Active ingredients: Etizolam
PASADEN 0.5 mg coated tablets
PASADEN 1 mg coated tablets
PASADEN 0.5 mg / ml oral drops, solution
Why is Pasaden used? What is it for?
Pharmacotherapeutic group
"Etizolam is the first representative of the chemical class of" thienotriazolodiazepines "(it is a benzodiazepine-like substance), and as such belongs to the category of sedative-hypnotic drugs. The chemical structure of" etizolam is easily oxidized and therefore rapidly metabolized into " organism: the risk of accumulation is thus significantly reduced, even in prolonged treatments.
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 Pasaden should not be used
Myasthenia gravis (a severe muscle function disorder). Hypersensitivity to benzodiazepines or to any of the excipients. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea (shortness of breath) syndrome at night. Acute angle-closure glaucoma.
Precautions for use What you need to know before taking Pasaden
Treatment with Pasaden, as with similar drugs, should be as short as possible in relation to the therapeutic indication: maximum four weeks for sleep disorders and eight to twelve weeks for anxiety, including a gradual withdrawal period. end.
Some loss of efficacy ("tolerance") may develop after repeated use of benzodiazepines and related substances.
Prolonged use can also lead to the development of physical and mental dependence; the risk in this sense increases with dose and duration of treatment, and is greater in patients who abuse drugs or alcohol.
In subjects with physical dependence on benzodiazepines, "abrupt cessation of treatment will produce so-called" withdrawal "symptoms: in most cases, headaches, muscle pains, severe anxiety, tension, restlessness, confusion and irritability. In severe cases they may occur. the following symptoms: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
When the treatment is interrupted, "rebound" phenomena may also occur, ie the same symptoms that led to the use of the drug, even more intense ones.
The risk of withdrawal and rebound symptoms is greater after abrupt discontinuation of treatment; this is why the dosage should be gradually decreased. In certain cases it may be necessary to extend the treatment beyond the maximum recommended period; in these cases the doctor will decide after careful re-evaluation of the patient's condition.
Pasaden should only be used in adult patients. If it is necessary to administer the drug to children, the actual need for the treatment must first be assessed and the same precautions must be taken.
Elderly people should take a reduced dose, as some adverse reactions such as lack of coordination in movement may occur. Likewise, a lower dose is suggested for patients with chronic respiratory failure, due to the risk of respiratory depression. Furthermore, benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can lead to encephalopathy, nor are they recommended for the primary treatment of psychotic illnesses; they should not be used alone to treat depression or anxiety associated with depression ( suicide can be precipitated in patients with these conditions) and should be used with extreme caution in patients with a history of drug or alcohol abuse.
Pasaden should be administered with caution in subjects with organic brain disorders, renal or hepatic disorders and hypotonia, as potentiation of the effect of the drug may occur in such patients.
Caution should also be used with people with heart disease as the medicine can lead to a lowering of blood pressure and this effect may be aggravated in this group of patients.
Interactions Which drugs or foods can modify the Pasaden effect
The association with all drugs that act depressingly on the Central Nervous System (eg. Other anxiolytics and / or hypnotics, antidepressants, analgesics, antiepileptics, phenothiazine derivatives, and derivatives of barbiturates) antiepileptics, antipsychotics (neuroleptics), anesthetics and sedative antihistamines, etc. should be avoided, as well as concomitant use with alcoholic beverages. In these cases, in fact, the sedative effect increases and somnolence, hypotension, ataxia and disturbances of consciousness can occur.
In the case of analgesic narcotics, an increase in the euphoric effect of the narcotic may occur.
Compounds that inhibit certain liver enzymes (cytochrome P450, monoamine oxidase inhibitors) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines metabolized only by conjugation.
Drugs capable of inhibiting the cytochromial isoenzymes CYP2C9 and CYP3A4, such as fluvoxamine maleate, may also increase the plasma concentrations of Pasaden and enhance its effects; in combination with fluvoxamine maleate Pasaden should be administered with caution, reducing the dose
Warnings It is important to know that:
Pasaden, in the same way as similar drugs (see above), can negatively modify the ability to react, concentration, muscle function. Therefore it can be dangerous for the patient under treatment to engage in activities that require promptness and precision, as required, in particular, in driving vehicles or in the use of potentially dangerous machinery.
Use in pregnancy and lactation
Women of childbearing age who take the product should contact their doctor if they intend to become pregnant or suspect they may be pregnant.
The drug should be administered only in case of real need and under direct medical supervision, for short periods of time. Administration in late pregnancy and during labor at high doses may produce effects on the newborn (reduced activity, decreased sucking, lethargy, tachycardia, vomiting, increased serum CK, lowering of temperature and muscle tone, difficulty in breathing ).
In addition, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence and have a certain risk of developing withdrawal symptoms in the postnatal period and have symptoms such as apnea, cyanosis, decreased sucking, decreased muscle tone, reduced activity and withdrawal syndrome. The drug passes into breast milk, therefore it should not be given to mothers who are breastfeeding. If Pasaden is needed, the patient should stop breastfeeding, as the medicine can pass into breast milk blocking weight gain in the newborn and can also cause worsening of jaundice.
Special warnings for Pasaden 0.5 mg / ml oral drops, solution
For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positivity to doping tests in relation to the alcohol concentration limits indicated by some sports federations
Dosage and method of use How to use Pasaden: Dosage
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome: 0.25-0.50 mg two or three times a day, or 1 mg, two tablets a day (one in the morning and one in the evening) in major disorders intensity.
Insomnia: 1-2 mg before bedtime, according to individual needs, according to medical prescription.
The indicated dosage can also be taken using the package in drops, considering that 10 drops are equal to 0.25 mg.
In the treatment of elderly patients, and of patients with impaired hepatic and / or renal function, the posology must be carefully established by the physician, who will have to evaluate a "possible reduction of the dosages indicated above. In elderly patients, the daily dose should not be higher than 1.5 mg.
The use of the product is intended for adult patients.
Treatment should be started with the lowest recommended dose, to be increased taking care not to exceed the maximum dose, and be as short as possible.
The anxious 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 the case of sleep disorders, the duration of treatment usually ranges from a few days to two weeks, including a gradual withdrawal period.
In certain cases it may be necessary to extend beyond the maximum treatment period, in which case this should not be done without the physician's re-evaluation of the patient's condition.
Overdose What to do if you have taken too much Pasaden
Taking excessive doses of Pasaden, as well as similar drugs, should not be life-threatening unless other CNS depressant drugs, including alcohol, are taken at the same time.
Overdose presents with a range of CNS symptoms ranging from somnolence and confusion in less severe cases to coma, rarely, and death, very rarely. In addition, there have been reports of lack of coordination in movements, hypotension, respiratory failure.
Treatment of overdose consists of immediate induction of vomiting if the patient is conscious, and gastric lavage with respiratory protection and possible administration of activated charcoal, to reduce absorption, if the patient is unconscious.
As an antidote (to nullify the harmful effects of the drug) flumazenil can be used.
Side Effects What are the side effects of Pasaden
Pasaden is generally well tolerated. If the dosage is not adapted to individual needs, the following undesirable effects may nevertheless appear: drowsiness (during the day if the product is used for sleep disorders), dulling of emotions, decreased alertness, confusion, speech disturbances, fatigue, headache, dizziness, muscle weakness, lack of coordination in movements, double vision, thirst, nausea and skin rash. These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations. Other reactions have occasionally been reported, including: gastrointestinal disturbances, changes in libido, erythema and skin reactions, feeling of difficulty in breathing, palpitations, gynaecomastia, hyperprolactinaemia, bleferospasm (if eye symptoms such as excessive blinking are observed , photophobia and dry eyes, intervene with the appropriate therapy), sweating, edema, urination disorders and nasal obstruction. Anterograde amnesia (impaired forward memory) may occur, more likely with the use of higher dosages.
In patients with a pre-existing depressive state, and in any case with greater frequency in children and the elderly, the use of benzodiazepine substances can cause psychiatric and "paradoxical" reactions (contrary to those expected) such as restlessness, agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes. These reactions can be quite severe. They are more likely in children and the elderly. Physical dependence may develop, in which case abrupt discontinuation of therapy may cause rebound or abstinence.
Psychic dependence can occur. Abuse of benzodiazepines has been reported.
The following clinically significant adverse reactions of unknown incidence were also observed:
Respiratory depression, CO2 narcosis: Respiratory depression and CO2 narcosis may occur in patients with severely impaired respiratory function. If any of these symptoms occur, take appropriate measures, such as airway control and ventilation.
Malignant syndrome: this syndrome, in addition to the administration of this drug, can be caused by the concomitant use of antipsychotics and other drugs, abrupt dose reduction and discontinuation of administration. If fever, severe muscle stiffness, dysphagia, tachycardia appear, change in blood pressure, sweating, increase in white blood cells and serum CK levels (CPK), etc. it is necessary to intervene with total body measures, such as body cooling and hydration. In addition, if this syndrome occurs, renal hypofunction may appear with myoglobinuria.
Rhabdomyolysis: This condition is characterized by myalgia, weakness, increased levels of CK (CPK) and myoglobin in the blood / urine. If rhabdomyolysis occurs, discontinue drug administration and take appropriate therapeutic measures.
Interstitial pneumonia: Interstitial pneumonia may occur. Discontinue drug administration and take chest x-rays for fever, cough, dyspnoea, and abnormal chest sounds (crackles).
Adopt appropriate therapeutic measures, such as administering adrenocorticoid hormones.
Liver function impairment, jaundice: Liver function disorders (increased AST (GOT), ALT (GPT), γ-GT, LDH, ALP and bilirubin, etc.) and jaundice may occur. The patient should be monitored closely and treatment discontinued in case of abnormal test results.
The occurrence of any undesirable effect not described in this leaflet during treatment with Pasaden must be promptly reported by the patient to the treating physician or pharmacist.
Expiry and Retention
Do not use the drug beyond the expiration date indicated on the package, which refers to the intact and correctly stored product.
Do not store above 25 ° C.
Composition and pharmaceutical form
Composition
Each 0.5 mg coated tablet contains:
Active ingredient: etizolam 0.5 mg
Excipients: lactose, microcrystalline cellulose, corn starch, talc, magnesium stearate, polymethacrylic esters, macrogol 5/6000, polysorbate 80, sodium carboxymethylcellulose, silicone oil, Opadry Blue *.
* Opadry Blue components: hypromellose, titanium dioxide, macrogol 400, Brilliant Blue FCF (E 133), Carmoisin (E 122).
Each 1 mg coated tablet contains:
Active ingredient: etizolam 1 mg
Excipients: lactose, microcrystalline cellulose, corn starch, talc, magnesium stearate, polymethacrylic esters, macrogol 5/6000, polysorbate 80, sodium carboxymethylcellulose, silicone oil, titanium dioxide.
100 ml of solution contain:
Active ingredient: etizolam 0.05 g
Excipients: sodium saccharin, ethanol, glycerol, orange flavor, caramel flavor, lemon flavor, propylene glycol.
Pharmaceutical forms and content
Coated tablets and oral drops, solution. Coated tablets 0.5 mg etizolam: pack with 30 tablets; coated tablets 1 mg etizolam: pack with 20 tablets. Oral drops, solution: bottle of 30 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
PASADEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active principle:
Each 0.5 mg coated tablet contains etizolam 0.5 mg.
Each 1 mg coated tablet contains etizolam 1 mg.
100 ml of solution in drops contain etizolam 0.05 g.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablets; 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
Dosage
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome: 0.25-0.50 mg two or three times a day; or 1 mg, two tablets a day (one in the morning and one in the evening) in the most intense disorders.
Insomnia: 1-2 mg before bedtime, according to individual needs, according to medical prescription. The indicated dosage can also be taken using the package in drops, considering that 10 drops are equal to 0.25 mg.
Special populations
Renal and / or hepatic impairment
In the treatment of patients with impaired hepatic and / or renal function, the posology must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.
Elderly population
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
However, the daily dose should not exceed 1.5 mg.
Pediatric population
The use of the product is reserved for adult patients.
Treatment should be started with the lowest recommended dose, to be increased taking care not to exceed the maximum dose, and be as short as possible.
The anxious 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 the case of sleep disorders, the duration of treatment usually ranges from a few days to two weeks, including a gradual withdrawal period.
In certain cases, it may be necessary to extend beyond the maximum treatment period, in which case this should not be done without the physician's re-evaluation of the patient's condition.
04.3 Contraindications
Myasthenia gravis (symptoms may be aggravated by the muscle relaxant effect) Severe respiratory failure Severe liver failure Sleep apnea syndrome Acute narrow-angle glaucoma (symptoms may be aggravated by the anticholinergic effect).
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
04.4 Special warnings and appropriate precautions for use
Tolerance
After repeated use of benzodiazepines for a few weeks, some loss of efficacy of their hypnotic effects may develop.
Dependence
The use of benzodiazepines can lead to the development of physical and psychological dependence on them. The risk of addiction increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse. physical dependence has developed, abrupt cessation of treatment will be accompanied by withdrawal symptoms. Headache, muscle aches, extreme anxiety, tension, restlessness, confusion, and irritability may be experienced. 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, epileptic seizures.
Rebound insomnia and anxiety: a transient syndrome may occur upon discontinuation of treatment in which the same symptoms that led to treatment with benzodiazepines recur in an aggravated form, and sometimes other reactions, including mood changes, anxiety, restlessness and sleep disturbances .
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, it is suggested to gradually decrease the dosage.
Duration of treatment
The duration of treatment should be as short as possible (see 4.2 "Posology and method of administration") in relation to the indication, and should not exceed four weeks for insomnia and eight to twelve weeks for anxiety, including a gradual withdrawal period. Extension of therapy beyond these terms 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. Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, in order to minimize the anxiety that would develop if these symptoms were to 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 occur within the dosing interval between doses, particularly in the case of high dosages. When using long-acting benzodiazepines, it is important to warn the patient that sudden change to a short-acting benzodiazepine is inadvisable as withdrawal symptoms may occur.
Amnesia
Benzodiazepines can induce antegrade amnesia. This most often occurs several hours after ingestion of the drug, therefore, to reduce the risk, it should be ensured that patients can have 7-8 hours of uninterrupted sleep (see 4.8 "Undesirable Effects").
Psychiatric and paradoxical reactions. It is known that reactions such as restlessness, agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes may occur with the use of benzodiazepines. If this occurs, the use of the drug should be discontinued. Such 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 as the safety of the drug in children has not been determined; treatment duration should be as short as possible. Elderly people should take a reduced dose, as they can some adverse reactions such as motor ataxia may occur (see 4.2 "Posology and method 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 lead to 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 patients with these conditions). Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse .
Pasaden should be administered with caution in subjects with organic brain disorders, renal or hepatic disorders and hypotonia, as potentiation of the effect of the drug may occur in such patients.
Caution should also be used with people with heart disease as the medicine can lead to a lowering of blood pressure and this effect may be aggravated in this group of patients.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant intake of the medicinal product with alcohol should be avoided as the sedative effect may be increased. This adversely affects the ability to drive and use machines.
Combination with CNS depressant drugs: the central depressive effect may be potentiated in cases of concomitant use with antipsychotics (eg phenothiazines), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics (eg barbiturates), anesthetics and sedative antihistamines In these conditions drowsiness, hypotension, ataxia and altered state of consciousness may occur.
In the case of narcotic analgesics, the possible increase in euphoria can lead to an increase in psychic dependence.
Combination with drugs that affect liver enzymes: 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.
Pasaden is metabolised in the liver by cytochromial isoenzymes CYP2C9 and CYP3A4. Among the drugs capable of inhibiting its hepatic metabolism, with a consequent increase in its plasma concentrations and possible enhancement of its effects, there is fluvoxamine maleate. It is therefore recommended to administer Pasaden with caution, reducing its dose, in combination with fluvoxamine maleate.
Combination with monoamine oxidase inhibitors (MAO): monoamine oxidase inhibitor drugs can inhibit the metabolization of Pasaden in the liver which leads to a prolongation of the half-life and an increase in blood concentration. The use of these drugs can enhance the effect of Pasaden and excessive sedation, coma, convulsions, agitation, etc. may occur.
04.6 Pregnancy and lactation
Women of childbearing potential
If the product is taken by a woman of childbearing potential, she will need to contact her doctor if she intends to become pregnant or suspects that she is pregnant regarding discontinuation of the medicine.
Pregnancy
The drug should be administered only in case of real need and under direct medical supervision, for short periods of time. 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 reduced activity, feeding disturbance, lethargy, tachycardia, vomiting, increased CK serum, hypothermia, hypotonia and moderate respiratory depression due to the pharmacological action of the substance.
In addition, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence, may have some risk of developing withdrawal symptoms in the postnatal period, and have symptoms such as apnea, cyanosis, decreased sucking, decreased muscle tone. , reduced activity and withdrawal syndrome.
Feeding time
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers. If Pasaden is needed, the patient should stop breastfeeding, as the medicine can pass into breast milk blocking weight gain in the newborn and can also cause worsening of jaundice.
04.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function (side effects possible with the use of benzodiazepines) can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood that alertness is impaired may be increased (see 4.5 "Interaction with other medicinal products and other forms of interaction").
04.8 Undesirable effects
Pasaden is generally well tolerated. If the dosage is not adapted to individual needs, the following undesirable effects may nevertheless appear: drowsiness (during the day if the product is used for sleep disorders), dulling of emotions, decreased alertness, confusion, speech disturbances, fatigue, headache, dizziness, muscle weakness, ataxia, ocular disturbances, double vision, thirst, nausea and skin rash. 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, erythema and skin reactions, sensation of difficulty in breathing, palpitations, gynaecomastia, hyperprolactinaemia, bleferospasm (if eye symptoms are observed, such as excessive blinking, photophobia and dry eyes, intervene with suitable therapy), sweating, edema, urination disorders and nasal obstruction.
Amnesia. Anterograde amnesia can also occur at therapeutic dosages; the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see 4.4 "Special warnings and precautions for use").
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, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes. they can be 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: abrupt discontinuation of therapy can cause rebound or withdrawal phenomena such as convulsive attacks, delirium, tremor, insomnia, anxiety, hallucinations, etc. (see 4.4 "Special warnings and precautions for" use "). Psychic dependence can occur. Abuse of benzodiazepines has been reported.
The following clinically significant adverse reactions of unknown incidence were also observed:
Respiratory depression, hypercapnia: respiratory depression and CO2 narcosis may occur in patients with severely impaired respiratory function. If any of these symptoms occur, take appropriate measures, such as airway control and ventilation.
Malignant syndrome: this syndrome, in addition to the administration of this drug, can be caused by the concomitant use of antipsychotics and other drugs, the abrupt reduction of the dosage and the interruption of the administration. If fever, muscle stiffness, dysphagia, tachycardia, pressure fluctuation appear blood, sweating, increase in white blood cells and increase in blood creatine phosphokinase, etc. it is necessary to intervene with total body measures, such as body cooling and hydration.
Rhabdomyolysis: This condition is characterized by myalgia, asthenia, increased levels of CK (CPK), increased blood levels of myoglobin and the presence of myoglobin in the urine.
If rhabdomyolysis occurs, discontinue drug administration and take appropriate therapeutic measures.
Interstitial pneumonia: Interstitial pneumonia may occur. Discontinue drug administration and take chest x-rays for fever, cough, dyspnoea, and abnormal crackles and noises. Adopt appropriate therapeutic measures, such as administering adrenocorticoid hormones.
Abnormal liver function, jaundice: Disturbances in liver function may occur (increased level of aspartate aminotransferase (AST) (GOT), alanine aminotransferase (ALT (GPT), gamma glutamyl transferase (γ-GT), blood lactate dehydrogenase (LDH), blood alkaline phosphatase (ALP) ) and bilirubin, etc.) and jaundice The patient should be monitored closely and treatment discontinued in case of abnormal test results.
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 www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
As with other benzodiazepines, an overdose of Pasaden should not be life-threatening unless concomitant other CNS depressant drugs (including alcohol) are taken. In the treatment of overdose of any drug it should always be considering the possibility that other substances were taken at the same time.
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.
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. 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. Flumazenil can be used as an antidote.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anxiolytics, benzodiazepine derivatives.
ATC code: N05BA19.
Etizolam is the progenitor of an original chemical class of diazepines, the thienotriazolodiazepines. The thiophenic ring, which replaces the benzene ring, makes the molecule more easily oxidizable and therefore more rapidly metabolized in the organism; the risk of accumulation is thus considerably reduced, even in prolonged treatments.
Mechanism of action
In the context of pharmacological tests, etizolam has been shown to have a powerful anxiolytic action (up to six times higher than that of diazepam). Etizolam also determines, especially at higher dosages, a reduction in the time of falling asleep, an increase in the total duration of nocturnal sleep and a reduction in the number of awakenings.
This hypno-inducing effect is not accompanied by a significant reduction in slow sleep. The decrease in REM activity is not followed, on suspension of administration, by a compensatory increase (rebound phenomenon).
In some pharmacological studies (turnover of cerebral monoamines in animals and EEG drug studies in healthy volunteers), qualitative characteristics similar to those observed with some antidepressant drugs (tricyclics) have been highlighted by etizolam.
Etizolam was found to have no significant action on the cardiovascular and respiratory systems.
05.2 Pharmacokinetic properties
Absorption
In humans, after administration of therapeutic doses, etizolam is completely and rapidly absorbed from the gastrointestinal tract and reaches the maximum blood concentration after 3.2 hours. The binding to plasma proteins appears to be of the order of 93%. The elimination half-life in humans is 6.2 hours. Therefore, etizolam should be classified in the context of medium-short-acting diazepines.
Following repeated administration of a 1 mg tablet three times / day, from 30 minutes to 1 hour after a meal, the plasma concentration of the drug in the patients considered was similar after 7, 14 and 28 days. This finding suggests that etizolam, at the doses used in the clinic, exhibits linear kinetics.
After absorption, etizolam is rapidly and extensively metabolised in the liver (by hydroxylation and oxidation) and conjugated with glucuronic acid. The unchanged drug and its metabolites are excreted via the kidney. Ethizolam does not significantly interfere with enzymes. of the hepatic microsomal system and does not cause accumulation phenomena.
05.3 Preclinical safety data
Acute toxicity (single administration):
Chronic toxicity (repeated administrations):
In the long-term toxicity studies conducted on various animal species using high doses (up to 50 mg / kg in rats and up to 10 mg / kg in dogs) no particular pathological lesions or dysfunctions affecting organs or systems were found, nor did any significant alterations in biohumoral indices emerge. In all cases, mortality never significantly differed from that expected for this type of test.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Coated tablets 0.5 mg:
lactose, microcrystalline cellulose, corn starch, talc, magnesium stearate, polymethacrylic esters, macrogol 5/6000, polysorbate 80, sodium carboxymethylcellulose, silicone oil, Opadry Blue *.
* Opadry Blue components: hypromellose, titanium dioxide, macrogol 400, Brilliant Blue FCF (E 133), Carmoisin (E 122).
Coated tablets 1 mg:
lactose, microcrystalline cellulose, corn starch, talc, magnesium stearate, polymethacrylic esters, macrogol 5/6000, polysorbate 80, sodium carboxymethylcellulose, silicone oil, titanium dioxide.
Drops:
sodium saccharin, ethanol, glycerol, orange flavor, caramel flavor, lemon flavor, propylene glycol.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
For the intact packaged product, properly stored:
3 years.
06.4 Special precautions for storage
Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Pasaden tablets 0.5 mg: Cardboard box of 30 tablets in opaque blister pack consisting of PVC / aluminum.
Pasaden tablets 1 mg: Cardboard box of 20 tablets in opaque blister pack consisting of PVC / aluminum.
Pasaden oral drops: cardboard box containing a 30 ml neutral yellow glass bottle, fitted with a dropper and a child resistant screw cap.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer S.p.A. - Viale Certosa, 130 - 20156 Milan
08.0 MARKETING AUTHORIZATION NUMBER
30 tablets of 0.5 mg: A.I.C. n. 026368050
20 tablets of 1 mg: A.I.C. n. 026368062
0.5 mg / ml drops: A.I.C. n. 026368086
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 08.03.1989
Date of most recent renewal: 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
12/2015
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