Normodipin tablets 10mg, No. 30

• arterial hypertension (as monotherapy or in combination with other antihypertensive drugs);

• stable angina pectoris (as monotherapy or in combination with other antianginal drugs);

• vasospastic angina (Prinzmetal's angina or variant angina) (as monotherapy or in combination with other antianginal agents).

The drug is taken orally, 1 time / day, with the required amount of water (100 ml).

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

In elderly patients (over 65 years of age), NormodipinЃ is recommended to be used in an average therapeutic dose; dose adjustment is not required.

Despite the fact that T1 / 2 of amlodipine, like all BMCC, increases in patients with impaired liver function , dose adjustment is usually not required.

In patients with impaired renal function, it is recommended to use amlodipine in usual doses, however, a possible slight increase in T1 / 2 must be taken into account.

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

Active substance: amlodipine

• 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 up to 18 years (efficacy and safety have not been studied);

• hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as excipients that make up the drug.

The drug should be prescribed with caution in liver failure, CHF of non-ischemic etiology of III-IV functional class according to NYHA classification, unstable angina pectoris, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), sick sinus syndrome node (severe tachycardia, bradycardia), arterial hypotension, simultaneous use with inhibitors or inducers of the CYP3A4 isoenzyme.

Clinical and pharmacological group: Calcium channel blocker

Pharmaco-therapeutic group: BMCC

pharmachologic effect

A blocker of slow calcium channels, a derivative of dihydropyridine, has an antianginal and hypotensive effect, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles:

Х with angina pectoris reduces the severity of myocardial ischemia; expanding the peripheral arterioles, reduces the systemic vascular resistance, reduces the preload on the heart, reduces myocardial oxygen demand;

Х expands the coronary arteries and arterioles in the unchanged and ischemic zones of the myocardium, increases the flow of oxygen to the myocardium (especially with vasospastic angina); prevents the development of spasm of the coronary arteries (including those caused by smoking).

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

It has a long-term dose-dependent hypotensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle. In case of arterial hypertension, a single dose provides a clinically significant decrease in blood pressure for 24 hours (in the position of the patient 'lying' and 'standing').

Orthostatic hypotension with the appointment 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 conductivity of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentration and can be used in the treatment 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 damage to one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the carotid arteries), after myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina pectoris, 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; leads to a decrease in the number of hospitalizations due to unstable angina pectoris and the progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

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

Pharmacokinetics

Suction

After oral administration, it is well absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-80%. Cmax in blood plasma is reached after 6-12 hours. Simultaneous food intake does not affect the absorption of amlodipine.

Distribution

Css is achieved after 7-8 days of therapy. The average Vd is 21 L / kg of body weight, which indicates that most of the drug is in the tissues, and a smaller part is in the blood. Most of the drug in the blood (97.5%) binds to blood plasma proteins. Amlodipine penetrates the BBB.

Metabolism

Amlodipine undergoes a slow but vigorous hepatic metabolism with no significant hepatic 'first pass' effect. Metabolites have no significant pharmacological activity.

Withdrawal

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

It is not removed during hemodialysis.

Pharmacokinetics in special clinical situations

In elderly patients (over 65 years old), the excretion of amlodipine is slowed down (T1 / 2 - 65 hours) compared with young patients, however, these differences have no clinical significance.

Prolongation of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged administration, the accumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours).

The presence of renal failure in a patient does not significantly affect the pharmacokinetics of amlodipine.

Indications

• arterial hypertension (as monotherapy or in combination with other antihypertensive drugs);

• stable angina pectoris (as monotherapy or in combination with other antianginal drugs);

• vasospastic angina (Prinzmetal's angina or variant angina) (as monotherapy or in combination with other antianginal agents).

Dosage regimen

The drug is taken orally, 1 time / day, with the required amount of water (100 ml).

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

In elderly patients (over 65 years of age), NormodipinЃ is recommended to be used in an average therapeutic dose; dose adjustment is not required.

Despite the fact that T1 / 2 of amlodipine, like all BMCC, increases in patients with impaired liver function , dose adjustment is usually not required.

In patients with impaired renal function, it is recommended to use amlodipine in usual doses, however, a possible slight increase in T1 / 2 must be taken into account.

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

Side effect

WHO classification of the incidence of side effects: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10000, < 1/1000), very rare (<10000), including isolated messages, the frequency is unknown (it is impossible to estimate the frequency from the available data).

From the hematopoietic system: very rarely - leukopenia, thrombocytopenia.

From the immune system: very rarely - allergic reactions.

From the side of metabolism and nutrition: very rarely - hyperglycemia.

Mental disorders: infrequently - mood lability, insomnia, anxiety, depression; rarely - confusion.

From the nervous system: often - headache, dizziness, drowsiness; infrequently - tremor, dysgeusia, fainting, hypesthesia, paresthesia; very rarely - muscle hypertonicity, peripheral neuropathy; frequency unknown - extrapyramidal disorders.

From the side of the organ of vision: often - visual impairment (including diplopia).

On the part of the organ of hearing and labyrinthine disorders: infrequently - tinnitus.

From the side of the cardiovascular system: often - a feeling of palpitations, 'hot flushes' of blood to the skin of the face; infrequently - heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), excessive decrease in blood pressure; very rarely - myocardial infarction, vasculitis.

From the respiratory system: often - shortness of breath; infrequently - rhinitis, cough.

From the digestive system: often - abdominal pain, nausea, dyspepsia, change in the rhythm of bowel movements; infrequently - vomiting, dry mouth; very rarely - pancreatitis, gastritis, gingival hyperplasia.

From the liver and biliary tract: very rarely - hepatitis, jaundice, increased activity of liver enzymes (associated with cholestasis).

Skin and subcutaneous tissue disorders: infrequently - alopecia, purpura, skin depigmentation, hyperhidrosis, itching, rash, exanthema, urticaria; very rarely - angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity; frequency unknown - toxic epidermal necrolysis.

From the musculoskeletal system: often - swelling of the ankles and feet, muscle cramps; infrequently - arthralgia, myalgia, back pain.

From the urinary system: infrequently - urination disorder, nocturia, frequent urination.

From the genitals and mammary gland: infrequently - gynecomastia, impotence.

General disorders and disorders at the injection site: very often - edema; often - increased fatigue, asthenia; infrequently - chest pain, pain, malaise.

Laboratory and instrumental data: infrequently - increase / decrease in body weight.

Contraindications for use

• 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 up to 18 years (efficacy and safety have not been studied);

• hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as excipients that make up the drug.

The drug should be prescribed with caution in liver failure, CHF of non-ischemic etiology of III-IV functional class according to NYHA classification, unstable angina pectoris, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), sick sinus syndrome node (severe tachycardia, bradycardia), arterial hypotension, simultaneous use with inhibitors or inducers of the CYP3A4 isoenzyme.

Application during pregnancy and lactation

The safety of using amlodipine during pregnancy and during breastfeeding has not been established.

The use of amlodipine during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus. It is necessary to consult a doctor.

The experience of using the drug shows that amlodipine is excreted in breast milk. The average milk / plasma ratio for amlodipine concentration was 0.85 among 31 lactating women who suffered from pregnancy-related hypertension and received amlodipine at an initial dose of 5 mg / day. The dose of the drug was adjusted if necessary (depending on the average daily dose and weight: 6 mg and 98.7 ?g / kg, respectively). The estimated daily dose of amlodipine received by an infant through breast milk is 4.17 mcg / kg.

The use of amlodipine during breastfeeding is contraindicated. If necessary, the use of the drug during lactation should stop breastfeeding.

In some patients receiving calcium channel blockers, reversible biochemical changes in the sperm head were found, which may be clinically significant during in vitro fertilization (IVF). However, there is currently no sufficient clinical data regarding the potential effect of amlodipine on fertility. In a preclinical study, undesirable effects on fertility in males were identified.

Application for violations of liver function

The drug should be prescribed with caution in liver failure.

Application for impaired renal function

In patients with impaired renal function, it is recommended to use amlodipine in usual doses, however, a possible slight increase in T1 / 2 must be taken into account.

Application in children

Contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been studied).

Use in elderly patients

In elderly patients (over 65 years of age), NormodipinЃ is recommended to be used in an average therapeutic dose; dose adjustment is not required.

special instructions

Maintaining dental hygiene and monitoring by the dentist (to prevent soreness, bleeding and gingival hyperplasia) is necessary.

In elderly patients, T1 / 2 may be lengthened and drug clearance may decrease. Dose changes are not required for elderly patients; with an increase in the dose, more careful monitoring of patients is necessary.

The efficacy and safety of amlodipine in hypertensive crisis have not been established.

Despite the absence of a 'withdrawal' syndrome in BMCC, it is advisable to discontinue treatment with NormodipinЃ by gradually reducing the dose of the drug.

Against the background of the use of amlodipine in patients with CHF III and IV functional classes according to the NYHA classification of non-ischemic genesis, 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 use mechanisms

Although against the background of the use of the drug NormodipinЃ, no negative effect on the ability to drive vehicles or other complex mechanisms was observed, however, due to a possible excessive decrease in blood pressure, the development of dizziness, drowsiness and other adverse reactions, caution should be exercised in these situations, especially in the beginning of treatment and when the dose is increased.

Overdose

Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing 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, elevated, above the level of the head, the position of the lower extremities, monitoring the performance of the heart and lungs, monitoring BCC and diuresis. To restore vascular tone - the use of vasoconstrictors (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade - intravenous administration of calcium gluconate. Hemodialysis is ineffective.

Drug interactions

Contraindicated drug combinations

Dantrolene (i.v. introduction)

” лабораторных животных были отмечены случаи фибрилл¤ции желудочков с летальным исходом и коллапсом на фоне применени¤ верапамила и в/в введени¤ дантролена, сопровождавшиес¤ гиперкалиемией. ¬следствие риска развити¤ гиперкалиемии следует исключить одновременный прием препарата ЌормодипинЃ, содержащий амлодипин, блокатор медленных кальциевых каналов, у пациентов, подверженных злокачественной гипертермии, а также при лечении злокачественной гипертермии.

Ќерекомендуемые комбинации лекарственных средств

vрейпфрутовый сок

ѕрием амлодипина с грейпфрутом или грейпфрутовым соком не рекомендуетс¤, поскольку у некоторых пациентов может увеличиватьс¤ биодоступность амлодипина, что приводит к усилению эффектов снижени¤ ј?.

 омбинации лекарственных средств, требующие особой осторожности при применении

»ндукторы изофермента CYP3A4

?анные о вли¤нии индукторов изофермента CYP3A4 на фармакокинетику амлодипина отсутствуют. ќдновременный прием индукторов изофермента CYP3A4 (например, рифампицина, препаратов зверобо¤ продыр¤вленного (Hypericum perforatum)) и амлодипина может привести к снижению плазменной концентрации амлодипина. —ледует соблюдать осторожность при одновременном применении препарата ЌормодипинЃ и индукторов изофермента CYP3A4.

»нгибиторы изофермента CYP3A4

ќдновременный прием амлодипина и сильных, либо умеренных ингибиторов CYP3A4 (ингибиторы протеазы, например, ритонавир, противогрибковые препараты группы азолов, макролиды, например, эритромицин или кларитромицин, верапамил или дилтиазем) может привести к существенному увеличению концентрации амлодипина.  линические про¤влени¤ указанных фармакокинетических отклонений могут быть более выраженными у пациентов пожилого возраста. ¬ св¤зи с этим может потребоватьс¤ мониторинг клинического состо¤ни¤ и коррекци¤ дозы препарата ЌормодипинЃ.

 омбинации лекарственных средств, требующие осторожности при применении

—имвастатин

ћногократный прием амлодипина в дозе 10 мг в комбинации с симвастатином в дозе 80 мг приводил к увеличению экспозиции симвастатина на 77% по сравнению с монотерапией симвастатином. “аким образом, пациентам, получающим амлодипин, следует принимать симвастатин в суточной дозе не выше 20 мг.

ѕрепараты кальци¤

ћогут уменьшать эффект Ѕћ  .

ѕрепараты лити¤

ѕри совместном применении Ѕћ   с препаратами лити¤ (дл¤ амлодипина данные отсутствуют) возможно усиление про¤влени¤ их нейротоксичности (тошнота, рвота, диаре¤, атакси¤, тремор или шум в ушах).

Ѕаклофен

”силение антигипертензивного эффекта. —ледует контролировать ј? и функцию почек, при необходимости - корректировать дозу амлодипина.

јмифостин

¬озможно усиление антигипертензивного действи¤ амлодипина.

v —

—нижение антигипертензивного действи¤ (задержка жидкости и ионов натри¤ в результате действи¤ кортикостероидов).

“рициклические антидепрессанты, нейролептики, изофлуран

—уществует повышенный риск ортостатической гипотензии и усилени¤ антигипертензивного эффекта (аддитивный эффект).

“акролимус

ѕри одновременном применении с амлодипином есть риск увеличени¤ концентрации такролимуса в плазме крови. ?л¤ того чтобы избежать токсичности такролимуса при одновременном применении с амлодипином, следует контролировать концентрацию такролимуса в плазме крови пациентов и корректировать дозу такролимуса при необходимости.

“асонермин

ѕри одновременном применении амлодипин может повышать системную экспозицию тасонермина в плазме крови. ¬ таких случа¤х необходим регул¤рный контроль тасонермина в крови и коррекци¤ дозы при необходимости.

»нгибиторы mTOR (mammalian Target of Rapamycin - мишень рапамицина в клетках млекопитающих)

»нгибиторы mTOR, такие как сиролимус, темсиролимус и эверолимус представл¤ют собой субстраты изофермента CYP3A. јмлодипин ¤вл¤етс¤ слабым ингибитором изофермента CYP3A. ѕри одновременном применении с ингибиторами mTOR амлодипин может повышать их экспозицию.

?ругое взаимодействие с амлодипином

?л¤ лечени¤ артериальной гипертензии амлодипин можно безопасно примен¤ть с тиазидными диуретиками, альфа-адреноблокаторами, бета-адреноблокаторами и ингибиторами јѕ‘. ” пациентов со стабильной стенокардией возможно одновременное применение амлодипина с другими антиангинальными препаратами, такими как нитраты длительного и короткого действи¤, бета-адреноблокаторы.

¬еро¤тно усиление антиангинального и антигипертензивного действи¤ Ѕћ   при одновременном применении с тиазидными и петлевыми диуретиками, ингибиторами јѕ‘, бета-адреноблокаторами и нитратами, а также усиление их антигипертензивного действи¤ при назначении с альфа-1-адреноблокаторами и нейролептиками.

јмлодипин не вызывает отрицательного инотропного эффекта. “ем не менее, некоторые Ѕћ   могут увеличивать выраженность отрицательного инотропного эффекта антиаритмических препаратов, которые вызывают удлинение интервала QT (например, амиодарон и хинидин).

¬ отличие от других Ѕћ  , не вы¤влено значимого взаимодействи¤ амлодипина (3-е поколение Ѕћ  ) и Ќѕ¬ѕ, включа¤ индометацин.

Ѕезопасно назначать амлодипин с пероральными гипогликемическими препаратами.

ќднократный прием силденафила в дозе 100 мг пациентами с эссенциальной артериальной гипертензией не оказывал вли¤ни¤ на фармакокинетику амлодипина.

—овместный многократный прием амлодипина в дозе 10 мг и аторвастатина в дозе 80 мг приводил к незначимому изменению фармакокинетических параметров аторвастатина в состо¤нии равновесной концентрации.

Ётанол (напитки, содержащие алкоголь): амлодипин не оказывает значимого вли¤ни¤ на фармакокинетику этанола при однократном и многократном применении в дозе 10 мг.

»сследовани¤ взаимодействи¤ циклоспорина и амлодипина у здоровых добровольцев и в особых группах пациентов не проводились, за исключением пациентов после трансплантации почки. –азличные исследовани¤ взаимодействи¤ амлодипина с циклоспорином у пациентов после трансплантации почки показывают, что применение данной комбинации может либо не приводить к какому-либо эффекту, либо повышать минимальную концентрацию циклоспорина в различной степени до 40%. —ледует проводить контроль концентрации циклоспорина у пациентов после трансплантации почки.

ѕри одновременном применении амлодипина и дигоксина почечный клиренс и концентраци¤ дигоксина в сыворотке крови не мен¤ютс¤.

ѕри одновременном применении варфарина с амлодипином протромбиновое врем¤ не измен¤етс¤.

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

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

Aluminum and magnesium-containing antacids: a single dose of such antacids together with amlodipine does not significantly affect the pharmacokinetics of amlodipine.

Storage conditions

The drug should be stored in its original packaging, protected from light, out of the reach of children, at a temperature not exceeding 30 ? C.

Shelf life

Shelf life is 3 years. Do not use after the expiration date.

Terms of sale

The drug is available with a prescription.