Active ingredients: Diazepam
TRANQUIRIT 5 mg / ml oral drops, solution
Indications Why is Tranquirit used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
TRANQUIRIT is an anxiolytic product, regulator of the autonomic, sedative, hypnogenic, muscle relaxant and anticonvulsant system.
THERAPEUTIC INDICATIONS
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Insomnia.
Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
Contraindications When Tranquirit should not be used
Myasthenia gravis. Hypersensitivity to benzodiazepines. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome.
Precautions for use What you need to know before taking Tranquirit
Due to the highly variable reactivity to psychotropic drugs, the dosage of diazepam should be set within prudent limits in elderly or debilitated patients and in those with organic cerebral changes (especially atherosclerotic) or with cardio-respiratory insufficiency.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
In the case of treatment lasting 8-12 weeks, it is advisable to carry out checks on the blood picture and liver function.
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 mental dependence on these drugs. The risk of addiction 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 leading to treatment with a benzodiazepine 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.
Since 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 also section "Dose, method and time of administration") depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks in the case of anxiety, including a gradual withdrawal period. Extending therapy beyond these periods should not take place without reassessment 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. In addition, it is important to 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 diazepam is a long-acting benzodiazepine therefore sudden change to a short-acting benzodiazepine 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.
Particular 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. 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 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.
Interactions Which drugs or foods can modify the effect of Tranquirit
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 leading to an increase in psychic dependence. Compounds that inhibit certain liver enzymes (especially cytochrome P450) can increase the activity of benzodiazepines.
Warnings It is important to know that:
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.
Use during pregnancy and lactation
Do not administer in the first trimester of pregnancy. In the following period, the drug should be administered only in case of real need and under direct medical supervision.
If the drug is prescribed to a woman of childbearing potential, she should be advised to contact her doctor to discontinue treatment, whether she intends to become pregnant or suspects that she is pregnant.
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 taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since the active ingredient diazepam passes into breast milk, breastfeeding should be discontinued if the product is to be taken regularly.
Effects on driving and use of machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive or operate machinery. If sleep duration has been insufficient, the likelihood of impaired alertness can be increased (see also "Interactions" section).
Dosage and method of use How to use Tranquirit: Dosage
Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
The patient should be monitored regularly at the start of treatment to decrease, if necessary, the dose or frequency of intake to prevent overdose due to accumulation.
Dosage
Drops (1ml = 25drops = 5mg) The dosage should be adjusted case by case. The drops should be diluted in water or another beverage.
Adults: the single dose to be repeated 2-3 times a day is 15-25 drops.
Children: 1 to 3 years: 1-6 mg (5-30 drops) per day; from 4 to 14 years: 4-12 mg (20-60 drops) per day.
Elderly, debilitated subjects, patients with impaired hepatic and / or renal function: in these patients it is advisable to administer single doses of 2 mg (10 drops) which can possibly be repeated 2-3 times a day.
Period 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 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.
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, in which case this should not be done without reassessment of the patient's condition.
The drug should be taken at bedtime.
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 dispensing operation as indicated above.
Overdose What to do if you have taken too much Tranquirit
As with other benzodiazepines, overdose should not pose a risk to life unless concomitant intake of other CNS depressants (including alcohol). As in the treatment of overdose of any drug, it should be considered. the possibility that other substances were taken at the same time.
Following an overdose of oral benzodiazepines, vomiting should be induced (within 1 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 CNS 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.
Side Effects What are the side effects of Tranquirit
Drowsiness during the day, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision. These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances, changes in libido and skin reactions; in rare cases: dysarthria, hypotension, constipation , incontinence or urinary retention, jaundice and nausea.
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see "Appropriate precautions for" use ").
Depression
During the use of benzodiazepines a pre-existing state of depression can be unmasked. Benzodiazepines can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes. These reactions can be quite serious. They are more likely in the elderly and children.
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 "Appropriate precautions for use"). Psychic dependence can occur. Cases of abuse have been reported.
If undesirable effects occur - even different from those described - the patient is invited to communicate them to their doctor or pharmacist.
Expiry and Retention
The expiry date indicated refers to the product in intact and correctly stored packaging.
WARNING: do not use the medicine after the expiry date indicated on the package.
Keep out of the reach and sight of children.
Date of last revision of the text by the Italian Medicines Agency: August 2011
Composition and pharmaceutical form
COMPOSITION
1ml of solution contains:
Active ingredient: diazepam 5 mg.
Excipients: ethyl alcohol, glycerin, propylene glycol, sodium saccharin, lemon essence and distilled water.
PHARMACEUTICAL FORM AND PACKAGING
Oral drops, solution 1 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
TRANQUIRIT 5 MG / ML ORAL DROPS, SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of solution contains:
Active ingredient: diazepam 5 mg.
03.0 PHARMACEUTICAL FORM
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 indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
04.2 Posology and method of administration
Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
The patient should be monitored regularly at the start of treatment to decrease, if necessary, the dose or frequency of intake to prevent overdose due to accumulation.
Dosage
Drops (1ml = 25 drops = 5mg)
The dosage should be adjusted on a case-by-case basis. The drops should be diluted in water or another beverage.
Adults: the single dose to be repeated 2-3 times a day is 15-25 drops.
Children: from 1 to 3 years: 1-6 mg (5-30 drops) per day;
from 4 to 14 years: 4-12 mg (20-60 drops) per day.
Elderly, debilitated subjects, patients with impaired hepatic and / or renal function: in these patients it is advisable to administer single doses of 2 mg (10 drops) which can possibly be repeated 2-3 times a day.
Period 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 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.
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, in which case this should not be done without reassessment of the patient's condition.
The drug should be taken at bedtime.
04.3 Contraindications
Myasthenia gravis. Hypersensitivity to benzodiazepines. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome.
04.4 Special warnings and appropriate precautions for use
Due to the highly variable reactivity to psychotropic drugs, the dosage of diazepam should be set within prudent limits in elderly or debilitated patients and in those with organic cerebral changes (especially atherosclerotic) or with cardio-respiratory insufficiency.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
In the case of treatment lasting 8-12 weeks, it is advisable to carry out checks on the blood picture and liver function.
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 mental dependence on these drugs. The risk of addiction 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 leading to treatment with a benzodiazepine 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.
Since 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 also section "Posology and method of administration") depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks for anxiety. including a phasing-out period. Extending therapy beyond these periods should not occur without reassessment 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.
Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about such symptoms should they occur when the drug is discontinued.
It is important to warn the patient that diazepam is a long-acting benzodiazepine therefore sudden change to a short-acting benzodiazepine 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 an uninterrupted sleep of 7 to 8 hours (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.
Particular 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 "Posology and method of administration"). Likewise, a lower dose is suggested for patients with chronic respiratory failure 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 psychotic illness. 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.
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.
In the case of narcotic analgesics, an increase in euphoria can occur, leading to an increase in psychic dependence.
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines.
04.6 Pregnancy and breastfeeding
Do not administer in the first trimester of pregnancy. In the following period, the drug should be administered only in case of real need and under direct medical supervision.
If the drug is prescribed to a woman of childbearing potential, she should be advised to contact her doctor to discontinue treatment, whether she intends to become pregnant or suspects that she is pregnant.
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 taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since the active ingredient diazepam passes into breast milk, breastfeeding should be discontinued if the product is to be taken regularly.
04.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive or operate machinery. If sleep duration has been insufficient, the likelihood of impaired alertness can be increased (see also "Interactions" section).
04.8 Undesirable effects
Drowsiness during the day, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision. These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances, changes in libido and skin reactions; in rare cases: dysarthria, hypotension, constipation , incontinence or urinary retention, jaundice and nausea.
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects can be associated with behavioral changes. (see "Special warnings and precautions for" use ").
Depression
A pre-existing state of depression may be unmasked during the use of benzodiazepines.
Benzodiazepines 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 the elderly and children.
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. Cases of abuse have been reported.
04.9 Overdose
As with other benzodiazepines, an overdose is not expected to pose a risk to life unless there is concomitant intake of other CNS depressants (including alcohol).
As 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 1 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 CNS 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.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: psycholeptics, anxiolytics, benzodiazepine derivatives.
ATC code: N05BA01.
Diazepam acts on the limbic system, on the thalamus and on the hypothalamus, exerting a sedative effect.
Compared to chlordiazepoxide, as reference benzodiazepine, diazepam produces a 5 to 10 times greater tranquilizing, muscle relaxant and anticonvulsant effect in mice; it is more powerful in inducing myolytic effects in mice and in preventing stiffness from decerebration and in depressing the limbic system in cats; it has an equal domesticating effect in monkeys and deconditioning in rats; less powerful, on the other hand, on the aggressiveness of septal rat.
In the clinic it has a muscle relaxant and tranquilizing effect superior to that of chlordiazepoxide and a remarkable antiepileptic and hypnotic effect.
05.2 Pharmacokinetic properties
Administered orally, diazepam is rapidly absorbed, reaching maximum plasma concentration within 30-90 minutes.
Serum protein binding is approximately 95%.
The half-life is around 32 hours and, following daily oral administration of 10 mg, the equilibrium level is reached on the fifth day.
Diazepam is rapidly metabolised to N-dimethyldiazepam and then to oxazepam, active metabolites; elimination occurs mainly via the kidneys in the inactive conjugate form.
The volume of distribution of diazepam is 1.1 l / kg.
Elimination may be slowed in the elderly, in premature infants and in patients with liver or kidney disease.
Diazepam, like other benzodiazepines, passes into breast milk and crosses the hematoplacental barrier.
05.3 Preclinical safety data
The LD50 of orally administered diazepam is 720 mg / kg in mice and 1240 mg / kg in rats.
The continued administration for 50 days of 2.5 mg / kg in rats and 2.5 mg / kg and 12.5 mg / kg in mice, respectively, did not cause mortality.
Some studies have shown that the use of benzodiazepines, and therefore of diazepam, in the first trimester of pregnancy may increase the risk of congenital malformations. Therefore, the product should not be used in the first three months of pregnancy.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Ethyl alcohol, glycerin, propylene glycol, sodium saccharin, lemon essence and distilled water.
06.2 Incompatibility
Not known.
06.3 Period of validity
In intact packaging: 5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Cardboard box with 20 ml glass bottle with safety cap.
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
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 020445021
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
20.11.1971 / 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
Medicinal product subject to Presidential Decree 309/90 and succ. mod. - Table II E.
11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY
October 2014
