Hypertension.

Angina chronic stable.

Angina vasospastic (Prinzmetal syndrome).

Dosage

Adults

For hypertension and angina, the usual initial dosage is 5 mg of AMLOR once daily, which may be increased to a maximum dosage of 10 mg depending on the patient's individual response .

In hypertensive patients, AMLOR has been used in combination with a thiazide diuretic, an alpha blocker, a beta-blocker, or an angiotensin-converting enzyme inhibitor. In angina, AMLOR may be used as monotherapy or in combination with other anti-angina drugs in patients with angina, refractory to nitrates and / or adequate doses of beta-blockers. >

No dose adjustment of AMLOR is required for the concomitant administration of thiazide diuretics, β-blockers, and angiotensin converting enzyme inhibitors.
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Special Populations

Elderly subjects

AMLOR used in doses and similar shows equivalent tolerance in elderly patients and younger patients Normal dosing regimens are recommended, but in elderly patients an increase in dosage should be done with caution. See Warnings and Precautions, and Pharmacokinetics).
Patients with hepatic impairment

Dosage recommendations have not been established in patients with mild to moderate hepatic impairment so the dose should be selected with caution and should start at the lowest effective dose (see section 4.4). And precautions for use and pharmacokinetic properties). The pharmacokinetic properties of amlodipine have not been studied in patients with severe hepatic impairment. Amlodipine should be started at the lowest dose and increased slowly in patients with severe hepatic impairment

Patients with renal insufficiency

Changes in amlodipine plasma concentrations are not correlated with the degree of renal insufficiency, a usual dosage, is therefore recommended. Amlodipine is not dialyzable.

Children and adolescents

Children and adolescents with hypertension from 6 years to 17 years

The oral antihypertensive dose recommended in children aged 6 to 17 years is 2.5 mg once daily as an initial dose which can be increased to 5 mg once daily if the desired blood pressure Is not reached after four weeks. Dosages greater than 5 mg once daily have not been studied in pediatric patients (see sections on pharmacodynamic properties and pharmacokinetic properties).
An amlodipine dose of 2.5 mg is not possible with this medication.

Children under 6 years of age

There is no data available

Mode of administration

Capsule for oral administration.

Capsule gray with printing, AML 10 on one side and Pfizer logo on the other side

Class: Pharmacotherapeutic: calcium channel blocker, selective for predominantly vascular effect

ATC Code: C08 CA01.

Amlodipine is an inhibitor of calcium ion ions from the dihydropyridine group (slow channel inhibitor or calcium ion antagonist) and transmembrane influx of calcium ions into the heart muscle and muscles Vascular smooth.

The mechanism of the antihypertensive effect of amlodipine is related to a direct relaxing effect on the vascular smooth muscle. The precise mechanism by which amlodipine relieves, angina has not been fully determined, but amlodipine reduces the total ischemic load by the following two actions

1) Amlodipine dilates the peripheral arterioles and therefore reduces the total peripheral (postload) resistance against which the heart acts. To the extent that the heart rate remains stable, this reduction in heart work decreases myocardial energy consumption and oxygen requirements.

(2) The amlodipine mechanism of action also probably involves the dilation of the major coronary arteries and arterioles, coronary arteries in normal and ischemic regions.This dilation increases the delivery of oxygen to the myocardium in patients with A spasm of the coronary arteries (Prinzmetal's angina).

In hypertensive patients, once-daily administration provides clinically significant reductions in arterial pressure both in the supine position and in the standing position for an interval of 24 hours. Because of the slow action time, acute hypotension is not associated with administration of amlopidine.


Use in patients with coronary artery disease

The efficacy of amlopidine for the prevention of clinical events in patients with coronary artery disease has been evaluated in an independent, multicenter, randomized, double-blind, controlled, placebo-controlled study in 1,997 patients , The CAMELOT study (Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis, comparison of amlopidine and enalapril in the limitation of episodes of thrombosis). Of these patients, 663 were treated with amlopidine 5-10 mg, 673 were treated with enalapril 10-20 mg, and 655 with placebo, in addition to standard treatment with Statins, beta-blockers, diuretics and aspirin for two years. The main efficacy results are presented in Table 1. The results indicate that treatment with amlopidine has been associated with fewer hospitalizations for angina and revascularization procedures in patients; With coronary artery disease

Table 1. Incidence of Clinical Evaluation Criteria in the CAMELOT Study

Rate of events, cardiovascular, number (%)

Amlopidine versus placebo

Criteria, evaluation

Amlopidine

Placebo

Enalapril

Risk, Relative

(95% CI)

Value of p

Criterion, main

Events, undesirable cardiovascular

110 (16,6)

151 (23,1)

136 (20,2)

0.69 (0.54-0.88)

0.003

Components, individual

Revascularization, coronary

78 (11,8)

103 (15,7)

95 (14,1)

0.73 (0.54-0.98)

0.03

Hospitalization for angor

51 (7,7)

84 (12,8)

86 (12,8)

0.58 (0.41-0.82)

0.002

Non-fatal IDM

14 (2,1)

19 (2,9)

11 (1,6)

0.73 (0.37-1.46)

0.37

AVC or AIT

6 (0,9)

12 (1,8)

8 (1,2)

0.50 (0.19-1.32)

0.15

Mortality, cardiovascular

5 (0.8)

2 (0,3)

5 (0,7)

2.46 (0.48-12.7)

0.27

Hospitalization for ICC

3 (0,5)

5 (0.8)

4 (0,6)

0.59 (0.14-2.47)

0.46

Resuscitation after cardiac arrest

0

4 (0,6)

1 (0,1)

NA

0.04

Appearance of disease, peripheral vascular

5 (0.8)

2 (0,3)

8 (1,2)

2.6 (0.50-13.4)

0.24

Abbreviations: ICC, congestive heart failure, congestive heart failure, heart failure, heart failure, heart failure, heart failure, heart failure, heart failure, Code>
Use in patients with heart failure

Hemodynamic studies and controlled studies based on stress tests in patients with NYHA II-IV heart failure showed that AMLOR did not result in any clinical deterioration of tolerance; To the effort, the left ventricular ejection fraction and the clinical symptomatology

A placebo-controlled (PRAISE) study designed to evaluate patients with NYHA III-IV heart failure receiving digoxin, diuretics, and ACE inhibitors showed that AMLOR did not cause; No increased risk of mortality or mortality and morbidity combined with heart failure.

In a long-term, placebo-controlled follow-up study (PRAISE-2), on AMLOR in patients with NYHA III and IV heart failure without clinical symptoms or suggestive or underlying Ischemic disease, treated with stable doses of ACE inhibitors, digitalis and diuretics, AMLOR had no effect on total cardiovascular mortality. In this same population, AMLOR has been associated with an increase in notifications of pulmonary edema.
Treatment to Prevent (Heart Attack Trial, ALLHAT)

The randomized, double-blind, morbidity and mortality study of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Study on Antihypertensive and Lipid-Preventive Treatment of Heart Attacks) was conducted For comparison of recent treatments: amlodipine 2.5 to 10 mg / day (calcium channel blocker) or lisinopril 10 to 40 mg / day (ACE inhibitor) as a first-line treatment with a thiazide diuretic, Chlortalidone at a dose of 12.5 to 25 mg / day in mild to moderate hypertension
A total of 33,357 hypertensive patients aged 55 years or older were randomized and followed for an average of 4.9 years. Patients had at least one additional risk factor for coronary artery disease, including a history of myocardial infarction or stroke (more than six months before the inclusion) or documentation of other cardiovascular diseases Atherosclerotic (51.5%), type 2 diabetes (36.1%), HDL cholesterol,

Amlopidine may have a minor or moderate influence on the ability to drive, vehicles and use machines. If amlopidine-treated patients experience dizziness, headache, fatigue, or nausea, their ability to react may be impaired. Precautions are recommended especially at the beginning of treatment.

Amlodipine is contraindicated in patients with

· Hypersensitivity to derivatives of dihydropyridine, amlodipine or any of the excipients mentioned under Composition.


· A shock (including cardiogenic shock).

· An obstruction of the left ventricular ejection pathway (eg, high degree of aortic stenosis)

· Hemodynamically unstable heart failure after acute myocardial infarction

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


In a long-term, placebo-controlled study in patients with severe heart failure (NYHA III and IV), the reported incidence of cardiac insufficiency in patients with heart failure should be treated with caution. Pulmonary edema was greater in the treated group than amlodipine compared to the placebo group (see section 5.1 Pharmacodynamic properties) Calcium channel blockers including amlodipine should be used with caution in patients with deficiency Cardiac congestion because they may increase the risk of cardiovascular events and mortality.

Use in patients with impaired function, hepatic

The half-life of amlodipine is increased and its AUC (Area Under Curve) is greater, and in patients with hepatic impairment, dosage recommendations have not been established. Therefore, amlodipine should be initiated at the lowest effective dose, and cautiously, both during the initiation of treatment and when the dose is increased. Slow increase in dosage and careful monitoring may be required in patients with severe hepatic insufficiency


In elderly patients, an increase in the dosage should be made with caution (see sections 4.2 and 4.2).
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Use in patients with renal insufficiency

Amlodipine may be used in these patients at normal doses. Changes in plasma amlopidine concentrations were not correlated with the degree of renal insufficiency. Amlopidine is not dialysable

Effects of other medicines on amlopidine

Inhibitors of CYP3A4

The concomitant use of amlodipine with strong or moderate inhibitors of CYP3A4 (inhibitors, protease, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) Significant increase in amlodipine plasma concentration

The clinical translation of these pharmacokinetic variations may be more pronounced in the elderly. Therefore, clinical monitoring and dose adjustment may be necessary.


No data are available on the effect of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (eg, rifampicin, St. John's wort [Hypericum; perforatum]) may result in decreased plasma amlopidine concentration. Amlopidine should be used with caution with the inducers of the CYP3A4 isoenzyme.

Administration of amlopidine with grapefruit or grapefruit juice is not recommended because bioavailability may be increased in some patients, which may lead to increased hypotensive effects.

Dantrolene (infusion)

In animals, ventricular fibrillation and lethal cardio-vascular collapse were observed in association with hyperkalaemia following administration of verapamil and dantrolene IV. Because of the risk of hyperkalaemia, concomitant use of calcium channel blockers such as amlodipine in patients with malignant hyperthermia and in the management of hyperthermia should be avoided; Malignant.

Effects of amlodipine on other medicines

The hypotensive effects of amlodipine are in addition to those of other drugs with antihypertensive properties

In clinical interaction studies, amlodipine did not affect the pharmacokinetic properties of atorvastatin, digoxin or warfarin.

Ciclosporin

No interaction studies have been conducted with ciclosporin and amlodipine, and in healthy volunteers or other populations, with the exception of patients who underwent renal transplantation, Observed a variable increase in the minimum concentration of ciclosporin (from 0% to 40% on average). The ciclosporin level should be monitored in subjects having undergone renal transplantation and treated with amlodipine and a reduction in the dosage of ciclosporin should be considered if necessary

Simvastatin

Concomitant administration of repeated doses of 10 mg amlodipine with 80 mg simvastatin results in a 77% increase in exposure to simvastatin compared with simvastatin alone. The daily dose of simvastatin should be limited to 20 mg in patients treated with amlodipine.

Not applicable.

In humans, the experience of an intentional overdose is limited.

Symptoms

Available data suggest that significant overdosage may lead to excessive peripheral vasodilatation and possibly reflex tachycardia. Significant and probably prolonged systemic hypotension that may reach a shock with fatal outcome has been reported.
Processing

Clinically significant hypotension due to overdosage with amlodipine requires active cardiovascular support including frequent monitoring of respiratory and cardiac function, elevation of limbs, and management of blood volume and blood flow Urinary.

A vasoconstrictor may be useful, to restore vascular tone and arterial pressure, provided there is no contraindication to its use. Intravenous administration of calcium gluconate may be beneficial in reversing the effects of calcium channel inhibition.

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Since amlodipine is strongly bound to proteins, dialysis is unlikely to bring any benefit.

Pregnancy

In women, safety of use of amlodipine during pregnancy has not been established.

In animal studies, reprotoxicity was observed at high doses (see section Preclinical safety data).

Use during pregnancy is recommended only if no safer alternative is available and when the disease itself poses greater risks to the mother and the fetus. >

Breastfeeding

It has not been established whether amlopidine is excreted in human milk The decision to continue or discontinue breast-feeding or to continue or discontinue amlodipine should be Taking into account the benefit of breastfeeding for the child and the benefit of treatment with amlopidine for the mother.

Fertility

Biochemical and reversible changes in the head of the spermatozoa have been reported in some patients treated with calcium channel blockers. There is insufficient clinical data on the effect of amlopidine on fertility. In a study in the rat, adverse effects were detected on the fertility of males (see Preclinical safety data).

Security Profile Summary

The most commonly reported adverse reactions during treatment include drowsiness, dizziness, headache, palpitations, puffiness, vasomotor pain, abdominal pain, nausea, ankle edema, swelling and The fatigue.

List of adverse reactions

The following adverse reactions have been observed and reported in the course of treatment with amlopidine at frequencies: very common (≥ 1/10), frequent (≥ 1/100 to

In each frequency group, undesirable effects are presented in order of severity, decreasing.
Class of organ systems

Frequency

Undesirable effects

Blood and lymphatic system disorders

Very rarely

Leukocytopenia, thrombocytopenia

Immune system disorders

Very rarely

Allergic reaction

Disorders, metabolism and nutrition

Very rarely

Hyperglycemia

Psychiatric disorders

Uncommon

Depression, change in mood (including anxiety), insomnia

Rare

Confusion

Nervous system disorders

Common

Dizziness, dizziness, headache (especially at the beginning of treatment)

Uncommon

Tremor, dysgeusia, syncope, hypoesthesia, paresthesia

Very rare

Hypertonia, neuropathy, device

Eye disorders

Common

Visual disturbance (including, diplopia)

Ear and labyrinth disorders

Uncommon

Tinnitus
Cardiac disorders

Common

Palpitations

Uncommon

Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation)

Hypertension, Chronic stable angina, Vasospastic angina (Prinzmetal syndrome).
Very rare

Myocardial infarction

Vascular disorders

Common

Vasomotor flush

Uncommon

Hypotension

Very rare

Vasculitis

Respiratory, thoracic and mediastinal disorders

Common

Dyspnea

Uncommon

Cough, rhinitis

Gastrointestinal disorders

Common

Abdominal pain, nausea, dyspepsia, transit disorders (including diarrhea and constipation)

Uncommon

Vomiting, dry mouth

Very rare

Pancreatitis, gastritis, hyperplasia, gingival

Hepatobiliary disorders

Very rare

Hepatitis, jaundice, elevation of the hepatic enzyme *

Skin and tissue disorders, subcutaneous

Uncommon

Alopecia, purpura, change in skin color, hyperhidrosis, pruritus, rash, cutaneous, exanthema, urticaria
Very rare

Angioedema, erythema multiforme, exfoliating dermatitis, Stevens-Johnson's syndrome, angioedema, photosensitivity

Musculoskeletal, connective tissue and bone disorders

Common

Edema of the ankles, cramps, muscles

Uncommon

Arthralgia, myalgia, back pain

Renal and Urinary Tract Disorders

Uncommon

Urinary frequency disorder, nocturia, increased urinary frequency

Diseases of the reproductive organs and breast

Uncommon

Impotence, gynecomastia

General disorders and administration site abnormalities

Very common

Edema

Common

Fatigue, asthenia
Uncommon

Chest pain, pain, malaise

Investigations

Uncommon

Increased weight, decreased weight

* Challenging, usually cholestasis.

Exceptional cases of extrapyramidal syndrome have been reported.
Reporting of suspected adverse reactions

The reporting of suspected adverse effects after authorization of the drug is important. It provides continuous monitoring of the benefit / risk ratio of the drug. Healthcare professionals report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (Ansm) and network of Regional Centers, Pharmacovigilance -