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

One tablet contains: active substance: amlodipine besylate (in terms of amlodipine) - 5,000 mg; Excipients: potato starch - 19,965 mg, pregelatinized starch - 7,920 mg, calcium stearate - 1,650 mg, silicon dioxide colloid - 2,970 mg, microcrystalline cellulose - 30,030 mg, calcium hydrophosphate dihydrag - 95,520 mg.

One tablet contains: active substance: Amlodipine besylate (in terms of amlodipine) - 10,000 mg; Excipients: starch potato - 19,965 mg, pregelatinized starch - 7,920 mg, calcium stearate - 1,650 mg, silicon dioxide colloid - 2,970 mg, microcrystalline cellulose - 30,030 mg, calcium hydrophosphate dihydrate - 88,575 mg.

Description:Tablets of white color, flat-cylindrical, with a facet.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Amlodipine - a blocker of "slow" calcium channels, a derivative of dihydropyridine, has an anti-anginal and hypotensive effect. Blocks calcium channels, reduces the transmembrane transition of calcium ions in a cell(in more in the smooth muscle cells of the vessels than in the cardiomyocytes).

Antianginal action is due to the expansion 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 vasospasmic angina); prevents spasm of the coronary arteries (including caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina pectoris 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. When hypertension single dose provides a clinically significant decrease in blood pressure (BP) over 24 hours (with the patient "lying" and "standing"). Orthostatic hypotension with amlodipine is rare. Does not cause a decrease in exercise tolerance, a 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, nc causes a reflex increase in the heart rate (HR), inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect.

With diabetic nephropathy, nc increases the severity of microalbuminuria. Does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used in the therapy of patients with bronchial asthma,diabetes and gout. A significant reduction in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

In patients with diseases of the cardiovascular system, including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries, atherosclerosis of carotid arteries after myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) of coronary arteries or patients with angina, use of amlodipine prevents the development of thickening of intima-media of carotid arteries, reduces mortality from myocardial infarction, stroke, TLP, aortocoronary shunting; leads to a decrease in the number of hospitalizations angina and progression of chronic heart failure (CHF), reduces 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 NYIIA) on the background of therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (II1-IV functional class by classification NYIIA) 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 absolute bioavailability is 64%, the maximum concentration (C_m_Oh) in serum is observed after 6-9 hours. Equilibrium concentration (C_ss) is 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 amlodipine is in the tissues, and the smaller is in the blood. Most of the amlodipine, which is in the blood (95%), 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 elimination half-life (T_1/2) varies from 35 to 50 hours, with repeated application T_1/2 is about 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 about 0.116 ml / s / kg (7 ml / min / kg or 0.42 l / h / kg).

In elderly patients (over 65 years of age) the excretion of amlodipine is slowed down (T_1/2 - 65 h) compared with young patients, but this difference has no clinical significance. Elongation T_1/2 in patients with hepatic insufficiency suggests that with prolonged use, cumulation of the drug in the body will be higher (T_1/2 - up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. In patients with impaired renal function, changes in amlodipine concentration in the blood plasma do not correlate with the degree of renal failure. Possible slight increase T_1/2.

Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

Arterial hypertension (monotherapy with antihypertensive drugs)

Stable angina pectoris and vasospastic angina pectoris (Princmetal), incl. in patients who are resistant to nitrate therapy or beta-blockers.

Contraindications:

Hypersensitivity to amlodipine, other derivatives of dihydropyridine or other components of the drug;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
shock, including cardiogenic;
hemodynamically unstable heart failure after acute myocardial infarction;
unstable angina (with the exception of Prinzmetal's stenocardia);
obstruction of the outflow tract of the left ventricle (including, severe aortic stenosis);
clinically significant aortic stenosis;
age to 18 years (effectiveness and safety not established);
pregnancy and lactation.

Carefully:

Aortic stenosis, heart failure, CHF of non-ischemic etiology III-IV functional class by classification NYHA, acute myocardial infarction (and within 1 month after it), arterial hypotension, simultaneous application with inhibitors or inducers of isoenzyme CYP3A4, hepatic dysfunction, sinus node weakness syndrome (severe bradycardia, tachycardia), mitral stenosis, hypertrophic obstructive cardiomyopathy, advanced age, impaired renal function.

If you have one of the listed diseases, before taking the drug always consult a doctor.

Pregnancy and lactation:

In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established,but use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

There is no evidence of excretion of amlodipine in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, if it is necessary to prescribe the drug during lactation, it is necessary to solve the problem of stopping breastfeeding.

Dosing and Administration:

Dosing and Administration Inside, once a day, regardless of the reception of poverty, washed down with the necessary amount of water (100 ml).

With arterial hypertension and angina, the initial dose is 5 mg once a day. In the absence of therapeutic effect for 2-4 weeks, the dose of the drug can be increased to 10 mg / day once.

If you miss the drug Amlodipine-Borimed should not double the dose. Skipping the next dose of the drug may be accompanied by a decrease in the effectiveness of treatment.

Have elderly patients

Correction of the dose is not required.

Have patients with impaired liver function

Although T_1/2 Amlodipine, like all BCCI, increases in patients with impaired liver function,dose adjustment is usually not required (see section "Precautions for Use").

Have patients with renal insufficiency

It is recommended that amlodipine in normal doses (see section "Precautions for use").

Side effects:

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%., including individual messages.

From the central nervous system: often - headache (especially at the beginning of treatment), dizziness, fatigue, drowsiness; infrequent - general malaise, hypesthesia / paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, increased excitability, depression, anxiety; very rarely - migraine, apathy, agitation, ataxia, amnesia, asthenia, increased sweating; extrapyramidal disorders (frequency unknown).

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

From the cardiovascular system: often - palpitations, "hot flashes" of blood to the skin of the face; infrequent reduction of blood pressure; very rarely - fainting, shortness of breath, vasculitis, orthostatic hypotension, development or exacerbation of current CHF, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), heart attack, chest pain, pulmonary edema, swelling of the lower extremities.

From the hematopoietic and lymphatic systems: rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

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

On the part of the reproductive system and mammary glands: infrequently - gynecomastia, impotence.

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

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

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

Allergic reactions: very rarely - skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema, erythema multiformapa.

From the sense organs: infrequent - ringing in the ears, diplopia, disruption of accommodation, xerophthalmia, conjunctivitis, pain in the eyes; very rarely - parosmia.

From the side of metabolism: very rarely - hyperglycemia.

Other: infrequently - the pain of unspecified localization, weight loss, weight gain, nosebleeds.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

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, incl.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, elevating the position of the lower extremities, monitoring heart and lung performance, monitoring 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 for the therapy of arterial hypertension along with thiazide diuretics, alpha-adrenoblockers or angiotensin-converting enzyme (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.

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 (NG1VP), including indomethacin.

It is possible to strengthen the anti-anginal and hypotensive action of BCCC when combined with thiazide and loop diuretics, ACE inhibitors and nitrates, as well as enhance their hypotensive effect when combined with alpha1-adrenoblockers, beta-blockers, and antipsychotics.

Erythromycin in a joint application increases C_m_Oh Amlodipine in young patients at 22%, and in the elderly - 50%.

Beta-adrenoblockers with simultaneous administration with amlodipine may cause an exacerbation of the course of heart failure.

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

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

The repeated use of amlodipine in a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Ethanol (drinks containing alcohol): amlodipine at a single and repeated application in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiretroviral agents (ritonavir) increases plasma concentrations of BCCC, including amlodipine.

Neuroleptics and isoflurane - Increased hypotensive effect of dihydropyridine derivatives.

Calcium preparations can reduce the effect of BCCC.

When amlodipine is used together with lithium preparations, it is possible to intensify manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not change the pharmacokinetics of cyclosporine.

Does not affect the serum concentration to clearance.

Has no significant effect on the effect of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.

In studies in vitro Amlodipine does not affect the binding of blood 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.

Aluminum- or magnesium-containing antacids: their single administration does not have a significant effect on the pharmacokinetics of amlodipine.

It is necessary to consult a doctor, if other medications are taken.

Special instructions:

During the period of drug therapy, it is necessary to control body weight and sodium intake, and the purpose of the appropriate diet is indicated.

No features of the action at the first reception are registered.

It should be avoided abrupt discontinuation of the drug because of the risk of worsening of the course of angina pectoris. It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Amlodipine does not affect plasma concentrations of K +, glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), uric acid, creatinine and urea nitrogen.

Women of childbearing age in the period of treatment should use reliable methods of contraception.

When using the drug in patients with chronic heart failure III and IV functional class by classification NYHA possibly the development of pulmonary edema.

With acute myocardial infarction, the drug is prescribed after stabilization of the indices hemodynamics (see section "Contraindications for use").

Patients with hepatic insufficiency should, if necessary, receive amlodipine under the supervision of a physician.

In elderly patients may increase T_1/2 and decrease the clearance of the drug. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

Patients with low body weight, low growth patients and patients with severe liver function impairment may need a smaller dose of the drug.

In patients with impaired renal function, monitoring of the condition is necessary. The effectiveness and safety of the drug during hypertensive crisis is not established.

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

Although patients receiving amlodipine any negative effect on the ability to drive vehicles or other complex mechanisms were observed, however, due to the possible excessive reduction in blood pressure, development of dizziness, drowsiness and other side effects, caution should be exercised in these situations,especially at the beginning of treatment and with increasing doses.

Form release / dosage:

Tablets 5 mg or 10 mg.

Packaging:10 tablets per contour cell pack. 2, 3 contoured cell packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002893

Date of registration:03.03.2015

Expiration Date:03.03.2020

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Information update date: & nbsp24.07.2017

Illustrated instructions

Instructions

Amlodipine-Borimed (Amlodipine Borimed)