Norvasc, pills 10mg, 30pcs

Composition

Active ingredient:

amlodipine 10 mg;

Auxiliary substances:

MCC-248,111 mg;

calcium hydrophosphate 126 mg;

sodium carboxymethyl starch-8 mg;

magnesium stearate-4 mg;

Pharmacological action

Norvask – antihypertensive, antianginal.

Pharmacodynamics

A derivative of dihydropyridine-BCC of the third generation, has a hypotensive and antianginal effect. Blocks slow calcium channels, reduces the transmembrane transfer of calcium ions into the cell (to a greater extent — into vascular smooth muscle cells than into cardiomyocytes).

The antianginal effect is caused by dilation of the coronary and peripheral arteries and arterioles:

– with angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for oxygen in the myocardium;

– expanding the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the supply of oxygen to the myocardium (especially in vasospastic angina pectoris); prevents spasm of the coronary arteries (including caused by smoking).

In patients with stable angina, a single daily dose increases exercise tolerance, slows down the development of angina attacks and ST-segment ischemic depression, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to the direct vasodilating effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction Blood pressure for 24 hours (in the patient’s lying and standing position).

Orthostatic hypotension with the use of amlodipine is quite rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect.

In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. Significant reduction Blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

In patients with cardiovascular diseases (including coronary atherosclerosis with damage to one vessel and up to stenosis of 3 or more arteries, carotid artery atherosclerosis), who have had a 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 the carotid arteries, reduces mortality from myocardial infarction, stroke, PTCA, coronary artery bypass grafting; reduces the number of hospitalizations for unstable angina and the progression of CHF; reduces the frequency of interventions aimed at restoring coronary blood flow.

It does not increase the risk of death or development of complications and deaths in patients with CHF (NYHA functional class III–IV) during therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (NYHA functional class III–IV) of non-ischemic etiology, amlodipine is likely to cause pulmonary edema.

Pharmacokinetics

After oral use, amlodipine is well absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-80%, Tmax in blood serum is 6-12 h. Css is achieved after 7-8 days of therapy.

Food intake does not affect the absorption of amlodipine. The average Vd is 21 l / kg, which indicates that most of the drug is in the tissues, and less in the blood. Most of the drug in the blood (97.5%) binds to plasma proteins. Amlodipine undergoes slow but active metabolism in the liver in the absence of a significant first-pass effect. The metabolites do not have significant pharmacological activity.

After a single dose, T1 / 2 varies from 35 to 50 hours, with repeated use, T1 / 2 is approximately 45 hours. About 60% of the oral 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).

Use in elderly patients. In elderly patients (over 65 years of age), the elimination of amlodipine is slowed (T1/2 — 65 hours) compared to young patients, but this difference is not clinically significant.

Use in patients with hepatic insufficiency. Prolongation of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged use, the accumulation 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 through the BBB. It is not removed during hemodialysis.

Indications

Arterial hypertension (both in monotherapy and in combination with other antihypertensive agents);

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

Use during pregnancy and lactation

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

There are no data indicating the elimination of amlodipine in breast milk.

However, other slow calcium channel blockers (dihydropyridine derivatives) are known to be excreted in breast milk.

In this regard, if it is necessary to use the drug Norvask during lactation, the question of stopping breastfeeding should be decided.

Contraindications

• hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as auxiliary substances included in the composition of the drug;
• severe hypotension (SBP less than 90 mm Hg. calendar);
• obstruction of the outflow tract of the left ventricle (including severe aortic stenosis;
• hemodynamically unstable heart failure after myocardial infarction;
• the age of 18 years (effectiveness and safety not established).

With caution:  hepatic insufficiency; chronic heart failure of non–ischemic etiology of NYHA functional class III-IV; unstable angina; aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy; acute myocardial infarction (and the period within 1 month after it); sinus node weakness syndrome (pronounced tachycardia, bradycardia); arterial hypotension; simultaneous use with inhibitors or inducers of isoenzyme CYP3A4.

Side effects

From the CCC side:  often — palpitation of the heart, peripheral edema (ankles and feet), flushes of blood to the skin of the face; infrequently-excessive decrease in blood pressure. Very rarely-syncope, shortness of breath, vasculitis, orthostatic hypotension, development or worsening of the course of CHF, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

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

Nervous system disorders:  often — headache, dizziness, increased fatigue, drowsiness; infrequently-asthenia, general malaise, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, increased excitability, depression, anxiety, ringing in the ears, taste distortion; very rarely — migraine, increased sweating, apathy, agitation, ataxia, amnesia.

From the digestive system:  often — nausea, abdominal pain; infrequently-vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dry oral mucosa, thirst; rarely-gum hyperplasia, increased appetite; very rarely-pancreatitis, gastritis, jaundice (due to cholestasis), hyperbilirubinemia, increased activity of liver transaminases, hepatitis.

From the side of hematopoietic organs:  very rarely — thrombocytopenic purpura, leukopenia, thrombocytopenia.

Respiratory system disorders:  infrequently — shortness of breath, rhinitis, nosebleeds; very rarely-cough.

From the side of the senses:  infrequently — diplopia, accommodation disorders, xerophthalmia, conjunctivitis, eye pain, visual disturbances.

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

From the side of the skin:  rarely-dermatitis; very rarely-alopecia, xeroderma, cold sweat, skin pigmentation disorder.

Metabolic disorders:  very rarely-hyperglycemia; infrequently-weight gain/loss.

Allergic reactions:  infrequently — skin pruritus, rash (incl. erythematous, maculopapular rash, urticaria); very rarely — angioedema, erythema multiforme.

Laboratory parameters: very rarely — hyperglycemia.

Other services: infrequently-chills, gynecomastia; very rarely-parosmia.

Interaction

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

Unlike other BCAAs, no clinically significant interaction of amlodipine (third generation BCAAs) was found when co-administered with NSAIDs, including Indometacin.

It is possible to enhance the antianginal and antihypertensive effects of BCC when combined with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as to enhance their hypotensive effect when combined with α1-blockers, neuroleptics.

Although no negative inotropic effects have usually been observed in studies of amlodipine, however, some BCCs may increase the severity of the negative inotropic effects of antiarrhythmic agents that cause prolongation of the QT interval (for example, amiodarone and quinidine).

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

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

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.

Simvastatin: simultaneous multiple use of 10 mg amlodipine and 80 mg simvastatin resulted in a 77% increase in simvastatin exposure. In such cases, the dose of simvastatin should be limited to 20 mg.

Ethanol (beverages containing alcohol): amlodipine with a single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

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

Antipsychotics and isoflurane: increased hypotensive effect of dihydropyridine derivatives.

Calcium supplements can reduce the effect of BCC.

When BCC is co-administered with lithium preparations (no data available for Norvask®), their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Studies on the concomitant use of amlodipine and cyclosporine in healthy volunteers and all groups of patients, with the exception of 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 Cmin of cyclosporine to varying degrees up to 40%. These data should be taken into account and the concentration of cyclosporine should be monitored in this group of patients with concomitant use of cyclosporine and amlodipine.

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

It does not significantly affect the effect of warfarin (PV).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In vitro studies, amlodipine did not affect the binding of digoxin, phenytoin, warfarin, and Indometacin to plasma proteins.

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

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

Inhibitors of the SUR 3A4 isoenzyme: with the simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (69 to 87 years) with arterial hypertension, there is an increase in systemic exposure to amlodipine by 57%. Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years of age) did not result in significant changes in amlodipine exposure (a 22% increase in AUC). Although the clinical significance of these effects is not fully understood, they may be more pronounced in older patients.

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

Inducers of the CYP3A4 isoenzyme: There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored with concomitant use of amlodipine and inducers of the CYP3A4 isoenzyme.

How to take, course of use and dosage

Inside,1 time a day, with the required amount of water (100 ml).

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

Use in the elderly. It is recommended to use in normal doses, no dose change is required.

Use in patients with impaired liver function. Despite the fact that the T1/2 of amlodipine, like all BCC, increases in patients with this pathology, dose adjustment is usually not required (see “Special Instructions”).

Use in patients with impaired renal function. It is recommended to use Norvask® in normal doses, but it is necessary to take into account the possible slight increase in T1 / 2.

No dose adjustment is required when used concomitantly with thiazide diuretics, beta-blockers and ACE inhibitors.

Overdose

Symptoms: marked decrease Blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (there is a possibility of severe and persistent arterial hypotension, including shock and death).

Treatment: use of activated charcoal (especially in the first 2 hours after an overdose), gastric lavage, elevation of the lower extremities, active maintenance of the cardiovascular system, monitoring of heart and lung function, control of BCC and diuresis.

To restore vascular tone — the use of vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade —intravenous use of calcium gluconate. Hemodialysis is ineffective.

Special instructions

It is necessary to maintain dental hygiene and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

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

The efficacy and safety of Norvask® in hypertensive crisis has not been established.

Despite the absence of withdrawal symptoms in BCC, it is advisable to discontinue treatment with Norvask®by gradually reducing the dose of the drug.

When amlodipine was used in patients with non-ischemic NYHA class III and IV CHF, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

Influence on the ability to drive vehicles and work with mechanisms.

Although no adverse effects on the ability to drive vehicles or other complex mechanisms have been observed with the use of Norvask®, however, due to a possible excessive decrease in blood pressure, dizziness, drowsiness and other adverse reactions, caution should be exercised in these situations, especially at the beginning of treatment and when increasing the dose.

Composition

Tablet Form of production

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

4 years

Active ingredient

Amlodipine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Angina