PRAZEPAM EG - GENERIC DRUG - PACKAGE LEAFLET - LEAFLETS

Home / leaflets / 2021

Prazepam EG - Generic Medication - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Prazepam

PRAZEPAM EG 10 mg tablets
PRAZEPAM EG 20 mg tablets
PRAZEPAM EG 15 mg / ml oral drops, solution

Why is Prazepam EG - Generic Medication used? What is it for?

The active substance contained in Prazepam EG is prazepam. Prazepam is a benzodiazepine derivative and is indicated for the treatment of anxiety symptoms.

Benzodiazepines are used to treat severe disabling symptoms or symptoms that place the patient in severe distress.

Prazepam EG is used to treat anxiety and nervous tension that require sedative treatment.

Contraindications When Prazepam EG should not be used - Generic drug

DO NOT take Prazepam EG

if you are allergic (hypersensitive) to prazepam or any of the other ingredients of Prazepam EG.
if you have a history of allergic reactions to other benzodiazepines
if you suffer from glaucoma (an eye disorder characterized by increased pressure in the eye) or severe myasthenia (muscle weakness)
if you have severe breathing difficulties
in children under 6 years of age
if you suffer from sleep apnea syndrome (when you stop breathing for a short time during sleep)
if you have severe liver failure (severe liver disease)

Precautions for use What you need to know before taking Prazepam EG - Generic drug

Take special care with Prazepam EG

It is recommended that Prazepam EG be used only for the treatment of nervous disorders mostly characterized by anxiety. Therefore, if you suffer from severe mental illness, prazepam will only be given to you as an additional treatment.
if you are elderly or physically debilitated you may develop mild drowsiness and / or decreased mental acuity while exercising as well as decreased muscle tone.
if you are elderly or severely debilitated, start treatment with 10 or 15 mg of prazepam (divided over the course of the day) and increase the dose thereafter if necessary.
if you have chronic, non-specific breathing difficulties and dyspnoea (shortness of breath) your doctor will prescribe a lower dose.
adolescents between the ages of 12 and 17 will receive a reduced dose depending on their age and body weight.
tell your doctor if you have kidney or liver problems (see section "Do not take Prazepam EG").
benzodiazepines can cause addiction. The risk of addiction increases with dose and duration of treatment and in patients with a history of alcoholism or drug addiction. In this case, a sudden discontinuation of the treatment can cause the appearance of withdrawal symptoms, such as: headache, muscle pain, extreme anxiety, tension, confusion and irritability. In severe cases, the following symptoms may occur: derealization (when things seem strange or unreal), depersonalization (when you have an altered perception of yourself), hyperacusis (when you are unable to tolerate everyday noises) numbness and tingling of the hands and feet (pins and needles), hypersensitivity to light, noise and physical contact, hallucinations (when perceiving things that are not real), seizures
the interruption of the treatment can activate a syndrome of short duration, due to which the original symptoms can recur in an aggravated form. Other reactions such as mood alterations, sleep disturbances, convulsions, tremors, muscle and abdominal cramps, vomiting may occur , sweating and shaking. The risk of withdrawal symptoms or rebound phenomena increases significantly when treatment is stopped abruptly, therefore the doctor will reduce the dose gradually.
you may experience rebound anxiety when stopping treatment with Prazepam EG.
You must take Prazepam EG for the shortest possible time, depending on the disease you suffer from, and for no longer than 8-12 weeks, including the tapering period. Your doctor will need to re-evaluate your condition before you can take Prazepam for a longer period of time.
benzodiazepines can cause short-term memory loss, which usually happens within hours of ingesting the medicine.
extreme caution is required in case of alcoholism or drug addiction.
if you are already taking other medicines please also read the section "Taking Prazepam EG with other medicines".

Interactions Which drugs or foods may change the effect of Prazepam EG - Generic drug

Prazepam EG should not be used at the same time as other medicines that can impair brain activity such as:

Narcotics
Anesthetics
Anticonvulsants
Sedative antihistamines
Barbiturates
Antidepressants
Antipsychotics
Monoamine oxidase inhibitors
Hypnotics
Anxiolytics / sedatives
Pain relievers

The combination of benzodiazepines and valproic acid increases the risk of psychosis (lack of contact with reality).

Any combination of benzodiazepines and clozapine should be carefully considered. In this case, the doctor will decide to reduce the benzodiazepine dose at the start of treatment.

Combination with cimetidine or omeprazole (medicines to treat ulcers) may cause a prolongation of the effect of Prazepam EG.

The combination with oral contraceptives (the pill) and with additional hormone treatments, eg hormone replacement therapy, may enhance the effect of Prazepam EG. The use of narcotic analgesics (eg morphine) can make you more euphoric with a consequent increase in psychological dependence (addiction).

Theophylline (a medicine to treat asthma) antagonizes the pharmacological effect of benzodiazepines.

The combination of prazepam and buprenorphine is only possible after careful consideration of the risk / benefit ratio. Consult your doctor before taking Prazepam EG.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Taking Prazepam EG with food and drink

Prazepam EG should not be used at the same time as other medicines that can impair brain activity, including alcohol.

Do not drink alcohol during the treatment. In case of concomitant alcohol intake, an enhancement of the sedative effect of Prazepam EG is possible with probable consequences on your ability to drive and use machines.

Warnings It is important to know that:

Pregnancy and breastfeeding

Do not take Prazepam EG if you are pregnant or think you are pregnant. Tell your doctor if you are pregnant or planning to become pregnant. In particular, Prazepam EG should not be taken in the first three months of pregnancy.

Prazepam should not be taken during childbirth.

Tell your doctor if you are breastfeeding. Do not take prazepam if you are breastfeeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Depending on your individual sensitivity, the following side effects may occur:

Drowsiness and / or impaired ability to concentrate
Amnesia (memory loss)
Lack of concentration
Reduced muscle function
Reduced muscle tone
Slowing of reflexes

These effects may impair your ability to drive or use machines. The risk of a reduction in concentration is greater in the face of insufficient sleep duration. Therefore, be especially careful when driving or using dangerous tools, especially at the beginning of the treatment.

Important information about some of the ingredients of Prazepam EG

Prazepam EG tablets contain lactose. If your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Dose, Method and Time of Administration How to use Prazepam EG - Generic drug: Posology

Always take Prazepam EG in strict accordance with the prescriptions of your doctor. If in doubt, consult your doctor or pharmacist.

All formulations of Prazepam EG are intended for oral use.

Your doctor will decide the daily dose for you. The usual dose is between 10 and 60 mg of prazepam, depending on how you respond to the medicine.

For elderly patients

If you are elderly or severely debilitated, start treatment with 10 or 15 mg of prazepam (divided over the course of the day) and increase the dose thereafter if necessary.

For adolescents (12 to 17 years of age)

If you are under 18 the dose will be adjusted according to your age and body weight. The maximum dose corresponds to 1 mg / kg of body weight per day.

Duration of treatment

Your doctor will tell you how long to take Prazepam EG for. In many cases it is necessary to take benzodiazepines occasionally or temporarily, i.e. for a short time. Sometimes the state of health requires the use of Prazepam EG to continue for longer periods.

Whenever benzodiazepines are used for longer periods, your doctor will regularly assess the need for you to continue treatment.

It is important that caution is exercised upon discontinuation of treatment.

Patients with liver or kidney disease

Consider administration of reduced doses in patients with impaired renal or hepatic function.

If you forget to take Prazepam EG

If you have forgotten your dose, take the next one at the usual time. Do not take a double dose of Prazepam EG to make up for a forgotten dose.

If you stop taking Prazepam EG

Never stop taking Prazepam EG suddenly, especially if you have been taking it for a long time. Symptoms may appear after abruptly stopping long-term benzodiazepine treatment (see "Take special care with Prazepam EG"). Always talk to your doctor who will explain how to gradually reduce the dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Overdose What to do if you have taken too much Prazepam EG - Generic drug

The visible signs of an overdose are fatigue, sometimes associated with uncoordinated movements and confusion. As in all cases of overdose, consider the possibility of the involvement of several substances (ie that other substances have been taken at the same time).

Side Effects What are the side effects of Prazepam EG - Generic drug

Like all medicines, Prazepam EG can cause side effects, although not everyone gets them. The reported undesirable effects are summarized in the table below by system and frequency. Frequencies are defined as follows:

Very common: affects more than 1 in 10 patients

Common: affects 1 to 10 users in 100

Uncommon: affects 1 to 10 users in 1,000

Rare: affects 1 to 10 users in 10,000

Very rare: affects less than 1 in 10,000 patients

Not known: frequency cannot be estimated from the available data

The following side effects have been identified following the use of benzodiazepines in general. Most of them appear at the start of treatment and usually disappear with subsequent administrations.

Blood and lymphatic system disorders: Rare: blood disorders (agranulocytosis).

Cardiac disorders: Common: heart palpitations

Eye disorders: Uncommon: blurred vision, double vision

Gastrointestinal disorders: Common: dry mouth, various gastrointestinal disorders

General Disorders and Administration Site Conditions: Common: Fatigue, weakness, libido disturbance, drunkenness

Hepatobiliary disorders Rare: jaundice Investigations: Rare: reduced bile production

Musculoskeletal and connective tissue disorders: Common: joint pain Uncommon: swollen feet

Nervous system disorders: Very common: somnolence Common: drowsiness, dizziness, bouts of confusion, uncoordinated movements, headache, tremors, self-expression problems Uncommon: syncope, impaired consciousness, memory impairment (especially if is elderly), seizures, reduced alertness

Psychiatric disorders: Common: confusion, vivid dreams Uncommon: agitation, irritability, worsening of insomnia, aggression, worsening of anxiety, confusion Rare: multiple personality, depression, psychosis, apathy or paradoxical reactions, persecution mania

Renal and urinary disorders: Uncommon: various genital and urinary symptoms

Reproductive system and breast disorders: Rare: menstrual, ovulatory and sexual disorders Very rare: breast enlargement in men (gynaecomastia)

Respiratory, thoracic and mediastinal disorders: Not known: respiratory depression in patients with chronic nonspecific respiratory disease.

Skin and subcutaneous tissue disorders: Common: periods of severe sweating, temporary rash Uncommon: pruritus Very rare: hypersensitivity to external substances, anaphylactic shock

Amnesia:

Memory loss (anterograde amnesia) is possible even after administration of Prazepam EG at therapeutic doses. The risk increases at higher doses. The effects of memory loss may be associated with inappropriate behavior (see section "Take special care with Prazepam EG").

Depression:

Latent depression may become evident during treatment with benzodiazepines.

Psychiatric and paradoxical reactions: Reactions such as:

Agitation
Irritability
Aggression
Delirium (sudden inability to focus attention)
Attacks of anger
Nightmares
Hallucinations (perception of things that are not actually present)
Psychosis (mental disorders)
Inappropriate behavior and other behavioral problems

are reactions known to occur during treatment with benzodiazepines or benzodiazepine-like medicines. These reactions can also be relatively dangerous and occur more frequently in elderly patients.

If you notice worsening of any side effects or the onset of side effects not mentioned in this leaflet, please tell your doctor or pharmacist.

Expiry and Retention

Keep out of the reach and sight of children.

This medicinal product does not require any special storage conditions.

Drops: Prazepam EG 15 mg / ml oral drops, solution should be used within 30 days of first opening.

Do not use Prazepam EG after the expiry date which is stated on the carton, blister or bottle after EXP. The expiry date refers to the last day of the month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Other Information

What Prazepam EG contains

The active ingredient is: prazepam.

Each tablet contains 10 mg or 20 mg of prazepam.

Each ml of solution contains 15 mg of prazepam (equivalent to 30 drops).

The other excipients are:

Prazepam EG 10 mg tablets:

Lactose monohydrate

Microcrystalline cellulose

Cornstarch

Magnesium stearate

Indigo carmine lacquer (E132)

Prazepam EG 20 mg tablets:

Lactose monohydrate
Microcrystalline cellulose
Cornstarch
Magnesium stearate
Colloidal silica

Prazepam EG 15 mg / ml oral drops, solution:

Propylene glycol
Monoethylether diethylene glycol
Sodium saccharin
Polysorbate 80
Menthol
Anethole
Patent blue V (E 131)

What Prazepam EG looks like and contents of the pack

Prazepam EG 10 mg tablets are available as blue scored tablets in aluminum / PVC blister packs of 20, 30, 40 and 50 tablets. The tablet can be divided into equal halves.

Prazepam EG 20 mg tablets are available as white scored tablets in aluminum / PVC blister packs of 20 and 50 tablets. The tablet can be divided into equal halves.

Prazepam EG 15 mg / ml oral drops, solution is available in 20 ml bottles with droppers. 30 drops of solution correspond to 1 ml and therefore to 15 mg of prazepam.

Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

More information on Prazepam EG - Generic drug can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

PRAZEPAM EG

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Prazepam EG 10 mg tablets

Each tablet contains 10 mg of prazepam.

Excipients: lactose 119.60 mg

Prazepam EG 20 mg tablets

Each tablet contains 20 mg of prazepam.

Excipients: lactose 83.80 mg

Prazepam EG 15 mg / ml oral drops, solution

Each ml contains 15 mg of prazepam (equivalent to 30 drops).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Tablets.

Prazepam EG 10 mg tablets

Flat, round, blue tablets with a notch on one side.

Prazepam EG 20 mg tablets

Flat, round, white tablets with a notch on one side.

The tablet can be divided into equal halves.

Oral drops, solution.

Prazepam EG 15 mg / ml oral drops, solution

Blue colored solution with characteristic smell and taste of mint and anethole.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Symptomatic treatment of anxiety.

Benzodiazepines are indicated only when the disorder is severe and disabling or makes the subject very uncomfortable.

04.2 Posology and method of administration

Adults

The recommended dose should correspond to 10-30 mg / day. Higher doses up to 60 mg should be reserved for psychiatric patients suffering from particularly severe anxious conditions.

This dosage can be given as a single dose or in divided doses over 24 hours, for example:

a) One full dose in the evening or

b) ¼ of the dose in the morning, ¼ at noon and ½ in the evening or

c) ½ of the dose in the morning, ½ in the evening

Elderly patients

In elderly or debilitated patients it is recommended to start treatment with a dose of 10 or 15 mg of prazepam, to be administered in divided doses throughout the day and subsequently increased if necessary. It is usually sufficient to halve the doses to achieve the therapeutic response (see section 4.4).

Adolescents (12 to 17 years of age)

In children under the age of 18 it is recommended that the dose be adjusted according to the age and weight of the patient. The dose should not exceed 1 mg per kg body weight per day.

Children

No clinical data are available regarding the use of prazepam in children less than 6 years of age (see sections 4.3, 4.4).

For all patients

In some cases the patient's health status may require long-term administration. In all cases where benzodiazepines are used for a prolonged period it is necessary for the doctor to regularly re-evaluate the patient's condition. Caution is advised upon discontinuation of treatment.

Consider dose reduction in patients with reduced renal function or mild to moderate hepatic impairment.

Duration of treatment

The duration of treatment should be as short as possible. The patient's state of health and the need for continued treatment should be regularly reassessed, especially in the case of asymptomatic patients. The overall duration of treatment should generally not exceed 8-12 weeks, including the gradual withdrawal period.

In certain cases, extension beyond the maximum recommended treatment period may be necessary, in which case this should be done after re-evaluation of the patient's condition by a specialist.

Treatment should be initiated with the lowest effective dose. The maximum dose should not be exceeded.

04.3 Contraindications

• Patients with a history of hypersensitivity to the active substance or to any of the excipients.

• Patients with a history of hypersensitivity to other benzodiazepines.

• Cases of glaucoma and myasthenia gravis.

• Children under 6 years of age.

• Patients with severe respiratory insufficiency.

• Apneic syndrome during sleep.

• Benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy.

04.4 Special warnings and appropriate precautions for use

The use of Prazepam EG for the treatment of psychiatric disorders and psychotic states in which anxiety is not a predominant factor is not recommended. Consequently, prazepam should only be used as an adjuvant in the treatment of psychosis.

Elderly patients

Mild drowsiness and / or decreased ability to concentrate as well as decreased muscle tone may occur in the elderly and debilitated patients.

In elderly or very debilitated patients it is recommended to start treatment with a lower dose, for example 10 or 15 mg of prazepam, to be administered in divided doses throughout the day and to be increased later if necessary.

Adolescents (12 to 17 years of age)

In adolescents a dose reduction is recommended based on the age and weight of the patient.

Children

No clinical data are available regarding the use of prazepam in children less than 6 years of age.

Renal impairment

Consider dose reduction in patients with impaired renal function.

Hepatic impairment

Consider dose reduction in patients with mild to moderate hepatic impairment.

Tolerance

Benzodiazepines can induce tolerance symptoms.

Dependence

Administration of benzodiazepines can lead to the development of physical and psychological dependence. The risk of dependence increases with dose and duration of treatment.

It is also greater in patients with a history of alcoholism or drug addiction. If physical dependence occurs, abruptly discontinuing treatment may lead to withdrawal symptoms (refer to the list of these symptoms in section 4.8).

Rebound anxiety: A transient syndrome in which symptoms that led to benzodiazepine treatment recur in an aggravated form may occur upon discontinuation of treatment. Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, recommends gradually decreasing the dose.

For a list of withdrawal symptoms, see section 4.8.

Progressive decrease in dose

The procedure must be explained to the patient in detail.

The patient should be informed of the need for a gradual reduction of the dose as well as of the possibility of rebound phenomena, in order to minimize the anxious reaction that the eventual appearance of such symptoms could trigger upon discontinuation of the medicinal product, even if gradually.

The patient should be informed of the possibility that this period may be particularly uncomfortable.

Duration of treatment

The duration of treatment should be as short as possible (See section "Posology and method of administration") and should not exceed eight to twelve weeks, including the period of gradual withdrawal of the medicinal product. Extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation.

In the case of patients with a history of addiction, see the section "Undesirable effects".

Amnesia

Benzodiazepines can induce anterograde amnesia. This usually happens several hours after ingestion of the medicine.

In the case of patients with a history of addiction, see the section "Undesirable effects".

Epilepsy

Although seizures may be possible following abrupt discontinuation of treatment, this risk is likely to be greater with short-lived benzodiazepines. This should be considered when treating patients with a history of epilepsy.

Psychiatric and paradoxical reactions

Reactions such as restlessness, agitation, irritability, aggression, delirium, anger, nightmares, delusion, hallucinations, psychosis, inappropriate behavior and other undesirable behavioral effects may occur during the use of benzodiazepines. If this occurs, the use of Prazepam EG must be suspended. Such reactions are more frequent in children and the elderly.

Benzodiazepines are not recommended for the primary treatment of psychotic illness.

Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide can be precipitated in such patients).

Alcohol

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. Concerning the concomitant use of alcohol, see the paragraph "Interaction with other medicinal products and other forms of interaction".

Patients with respiratory disorders

Due to the risk of severe respiratory depression it is recommended that a lower dose be given to patients with non-specific chronic respiratory conditions or respiratory insufficiency. See section "Contraindications".

Lactose

Prazepam EG tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

04.5 Interactions with other medicinal products and other forms of interaction

Concomitant administration of Prazepam EG and other CNS depressant substances (e.g. narcotics, anesthetics, anticonvulsants, sedative antihistamines, barbiturates, MAO inhibitors, antidepressants, antipsychotics, hypnotics, anxiolytics / sedatives, analgesics and alcohol) is not recommended. The simultaneous intake of alcohol is not recommended. The sedative effect may be enhanced in cases of concomitant use of alcohol-containing products with possible effects on the ability to drive and use machines. In the case of narcotic analgesics, an increase in euphoria may occur with consequent increase in psychic dependence.

Concomitant use of benzodiazepines and valproic acid appears to cause an increased risk of psychosis.

The simultaneous use of cimetidine and / or omeprazole results in an increase in plasma concentrations of benzodiazepines.

Pharmacokinetic interactions, the clinical impact of which is not completely clear, have been observed between the various benzodiazepines and the following drugs: barbiturates, rifampicin, phenytoin, oral contraceptives, isoniazid and disulfiram.

CYP3A4 and CYP450 inhibitors may reduce the metabolism of prazepam and increase the potential toxicity.

Theophylline antagonizes the pharmacological effect of benzodiazepines.

Oral contraceptives and hormone replacement therapies may enhance the effects of prazepam by inhibiting oxidative metabolism resulting in increased serum concentrations of benzodiazepines metabolised by oxidation when administered concurrently. Patients taking oral contraceptives should be monitored for any increase in the effects of prazepam.

Concomitant administration of clozapine and benzodiazepines should be done with caution due to the possibility of additional CNS depressant effects. Severe confusion, hypotension and respiratory depression have rarely been observed in patients receiving clozapine concurrently with or following benzodiazepine treatment. Patients receiving concomitant clozapine should initially be given half the normal dose of benzodiazepine. This dosing schedule should be maintained until sufficient patient experience is achieved.

In case of concomitant administration of buprenorphine and prazepam, the risk of possible respiratory depression is increased. It is therefore necessary to carefully evaluate the risk / benefit ratio of this combination and to inform the patient of the need to strictly comply with the prescribed doses.

04.6 Pregnancy and breastfeeding

Administration of benzodiazepines is not recommended in cases of suspected or confirmed pregnancy and during lactation.

Pregnancy

In cases where prazepam is prescribed to women of childbearing potential, it is recommended that the patient inform their doctor if they are planning to become pregnant or are already pregnant, so that the doctor can decide to stop treatment.

Studies on prazepam to date have not established whether there is a risk of congenital malformations if the product is used during pregnancy. However, some animal studies have shown reproductive toxicity (see section 5.3). The potential risks to humans are unknown. Since the use of prazepam is only rarely extremely urgent, it is preferable that it is not given during the first trimester of pregnancy.

Effects on the newborn such as hypothermia, hypotension and respiratory depression may occur if the drug is administered during late pregnancy, or during labor.

Since infants born to mothers who have taken benzodiazepines during pregnancy can develop physical dependence, withdrawal symptoms may develop in the postnatal period.

Feeding time

Administration of prazepam during delivery and during lactation is not recommended due to the risk of hypotension, hypothermia and even withdrawal symptoms in the newborn.

Benzodiazepines cross the fetal-placental barrier and are excreted in breast milk.

04.7 Effects on ability to drive and use machines

Depending on individual sensitivity to benzodiazepines, which is inherently unpredictable, patients may develop drowsiness and / or decreased ability to concentrate, amnesia, deterioration in concentration and muscle function as well as decreased muscle tone and slowing of reflexes. These reactions may impair the ability to drive or use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see "Interaction with other medicinal products and other forms of interaction").

Therefore, caution is required when driving vehicles or while operating dangerous machinery, especially at the start of treatment.

04.8 Undesirable effects

The reported undesirable effects are summarized in the table below by system and frequency. Frequencies are defined as follows: very common (≥1 / 10), common (≥1 / 100,

MeDRa classification Very common (≥1 / 10) Common (≥1 / 100 Uncommon (≥1 / 1,000 Rare (≥1 / 10,000 Very rare ( Psychiatric disorders Confusion, abnormal dreams Nervous system disorders Drowsiness Somnolence, dizziness, ataxia, headache, tremors, speech disorders Syncope Eye disorders Vision alteration Cardiac pathologies Palpitations Gastrointestinal disorders Dry mouth, various gastrointestinal disorders Skin and subcutaneous tissue disorders Diaphoresis, rash Itching Anaphylactic shock Musculoskeletal and connective tissue disorders Arthralgia Foot edema Renal and urinary tract disorders Different genital and urinal symptoms Reproductive system and breast disorders Menstrual, ovulatory and sexual disorders Gynecomastia General disorders and administration site conditions Fatigue, asthenia

The following side effects are typically related to the use of benzodiazepines. Most of them appear at the start of treatment and usually disappear with subsequent administrations.

Reducing the dose may relieve symptoms.

General ailments

Asthenia, muscle weakness, libido changes, drunkenness.

Nervous system disorders

Uncommon: altered state of consciousness, memory disturbances (especially in the elderly), possible occurrence of paradoxical reactions (especially in the elderly, eg worsening of insomnia, aggression, agitation, increased anxiety and seizures), irritability , decreased alertness, confusion.

Psychiatric disorders such as depersonalization, psychosis, dulling of emotions or paradoxical reactions due to rapid fluctuations in blood levels of benzodiazepines are rarely possible.

Pathologies of the hepatobiliary system

Cholestasis and jaundice (rare).

Respiratory pathologies

Respiratory depression in patients with a chronic nonspecific respiratory condition.

Disorders of the blood and lymphatic system

Rarely, agranulocytosis.

Eye disorders

Diplopia.

Amnesia

Anterograde amnesia may occur after administration of therapeutic doses.The risk increases at higher doses. The effects of amnesia may be associated with inappropriate behavior (see section "Special warnings and precautions for use").

Depression

Pre-existing states of depression may occur during the use of benzodiazepines.

Psychiatric and paradoxical reactions

Agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, inappropriate behavior and other behavioral effects are known reactions to treatment with benzodiazepines or benzodiazepine-like substances. These reactions can be relatively severe and are more likely to occur in the elderly.

Dependence

Administration of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence. Consequently, discontinuation of treatment may induce withdrawal or rebound effects (see section "Special warnings and precautions for use"). Psychological dependence may also develop. Abuse of benzodiazepines has been reported.

Prolonged use can undeniably cause physical and psychological dependence.

Because the half-life of the active metabolite of prazepam in the blood is very long, the risk of withdrawal symptoms is relatively low. The following symptoms may appear after abruptly stopping long-term benzodiazepine treatment: mood changes, (extreme) anxiety or sleep disturbances, agitation, convulsions, tremors, muscle and abdominal cramps, vomiting, sweating, headache, muscle pain, tension, confusion and irritability. In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.

04.9 Overdose

Symptoms of benzodiazepine overdose may consist of: fatigue possibly associated with ataxia, inability to coordinate movements and confusion.

In the treatment of overdosage of any medicinal product, the possibility that other substances have been taken at the same time should be considered. An overdose of benzodiazepine associated with concomitant use of alcohol, another medicinal product or an underlying disease may pose a risk to the life.

Following an overdose of benzodiazepines, vomiting should be induced, if it does not occur spontaneously, gastric lavage undertaken or immediate administration of activated charcoal, while keeping the patient's vital functions monitored.

If the patient has hypotension (although unlikely), this can be controlled by injecting L-norepinephrine bitartrate or vasopressor drugs (eg metaraminol bitartrate).

Flumazenil is a specific benzodiazepine receptor antagonist and can be used as an adjuvant to resuscitation techniques in case of severe intoxication associated with coma. The use of flumazenil as an antidote is contraindicated in the following cases: if tricyclic antidepressants are taken, when concomitant drugs that induce convulsions are administered, ECG abnormalities such as prolongation of the QRS interval or QT interval (indicative concomitant therapy with tricyclic antidepressants). Patients treated with flumazenil should be followed up for some time after treatment in case sedation, respiratory depression and any other residual effects associated with benzodiazepines reappear. The physician should be aware of the risk of seizures following combination with benzodiazepines, particularly in long-term treatment with benzodiazepines or in the event of an overdose of cyclic antidepressants.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: anxiolytics, ATC code: N05BA11

Mechanism of action

Prazepam is a benzodiazepine derivative. Benzodiazepines act on the limbic, thalamic and hypothalamic regions of the CNS and are capable of producing the required degree of CNS depression, namely sedation, hypnosis, relaxation of the skeletal muscles and anticonvulsive activity. Recent data indicate that benzodiazepines act by stimulating receptors belonging to the benzodiazepine receptor complex GABA (gamma-aminobutyric acid). GABA is an inhibitory neurotransmitter that acts on specific subtypes of receptors designated by GABA-A and GABA-B. GABA-A is the major receptor subtype of the CNS and is supposed to act as a mediator of anxiolytic and sedative actions.

Specific benzodiazepine receptor subtypes (BNZ) are thought to be coupled to GABA-A receptors. Three types of BNZ receptors have been observed in the CNS and other tissues; BNZ1 receptors are located in the cerebellum and cerebral cortex, BNZ2 receptors in the cerebral cortex and spinal cord and BNZ3 receptors in peripheral tissues. Activation of the BNZ1 receptor is supposed to mediate sleep, while the BNZ2 receptor encourages muscle relaxation, anticonvulsant activity, motor coordination and memory.

Benzodiazepines are bound to BNZ1 and BNZ2 receptors which stimulate the effects of GABA. Unlike barbiturates which increase GABA responses by prolonging the opening times of chloride channels, benzodiazepines stimulate the effects of GABA by increasing the affinity of GABA for the GABA receptor. The binding of GABA to the receptor site causes it to open. of the chloride channel with consequent hyperpolarization of the cell membrane thus preventing any subsequent excitation of the cell.

05.2 Pharmacokinetic properties

Absorption / biotransformation

After absorption, no trace of prazepam is found in the blood. The metabolite obtained by enzymatic transformation is N-desalkylprazepam, which is responsible for the pharmacodynamic activity of the product.

N-desalkylprazepam is strongly bound to plasma proteins, the free fraction is quantifiable in about 3.5%.

The maximum blood level of this metabolite is reached after 4-6 hours and the mean half-life is in the order of ± 65 hours.

Elimination

The excretion of this metabolite occurs mostly via the kidney as 3-hydroxyprazepam in the glucuronated form and oxazepam.

05.3 Preclinical safety data

The effects of non-clinical studies, observed only at exposures considered sufficiently in excess of the maximum human exposure, were minimally relevant to clinical use. In rats, oral administration of 10 mg / kg of prazepam however caused an increase in the frequency of fetal hydrops, tail skeletal abnormalities, decreased body weight and weight of the most important internal organs in the offspring. In rabbits, no congenital defects were observed after administration of oral doses of prazepam between 5 and 50 mg / kg.