established, so the use during pregnancy is possible only when the benefit to the mother exceeds the risk to the fetus and newborn.

For the period of breastfeeding it is recommended to stop either taking the drug or breastfeeding (data on the elimination of amlodipine with breast milk are not available).

Side effect:

Further, the frequency of adverse reactions is understood as: frequent (>1%), infrequent (<1%), rare (<0, 1%), very rare (<0, 01%).

Cardiovascular system: peripheral edema (ankles and feet), palpitations, rare — excessive lowering AD, ortostatical gipotenzia, vasculitis, rarely — the development or worsening of heart failure very rarely — violations heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, migraine.

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

From the Central and peripheral nervous system: a feeling of heat and blood tides to the skin, fatigue, dizziness, headache, drowsiness, infrequent-malaise, fainting, sweating, asthenia, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, lability of mood, unusual dreams, nervousness, depression, anxiety rarely-convulsions, apathy, agitation very rarely — ataxia, amnesia.

Digestive tract: abdominal pain, nausea, infrequent vomiting, changes in defecation (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry mouth, thirst, rarely — hyperplasia of the gums, increased appetite, very rarely — gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis.

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

Metabolic disorders: very rare — hyperglycemia.

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

From the urogenital system: rarely — urinary frequency, painful urination, nocturia, impotence, gynecomastia rarely — dysuria, polyuria.

Allergic reactions: rare — skin itching, rash, very rarely — angioneurotic edema, erthema multiforme, urticaria.

Other: rarely — alopecia, tinnitus, increase/decrease in body weight, blurred vision, diplopia, violation ccomodation, xerophthalmia, conjunctivitis, eye pain, taste perversion, chills, nasal bleeding rarely — dermatitis rarely — parosmia, xeroderma, cold sweat, disturbance of skin pigmentation.

Drug interaction:

It can be expected that inhibitors of microsomal oxidation will increase the concentration of amlodipine in the plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes — reduce.

Cimetidine. With the simultaneous use of amlodipine with cimetidine, the pharmacokinetics of amlodipine does not change.

Grapefruit juice. 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.

Unlike other BCC, clinically significant drug-norvask interaction (BCC III generation) was not detected in the joint application with NSAIDs, especially indomethacin.

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

Although the study of the drug norvask negative inotropic effect is not usually observed, however, some BCC may increase the severity of the negative inotropic action of antiarrhythmic drugs that cause prolongation of THE Qt interval (eg amiodarone and quinidine).

Lithium preparations. When combined with the use of BCC lithium drugs (for Norvaska data are not available) may increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not affect the degree of in vitro binding to plasma proteins digoxin, phenytoin, warfarin and indomethacin.

Aluminum - / magnesium-containing antacids. Single administration of these drugs does not have a significant effect on the pharmacokinetics of amlodipine.

Sildenafil (Viagra). A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the parameters of the pharmacokinetics of amlodipine.

Atorvastatin. 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.

Digoxin. With the simultaneous use of amlodipine with digoxin in healthy volunteers serum levels and renal clearance of digoxin do not change.

Ethanol (alcoholic beverages). In a single and repeated use at a dose of 10 mg amlodipine does not have a significant effect on the pharmacokinetics of ethanol.

Warfarin. Amlodipine does not affect the change in PV caused by warfarin.

Cyclosporine. Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Dosage and administration:

Inside, 1 time per day, drinking the required amount of water (100 ml).

With hypertension and angina, the usual initial dose is 5 mg, depending on the individual patient's reaction, it can be increased to a maximum of 10 mg.

Application in the elderly. It is recommended to use in normal doses, changing the dose is not required.

Use in patients with impaired liver function. Although T1 / 2 Norvaska, like all BCC, increases in patients with this pathology, any changes in the dosage of the drug is usually not required (see "Special instructions").

Use in renal failure. It is recommended to use in normal doses, but it is necessary to take into account a possible slight increase in T1 / 2.

Changing Norvask dosing regimen with simultaneous use of thiazide diuretics, beta-blockers or ACE inhibitors is not required.

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 arterial hypotension, including the development of shock and death).

Treatment: the appointment of activated charcoal (especially in the first 2 hours after an overdose), gastric lavage (in some cases), giving an elevated position to the lower extremities, active maintenance of the CCC function, monitoring of the heart and lungs, control of BCC and diuresis.

To restore vascular tone and blood PRESSURE, if there are no contraindications, it may be useful to use vasoconstrictive drugs. Use/in the introduction of calcium gluconate. Because amlodipine is largely bound to serum proteins, hemodialysis is ineffective..

Special instruction:

In the treatment of hypertension norvasc can be used in combination with thiazide diuretics, alpha - and beta-blockers, ACE inhibitors, nitrates of prolonged action, sublingual nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic agents.

For the treatment of angina norvask can be prescribed as a monotherapy or in combination with other antianginal agents, including patients refractory to treatment with nitrates and/or beta-blockers in adequate doses.

Norvask does not have any adverse effect on the metabolism and plasma lipids and can be used in the treatment of patients with asthma, diabetes and gout.

Norvask can be applied in cases where the patient is predisposed to vasospasm/vasoconstriction.

Patients with low body weight, patients of low growth and patients with severe liver dysfunction may require a smaller dosage.

During treatment, it is necessary to control body weight and supervision at the dentist (to prevent pain, bleeding and hyperplasia of the gums).

Influence on the ability to drive and use technology. Although there was no negative effect on the ability to drive a car or other technical means against the background of Norvask, however, due to a possible excessive decrease in blood pressure, the development of dizziness, drowsiness, etc.side effects should be carefully treated to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.