Norvasc

Active material: Amlodipine
When ATH: C08CA01
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1
When CSF: 01.03.02
Manufacturer: PFIZER GmbH (Germany)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills white or nearly white, in the form of emeralds (octahedron with uneven sides), with logo “Pfizer” on one side and “AML-5” – another.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, anhydrous, sodium starch glycolate type A, magnesium stearate.

10 PC. – packings Valium planimetric (3) – packs cardboard.
14 PC. – packings Valium planimetric (1) – packs cardboard.

Pills white or nearly white, in the form of emeralds (octahedron with uneven sides), with logo “Pfizer” on one side and “AML-10” – another.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, anhydrous, sodium starch glycolate type A, magnesium stearate.

10 PC. – packings Valium planimetric (3) – packs cardboard.
14 PC. – packings Valium planimetric (1) – packs cardboard.

* international non-proprietary name, recommended by the WHO – amlodipine besylate.

Pharmacological action

Calcium channel blocker slow, dihydropyridine derivative. Svyazыvayas with dyhydropyrydynovыmy receptors, blocks the slow calcium channels, It inhibits the transmembrane passage of calcium into the smooth muscle cells of the heart and blood vessels (more – in vascular smooth muscle cells, than cardiomyocytes).

It has antihypertensive and antianginal effect.

The mechanism of the antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle.

Amlodipine reduces myocardial ischemia in two ways: expanding peripheral arterioles and thus reduces the peripheral vascular resistance (afterload), while the heart rate remains practically unchanged, which leads to lower energy consumption and myocardial oxygen demand; and dilates coronary and peripheral arteries and arterioles in normal, and in ischemic areas of the myocardium, which increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal angina) and prevents the development of coronary spasm, caused by smoking.

In patients with hypertension single daily dose of Norvasc^® reduces blood pressure over 24 h in the supine position, and standing. Due to the slow onset of action of amlodipine does not cause a sharp decline in blood pressure.

In patients with angina and single daily dose of amlodipine increases the run-time physical activity, retards the development of the next attack of angina and ST-segment depression (on 1 mm) during its execution, It reduces the frequency of angina attacks and consumption of nitroglycerin tablets.

In patients with cardiovascular disease (including coronary atherosclerosis with the defeat of the vessel and to the stenosis 3 or more arteries and carotid atherosclerosis), myocardial infarction, percutaneous transluminal coronary angioplasty (TLP) or angina pectoris, use Norvasc^® prevents thickening of the intima-media carotid arteries, significantly reduces the mortality from cardiovascular causes, myocardial infarction, stroke, TLP, coronary artery bypass grafting, It reduces the number of hospitalizations for unstable angina and progression of chronic heart failure, reduces the frequency of interventions, aimed at restoring coronary blood flow.

Norvasc^® It does not increase the risk of death or complications, leading to the deaths in patients with chronic heart failure (III-IV functional class NYHA classification) during therapy with digoxin, diuretics and ACE inhibitors.

Patients with chronic heart failure (III-IV functional class NYHA classification) non-ischemic etiology when using Norvasc^® There is the risk of pulmonary edema.

Norvasc^® It does not have any adverse effect on metabolism and lipid concentration of blood plasma.

Pharmacokinetics

Absorption and distribution

After oral administration of therapeutic doses, amlodipine is well absorbed, C_max blood achieved through 6-12 h after administration. The absolute bioavailability of 64-80%. Eating does not affect the absorption of amlodipine.

V_d is about 21 l / kg. Plasma protein binding is approximately 97.5%. Amlodipine penetrate the BBB.

C_ss plasma achieved through 7-8 days of continuous use of the drug.

Metabolism and excretion

Amlodipine biotransformed in the liver with the formation of active metabolites. T_1/2 from plasma is about 35-50 no, which corresponds to the prescribing 1 time / day. Total clearance – 0.43 L / h / kg.

10% unchanged active substance and 60% metabolites excreted in the urine.

Pharmacokinetics in special clinical situations

In patients with liver failure and severe chronic heart failure T_1/2 increases to 56-60 no.

T_1/2 from plasma in patients with renal insufficiency increases to 60 no. Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment.

Older and younger people's time, needed to achieve C_max amlodipine plasma, virtually identical. In elderly people with chronic heart failure showed a trend to decrease the clearance of amlodipine, which leads to an increase in AUC and T_1/2 (to 65 no).

Testimony

- Arterial hypertension (as a monotherapy, or in combination with other antihypertensives);

- Stable angina and angina angiospastic (Prinzmetal angina) (as a monotherapy, or in combination with other antianginal drugs).

Dosage regimen

At hypertension and angina The average initial dose is 5 mg 1 time / day, depending on the individual response of the patient can be increased up to a maximum dose of, component 10 mg.

The tablets are taken orally 1 time / day, drinking the necessary amount of water (to 100 ml).

Changes dosing regimen Norvasc^® while the use of thiazide diuretics, beta-blockers or ACE inhibitors is not required.

In elderly patients the drug is recommended in high therapeutic doses, dose change is not needed.

Despite, that T_1/2 amlodipine, like all calcium channel blockers, increases in patients with impaired liver function, any changes to the dose in these patients is not usually required.

At renal failure recommended Norvasc^® at conventional doses, However, you must consider the possible slight increase in T_1/2.

Side effect

Determination of the frequency of adverse reactions: often (>1%), sometimes (<1%), rarely (<0.1%), rarely (<0.01%).

Cardio-vascular system: often – peripheral edema (ankles and feet), heartbeat; sometimes – excessive reduction of blood pressure, orthostatic hypotension, vasculitis; rarely – development or exacerbation of congestive heart failure; rarely – heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, migraine.

On the part of the musculoskeletal system: sometimes – arthralgia, muscle cramps, myalgia, backache, arthrosis; rarely – myasthenia.

From the central and peripheral nervous system: often – sensation of heat and “tides” of blood to the skin of the face, fatigue, dizziness, headache, drowsiness; sometimes – malaise, fainting, increased perspiration, asthenia, gipestezii, paresthesia, perifericheskaya neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, alarm; rarely – convulsions, apathy, ažitaciâ; rarely – ataxia, amnesia.

From the digestive system: often – abdominal pain, nausea; sometimes – vomiting, constipation, flatulence, dyspepsia, diarrhea, anorexia, dry mouth, thirst; rarely – giperplaziya right, increased appetite; rarely – gastritis, pancreatitis, giperʙiliruʙinemija, jaundice (usually cholestatic), increase in liver transaminases, hepatitis.

From the hematopoietic system: rarely – trombotsitopenicheskaya purpura, leukopenia, thrombocytopenia.

Metabolism: very rarely - hyperglycemia.

The respiratory system: sometimes – breathlessness, rhinitis; very rarely - Cough.

From the urinary system: sometimes – frequent urination, urodynia, nocturia, impotence; rarely – dizurija, polyuria.

Allergic reactions: sometimes – itching, rash; rarely – angioedema, erythema multiforme, hives.

Other: sometimes – alopecia, tinnitus, gynecomastia, increase / decrease in body weight, visual impairment, diplopia, ccomodation, xerophthalmia, conjunctivitis, sore eyes, dysgeusia, chills, nose bleed; rarely – dermatitis; rarely – parosmija, dermatoxerasia, cold sweat, violation of skin pigmentation.

Contraindications

- Severe hypotension;

- Hypersensitivity to the drug;

- Hypersensitivity to other dihydropyridine derivatives.

Pregnancy and lactation

The safety of Norvasc^® Pregnancy and lactation (breast-feeding) not installed, therefore use during pregnancy is possible only in the case, when the benefit to the mother outweighs the risk to the fetus and newborn.

The data on the excretion of amlodipine in breast milk are absent, however lactation (breast-feeding) should stop taking the drug or, or breastfeeding.

Cautions

Precautions should use the drug in patients with impaired hepatic function, chronic heart failure (III-IV functional class NYHA classification) non-ischemic etiology, aortic stenosis, acute myocardial infarction (and for 1 months thereafter).

As for the appointment of other calcium channel blockers, Care must be taken while taking Norvasc^® patients with sick sinus syndrome, mitral stenosis, hypertrophic obstructive cardiomyopathy, hypotension.

In the treatment of hypertension Norvasc^® It can be used in combination with thiazide diuretics, alpha- and beta-blockers, ACE inhibitors, The long-acting nitrates, sublingual nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic agents.

For the treatment of angina Norvasc^® It can be administered alone or in combination with other antianginal drugs incl. patients, refractory to treatment with nitrates and / or beta-blockers in adequate doses.

Norvasc^® It does not have any adverse effect on metabolism and plasma lipids and can be used in the treatment of bronchial asthma, diabetes and gout.

Norvasc^® It can be used in cases, when the patient is predisposed to vascular spasm (vasoconstriction).

Patients with low body weight, patients of small stature and in patients with severe hepatic impairment may require dose reduction.

During treatment requires monitoring of body weight and seeing your dentist (to prevent pain, krovotochivosti and giperplazii right).

Use in Pediatrics

Precautions should be prescribed the drug children and adolescents under the age of 18 years, tk. the efficacy and safety of its use in these patients is not well established.

Effects on ability to drive vehicles and management mechanisms

Although while taking Norvasc^® any negative impact on the ability to drive a car or other technical means were observed, however, due to a possible excessive reduction of blood pressure, of vertigo, drowsiness and other side effects should be attentive to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosing.

Overdose

Symptoms: marked reduction in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (there is a probability of occurrence of severe and persistent hypotension, incl. with the development of shock and mortality).

Treatment: appointment of activated carbon (particularly in the first 2 h after overdose), gastric lavage (in some cases), giving the sublime position of the limbs, actively maintaining the function of the cardiovascular system, monitoring the performance of the heart and lungs, kontroly for OCK and diurezom. To restore vascular tone and blood pressure, If there are no contraindications, possible use of vasopressors. Used in / with the introduction of calcium gluconate. Because amlodipine largely bound to serum proteins – Hemodialysis is not effective.

Drug Interactions

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

With simultaneous use of Norvasc^® The pharmacokinetics of amlodipine with cimetidine does not change.

Unlike other calcium channel blockers significant drug interactions Norvasc^® when combined with the use of NSAIDs, particularly with indomethacin, It was found.

Perhaps greater antianginal and hypotensive action of calcium channel blockers when combined with thiazide and “loop” Diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates; as well as increase their hypotensive effect when combined with alpha₁-adrenoblokatorami, neuroleptics.

Although the study of the drug Norvasc^® negative inotropic effect not normally seen, However, some calcium channel blockers may increase the severity of the negative inotropic effects of antiarrhythmic drugs, causing QT prolongation (eg, amiodarone and quinidine).

In a joint application with lithium calcium channel blockers (for Norvasc^® not available) may gain manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, noise in ears).

Amlodipine has no effect in vitro on the binding of plasma proteins digoxin, phenytoin, warfarin and indomethacin.

A single dose of aluminum / magnesium-containing antacids has no significant effect on the pharmacokinetics of amlodipine.

A single dose of sildenafil at a dose of 100 mg in patients with essential hypertension have not effect on the pharmacokinetic parameters of amlodipine.

Reapply at a dose of amlodipine 10 mg atorvastatin 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

With simultaneous use of amlodipine with digoxin in healthy volunteers serum levels and renal clearance of digoxin are not changed.

In single and repeated administration at a dose of 10 mg of amlodipine had no significant effect on the pharmacokinetics of ethanol.

Amlodipine has no effect on the changes of prothrombin time, caused by warfarin.

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

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

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored at temperatures not exceeding 25 ° C, out of reach of children. Shelf life – 4 year.