Norvasc - instructions for use, dose, side effects, contraindications

Active substance: Amlodipine - 5 mg (in the form of amlodipine besylate - 6,944 mg). Excipients: cellulose microcrystalline - 124,056 mg, calcium hydrophosphate - 63 mg, sodium carboxymethyl starch - 4 mg, magnesium stearate - 2 mg.

1 tablet with a dosage of 10 mg contains:

Active substance: Amlodipine - 10 mg (in the form of amlodipine besylate - 13.889 mg). Excipients: cellulose microcrystalline -248,111 mg, calcium hydrophosphate - 126 mg, sodium carboxymethyl starch - 8 mg, magnesium stearate - 4 mg.

Description:Tablets 5 mg - white or almost white tablets in the form of an emerald (octahedron with uneven sides) with an engraving Pfizer on one side and AML-5 another.
Tablets 10 mg - white or almost white tablets in the form of an emerald (octahedron with uneven sides) with an engraving Pfizer on one side and AML-10 on the other.

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

The dihydropyridine derivative blocking the "slow" calcium channels (BCCC) has an antihypertensive effect. It blocks "slow" calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels, rather than in cardiomyocytes). Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles:

- with stenocardia reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance, reduces afterload on the heart, reduces the need for myocardium in oxygen;

- expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including caused by smoking).

Have patients stable angina, a single daily dose increases exercise tolerance, slows the development of angina attacks and the "ischemic" depression of the segment ST, reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing").

Orthostatic hypotension with amlodipine is rare. Amlodipine does not cause a decrease in exercise tolerance, or a fraction of the left ventricular ejection. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used when therapy 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 one vessel and up to stenosis of 3 or more arteries, carotid atherosclerosis), 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 of carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, aorto-coronary shunting; 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.

Does not increase the death rate or the development of complications and deaths in patients with CHF (III-IV functional class by classification NYHA) on the background of therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In patients with CHF (III-IV functional class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

Pharmacokinetics:

Near the reception inside amlodipine well absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-80%, the maximum concentration in serum is determined after 6-12 hours. Equilibrium concentrations are reached near 7-8 days of therapy.

Simultaneous food intake does not affect the absorption of amlodipine. The average volume of distribution is 21 l / kg body weight, indicating that most of the drug is in the tissues, and the smaller - in the blood. Most of the drug in the blood (97.5%) binds to blood plasma proteins. Amlodipine is subjected to a slow but active metabolism in the liver in the absence of a significant "primary passage" effect through the liver. Metabolites do not have significant pharmacological activity.

After a single admission, the elimination half-life (T1/2) varies from 35 to 50 hours with a reappointment T1/2 is approximately 45 hours. About 60% of the ingested 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).

Application in elderly patients

In elderly patients (over 65 years of age) the excretion of amlodipine is slowed down (T1/2 - 65 h) compared with young patients, but this difference has no clinical significance.

Use in patients with hepatic impairment

Elongation T1/2 y patients with hepatic insufficiency suggests that with prolonged use, cumulation of the drug in the body will be higher (T1/2 - up to 60 hours). Use in patients with renal insufficiency

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

Indications:

- Arterial hypertension (as in monotherapy, hack and in combination with other antihypertensive drugs).

- Stable angina and vasospastic angina (Prinzmetal angina or variant angina) both in monotherapy and in combination with other antianginal agents.

Contraindications:

- Hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as the auxiliary substances that make up the drug.

- Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).

- Obstruction of the outflow tract of the left ventricle (including, severe aortic stenosis).

- Shock (including cardiogenic)

- Hemodynamically unstable heart failure after myocardial infarction.

- Age to 18 years (effectiveness and safety not established).

Carefully:

With CAUTION apply in patients with hepatic insufficiency, CHF of non-ischemic etiology III-IV functional class by classification NYHA, unstable angina, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), weakness syndrome of the sinus node (pronounced tachycardia, bradycardia), arterial hypotension, when used simultaneously with inhibitors or inducers of isoenzyme CYP3A4.

Pregnancy and lactation:

The safety of the use of Norvasc® during pregnancy is not established, so use during pregnancy is only possible if the benefit to the mother exceeds the risk for the fetus and the newborn.

Data showing the isolation of amlodipine in breast milk are not available. However, it is known that other BCCC - dihydropyridine derivatives are secreted into breast milk. Therefore, if you need to use Norvasc® during lactation, you should decide whether to stop breastfeeding.

There was no evidence of the effect of amlodipine on fertility in rats.

Dosing and Administration:

Inside, once a day, washing down with the necessary amount of water (100 ml).

With arterial hypertension, angina usually the initial dose is 5 mg, depending on the therapeutic response, it can be increased to a maximum daily dose of 10 mg.

Application in elderly patients

Norvasc® is recommended for use in an average therapeutic dose, no dose adjustment is required.

Use in patients with impaired liver function

Although T1 / 2 Norvasca®, like all BCCCs, is increasing in patients with violations of liver function, dose adjustment is usually not required (see section "Special instructions").

Use in patients with impaired renal function

It is recommended to apply Norvasc® in usual doses, however, it is necessary to take into account the possible slight increase T1 / 2.

Hc dose adjustment is required when used simultaneously with thiazide diuretics, beta-blockers and angiotensin-converting enzyme inhibitors.

Side effects:

The incidence of adverse reactions described below was determined respectively the following (World Health Organization classification):

very often - more than 1/10

often from more than 1/100 to less than 1/10
infrequently - from more than 1/1000 to less than 1/100,
rarely from more than 1/10000 to less than 1/1000,
very rarely - from less than 1/10000, including individual messages,
it is not known - it is impossible to estimate the frequency based on the available data.

From the side of the cardiovascular system: often - sensation of palpitations, peripheral edema (ankles and feet), "tides" of blood to the skin of the face; infrequently - excessive decrease in blood pressure; rarely - fainting, shortness of breath, vasculitis, orthostatic hypotension, development or exacerbation of CHF, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

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

From the nervous system: often - headaches, dizziness, fatigue, drowsiness; infrequently - asthenia, general malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, increased excitability, depression, anxiety, ringing in the ears, perversion of taste; rarely - Migraine, increased sweating, apathy, agitation, ataxia, amnesia; unknown extrapyramidal disorders.

From the digestive system: often - nausea, pain in the abdomen; infrequently - vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; rarely - pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity of "hepatic" transaminases, hepatitis.

On the part of the organs of hematopoiesis: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the respiratory system: infrequently - Shortness of breath, rhinitis, nosebleeds; rarely - cough.

From the senses: infrequently - Diplomacy, violation of accommodation, xerophthalmia, conjunctivitis, pain in the eyes, visual impairment;

From the genitourinary system: infrequently - frequent urination, painful urination, nocturia, impaired erectile function; rarely - dysuria, polyuria.

From the skin: rarely - dermatitis; rarely - Alopecia, xeroderma, cold notes, a violation of skin pigmentation.

Metabolic disorders: very rare - hyperglycemia; infrequently - increase / decrease in body weight

Allergic reactions: infrequently - skin itching, rash (including erythematous, maculopapular rash, hives), rarely - angioedema, erythema multiforme.

Laboratory indicators: very rarely hyperglycemia.

Other: infrequently - chills, gynecomastia, pain of unspecified localization; rarely - parosmia.

Overdose:

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

Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose),maintaining the function of the cardiovascular system, the exalted position of the lower extremities, monitoring indicators of the heart and lungs, monitoring blood volume (CBV), and urine output. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

Interaction:

Amlodipine can safely be used to treat arterial hypertension along with thiazide diuretics, alpha-adrenoblockers, beta-blockers, or ACE inhibitors. In patients with stable angina pectoris amlodipine can be combined with other antianginal agents, for example, with long-acting or short-acting nitrates, beta-blockers.

In contrast to other BCCC, the clinically significant interaction of amlodipine (III generation BCCI) was not detected when combined with non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin.

It is possible to enhance the anti-anginal and antihypertensive effect of BCCC when combined withthiazide and loop diuretics, ACE inhibitors, beta-adrenoblockers and nitrates, as well as strengthening their hypotensive effect when combined with alpha1-adrenoblockers, neuroleptics.

Although no negative inotropic effects were usually observed in the study of amlodipine, nevertheless, some BCCCs can increase the severity of the negative inotropic effect of antiarrhythmic agents that cause lengthening of the interval QT (eg, amiodarone and quinidine).

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

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

Repeated 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.

Simvastatin: simultaneous repeated use of amlodipine in a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in the exposure of simvastatin by 77%. In such cases, the dosage of simvastatin should be limited to 20 mg.

Ethanol (drinks containing alcohol): amlodipine with a single and repeated application in a dose of 10 mg ns affects the pharmacokinetics of ethanol.

Antiviral drugs (ritonavir): increases plasma concentrations of BCCI, including amlodipine.

Neuroleptics and isoflurane: strengthening of hypotensive action of derivatives dihydropyridine.

Calcium preparations can reduce the effect of BCCI.

In the joint application of BCCI with lithium preparations (for amlodipine, data are not available), possibly increasing the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Studies of simultaneous use of amlodipine and cyclosporine in healthy volunteers and all patient groups, except for 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 not lead to any effect, or increase the minimum concentration of cyclosporin to varying degrees to 40%. These data should be taken into account and the concentration of cyclosporine in this group of patientsuse of cyclosporine and amlodipine. Not has an effect on serum concentration digoxin and its renal clearance.

Has no significant effect on the action warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

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

Grapefruit juice: simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine inwards is not accompanied by a significant change in the pharmacokinetics of amlodipine. Nevertheless, it is not recommended to use grapefruit juice and amlodipine simultaneously, as in the genetic polymorphism of the isoenzyme CYP3A4 may increase the bioavailability of amlodipine and, as a result, this, increased hypotensive effect.

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

Inhibitor inhibitors CYP3A4: with the simultaneous use of diltiazem in a dose of 180 mg and amlodipine in a dose of 5 mg in patients from 69 to 87 years with hypertension, there is an increase in system exposure of amlodipine by 57%.The simultaneous use of amlodipine and erythromycin in healthy volunteers (18 to 43 years) does not lead to significant changes in the exposure of amlodipine (an increase in the area under the concentration-time curve, (AUC) on 22%). Despite the fact that the clinical significance of these effects is not completely clear, they can be more pronounced in elderly patients.

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

Clarithromycin: isoenzyme inhibitor CYP3A4. In patients taking both clarithromycin and amlodipine, increased risk of lowering blood pressure. Patients who take this combination are recommended to be under close medical supervision.

Inductors of isoenzyme CYP3A4: data on the effect of inducers of isoenzyme CYP3A4 there is no pharmacokinetics of amlodipine. You should carefully monitor blood pressure while using amlodipine and isoenzyme inducers CYP3A4.

Tacrolimus: with simultaneous use with amlodipine there is a risk of increasing tacrolimus concentration in the blood plasma. In order to avoid toxicity tacrolimus with simultaneous application with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus should be adjusted if necessary.

Special instructions:

It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

In elderly patients may increase T1/2 and decrease the clearance of the drug. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

The effectiveness and safety of Norvasc® in hypertensive crisis is not established.

Despite the absence of the "cancellation" syndrome in BCCC, it is desirable to stop the treatment with Norvasc®, gradually reducing the dose of the drug.

Against the backdrop of Norvask® in patients with chronic heart failure, class III and IV of the functional class according to the classification NYHA non-ischemic origin, there was an increased incidence of pulmonary edema,despite the absence of signs of worsening heart failure.

Effect on the ability to drive transp. cf. and fur:

Although there was no adverse effect on the ability to drive vehicles or other complex mechanisms against the background of Norvasc®, however, due to possible excessive BP reduction, dizziness, drowsiness, and other adverse reactions, care should be taken in these situations, especially at the beginning treatment and with increasing doses.

Form release / dosage:Tablets, 5 and 10 mg.

Packaging:

By 10 or 14 tablets in a PVC / aluminum foil blister.

3, 4 or 9 blisters for 10 tablets, or 1 blister for 14 tablets with instructions for use in a cardboard bundle, on the front side of which, for the purpose of controlling the first opening, a perforated stitch is applied.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

4 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N 015567/01

Date of registration:13.05.2009

The owner of the registration certificate:Pfizer GmbHPfizer GmbH Germany

Manufacturer: & nbsp

R-Pharm Germany, GmbH Germany

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp18.12.2015

Illustrated instructions

Instructions

Norvasc® (Norvasc®)