Amlodipine Zentiva - instructions for use, dose, side effects, contraindications

Each tablet, 5 mg. contains: active substance: Amlodipine - 5,000 mg (in the form of amlodipine besylate - 6,935 mg); Excipients: cellulose microcrystalline - 71.356 mg, calcium hydrophosphate dihydrate - 37,500 mg, sodium carboxymethyl starch (type A) - 2,400 mg, magnesium stearate - 1,800 mg.

Each tablet. 10 mg contains: active substance: Amlodipine - 10 mg (in the form of amlodipine besylate - 13.870 mg); Excipients: cellulose microcrystalline - 142,730 mg, calcium hydrophosphate dihydrate - 75,000 mg, sodium carboxymethyl starch (type A) - 4,800 mg, magnesium stearate - 3,600 mg.

Description:

Tablets 5 mg: tablets white or almost white, oblong, with a risk on one side and engraved "A" on the left and "5" to the right of the risks.

Tablets 10 mg: tablets white or almost white, oblong, with a risk on one side and engraved "A" on the left and "10" on the right of the risks.

Pharmacotherapeutic group:The 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 antianginal and hypotensive effect, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance (OPSS), 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).In patients with stable angina, a single daily dose increases exercise tolerance, increasing the time until the onset of an attack of angina 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 in the appointment of amlodipine is rare. Does not cause a decrease in the fraction of the ejection of the left ventricle. 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 in the treatment of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

Patients with cardiovascular diseases (CCC) (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries, carotid atherosclerosis) who underwent myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) of coronary arteries or patients with angina pectoris, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, aorto-coronary shunting; leads to a decrease in the frequency of attacks of unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

Does not increase the risk of death or 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:

After oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT). The average relative bioavailability is 64-80%, the maximum concentration (C_max) in serum is observed after 6-12 hours. Equilibrium concentrations (C_ss) are achieved after 7-8 days of therapy.

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 administration, the half-life period (T1 / 2) varies from 35 to 50 hours, with the repeated administration of T1 / 2 approximately 45 hours.About 60% of the dose taken internally 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).

In elderly patients (over 65 years), amlodipine withdrawal is slowed (T1 / 2 - 65 h) compared with young patients, but this difference has no clinical significance. Elongation of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged use, the cumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);

stable angina of tension;

vasospastic angina (Prinzmetal angina) (in the form of monotherapy or in combination with other antianginal agents).

Contraindications:

Hypersensitivity to amlodipine, other derivatives of dihydropyridine and other components of the drug;

severe arterial hypotension (systolic blood pressure less than 90 mm Hg); obstruction of the outflow tract of the left ventricle (eg, aortic stenosis of the third degree);

heart failure with unstable hemodynamics after a myocardial infarction;

age to 18 years (efficacy and safety not established).

Carefully:

With caution apply for violations of liver function, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), CHF of non-ischemic etiology III-IV functional class by classification NYHA, arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after myocardial infarction), unstable angina, with simultaneous application with inhibitors or inducers of isoenzyme CYP ZA4, in old age.

Pregnancy and lactation:

The safety of the use of amlodipine in pregnancy is not established, so use in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

Amlodipine penetrates into breast milk, therefore, if it is necessary to prescribe the drug AMLODIPINE ZENTIVA during lactation, breastfeeding should be stopped.

Dosing and Administration:

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

With arterial hypertension and angina, the initial dose is 5 mg once a day. If necessary, the daily dose can be increased to 10 mg in a single dose.

There is no need for dose adjustment with simultaneous use with thiazide diuretics, beta-blockers, alpha-blockers and ACE inhibitors. With angina, AMLODIPINE ZENTIVA can be used as a monotherapy or in combination with other antianginal drugs in the event that angina does not respond to treatment with nitrates and / or adequate doses of beta-blockers.

In elderly patients:

The drug AMLODIPINE ZENTIVA is recommended to be used in an average therapeutic dose, no dose adjustment is required.

In patients with impaired hepatic function:

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

In patients with renal insufficiency:

It is recommended to use the drug AMLODIPINE ZENTIVA in usual doses, but it is necessary to take into account the possible slight increase in T1 / 2.

Side effects:

The incidence of adverse reactions listed below was determined according to the following

(classification of the World Health Organization):

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.

Violations from the blood and lymphatic system: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

Heart Disease: often - a feeling of palpitations; very rarely - heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, development or exacerbation of CHF.

Vascular disorders: often - "tides" of blood to the skin of the face; infrequent reduction of blood pressure; very rarely - vasculitis, orthostatic hypotension.

Immune system disorders: infrequently - itchy skin, rash (including erythematous, maculopapular rash, urticaria); very rarely - allergic reactions, Quincke's edema, angioedema, Stevens-Johnson syndrome, exfoliative dermatitis, erythema multiforme.

Impaired nervous system: often - headache, dizziness, drowsiness; infrequently - hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, fainting; very rarely - hypertension, migraine, increased sweating, ataxia, amnesia.

Disorders of the psyche: infrequent - lability of mood, unusual dream, increased excitability, depression, anxiety; very rarely - apathy, agitation.

Disorders from the side of the organ of vision: infrequently - diplopia, a violation of accommodation, xerophthalmia, conjunctivitis, pain in the eyes.

Hearing disorders and labyrinthine disturbances: infrequent - ringing in the ears. Disturbances from the respiratory system, chest and mediastinal organs: infrequently - shortness of breath, rhinitis, nosebleeds; very rarely - cough, parosmia.

Disorders from the gastrointestinal tract: often - nausea, abdominal pain; infrequent - vomiting, constipation or diarrhea, flatulence, indigestion, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia; very rarely - pancreatitis, gastritis. Disorders from the liver and bile ducts: very rarely - jaundice, increased activity of "hepatic" transaminases, hepatitis, hyperbilirubinemia.

Disorders from the metabolism and nutrition: infrequent - increase / decrease in body weight; rarely - increased appetite; very rarely - hyperglycemia.

Disorders from the kidneys and urinary tract: infrequently - rapid urination, painful urination, nocturia; very rarely - dysuria, polyuria.

Violations of the genitals and breast: infrequently - erectile dysfunction, gynecomastia.

Disturbances from the musculoskeletal and connective tissue ', infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis, rarely - myasthenia gravis.

Disturbances from the skin and subcutaneous tissues: frequent - peripheral edema (ankle and foot), infrequently - alopecia, increased sweating, impaired skin pigmentation; very rarely - xeroderma, cold sweat, photosensitivity.

General disorders and disorders at the site of administration: often - increased fatigue; infrequently - pain in the chest, asthenia, general malaise.

Overdose:

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

Treatment: gastric lavage, taking activated charcoal (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, the patient should take a horizontal position with an elevated position of the lower limbs, control the performance of the heart and lungs, the volume of circulating blood (BCC) and diuresis. 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.

Reception amlodipine with grapefruit or grapefruit juice is not recommended,since in some patients the bioavailability of amlodipine may increase, which leads to an increase in its antihypertensive effect.

Inhibitor inhibitors CYP3A4: Simultaneous use of amlodipine with strong or moderate isoenzyme inhibitors CYP3A4 (HIV protease inhibitors, antifungal agents from the azole group, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in exposure to amlodipine. Clinical manifestations of these variants of joint application can be more pronounced in elderly patients, medical observation is necessary with a view to possible correction of the doses of the drugs.

Inductors of isoenzyme CYP3A4: Information on the influence of inducers of isoenzyme CYP3A4 on amlodipine is insufficient. Simultaneous application of isoenzyme inducers CYP3A4 (eg, rifampicin, St. John's wort pitted) can lead to a lower concentration of amlodipine in the plasma. The drug AMLODIPINE ZENTIVA should be used with caution in conjunction with isoenzyme inducers CYP3A4.

Dantrolene (infusion): In animals, ventricular fibrillation and cardiovasculara collapse with a lethal outcome along with hyperkalemia after the administration of verapamil and intravenous dantrolene. Due to the risk of developing hyperkalemia, it is recommended to avoid joint use of calcium channel blockers, such as amlodipine, in patients with a predisposition to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

In clinical trials of drug interactions amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine. maybe strengthening of the anti-anginal and hypotensive action of BCCC when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as intensifying their hypotensive effect when combined with alpha1-adrenoblockers, isoflurane, and antipsychotics. Simvastatin: Long-term combined use of 10 mg of amlodipine and 80 mg of simvastatin resulted in a 77% increase in simvastatin exposure compared to simvastatin monotherapy. In patients receiving amlodipine, the dose of simvastatin should not exceed 20 mg per day.

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).

Calcium preparations can reduce the effect of BCCC.

With the joint use of AMLODIPINE ZENTYVA with lithium preparations, the manifestation of symptoms of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, and tinnitus) can be exacerbated.

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

Special instructions:

During the period of therapy with the drug AMLODIPINE ZENTIVA, it is necessary to control body weight and sodium intake.

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

The effectiveness and safety of the drug AMLODIPIN ZENTIVA for hypertensive crisis is not established.

Application in elderly patients

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

Patients with heart failure

Patients with heart failure drug AMLODIPINE ZENTIVA should be administered with caution. In a long-term placebo-controlled study in patients with severe heart failure (Class III and IV according to classification NYHA) the incidence of pulmonary edema was higher in the group receiving amlodipine, than in the placebo group. Calcium channel blockers, including the drug AMLODIPIN ZENTIVA, should be used with caution in patients with congestive heart failure, as this may increase the risk of cardiovascular events and death.

Use in patients with impaired liver function

The drug AMLODIPIN ZENTIVA has a long half-life, in patients with impaired liver function, the area under the concentration-time curve (AUC) can be higher. Therefore, treatment with AMLODIPINE ZENTIVA for such patients should be started with 2.5 mg once a day. In patients with severe impairment of liver function, slow titration of the dose and careful medical monitoring may be required.

Despite the absence of the "cancellation" syndrome in BCCC, it is advisable to stop the treatment with AMLODIPINE ZENTIVA by gradually decreasing the dose of the drug.

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

Against the background of the drug AMLODIPIN ZENTYVA, there was no adverse effect on the ability to drive transport or other complex mechanisms, however, due to possible excessive blood pressure lowering, development of dizziness, drowsiness and other adverse reactions, care should be taken in these situations, especially at the beginning of treatment and with increasing dose.

Form release / dosage:

Tablets 5 mg, 10 mg.

Packaging:For 10 tablets in a blister of PVC / PVDC / A1. For 1, 3 or 9 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:

Does not require special storage conditions. Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015710 / 01

Date of registration:15.03.2012

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspZENTIVA ZENTIVA Czech Republic

Information update date: & nbsp15.07.2014

Illustrated instructions

Instructions

Amlodipine Zentiva (Amlodipine Zentiva)