Valium - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Diazepam

Valium 2 mg hard capsules
Valium 5 mg hard capsules
Valium 5 mg / ml oral drops, solution

Valium package inserts are available for pack sizes:
  • Valium 2 mg hard capsules, Valium 5 mg hard capsules, Valium 5 mg / ml oral drops, solution
  • Valium 10 mg / 2 ml solution for injection

Why is Valium used? What is it for?

Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Insomnia.

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

Contraindications When Valium should not be used

Hypersensitivity to diazepam, to other benzodiazepines or to any of the excipients.

Myasthenia gravis.

Severe respiratory failure.

Severe, acute or chronic liver failure.

Sleep apnea syndrome.

Precautions for use What you need to know before taking Valium

Due to the highly variable reactivity to psychotropic drugs, the dosage of Valium should be fixed within prudential limits in elderly or debilitated patients and in those with cerebral organic changes (especially atherosclerotic) or with cardiorespiratory insufficiency.

Concomitant use of alcohol / CNS depressants

The concomitant use of Valium with alcohol and / or drugs with central nervous system depressant activity should be avoided, as it may increase the clinical effects of Valium, including possible profound sedation and clinically relevant respiratory and / or cardiovascular depression.

History of alcohol abuse / CNS depressants

Valium should be used with extreme caution in patients with a history of alcohol or drug abuse. In patients with drug addiction with central nervous system depressant activity and in patients with alcohol dependence, Valium should be avoided, except when acute withdrawal treatment is required.

Tolerance

Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.

Dependence.

The use of benzodiazepines can lead to the development of physical and psychological dependence on these drugs. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle aches, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.

Rebound insomnia and anxiety.

A transient syndrome in which symptoms leading to treatment with benzodiazepines recur in an aggravated form may occur upon discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disturbances. withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, it is suggested to make a gradual decrease in dosage.

Duration of treatment.

The duration of treatment should be as short as possible (see posology) depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks for anxiety, including a gradual withdrawal period. "extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased. It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing the anxiety about these symptoms should they occur upon discontinuation of the drug. There are elements to predict that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses. When using benzodiazepines with a long duration of action, it is important to warn the patient that abrupt change to a benzodiazepine with a short duration of action is not recommended, as "withdrawal symptoms may occur."

Amnesia.

Benzodiazepines can induce anterograde amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it should be ensured that patients can have 7-8 hours of uninterrupted sleep (see side effects).

Psychiatric and paradoxical reactions.

When benzodiazepines are used it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes can occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in children and the elderly. Special patient populations.

Pediatric age

Benzodiazepines should not be given to children without careful consideration of the actual need for treatment; the duration of treatment should be as short as possible. As safety and efficacy in children under 6 months have not been established, Valium should be used. with the utmost caution in this age group and only if no therapeutic alternatives are available.

Senior citizens

Elderly people should take a reduced dose (see "Dose, method and time of administration). Likewise, a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression.

Hepatic and renal insufficiency

In patients with impaired hepatic or renal function, the precautions normally adopted for the treatment of such subjects should be followed. Benzodiazepines are contraindicated in patients with severe, acute or chronic hepatic insufficiency, as they can precipitate encephalopathy (see Contraindications). 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). Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse. A lower dosage should be used for debilitated patients.

Interactions Which drugs or foods can change the effect of Valium

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines. Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines. increase in euphoria leading to an increase in psychic dependence.

Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.

Warnings It is important to know that:

Valium capsules contain lactose, so if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Valium drops contains 11.9 vol% ethanol (alcohol), eg. up to 192 mg per 10 mg dose, equivalent to 4.8 ml of beer, 2 ml of wine per dose. It can be harmful to alcoholics. To be taken into consideration in pregnant or lactating women, children and high-risk groups such as people with liver disease or epilepsy.

For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.

Pregnancy and breastfeeding

Pregnancy

If Valium is prescribed to a woman of childbearing potential, she should be advised to contact her doctor to discontinue treatment if she intends to become pregnant or suspects that she is pregnant.

Do not administer in the first trimester of pregnancy.

If, for serious medical reasons, the product is administered during the last period of pregnancy or during labor at high doses, effects on the newborn may occur such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological action of the drug. Additionally, infants born to mothers who have chronically taken benzodiazepines during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

Feeding time

Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.

Effects on ability to drive and use machines

Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see interactions).

Dosage and method of use How to use Valium: Dosage

Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome

Treatment should be as short as possible. The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period. In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without reassessment of the patient's condition.

Insomnia

Treatment should be as short as possible. The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period.

In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without reassessment of the patient's condition. Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. In the treatment of insomnia the drug should be taken just before going to bed. The patient should be monitored regularly at the start of treatment to decrease the dose or frequency of intake if necessary to prevent overdose due to accumulation.

Average dose for adult patients: 2 mg (one 2 mg capsule or 10 drops) two to three times a day to 5 mg (one 5 mg capsule or 25 drops) once or twice a day.

Elderly or debilitated patients: 2 mg twice daily.

Inpatient treatment of anxiety states: 10-20 mg three times a day.

Children: up to 3 years, 1-6 mg (5-30 drops per day) from 4 to 14 years, 4-12 mg per day The drops of Valium should be diluted in water or other drink.

How to use the dropper bottle: to dispense the correct dose of drug it is necessary to hold the bottle upright with the opening facing downwards. If the liquid does not go down, it is advisable to shake the bottle or turn it upside down several times and repeat the operation as indicated above.

Overdose What to do if you have taken too much Valium

As with other benzodiazepines, an overdose should not be life-threatening unless concomitant other CNS depressants (including alcohol) are taken. In the treatment of overdose of any drug, consideration should be given to possibility that other substances were taken at the same time.

Following an overdose of benzodiazepines for oral use, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious. improvement with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Overdosage of benzodiazepines usually results in varying degrees of central nervous system depression ranging from clouding to coma.

In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death. "Flumazenil" can be useful as an antidote. In case of accidental ingestion / intake of an excessive dose of Valium, notify your doctor immediately or go to the nearest hospital.

IF YOU HAVE ANY DOUBTS ABOUT USING VALIUM, CONTACT YOUR DOCTOR OR PHARMACIST.

Side Effects What are the side effects of Valium

Like all medicines, Valium can cause side effects, although not everybody gets them.

Somnolence, even during the day, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision. These phenomena occur mainly at the start of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances, changes in libido and skin reactions.

Amnesia.

Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see special warnings and precautions).

Depression.

A pre-existing depressive state may be unmasked during the use of benzodiazepines. Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes. quite severe and are more likely in children and the elderly.

Dependence.

The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see special warnings and precautions). Psychic dependence may occur. Abuse has been reported. of benzodiazepines.

Post-marketing experience

Nervous system disorders: ataxia, dysarthria, speech difficulties, headache, tremors, dizziness.

Psychiatric Disorders: Paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, abnormal behavior and other adverse behavioral events are known to occur during treatment with benzodiazepines. With the appearance of such effects, the treatment should be stopped. These reactions occur more in children and the elderly. Confusion, poor emotional responsiveness, decreased alertness, depression, increased or decreased libido.

Injury, poisoning and procedural complications: falls and fractures. The risk of falls and fractures is increased in patients taking concomitant sedatives (including alcoholic beverages) and in elderly patients.

Gastrointestinal disorders: nausea, dry mouth or hypersalivation, constipation and other gastrointestinal disorders.

Eye disorders: diplopia, blurred vision.

Vascular disorders: hypotension, circulatory depression.

Investigations: irregular heart rate, very rarely increased transaminase levels, increased blood alkaline phosphatase.

Renal and urinary disorders: incontinence, urinary retention.

Skin and subcutaneous tissue disorders: skin reactions.

Ear and labyrinth disorders: vertigo.

Cardiac disorders: heart failure including cardiac arrest.

Respiratory disorders: respiratory depression including respiratory failure.

Hepatobiliary disorders: very rarely jaundice.

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine. "

Expiry and Retention

Expiry: see the expiry date indicated on the package.

Warning: do not use the medicine after the expiry date indicated on the package.

The expiry date indicated refers to the product in intact packaging, correctly stored.

KEEP THE MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN

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.

Composition and pharmaceutical form

COMPOSITION

Valium 2 mg hard capsules: one capsule contains: active ingredient: diazepam 2 mg. Excipients: corn starch, talc, lactose monohydrate, gelatin, titanium dioxide, yellow iron oxide (E172), black iron oxide (E172).

Valium 5 mg hard capsules: one capsule contains: active ingredient: diazepam 5 mg. Excipients: corn starch, talc, lactose monohydrate, gelatin, titanium dioxide, yellow iron oxide (E172), black iron oxide (E172).

Valium 5 mg / ml oral drops, solution: 1 ml (= 25 drops) contains: active ingredient: diazepam 5 mg.

Excipients: ethanol 96%, glycerol, propylene glycol, saccharin, orange soluble essence, lemon soluble essence, E 127, purified water.

PHARMACEUTICAL FORM AND CONTENT

Valium 2 mg - hard capsules - 30 capsules.

Valium 5 mg - hard capsules - 20 capsules.

Valium 5 mg / ml - oral drops, solution - 20 ml bottle.

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.

Further information on Valium 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 interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the primary packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

VALIUM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Valium 2 mg hard capsules

one capsule contains:

active ingredient: diazepam 2 mg.

Excipients with known effect: lactose monohydrate

Valium 5 mg hard capsules

one capsule contains:

active ingredient: diazepam 5 mg.

Excipients with known effect: lactose monohydrate

Valium 5 mg / ml oral drops solution

1 ml (25 drops) contains:

active ingredient: diazepam 5 mg.

Excipients with known effect: Ethanol, propylene glycol,

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Hard capsules and oral drops, solution.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Insomnia.

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

04.2 Posology and method of administration

Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome

Treatment should be as short as possible. The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.

In certain cases, extension beyond the maximum treatment period may be necessary, in which case it should not take place without reassessment of the patient's condition.

Insomnia

Treatment should be as short as possible. The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period.

In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without reassessment of the patient's condition.

Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.

In the treatment of insomnia the drug should be taken just before going to bed.

The patient should be monitored regularly at the start of treatment to decrease the dose or frequency of intake if necessary to prevent overdose due to accumulation.

Average dose for adult patients: from 2 mg (one 2 mg capsule or 10 drops) two-three times a day to 5 mg (one 5 mg capsule or 25 drops) once-twice a day.

Elderly or debilitated patients: 2 mg twice a day.

Inpatient treatment of anxiety states: 10-20 mg three times a day.

Children: up to 3 years, 1-6 mg (5-30 drops per day); from 4 to 14 years, 4-12 mg per day.

Valium drops should be diluted in water or other beverage.

04.3 Contraindications

Hypersensitivity to diazepam, to other benzodiazepines or to any of the excipients listed in section 6.1;

Myasthenia gravis;

Severe respiratory failure;

Severe, acute or chronic liver failure;

Sleep apnea syndrome.

04.4 Special warnings and appropriate precautions for use

Due to the highly variable reactivity to psychotropic drugs, the dosage of Valium should be fixed within prudential limits in elderly or debilitated patients and in those with cerebral organic changes (especially atherosclerotic) or with cardiorespiratory insufficiency.

The concomitant use of Valium with alcohol and / or drugs with central nervous system depressant activity should be avoided, as it may increase the clinical effects of Valium, including possible profound sedation and clinically relevant respiratory and / or cardiovascular depression (see paragraph 4.5).

Valium should be used with extreme caution in patients with a history of alcohol or drug abuse.

In patients with drug addiction with central nervous system depressant activity and in patients with alcohol dependence, Valium should be avoided, except when acute withdrawal treatment is required.

Tolerance

Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.

Dependence

The use of benzodiazepines can lead to the development of physical and psychological dependence on these drugs. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle aches, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.

Rebound insomnia and anxiety

A transient syndrome in which symptoms leading to treatment with benzodiazepines recur in an aggravated form may occur upon discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disturbances. withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, it is suggested to make a gradual decrease in dosage.

Duration of treatment

The duration of treatment should be as short as possible (see section 4.2) depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks for anxiety, including a gradual withdrawal period. Extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased. It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing the anxiety about these symptoms should they occur upon discontinuation of the drug. There are elements to predict that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses.

When using benzodiazepines with a long duration of action, it is important to warn the patient that abrupt change to a benzodiazepine with a short duration of action is not recommended, as withdrawal symptoms may occur.

Amnesia

Benzodiazepines can induce anterograde amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it should be ensured that patients can have 7-8 hours of uninterrupted sleep (see side effects).

Psychiatric and paradoxical reactions

When benzodiazepines are used it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes can occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in children and the elderly.

Special patient populations

Pediatric age

Benzodiazepines should not be given to children without careful consideration of the actual need for treatment; the duration of treatment should be as short as possible.

As safety and efficacy in children under 6 months have not been established, Valium should be used with the utmost caution in this age group and only if no therapeutic alternatives are available.

Senior citizens

Elderly people should take a reduced dose (see posology). Likewise, a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression.

Hepatic and renal insufficiency

In patients with impaired hepatic or renal function, the precautions normally adopted for the treatment of such subjects should be followed.

Benzodiazepines are contraindicated in patients with severe, acute or chronic hepatic insufficiency, as they can precipitate encephalopathy (see section 4.3).

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). Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.

A lower dosage should be used for debilitated patients.

Valium capsules contain lactose; therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines. Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines. increase in euphoria leading to an increase in psychic dependence.

Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the "activity" of benzodiazepines.

Substrates that modulate the activity of CYP2C19 and CYP3A, cytochrome P450 isoenzymes that regulate the oxidative metabolism of diazepam, may potentially alter the pharmacokinetics of diazepam (see section 5.2). Drugs such as cimetidine, ketoconazole, fluvoxamine, fluoxetine, inhibitors and omepram of CYP2C19 and CYP3A, can lead to an increased and prolonged sedative action.

To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.

04.6 Pregnancy and breastfeeding

If Valium is prescribed to a woman of childbearing potential, she should contact her doctor, both if she intends to become pregnant and if she suspects that she is pregnant regarding discontinuation of the medicine.

Do not administer in the first trimester of pregnancy.

If, for serious medical reasons, the product is administered during the last period of pregnancy or during labor at high doses, effects on the newborn may occur such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological action of the drug. Additionally, infants born to mothers who have chronically taken benzodiazepines during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.

04.7 Effects on ability to drive and use machines

Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section 4.5).

04.8 Undesirable effects

Somnolence, even during the day, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision. These phenomena occur mainly at the start of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances, changes in libido and skin reactions.

Amnesia

Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see section 4.4).

Depression

A pre-existing depressive state may be unmasked during the use of benzodiazepines. Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.

Such reactions can be quite severe. They are more likely in children and the elderly.

Dependence

The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see special warnings and precautions for use). Psychic dependence can occur. Abuse of benzodiazepines has been reported.

Post-marketing experience

Nervous system disorders: ataxia, dysarthria, speech difficulties, headache, tremors, dizziness.

Psychiatric disorders: It is known that paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, abnormal behavior and other adverse behavioral events are known to occur during treatment with benzodiazepines. With the appearance of such effects, the treatment should be stopped. These reactions occur more in children and the elderly.

Confusion, dulling of emotions, decreased alertness, depression, increased or decreased libido.

Injury, poisoning and procedural complications: falls and fractures. The risk of falls and fractures is increased in patients taking concomitant sedatives (including alcoholic beverages) and in elderly patients.

Gastrointestinal disorders: nausea, dry mouth or hypersalivation, constipation and other gastrointestinal disorders.

Eye disorders: diplopia, blurred vision.

Vascular pathologies: hypotension, circulatory depression.

Diagnostic tests: irregular heart rate, very rarely increased transaminase levels, increased blood alkaline phosphatase.

Renal and urinary disorders: incontinence, urinary retention.

Skin and subcutaneous tissue disorders: skin reactions.

Ear and labyrinth disorders: dizziness.

Cardiac pathologies: heart failure including cardiac arrest.

Respiratory pathologies: respiratory depression including respiratory failure.

Hepatobiliary disorders: very rarely jaundice.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address http://www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose

As with other benzodiazepines, an overdose should not be life-threatening unless concomitant other CNS depressants (including alcohol) are taken. In the treatment of overdose of any drug, consideration should be given to possibility that other substances were taken at the same time.

Following an overdose of benzodiazepines for oral use, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious. improvement with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Benzodiazepine overdose usually results in varying degrees of central nervous system depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death. "Flumazenil" may be useful as an antidote.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: anxiolytics, benzodiazepine derivatives. ATC code: N05BA01.

Through the selective involvement of well-defined brain structures such as the limbic system and the hypothalamus, Valium determines resolution of anxiety and autonomic stabilization and improves the disposition to sleep.

Thanks to a control of spinal reflexivity, Valium also provides, at adequate doses, a net relaxation of the skeletal muscles.

Tests aimed at evaluating the anticonvulsant activity of diazepam have yielded the following results:

rat: DE50 in blocking isoniazid convulsions: 0.14 mcM / kg;

rat: DE50 in blocking picrotoxin seizures: 1 mcM / kg.

As for the muscle relaxant activity, a dose of 1.6 mg / kg i.v. is able to reduce or eliminate the rigidity of the decerebrated cat.

The anti-anxiety activity, measured as the ability to resolve an experimentally induced conflict situation in the rat, has a DE50 of 10 mg / kg, while 67 mg / kg are needed to have a non-specific psychomotor inhibition.

05.2 Pharmacokinetic properties

Absorption

Diazepam is rapidly and completely absorbed from the gastrointestinal tract and peak plasma concentrations occur 30 to 90 minutes after oral administration.

Distribution

Diazepam and its metabolites are highly bound to plasma proteins (diazepam: 98%); they cross the blood-brain and placental barrier and are also found in milk in concentrations equal to about one-tenth of those of maternal plasma.

The steady-state volume of distribution is 0.8-1.0 l / kg.

Metabolism

Diazepam is extensively metabolised in the body and only 0.1% is excreted as such in the urine.

The oxidative metabolism of diazepam, leading to the formation of N-dysmethyldiazepam (nordiazepam), 3-hydroxydiazepam (tenazepam) and oxazepam, is mediated by CYP2C19 and CYP3A, cytochrome P450 isoenzymes. As demonstrated by studies in vitro, the hydroxylation reaction is mainly caused by the CYP3A isoform while the N-dysmethylation is mediated by both CYP2C19 and CYP3A. The results derived from studies in I live on volunteers confirmed the observations of the studies in vitro.

Oxazepam and tenazepam are further conjugated with glucuronic acid.

Elimination

The plasma concentration time curve is biphasic, a rapid and broad initial phase of distribution with a half-life of approximately three hours followed by a prolonged terminal elimination phase (half-life 20-50 hours).

The elimination half-life (t½ ß) of the active metabolite N-dysmethyldiazepam is up to 100 hours depending on age and liver function. Diazepam and its metabolites are eliminated mainly in the urine (approximately 70%) in free or predominantly conjugated form.

Elimination may be slowed in neonates, the elderly and in patients with liver or kidney disease, so it should be noted that plasma concentrations will take longer to reach steady state.

In steady state conditions, plasma clearance is approximately 23 ml / min.

The elimination half-life (ß) of diazepam is approximately 32 hours.

05.3 Preclinical safety data

Acute toxicity tests gave LD50 values ​​in the tested species from 720 to 1800 mg / kg after oral administration and from 32 to 100 mg / kg if administered i.v.

In chronic toxicity tests conducted for more than 6 months with high doses (in dogs 10-40 mg, in monkeys 5-40 mg, in rats 320 mg / kg per day), diazepam did not give rise to pathological manifestations of the fundamental biological functions of organs and systems, nor to histological alterations.

Carcinogenicity

The carcinogenic potential of oral diazepam has been studied in several rodent species. An increase in the incidence of hepatocellular tumors was found in the male mouse. There was no significant growth in the incidence of tumors in the female mouse, rats, hamsters or gerbils.

Mutagenicity

Some studies have shown little evidence of mutagenic potential at high concentrations which are, however, well above therapeutic doses in humans.

Impaired fertility

Reproductive studies in rats have shown a decrease in the number of pregnancies and in the number of live births after oral doses of 100 mg / kg / day before and during mating and during gestation and lactation.

Teratogenicity

Diazepam was found to be teratogenic in mice at dosages of 45-50 mg / kg, 100 mg / kg and 140 mg / kg / day, as well as in hamsters at dosages of 280 mg / kg. In contrast, this medicinal product was not found to be teratogenic at 80 and 300 mg / kg / day in rats and at 20 and 50 mg / kg / day in rabbits.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Valium 2 mg hard capsules:

Cornstarch; talc; lactose monohydrate; jelly; titanium dioxide; yellow iron oxide (E172); black iron oxide (E172).

Valium 5 mg hard capsules:

Cornstarch; talc; lactose monohydrate; jelly; titanium dioxide; yellow iron oxide (E172); black iron oxide (E172).

Valium 5 mg / ml oral drops solution:

96% ethanol; glycerol; propylene glycol; saccharin; soluble orange essence; soluble lemon essence; E127; purified water.

06.2 Incompatibility

No incompatibility phenomena were noted.

06.3 Period of validity

5 years.

06.4 Special precautions for storage

No special storage precautions.

06.5 Nature of the immediate packaging and contents of the package

Valium 5 mg / ml oral drops solution is presented in a glass vial enclosed in a cardboard box together with the package leaflet.

The other shapes are presented in blister packs of thermoformed plastic material coupled with aluminum tape enclosed in a cardboard box together with the illustrative leaflet.

06.6 Instructions for use and handling

How to use the dropper bottle:

To dispense the correct dose of drug it is necessary to hold the bottle upright with the opening facing downwards. If the liquid does not flow, it is advisable to shake the bottle or turn it upside down several times and repeat the dispensing operation as indicated above.

Disposal of expired / unused drugs:

The release of drugs into the environment should be minimized. Medicines should not be disposed of via wastewater or household waste. Use dedicated collection systems, if available.

07.0 MARKETING AUTHORIZATION HOLDER

Roche S.p.A. - Piazza Durante 11 - 20131 Milan

08.0 MARKETING AUTHORIZATION NUMBER

30 hard capsules 2 mg - AIC: 019995024

20 hard capsules 5 mg - AIC: 019995012

Oral drops, solution 20 ml - AIC: 019995048

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Renewal: June 2010

10.0 DATE OF REVISION OF THE TEXT

January 2014

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

none:  protein-snacks menopause natural-supplements