Hypertension

Angina chronic stable

Vasospastic angina (Prinzmetal's syndrome)

Dosage

Adults

For hypertension and angina, the usual initial dose is AMLODIPINE ACTAVIS 5 mg once daily, which may be increased up to a maximum dose of 10 mg depending on the individual response of Patient.
In hypertensive patients, AMLODIPINE, ACTAVIS has been used in combination with a thiazide diuretic, an alpha blocker, a beta-blocker or an angiotensin-converting enzyme inhibitor. In angina, AMLODIPINE ACTAVIS may be used as monotherapy or in combination with other antianginal drugs in patients with angina, refractory to nitrates and / or adequate doses of beta-blockers.

No dose adjustment of AMLODIPINE and ACTAVIS is required when concomitant thiazide diuretics, β-blockers and angiotensin converting enzyme inhibitors

Populations, special

Elderly subjects

AMLODIPINE ACTAVIS used at similar doses shows good tolerance, equivalent in elderly patients and younger patients. Normal dosage regimens are recommended in elderly patients, but an increase in dosage should be done with caution (see Warnings and Precautions for Use and Pharmacokinetic Properties).
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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

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 dosage recommended in children aged 6 to 17 years is 2.5 mg once daily as an initial dose which can be increased up to 5 mg once a day 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.

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

ATC Code: C08 CA01.

Amlodipine is an inhibitor of calcium ion influx from the group of dihydropyridine (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 the administration of amlodipine.

In patients with angina, once-daily administration of amlodipine increases the total duration of exercise, the time of occurrence of angina and sub-shift, and the ST segment Of 1 mm, and decreases both the frequency of angina attacks and the consumption of glyceryl trinitrate tablets.
Amlodipine has not been associated with undesirable metabolic effects or changes in plasma lipids and is suitable for patients with asthma, diabetes and gout. Br>

Use in patients with coronary artery disease

The efficacy of amlodipine for the prevention of clinical events in patients with coronary artery disease was evaluated in an independent, multicenter, randomized, double-blind, placebo-controlled study conducted at 1 997 patients: the CAMELOT study (Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis, comparison of amlodipine and enalapril in the limitation of episodes of thrombosis). Of these patients, 663 were treated with amlodipine, 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 shown in Table 1. The results indicate that treatment with amlodipine has been associated with a lower number of hospitalizations for angina and revascularization procedures in patients Of coronary artery disease

Table 1. Incidence, Significant Clinical Evaluation Criteria for the CAMELOT Study

Rate of cardiovascular events, number (%)

Amlodipine versus placebo

Criteria, evaluation

Amlodipine

Placebo

Enalapril

Relative risk (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

IDM not fatal

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, IC, confidence interval, MI, myocardial infarction, AIT, transient ischemic stroke, stroke, cerebral.
Use in Patients with Heart Failure: Studies, haemodynamic and controlled studies, based on stress tests conducted in patients with NYHA II-IV heart failure, Amlodipine did not result in any clinical deterioration of tolerance to exercise, left ventricular ejection fraction and 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 amlodipine Did not result in an increased risk of mortality, or mortality and morbidity combined with heart failure.

In a long-term, placebo-controlled follow-up study (PRAISE-2), amlodipine in patients with NYHA III and IV cardiac insufficiency without clinical symptoms, nor suggestive or underlying objective results; To ischemic disease, treated with stable doses of ACE inhibitors, digitalis and diuretics, amlodipine had no effect on total cardiovascular mortality. In this same population, amlodipine was associated with an increase in notifications of pulmonary edema.


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,
Use in renal insufficiency

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

Effects of Other Medicines on Amlodipine

Inhibitors of CYP3A4: concomitant use of amlodipine with strong or moderate inhibitors of CYP3A4 (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil, or diltiazem) may give Lead to a 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.


Concomitant use of CYP3A4 inducers (eg rifampicin, St. John's wort [Hypericum perforatum]) may result in decreased plasma amlodipine concentration, amlodipine should be used with caution, and with inducers Of the CYP3A4 isoenzyme.

Administration of amlodipine 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 the administration of verapamil and dantrolene IV. In view of the risk of hyperkalaemia, concomitant use of calcium channel blockers such as amlodipine in patients with malignant hyperthermia and in the management of malignant hyperthermia is recommended.

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, warfarin or ciclosporin.
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Simvastatin: Co-administration of repeated doses of 10 mg of amlodipine with 80 mg of 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 amlodipine patients.

In humans, the experience of 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 amlodipine is excreted in breast 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 amlodipine 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 amlodipine on fertility. In a study in the rat, undesirable effects were detected on the fertility of males (see section Safety data, preclinical). >
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 undesirable effects

The following adverse reactions have been observed and reported in the course of treatment with amlodipine 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 systems, organs

Frequency

Undesirable effects

Hematologic and lymphatic system disorders

Very rare

Leukocytopenia, thrombocytopenia

Immune system disorders

Very rare

Allergic reaction

Metabolism and nutrition disorders

Very rare

Hyperglycemia

Psychiatric disorders

Uncommon

Insomnia, change in mood (including anxiety), depression

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

Uncommon

Visual disturbance (including, diplopia)

Ear and labyrinth disorders

Uncommon

Tinnitus
Cardiac disorders

Common

Palpitations

Very rare

Myocardial infarction, arrhythmia (including bradycardia, ventricular tachycardia and fibrillation, atrial)

Vascular disorders

Common

Vasomotor flush

Uncommon

Hypotension

Very rare

Vasculitis

Respiratory, thoracic and mediastinal disorders

Uncommon

Dyspnea, rhinitis

Hypertension, chronic stable angina, vasospastic angina (Prinzmetal syndrome)

Very rare

Cough

Gastrointestinal disorders

Common

Abdominal pain, nausea

Uncommon

Vomiting, dyspepsia, transit disorders (including diarrhea and constipation), dry mouth

Very rare

Pancreatitis, gastritis, hyperplasia, gingival

Hepatobiliary disorders

Very rare

Hepatitis, jaundice, elevation of liver enzymes *

Skin and tissue disorders, subcutaneous

Uncommon

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

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