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

Excipients: microcrystalline cellulose 124 mg and 248 mg, calcium pyrophosphate 63 mg and 126 mg, sodium carboxymethyl starch 4 mg and 8 mg, magnesium stearate 2 mg and 4 mg.

Description:

Tablets 5 mg: Round flat with bevelled edges on both sides, even on one side and with risk on the other side from white to almost white colored tablets.

For dosage of 10 mg: Prolonged convex from white to almost white colored tablets.

The determination is made visually.

Pharmacotherapeutic group:blocker of "slow" calcium channels.

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

The dihydropyridine derivative blocking the "slow" calcium channels (BCCI) has an antianginal and hypotensive effect. Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes).

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, slows the development of another attack of angina and "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 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, 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 decrease in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

Patients with cardiovascular diseases (CCC) (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries, carotid arteries atherosclerosis) who underwent myocardial infarction, percutaneous transluminal angioplasty (TLC) 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, TPL, 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 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 absolute bioavailability is 64%, the maximum concentration (Cmah) in serum is observed after 6-9 hours. Equilibrium concentrations (Css) 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 (95%) binds to blood plasma proteins. Amlodipine is subjected to a slow but active metabolism in the liver in the absence of a significant "first passage" effect. Metabolites do not have significant pharmacological activity.

After a single administration, the half-life period (T1 / 2) varies from 31 to 48 hours, with repeated application is approximately 45 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites, 10% in unchanged form, 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 of age) amlodipine withdrawal is slowed (T | / 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 administration, 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 agents).

Stable angina and vasospastic angina pectoris (in 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);

- unstable angina (with the exception of vasospastic angina);

- clinically significant aortic stenosis;

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

Carefully:In case of violations of the 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), 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.

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 amlodipine during lactation, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Inside, 1 time per day, with a sufficient 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.

Have elderly patients

Amlodipine-Agio is recommended for use in an average therapeutic dose, no dose adjustment is required.

Have patients with impaired liver function

Despite the fact that T1 / 2 amlodipine, like all BCCCs, is increased in patients with impaired liver function, dose adjustment is usually not required (see section "Special instructions").

Have patients with renal insufficiency

It is recommended to use Amlodipine-Agio in usual doses, however, it is necessary to take into account the possible slight increase in T1 / 2.

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

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.

From the central nervous system: often - headache, dizziness, fatigue, drowsiness; infrequently - asthenia, general malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia lability of mood, unusual dreams,increased excitability, depression, anxiety; 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, dryness of the mucous membrane of the cavity mouth, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity hepatic transaminases, hepatitis.

From the cardiovascular system: often - palpitations, peripheral edema (ankles and feet), "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 CHF, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

From the hematopoiesis: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

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

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: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema, erythema multiforme.

Other: infrequent - ringing in the ears, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, chills, nosebleeds, gynecomastia; very rarely - parosmosis, hyperglycemia.

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 for the first time 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 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.

Unlike other BCCC, clinically significant interaction of amlodipine was not detected when combined with non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin.

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

Although the study of amlodipine negative inotropic action is usually not observed, nevertheless, some BCCI may increase the severity of the negative inotropic effects of antiarrhythmic agents causing the lengthening of the interval QT (eg, amiodarone and quinidine).

A single dose of 100 mg of sildenafil in patients with essential 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 with a single and repeated application in a dose of 10 mg does not affect the pharmacokinetics of ethanol

Antiviral drugs (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 combined with amlodipine drugs lithium may increase the neurotoxicity symptoms (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not change the pharmacokinetics of cyclosporine.

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

Special instructions:

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

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.

Patients with severe impairment of liver function may require a smaller dose of the drug.

The efficacy and safety of the use of amlodipine-Ajio in hypertensive crisis is not established.

Despite the absence of the "cancellation" syndrome in BCC, it is advisable to stop Amlodipine-Agio treatment, gradually reducing the dose of the drug.

Effect on the ability to drive transp. cf. and fur:although in patients receiving amlodipine-Adzhio any negative effect on the ability to drive vehicles fire 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 in the early treatment and with increasing doses.

Form release / dosage:

Tablets of 5 and 10 mg.

Packaging:For 10 tablets in AL / PVC blister. 1 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry, protected from light 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 product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000005

Date of registration:15.10.2010

The owner of the registration certificate:Agio Pharmaceuticals Ltd.Agio Pharmaceuticals Ltd. India

Manufacturer: & nbsp

AGIO PHARMACEUTICALS, Ltd. India

Information update date: & nbsp18.10.2011

Illustrated instructions

Instructions

Amlodipine-Agio (Amlodipine-Agio)