Active ingredients: Prazepam
PRAZENE 10 mg tablets
PRAZENE 20 mg tablets
PRAZENE 15 mg / ml oral drops, solution
Why is Prazene used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Benzodiazepine derivative with anxiolytic activity.
THERAPEUTIC INDICATIONS
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome.
Benzodiazepines are only indicated when the disorder is severe, disabling, or makes the subject very uncomfortable.
Contraindications When Prazene should not be used
Hypersensitivity to the active substance, to benzodiazepines or to any of the excipients.
Myasthenia gravis.
Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome. First trimester of pregnancy and during the breastfeeding period (see "Special Warnings").
Precautions for use What you need to know before taking Prazene
Duration of treatment
The duration of treatment should be limited and should be as short as possible (see "Dose, method and time of administration"), but should not exceed 8-12 weeks, 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 when the drug is discontinued.
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.
Specific groups of patients
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. The elderly should take a reduced dose (see "Dose, method and time of administration"). Likewise. , a lower dose is suggested for patients with chronic respiratory insufficiency due to the risk of respiratory depression. Benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy. 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.
The posology should be kept within prudent limits in patients with cerebral organic changes (especially atherosclerotic) or with cardio-respiratory insufficiency. In case of prolonged treatment, it is advisable to periodically check the blood picture and liver function.
Interactions Which drugs or foods can modify the effect of Prazene
Tell your doctor or pharmacist if you have recently taken any medicines, even those without a prescription.
Alcohol: concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the drug 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 metabolised only by conjugation. CYP3A4 inhibitors can reduce the metabolism of prazepam and increase its metabolism. potential degree of toxicity.
Oral contraceptives can enhance the effects of prazepam, as they inhibit oxidative metabolism. Consequently, the concomitant administration of oral contraceptives causes an increase in the serum concentrations of benzodiazepines undergoing oxidative metabolism. Patients on oral contraceptive therapy should be monitored for any increased effects of prazepam.
Benzodiazepines should be associated with caution with clozapine, as they may cause additional depressive effects on the central nervous system. Severe confusion, hypotension and respiratory depression have rarely been observed in patients receiving clozapine concurrently with or following benzodiazepine treatment. In patients on concomitant treatment with clozapine, the starting dose of benzodiazepine should be approximately half of the usual dose until sufficient patient experience has been achieved.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
No adequate controlled studies have been performed in pregnant women. There are insufficient data on teratogenicity from benzodiazepine exposure. Some initial studies have indicated that benziodiazepine exposure in utero may be associated with congenital malformations. Subsequent studies have provided no strong evidence on the correlation between benzodiazepine use and the development of malformations. In cases where a correlation with benzodiazepines was observed, exposure occurred mainly in the first trimester of pregnancy. Continued dosing during the last trimester may be associated with intrauterine growth retardation. Use during the last trimester to birth is associated with neonatal complications, including respiratory distress syndrome, "flaccid baby" syndrome (hypotonia, lethargy, and difficulty in sucking) and drug withdrawal syndrome (tremor, irritability, hypertonicity, diarrhea / vomiting and vigorous sucking). If benzodiazepines are taken during pregnancy or if the patient becomes pregnant while taking benzodiazepines, the patient should be advised of the potential danger to the fetus.
Do not administer in the first trimester of pregnancy and during the breastfeeding period.
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.
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 dependence increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body 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 that led to treatment with benzodiazepines recur in an aggravated form may occur on discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances As the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.
Amnesia
Benzodiazepines can induce antegrade 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.
Since prazepam has CNS depressant effects, patients should be advised to avoid simultaneous ingestion of alcohol and other CNS depressant drugs.
The combination of PRAZENE with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid undesirable effects of interaction (see "Interactions").
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").
Important information about some of the ingredients:
Prazene contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Prazene: Dosage
Adults
PRAZENE is administered orally in divided doses or as a single dose. In divided doses the usual average dosage is 30 mg / day, i.e. 1 tablet of 10 mg 3 times a day. The dosage should be gradually adjusted in the range between 20 and 60 mg / day in relation to the patient's response.
As a single dose PRAZENE can be administered at bedtime and the recommended starting dose is 20 mg. The patient's response to many days of treatment may allow the physician to increase or occasionally decrease the dose to achieve maximum anxiolytic effect with minimum daytime sleepiness. The optimal dosage is usually between 20 and 40 mg / day.
The same dosage schedules can be implemented with the solution in drops, taking into account that 20 drops contain 10 mg of active ingredient. The drops should be diluted in water or other beverage.
Elderly or debilitated patients, including those with impaired liver and / or renal function.
It is generally sufficient to halve the recommended adult dose for an adequate therapeutic response (see "Precautions for use").
Children
The safety and efficacy of the product in children have not been investigated. However, it is recommended to carefully read the "Precautions for use".
Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
Treatment should be as short as possible. 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 this should not be done without reassessment of the patient's condition.
Overdose What to do if you have taken too much Prazene
In case of accidental ingestion / intake of an overdose of Prazene, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Prazene, ask your doctor or pharmacist. As with other benzodiazepines, an overdose should not be life-threatening, unless concomitant intake of other CNS depressants (including alcohol).
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
Following an overdose of oral benzodiazepines, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious.
If no improvement is observed 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 rarely death. Hypotension, although unlikely, may be kept under control with vasopressors (such as levarterenol bitartrate or metaraminol bitartrate).
Flumazenil, a specific benzodiazepine receptor antagonist, is indicated as an antidote to complete or partial suppression of the sedative effect of benzodiazepines and can be used in case of suspected or confirmed benzodiazepine overdose. Flumazenil is intended as an adjunct treatment - and non-replacement - for optimal management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for sedation, respiratory depression and other residual effects of benzodiazepines, for an appropriate period of time after treatment. Physicians should take this into account. the risk of seizures associated with treatment with flumazenil, particularly in patients using benzodizepine for long periods and in the case of overdose of cyclic antidepressants. It is recommended that the package leaflet contained in the flumazenil package be consulted before use.
Side Effects What are the side effects of Prazene
Like all medicines, Prazene can cause side effects, although not everybody gets them.
PRAZENE is usually well tolerated.
The following undesirable effects have been reported in double-blind placebo-controlled clinical trials using a usual daily dose of 30mg in divided doses.
These effects are typical of benzodiazepines:
Psychiatric disorders: confusion, vivid dreams
Nervous system disorders: ataxia, dizziness, excitement, dizziness, daytime sleepiness, headache, hyperactivity, light-headedness, slurred speech, syncope, tremors
Eye disorders: blurred vision
Cardiac disorders: palpitations, slight lowering of blood pressure
Gastrointestinal disorders: dry mouth, gastrointestinal disorders
Hepatic disorders: hepatic dysfunction
Skin and subcutaneous tissue disorders: diaphoresis, pruritus, skin reactions
Musculoskeletal and connective tissue disorders: joint pain, muscle weakness
Renal and urinary disorders: genitourinary disorders
General disorders and administration site conditions: fatigue, swelling of the feet, weakness
Investigations: low blood pressure, abnormal liver function tests, weight gain.
Other reported side effects are: dulling of emotions, decreased alertness, 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: changes in libido, mydriasis, and granulocytopenia.
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").
Depression
During the use of benzodiazepines a pre-existing depressive state can be unmasked. 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 may cause rebound or withdrawal phenomena (see "Special Warnings"). Psychic dependence may occur. Abuse of benzodiazepines has been reported. .
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Warning: Do not use the medicine after the expiry date indicated on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children
Composition and pharmaceutical form
COMPOSITION
PRAZENE 10 mg tablets
1 tablet contains:
Active ingredient: prazepam 10 mg.
Excipients: lactose, microcrystalline cellulose, corn starch, magnesium stearate, anhydrous colloidal silica.
PRAZENE 20 mg tablets
1 tablet contains:
Active ingredient: prazepam 20 mg.
Excipients: lactose, microcrystalline cellulose, corn starch, magnesium stearate, anhydrous colloidal silica.
PRAZENE 15 mg / ml oral drops-solution
1 ml (equal to 30 drops) of solution contains:
Active ingredient: prazepam 15 mg.
Excipients: propylene glycol, ethyl ethylene glycol, polysorbate 80, sodium saccharinate, levomentol, anethole, patent blue V.
1 drop contains 0.5 mg prazepam
PHARMACEUTICAL FORM AND CONTENT
Tablets and oral drops-solution.
PRAZENE 10 mg tablets: box of 30 tablets of 10 mg.
PRAZENE 20 mg tablets: box of 20 tablets of 20 mg.
PRAZENE 15 mg / ml oral drops-solution: 1 dropper bottle of 20 ml.
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.
01.0 NAME OF THE MEDICINAL PRODUCT
PRAZENE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
PRAZENE 10 mg tablets
One tablet contains:
active ingredient: prazepam 10 mg.
PRAZENE 20 mg tablets
One tablet contains:
active ingredient: prazepam 20 mg.
PRAZENE 15 mg / ml oral drops, solution
1 ml (equal to 30 drops) of solution contains:
active ingredient: prazepam 15 mg.
1 drop = 0.5 mg.
For the full list of excipients, see 6.1
03.0 PHARMACEUTICAL FORM
Tablets and oral drops solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Anxiety.
States of anxiety, tension, agitation, irritability, moodiness; psycho-neurotic disorders; functional organic disorders and psychoneurotic disorders (organic neuroses).
Benzodiazepines are only indicated when the disorder is severe, disabling, or makes the subject very uncomfortable.
04.2 Posology and method of administration
Adults
PRAZENE is administered orally in divided doses or as a single dose.
In divided doses the usual average dosage is 30 mg / day, i.e. 1 tablet of 10 mg 3 times a day. The dosage should be gradually adjusted in the range between 20 and 60 mg / day in relation to the patient's response.
As a single dose PRAZENE can be administered at bedtime and the recommended starting dose is 20 mg. The patient's response to many days of treatment may allow the physician to increase or occasionally decrease the dose to achieve maximum anxiolytic effect with minimum daytime sleepiness. The optimal dosage is usually between 20 and 40 mg / day.
The same dosage schedules can be implemented with the solution in drops, taking into account that 20 drops contain 10 mg of active ingredient. The drops should be diluted in water or other beverage.
Specific groups of patients
Elderly or debilitated patients, including those with impaired liver and / or renal function
It is generally sufficient to halve the recommended adult doses to achieve an adequate therapeutic response (see section 4.4).
Children
The safety and efficacy of the product in children have not been investigated.
However, it is recommended to carefully read section 4.4. Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
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 this should not be done without reassessment of the patient's condition.
As with other long-acting benzodiazepines, 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.
04.3 Contraindications
Hypersensitivity to the active substance, to benzodiazepines or to any of the excipients.
Myasthenia gravis.
Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome. First trimester of pregnancy and during the breastfeeding period (see section 4.6)
04.4 Special warnings and appropriate precautions for use
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 dependence increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body 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 that led to treatment with benzodiazepines recur in an aggravated form may occur on discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances As the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2), but should not exceed 8-12 weeks, including a gradual withdrawal period. Extending 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 anxiety about these symptoms should they occur when the drug is discontinued.
It is important to warn the patient that since PRAZENE is a long-acting benzodiazepine, sudden change to a short-acting benzodiazepine is inadvisable, as withdrawal symptoms may occur.
Amnesia
Benzodiazepines can induce antegrade 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 section 4.8).
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.
Specific groups of patients
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. The elderly should take a reduced dose (see section 4.2). Equally, a lower dose is suggested. for patients with chronic respiratory insufficiency due to the risk of respiratory depression Benzodiazepines are not indicated in patients with severe 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.
As PRAZENE depresses the central nervous system, patients should be advised to avoid the simultaneous ingestion of alcohol and other drugs that depress the central nervous system.
The combination of PRAZENE with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid undesirable effects of interaction (see section 4.5).
The posology should be kept within prudent limits in patients with cerebral organic changes (especially atherosclerotic) or with cardio-respiratory insufficiency.
In case of prolonged treatment, it is advisable to periodically check the blood picture and liver function.
Important information about some of the ingredients
Prazene contains lactose. Patients with rare hereditary problems of galactose intolerance from lactase deficiency or glucose / galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Alcohol: 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. In the case of narcotic analgesics, increased euphoria may occur by 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 metabolised only by conjugation.
CYP3A4 inhibitors may reduce the metabolism of prazepam and increase its potential degree of toxicity.
Oral contraceptives may increase the effects of prazepam, as they inhibit oxidative metabolism. Consequently, the concomitant administration of oral contraceptives causes an increase in the serum concentrations of benzodiazepines undergoing oxidative metabolism.
Patients on oral contraceptive therapy should be monitored for any increase in the effects of prazepam.
Benzodiazepines should be used with caution with clozapine as they may cause additive depressive effects on the central nervous system. Severe confusion, hypotension and respiratory depression have rarely been observed in patients receiving clozapine concurrently with or following benzodiazepine treatment. In patients on concomitant treatment with clozapine, the starting dose of benzodiazepine should be approximately half of the usual dose until sufficient patient experience has been achieved.
04.6 Pregnancy and lactation
No adequate controlled studies have been performed in pregnant women.
There are insufficient data on teratogenicity from benzodiazepine exposure. Some initial studies have indicated that benziodiazepine exposure in utero may be associated with congenital malformations. Subsequent studies have provided no strong evidence on the correlation between benzodiazepine use and the development of malformations. In cases where a correlation with benzodiazepines was observed, exposure occurred mainly in the first trimester of pregnancy. Continued dosing during the last trimester may be associated with intrauterine growth retardation. Use during the last trimester to birth is associated with neonatal complications, including respiratory distress syndrome, "flaccid baby" syndrome (hypotonia, lethargy, and difficulty in sucking) and drug withdrawal syndrome (tremor, irritability, hypertonicity, diarrhea / vomiting and vigorous sucking). If benzodiazepines are taken during pregnancy or if the patient becomes pregnant while taking benzodiazepines, the patient should be advised of the potential danger to the fetus.
Do not administer in the first trimester of pregnancy and during the breastfeeding 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
PRAZENE is usually well tolerated.
The following undesirable effects have been reported in double-blind placebo-controlled clinical trials using a usual daily dose of 30mg in divided doses.
These effects are typical of benzodiazepines:
Psychiatric disorders: confusion, vivid dreams.
Nervous system disorders: ataxia, vertigo, excitement, dizziness, somnolence, headache, hyperactivity, light-headedness, slurred speech, syncope, tremors
Eye disorders: blurred vision.
Cardiac disorders: palpitations, slight lowering of blood pressure.
Gastrointestinal disorders: dry mouth, gastrointestinal disorders. Hepatic disorders: hepatic dysfunction.
Skin and subcutaneous tissue disorders: diaphoresis, pruritus, skin reactions.
Musculoskeletal and connective tissue disorders: joint pain.
Renal and urinary disorders: genitourinary disorders.
General disorders and administration site conditions: fatigue, swelling of the feet, weakness.
Investigations: low blood pressure, abnormal liver function tests, weight gain.
Other reported side effects are: dulling of emotions, decreased alertness, 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: changes in libido, mydriasis and granulocytopenia.
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 may cause rebound or withdrawal phenomena (see section 4.4). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
04.9 Overdose
As with other benzodiazepines, overdose is not expected to be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
Following an overdose of oral benzodiazepines, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious.
If no improvement is observed 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 rarely death.
Hypotension, although unlikely, can be controlled with vasopressors (such as levarterenol bitartrate or metaraminol bitartrate).
Flumazenil, a specific benzodiazepine receptor antagonist, is indicated as an antidote for complete or partial suppression of the sedative effect of benzodiazepines and can be used in case of suspected or known benzodiazepine overdose. Flumazenil is intended as an adjunct treatment - and non-replacement - for optimal management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for sedation, respiratory depression and other residual effects of benzodiazepines, for an appropriate period of time after treatment. Physicians should take this into account. the risk of seizures associated with flumazenil treatment, particularly in patients using benzodizepine for long periods and in the case of overdose of cyclic antidepressants. It is recommended that the package leaflet contained in the flumazenil package be consulted before use.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: benzodiazepine derivative with anxiolytic activity.
ATC: N05BA11
Prazepam is a drug belonging to the 1-4 benzodiazepine class.
Pharmacological experimentation in animals has shown that prazepam acts as a minor tranquilizer, that its action is similar to that of other benzodiazepines but with a wider margin between tranquilizing and hypnotic effects. It has also been shown that prazepam exerts a muscle relaxant action.
Benzodiazepines act in the limbic, thalamic and hypothalamic regions of the central nervous system and are capable of causing any required level of nervous system depression, including sedation, hypnosis, relaxation of the skeletal muscles and anticonvulsant effects.
Recent evidence indicates that benzodiazepines exert their effect through stimulation of the GABA (gamma-amino butyric acid) -benzodiazepine receptor complex.
GABA is an inhibitory neurotransmitter that exerts its activity at the level of specific receptor subtypes defined as GABA-A and GABA-B. GABA-A is the main receptor subtype present in the central nervous system and is thought to be involved in the action of anxiolytics and sedatives.
GABA-A receptors are thought to be coupled with benzodiazepine-specific receptor subtypes (BNZ). There are three types of BNZ receptors in the central nervous system and other tissues: BNZ1 receptors are located in the cerebellum and in the cerebral cortex; BNZ2 receptors are found in the cerebral cortex and spinal cord and BNZ3 receptors in peripheral tissues.
The activation of the BNZ1 receptor mediates sleep, while the BNZ2 receptor acts on muscle relaxation, anticonvulsant activity, motor coordination and memory. Benzodiazepines nonspecifically bind the BNZ1 and BNZ2 receptors which have the final effect of increasing the effects of GABA. Unlike barbiturates, which increase the effects mediated by GABA by prolonging the opening time of the chlorine channels, benzodiazepines enhance the effect of GABA by increasing the affinity of GABA for its receptor.
The binding of GABA to its receptor site causes the opening of the chlorine channels, causing the consequent hyperpolarization of the cell membrane and preventing the further excitation of the cell.
Human pharmacology experimentation has shown that prazepam has depressing effects on the central nervous system. Oral administration of a single 60 mg dose and divided doses up to 100 mg three times a day (300 mg / day total) showed no toxic effects. Prazepam has a marked anxiolytic activity with the characteristic of not causing any hypnotic effect: its low toxicity, together with the lack of depressive action on the respiratory centers and the protracted effect allow its use in all anxious forms.
05.2 Pharmacokinetic properties
Prazepam is readily absorbed from the gastrointestinal tract regardless of gastric pH values.
Metabolization occurs at the first passage through the liver and therefore in the peripheral blood prazepam as such is absent or present only in very limited quantities.
Its main transformation product, desalkylprazepam, is found in the peripheral blood and constitutes its active metabolite.
In addition to this, small quantities of 3-hydroxyprazepam and oxazepam are found, in a partially glucuronated form, ready for urinary excretion and therefore without any therapeutic effect.
The bioavailability of desalkylprazepam from prazepam is 51 ± 5%.
The pharmacokinetics of prazepam are characterized by constant blood levels and the absence of plasma peaks.
After single administration of a 20 mg tablet of prazepam, the maximum blood level of the active metabolite is reached at the 5th-6th hour, after which without a true peak, the blood level slowly decreases.
The elimination half-life of the active metabolite is approximately 60 hours and is more prolonged in the elderly, obese subjects, hepatopathic subjects and those with liver cirrhosis.
After repeated administration, the blood level rises for a few days and reaches steady state on day 9.
With discontinuation of the drug the blood levels do not fall abruptly, but gradually.
The volume of distribution is 14.4 ± 5.1 liters / kg.
Plasma protein binding is 97.5%.
05.3 Preclinical safety data
Carcinogenesis, mutagenesis and reduction of fertility
Long-term studies to evaluate carcinogenesis, mutagenesis and fertility have not been conducted with prazepam. Some initial studies revealed an increased congenital risk of malformations associated with the use of chlordiazepoxide, diazepam and meprobamate in the first trimester of pregnancy; these data have not been confirmed by subsequent studies. Prazepam, a benzodiazepine derivative, has not been studied. adequately to determine if it may be associated with an increased risk of fetal abnormalities (see section 4.6).
Long-term toxicological studies in rats and dogs have shown hepatomegaly and cholestasis.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
PRAZENE 10 mg tablets
One tablet contains: lactose, microcrystalline cellulose, corn starch, magnesium stearate, anhydrous colloidal silica.
PRAZENE 20 mg tablets
One tablet contains: lactose, microgranular cellulose, corn starch, magnesium stearate, anhydrous colloidal silica.
PRAZENE 15 mg / ml oral drops, solution
1 ml contains: propylene glycol, ethyl ethylene glycol, polysorbate 80, sodium saccharinate, levomentol, anethole, patent blue V.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
None.
06.5 Nature of the immediate packaging and contents of the package
PRAZENE 10 mg tablets
Box of 30 tablets in blister.
PRAZENE 20 mg tablets
Box of 20 tablets in blister.
PRAZENE 15 mg / ml oral drops, solution
1 glass bottle of 20ml with dropper.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l.
via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
PRAZENE 10 mg tablets 30 tablets of 10 mg - AIC n. 023762026
PRAZENE 20 mg tablets 20 tablets of 20 mg - AIC n. 023762038
PRAZENE 15 mg / ml oral drops, solution 1 bottle of 20 ml - AIC n. 023762053
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
PRAZENE 10 mg tablets January 26, 1979 / May 31, 2005
PRAZENE 20 mg tablets 20 December 1984/31 May 2005
PRAZENE 15 mg / ml oral drops, solution 20 December 1984/31 May 2005
10.0 DATE OF REVISION OF THE TEXT
11 June 2010
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