· Symptomatic treatment of severe and / or disabling anxiety disorders

· Prevention and treatment of delirium tremens and other withdrawal symptoms, alcoholic

Reserved for the adult

Oral use.

The dosage at 0.25 mg is more suitable for the elderly, renal or hepatic impairment

Dose

In all cases, treatment will be initiated at the lowest effective dose and the maximum dose of 4 mg / day will not be exceeded.
Generally, in adults, treatment will be started at the dosage of 0.75 mg to 1 mg per day, divided into 3 doses as follows

· 0.25 mg in the morning and at noon and 0.25 mg at 0.50 mg in the evening.
The dosage will then be individually adjusted according to the therapeutic response.
In the elderly, renal or hepatic insufficiency: it is recommended to decrease the dosage, in half for example

The safety and efficacy of alprazolam have not been studied in children and adolescents under the age of 18 years. Its use is not recommended in this population.

Duration

Treatment should be as short as possible. The indication will be re-evaluated regularly, especially in the absence of symptoms. The overall duration of treatment should not exceed 8 to 12 weeks for the majority of patients, including the period of dose reduction (see section Caveats and Precautions for Use). >

In some cases it may be necessary to prolong treatment beyond the recommended periods. This requires accurate and repeated assessments of the condition of the patient.

Prevention and treatment of delirium tremens and other manifestations of withdrawal, alcoholic: short treatment of 8 to 10 days,

Anxiolytics

ATC code: N05BA12

(N: central nervous system)

Alprazolam belongs to the class of 1-4 benzodiazepines and has a pharmacodynamic activity qualitatively similar to that of other compounds of this class

· Myorelaxante

· Anxiolytic

· Sedative

· Hypnotic

· Anticonvulsant

· Amnesiante.

These effects are related to a specific agonistic action on a central receptor forming part of the complex, macromolecular receptors GABA-OMEGA, also called BZ1 and BZ2 and modulating the opening of the chlorine channel.

Prevent vehicle drivers and machine users from the possible risk of drowsiness, amnesia or impaired concentration or muscle function. Code>
The combination with other medicines sedative should be discouraged or taken into account in case of driving, automobile or machine use (see section Interactions with other medicinal products and other forms of interactions) Code>
If the duration of sleep is insufficient, the risk of altering vigilance is increased.

This medication should never be used in the following situations

· Hypersensitivity to the active ingredient or to any of the other ingredients

· Respiratory failure, severe

· Sleep apnea syndrome

· Hepatic impairment, severe, acute or chronic (risk of occurrence, encephalopathy)

· Myasthenia.

Warnings

This medicine contains lactose and is not recommended for use in patients with galactose intolerance, lapp lactase deficiency or malabsorption syndrome, glucose or galactose (hereditary or rare diseases). >

Pharmacological tolerance

The anxiolytic effect of benzodiazepines and related drugs may be decreased progressively despite the use of the same dose and if administered for several weeks

Dependency

Any treatment with benzodiazepines and related drugs, and more particularly in cases of prolonged use, may lead to a state of drug dependence, both physical and psychological.

Various factors seem to favor the occurrence of dependence

· Duration of treatment

· Dose

· History of other addictions, medicinal or not, including alcoholic.

Drug dependence may occur in doses, therapeutics and / or in patients without an individualized risk factor.


Symptoms of withdrawal may occur within a few days after discontinuation of therapy, and for short-acting benzodiazepines, especially if given at high doses, symptoms may even occur in The interval that separates two takes.

The combination of several benzodiazepines, whatever the anxiolytic or hypnotic indication, may increase the risk of drug dependence.

Since the risk of withdrawal is greater when the drug is suddenly stopped, it is recommended that the daily dose be gradually reduced (see section 4.4), Precautions for Use, Duration and Modalities of termination of the processing).

Cases of abuse have also been reported.

Rebound of anxiety

This transient syndrome, the symptoms of which initially motivated the treatment, by benzodiazepines, can manifest itself in a way that is exacerbated upon discontinuation of treatment.
This syndrome may be accompanied by other reactions including changes in mood, anxiety and sleep disorders and impatience.


Amnesia and alterations of psychomotor functions

Anterograde amnesia, as well as alterations of the psychomotor functions, are liable to appear within hours of taking.

Psychiatric and paradoxical reactions

In some subjects, benzodiazepines and related products may cause a syndrome associating degrees, alterations in the state of consciousness and behavioral and memory disorders

Can be observed

· Aggravation of insomnia, nightmares, restlessness, nervousness

· Delusions, anger, hallucinations, confusing-dream state, psychotic symptoms

· Disinhibition with impulsivity

· Euphoria, irritability, aggressiveness

· Anterograde amnesia

· Suggestibility

· Impatiences.

This syndrome may be accompanied by disorders that are potentially dangerous for the patient, or for others, such as
· Unusual behavior for the patient

· Self or hetero-aggressive behavior, especially if the entourage tries to hinder the patient's activity

· Automatic behavior with amnesia, post-event.

These manifestations force the cessation of treatment.

These behavioral disorders can occur more in children and elderly patients.

Risk of accumulation

Benzodiazepines and related drugs (like all drugs) persist in the body for a period of about 5 half-lives (see section Pharmacokinetics).

In elderly or patients with renal or hepatic impairment, the half-life may increase considerably. When taken repeatedly, the drug or its metabolites reach the equilibrium plateau, much later and at a much higher level. It is only after achieving an equilibrium plateau that it is possible to evaluate both the efficacy and safety of the drug.
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Dosage adjustment may be necessary (see Dosage and Mode of Administration).


Benzodiazepines and related products should be used with caution, in the elderly, because of the risk of sedation and / or muscle relaxant which may lead to falls, with often serious consequences in this population. >

It is recommended that the lowest effective dose be used in the elderly and / or the weakened subject in order to avoid the occurrence of ataxia or excessive sedation (see Dosage and Mode d 'Administration'.

Precautions for use

This medicinal product contains 0.176 mg sodium per tablet: take this into account in people on a strict sodium diet.

Extreme caution is advised in case of a history of alcoholism, or other dependencies, medicated or not (see section Interactions with other medicines and other forms of interactions).

In the subject with a major depressive episode

Benzodiazepines and related compounds should not be used alone, to treat depression because they cause or increase the risk of suicide. Thus, alprazolam should be used with caution and its prescription should be framed in patients with signs and symptoms of depressive disorder or suicidal tendencies. >
Duration and methods of progressive cessation of treatment (see section Dosage and mode of administration)

Treatment should be as brief as possible.

At the beginning of treatment, it may be useful to inform the patient that the duration of treatment will be limited.
The procedures for the progressive cessation of treatment must be stated, to the patient in a precise manner.

In addition to the necessity of gradually decreasing doses, patients should be warned of the possibility of a rebound phenomenon in order to minimize the anxiety that might arise from the symptoms related to this even progressive break. Code>
The patient should be warned of the possible uncomfortable nature of this phase
In the case of prolonged use of long-acting benzodiazepines, it is important to warn against passage to a short-acting benzodiazepine with withdrawal symptoms that may occur. Br>

Elderly, inadequate, renal, inadequate hepatic

Benzodiazepines and related products should be used with caution in patients with renal impairment or mild to moderate hepatic impairment
The risk of accumulation leads to a reduction in the dosage, for example by half (see Posology and method of administration).

Insufficient breathing

In the inadequate respiratory system, consideration should be given to the depressant effect of benzodiazepines and related compounds (especially as anxiety and agitation may constitute signs of decompensation Respiratory function that justifies switching to an intensive care unit.

Children and adolescents

The safety and efficacy of alprazolam have not been studied in children and adolescents under the age of 18 years. Its use is not recommended in this population.

Associations, deprecated

+ Alcohol

Enhancement by Alcohol of the Sedative Effect of Benzodiazepines and Cognates Altering alertness can make it dangerous to drive and use machinery

Avoid drinking alcoholic beverages and medicines containing alcohol

Associations to be taken into account

+ Other central nervous system depressants

Morphine derivatives (analgesics, antitussives and substitution treatments other than buprenorphine), neuroleptics including clozapine, barbiturates, other anxiolytics, hypnotics, sedative antidepressants, antihistamines H1, sedatives, central antihypertensive agents, baclofen, thalidomide, pizotifene.

Increased depression, central. The alteration of alertness can make dangerous the driving of vehicles and the use of machines.

Moreover, for morphine derivatives (analgesics, antitussives and substitution treatments), barbiturates: increased risk of respiratory depression, especially present in the elderly, which can be fatal in case of overdose. >

+; Clozapine

Increased risk of collapse with stop, respiratory and / or cardiac.

+; Buprenorphine

With buprenorphine, used in substitution treatment: risk, increased respiratory depression, which can be fatal

Carefully evaluate the benefit / risk ratio of this association. Inform the patient of the need to comply with the doses prescribed.

Not applicable.

The vital prognosis may be threatened, especially in cases of poly-intoxication involving other central nervous system depressants (including alcohol).
It is important to keep in mind that a polymedication may be responsible for an overdose.

In the case of massive intake, signs of overdose are predominantly depressed, the CNS may range from somnolence to coma, depending on the amount ingested. >
Mild cases are manifested by: drowsiness, signs of mental confusion, lethargy.


In case of prior oral overdose, vomiting will be induced at 1 hour, if the patient is conscious or, if not, gastric lavage with airway protection. Past, this time the administration of activated charcoal can reduce absorption.
The administration of flumazenil may be useful for the diagnosis and / or treatment of an intentional or accidental overdose of benzodiazepines.
Flumazenil antagonism of the effect of benzodiazepines may favor the development of neurological disorders (seizures), especially in the patient, epileptic.
>
Pregnancy

Numerous data from the cohort study did not demonstrate the occurrence of malformative effects during exposure to benzodiazepines during the first trimester of pregnancy.
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However, preliminary case-control epidemiological studies have shown an increase in the occurrence of labio-palatal clefts. The incidence of this symptom in neonates after taking benzodiazepines during pregnancy is less than 2/1000 compared to a rate of 1/1000 in the general population, according to
In the case of benzodiazepines, at high doses in the 2nd and / or 3rd trimesters of pregnancy, a decrease in fetal activity and fetal heart rate variability was described. >

Treatment at the end of pregnancy by benzodiazepines even at low doses may be responsible in the newborn for signs of impregnation such as axial hypotonia, suction disorders leading to low weight gain. These signs are reversible but may last 1 to 3 weeks depending on the half-life of the prescribed benzodiazepine. A high doses, reversible respiratory depression or apnea, and hypothermia may occur in the newborn. Furthermore, a neonatal withdrawal syndrome is possible even in the absence of signs of impregnation. It is characterized, in particular, by hyperexcitability, agitation and tremulousness, of the newborn occurring at a distance from childbirth .; The time of occurrence depends on the half-life, elimination of the drug and may be important When this one is long.

In view of these data, the use of alprazolam is possible during pregnancy whatever the term, in strict accordance with indications and dosages.
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At the end of pregnancy, if alprazolam treatment is necessary, avoid high-dose prescribing and take into account effects described above for monitoring the newborn. Br>

Breastfeeding

Alprazolam is excreted in low-concentration breast milk. However, the use of this medication during breast-feeding is not recommended.
The following adverse events were observed and reported in the course of taking the frequency treatment:

Very common (≥ 1/10), Common (≥ 1/100,