· Prinzmetal’s Angor.

· Angina stable in combination with beta-blockers, when other anti-anginal therapies are contraindicated or insufficiently effective

· Symptomatic treatment of Raynaud's phenomena

Oral use. The capsule is to be swallowed without chewing with a little liquid

· Angor

In the angina of Prinzmetal, the recommended dosage is 1 capsule 4 times a day of which one at bedtime.

In stable angina, the usual dosage is 1 capsule 3 times daily in combination with a beta-blocker administered at an effective dosage. >
The maximum dosage is 60 mg / day.
· Phenomena of Raynaud: the usual dosage is 1 capsule 3 times a day.



Treatment should be initiated with caution in patients who may have an excessive reaction with nifedipine.
The interval between 2 doses of ADALATE 10 mg should be at least 2 hours.

Special Populations

Children and adolescents

The safety and efficacy of ADALATE 10 mg capsule have not been studied in children under the age of 18 years. The data currently available on the use of nifedipine in hypertensive arterial hypertension are described in the section "Pharmacodynamic properties."
Elderly patient

Since the bioavailability of nifedipine is increased in elderly patients, ADALATE 10 mg capsule should be administered with caution in this population.
Hepatic impairment

Because of its hepatic metabolism, nifedipine should be administered under supervision in patients with impaired hepatic function. Furthermore, there are no clinical data in patients with severe hepatic impairment

Renal insufficiency

There are no clinical data for renal failure. ADALATE 10 mg capsule should be administered with caution to these patients.
CALCIUM SELECTIVE INHIBITORS WITH EFFECTS, VASCULAR -

ATC code: C08CA05

Nifedipine is a calcium antagonist belonging to the dihydropyridine family. Nifedipine selectively inhibits, at very low concentrations, the entry of calcium ions into the voltage-type L-type channels and is mainly applied to the smooth muscle, vascular and to a lesser extent Of the heart muscle

Nifedipine decreases arterial vascular tone by this mechanism and results in peripheral and coronary vasodilation. Under normal conditions of coronary perfusion, the decrease in the post-load caused by nifedipine contributes to a decrease in cardiac work and normal or ischemic oxygen consumption of the myocardium

Nifedipine, by dilating the coronary arteries of the endocardium and epicardium, ensures an increase in oxygen supply to the heart.

The increase in coronary flow is particularly marked in the myocardium, non-ischemic, and has also been demonstrated within the ischemic myocardium, provided, however, that the coronary perfusion pressure does not drop excessively, A phenomenon of coronary theft may occur, leading to a paradoxical exacerbation of angina attacks These exacerbations are the consequence of hypotension, excessive (decreased coronary flow) and tachycardia, reflex (increased cardiac work And the consumption of oxygen).

By inhibiting the entry of calcium, in the cardiac myocyte nifedipine, like other calcium channel blockers, is inotropic negative.

This effect is normally neutralized by the reflex stimulation of the sympathetic and renin-angiotensin systems, following the deactivation of the baroreflexes.
In case of excessive blood pressure hypotension, an increase in heart rate and ventricular arrhythmias can be observed.

Thanks to their complementary mechanisms of pharmacological action, the association of nifedipine with beta-blockers leads to a synergy of effect.

In animals, according to the model used, nifedipine inhibits the accumulation of cholesterol in the walls of the aorta and arteries, conduction, decreases migration and proliferation, smooth muscle cells

In prolonged treatment, no weight gain was observed. This element is in favor of a lack of hydro-sodium retention.

Nifedipine does not alter lipid and carbohydrate metabolism

Population, pediatric

The comparison data between nifedipine and other antihypertensive agents in acute hypertension and long-term hypertension are limited and concern different formulations and dosages.

The antihypertensive effects of nifedipine have been demonstrated but dosage recommendations, tolerance and long-term cardiovascular effects have not been established. There are no forms, pediatric.

Drug reactions, which vary from one individual to another, may impair the ability to drive or use machines. Especially at the beginning or in case of modification of the treatment and in association with alcohol.

This medicinal product should not be used in the following cases

· Known hypersensitivity to nifedipine, or to any of the excipients

· Myocardial infarction dating less than 1 month

· Unstable angina (see section Caveats and precautions for use)

· Cardiovascular shock (see section Caveats and precautions for use)

· In association with diltiazem (see section Interactions with other medicinal products and other forms of interactions)

This medication is generally not recommended during pregnancy or lactation (see section Pregnancy and lactation).


The use of this drug with ciclosporin or dantrolene administered as an infusion is not recommended (see section Interactions with other medicinal products and other forms of interaction).

This specialty should not be administered in case of acute elevation: sublingual use of nifedipine by causing excessive and sudden drops in blood pressure may result in ischemic strokes. Nifedipine is not indicated in high blood pressure.

As with any molecule, vasoactive, angina pectoris can very rarely be observed especially at the beginning of treatment with immediate-release nifedipine
In patients with angina pectoris, an increase in angina frequency, duration and severity of seizures can be observed, especially in the early stages of treatment. >

Isolated cases of myocardial infarction have been described without being able to differentiate them from the usual course of the underlying disease (see section Effects, undesirable). >

Precautions for use

· Association with beta-blockers: in the coronary heart disease, stable angina, the introduction of treatment with nifedipine capsule requires prior treatment with effective beta-blocker. It will be performed under special medical supervision, in subjects, in latent heart failure (see section Interactions with other medicinal products and other forms of interactions). >
Caution is recommended in patients under precarious hemodynamic conditions (hypovolemia, severe hypotension with pressure, systolic lower than 90 mmHg, collapse, severe ventricular systolic dysfunction, left, clinically significant heart failure, severe aortic stenosis).

· In case of severe constipation it is advisable to administer lubricants to avoid the excessive aggravation of constipation

· For use in particular populations see section Posology and method of administration

This medicinal product contains an azo dye (E110) and may cause allergic reactions.


+; Diltiazem

Significant increase in concentrations of nifedipine by decreased metabolism, liver by diltiazem, with risk of hypotension, severe

Associations, deprecated

+; Ciclosporin

Risk of Addition of Adverse Events to Gingiva Type

Use another dihydropyridine

+ Dantrolene administered by infusion

In animals, cases of fatal ventricular fibrillations are constantly observed during the administration of verapamil and dantrolene IV The combination of a calcium antagonist and dantrolene is therefore potentially dangerous Br>

However, a few patients have received the combination of nifedipine and dantrolene without any inconvenience.


+; Baclofen

Increased effect, antihypertensive.

Blood Pressure Monitoring and Dosage Adjustment of the Antihypertensive Medication If Needed

+ Phenytoin

Increase in plasma concentrations of phenytoin with signs of overdose (in particular neurological). Mechanism invoked, displacement of protein binding of phenytoin and inhibition of its metabolism

Clinical monitoring and reduction of phenytoin doses as soon as signs of overdosage appear. Controlling phenytoin plasma concentrations

+ Strong inhibitors of CYP3A4.

Adverse effects of nifedipine, most commonly of type, hypotension, especially in the elderly

Clinical monitoring and adaptation, dosage during enzymatic inhibitor treatment and after discontinuation

+ Cimetidine (³ 800 mg / d)

Increase in the hypotensive effect of nifedipine by inhibition of its hepatic metabolism by cimetidine

Increased clinical monitoring, adjusting the dosage of nifedipine during treatment with cimetidine and after discontinuation.

+ Azole antifungals (i.e. Itraconazole, Ketoconazole)

Increased risk of adverse effects, including edema, by decreased hepatic metabolism of dihydropyridine

Clinical monitoring and possible adaptation of the dosage of dihydropyridine during treatment with azole antifungal and after its discontinuation

+ Anticonvulsants enzymatic inducers (carbamazepine, phenobarbital, phenytoin, primidone, fosphenytoin)

Decreased plasma concentrations of nifedipine by increasing its metabolism, liver by inducer

Clinical monitoring and possible adaptation of nifedipine dosage during treatment with inductor and after discontinuation

+; Rifampicin

Decreased plasma concentrations of nifedipine by increasing its metabolism, hepatic

Clinical monitoring and possible adaptation of the dosage of nifedipine during treatment with rifampicin and after its discontinuation

Associations to be taken into account

+ Arterial pressure-lowering drugs

Increased risk of hypotension, especially orthostatic.

+ Adrenergic alpha-adrenergic blocking agents including urologic (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin, trimazosin, urapidil)
Increase in hypotensive effect. Risk of increased orthostatic hypotension.

+ Amifostine

Increase in hypotension by addition of adverse effects

+ Antidepressants imipraminic, neuroleptic

Antihypertensive effect and risk of elevated orthostatic hypotension (additive effect)

+; Beta-blockers (except esmolol)

Hypotension, heart failure in patients with latent or uncontrolled heart failure. The presence of beta-blocking therapy can minimize the reflex sympathetic reaction in case of excessive haemodynamic repercussion and unmask a negative inotropic effect which may be added to that of the beta-blocker. Br>

In patients with heart failure treated with beta-blocker (bisoprolol, carvedilol, metoprolol or nebivolol), concomitant administration of nifedipine requires close monitoring of the patient due to aggravation of heart failure in Of isolated cases.

Glucocorticoids (except hydrocortisone for the treatment of substitution) and mineralocorticoids.

Decreased antihypertensive effect (hydrosodic retention of corticosteroids).

Not applicable.

The following symptoms are observed in case of overdose

An increase in heart rate, hypotension, cardiac arrhythmias, bradycardia / tachycardia, shock, cardiogenic pulmonary edema, hyperglycaemia, metabolic acidosis, hypoxia, impaired consciousness Up to the coma.
In the case of overdose, priority is based on the elimination of the active substance and the restoration of cardiovascular stability.
After oral ingestion of the product, thorough gastric lavage is recommended, with irrigation of the small intestine if necessary and intensive care unit supervision

In particular, in cases of poisoning, with prolonged-release forms, elimination should be as complete as possible, including in the small intestine, in order to avoid prolonged absorption of the substance; Active

Hemodialysis is not useful because nifedipine is not dialyzable, however, plasmapheresis is possible (considering the large plasma protein binding and the relatively low volume of distribution).

The bradycardia can be treated symptomatically by the administration of β-sympathomimetics, the temporary placement of a pacemaker is recommended if this disorder of the rhythm threatens the prognosis, vital.

In case of massive overdose: calcium gluconate perfusion appears to be indicated (10-20 ml, 10% calcium gluconate solution, slow IV administration, repetitively if necessary)

This action may increase serum calcium up to the upper limit of normal, or even slightly beyond.) If calcium effects prove to be inadequate, treatment will be continued by the addition of sympatho Vasoconstrictors, such as dopamine, or noradrenaline, at dosages based solely on the effects obtained.

Maintain rhythm, conduction and cardiac output. Significant hypotension may be controlled by careful IV infusion of any mode of volumic expansion taking into account the risk of water overload
In all cases inform of the concomitant taking of beta-blockers.

Pregnancy

Animal studies have demonstrated a teratogenic and fetotoxic risk of nifedipine.

In clinical studies, no malformative or fetotoxic effects have appeared to date.
However, the monitoring of pregnancies exposed to nifedipine is insufficient, to date to be able to exclude any risk.

Therefore, use of nifedipine is not recommended during pregnancy and in women of childbearing age who do not use contraception. However, the discovery of a pregnancy under nifedipine does not justify the interruption.

In the case of first-trimester exposure, pregnancy, prenatal-oriented monitoring, on the heart and the skeleton can be considered.

Breastfeeding

Nifedipine passes into the maternal milk. Therefore, as a precautionary measure, the administration of this medicinal product should be avoided if possible in the case of nursing mothers.

The risk of hypotension and / or decompensation of cardiac insufficiency should be given particular attention.
Code>
Adverse reactions classified as "frequent" were observed with an incidence of less than 3%, with the exception of edema (9.9%) and headache (3.9%). Br>

The frequency of undesirable effects reported with products containing nifedipine is summarized in the table below. In each frequency group, undesirable effects are presented in order of decreasing safety.
The frequencies are defined, as follows

· Common: ≥ 1/100 to