Active ingredients: Triazolam
HALCION 125 micrograms tablets
HALCION 250 micrograms tablets
Why is Halcion used? What is it for?
PHARMACO-THERAPEUTIC CATEGORY
Benzodiazepine with hypnotic action.
THERAPEUTIC INDICATIONS
Short-term treatment of insomnia.
Benzodiazepines are indicated only when the insomnia is severe, disabling or subjecting the subject to severe distress.
Contraindications When Halcion should not be used
Halcion is contraindicated in patients with hypersensitivity to benzodiazepines, triazolam, or to any of the excipients of Halcion (see "Composition" section).
Halcion is also contraindicated in patients with myasthenia gravis, severe respiratory failure, sleep apnea syndrome and severe hepatic insufficiency.
Co-administration of triazolam with ketoconazole, itraconazole, nefazodone, efavirenz and HIV protease inhibitors is contraindicated (see section Interactions).
Precautions for use What you need to know before taking Halcion
Caution should be used in patients with mild to moderate hepatic impairment receiving triazolam.
In patients with impaired respiratory function, respiratory depression and apnea have been reported infrequently.
Benzodiazepines produce an additive effect when administered concomitantly with alcohol or other central nervous system (CNS) depressants. Concomitant alcohol intake is not recommended. Triazolam should be used with caution when taken in combination with other CNS depressants (see Interactions section).
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Tolerance
Some loss of the hypnotic effect 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.
Triazolam should mainly be used for the occasional short-term treatment of insomnia, usually for up to 7-10 days, up to a maximum of 4 weeks (see section
Dose, method and time of administration). Use for longer than two weeks requires a complete reassessment of the patient.
Withdrawal Symptoms: Once addiction has developed, abrupt discontinuation 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, hypersensitivity / intolerance to sounds, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
Rebound insomnia
Rebound insomnia is a transient syndrome in which the indication for treatment (insomnia) leading to treatment with benzodiazepines is more severely interrupted than in the initial phase. It may be accompanied by other reactions, including mood changes, anxiety, sleep disturbances and restlessness. Since the risk of withdrawal or rebound phenomena is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is recommended.
Although benzodiazepines are not depressogenic, they can be associated with mental depression which may or may not be associated with suicidal thoughts or actual suicide attempts. This happens in a rare and unpredictable way. Therefore, triazolam should be used with caution and the quantity of the prescription should be limited in patients with signs and symptoms of depressive disorders or suicidal tendencies.
Duration of treatment
The duration of treatment should be as short as possible (see section Dose, method and time of administration "), but should not exceed four weeks, including a gradual withdrawal period. Extension of 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.
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.
There is evidence that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses.
Amnesia
Benzodiazepines can induce antegrade amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk, patients must ensure that they can have uninterrupted sleep for 7 to 8 hours.
Caution should be exercised in elderly and debilitated patients.
In elderly and / or debilitated patients, it is recommended that triazolam treatment be initiated with 0.125 mg to decrease the possibility of excessive sedation, dizziness or impaired coordination. In other adult patients a dosage of 0.25 mg is recommended (see section "Dose, method and time of administration").
Triazolam is not recommended in children and adolescents below 18 years of age as there are insufficient data on safety and efficacy.
Psychiatric and paradoxical reactions
Reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, inappropriate behavior and other behavioral disturbances are known to occur when using benzodiazepines. Should this occur, the use of the medicinal product should be discontinued. These reactions occur more frequently in children and the elderly.
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 "Dose, method and time of administration").
Likewise, a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression. 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 psychosis. 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.
Complex events related to sleep behavioral disturbances, such as "drowsiness while driving" (ie, when driving and not fully alert after taking a hypnotic-sedative, with amnesia of the event) have been reported in patients who were not fully alert after taking a hypnotic-sedative, including triazolam. These and other complex events related to sleep behavioral disturbances can occur with sedative hypnotics, including triazolam taken alone in therapeutic doses. Consumption of alcohol and other substances. which depress the central nervous system together with hypnotic-sedatives seems to increase the risk of such behaviors, as does hypnotic-sedatives taken at doses above the maximum recommended dose. Due to the risk for the patient and the community, the interruption of hypnotic-sedative treatment should be strongly considered in patients reporting such events (see Effects unwanted)
Serious anaphylactoid reactions and anaphylactic reactions, including rare fatal cases of anaphylaxis, have been reported in patients receiving triazolam. Cases of angioedema, including that of the tongue, glottis, or larynx have been reported in patients who received the first or subsequent doses of sedative hypnotics, including triazolam (see section "Undesirable effects").
The medicine contains lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Interactions Which drugs or foods can modify the effect of Halcion
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Pharmacokinetic interactions can occur when triazolam is administered with medicinal products that interfere with its metabolism. Compounds that inhibit certain liver enzymes (particularly cytochrome P4503A4) can increase the concentration of triazolam and enhance its activity. Data from clinical trials with triazolam, in vitro studies with triazolam and clinical trials with drugs metabolized similarly to triazolam , have provided evidence of varying levels of interaction and possible interactions with triazolam in a large number of drugs. Based on the level of interaction and the type of data available, the following recommendations should be followed:
- concomitant administration of triazolam with ketoconazole, itraconazole and nefazodone is contraindicated;
- interactions involving HIV protease inhibitors (eg ritonavir) and triazolam are complex and time-dependent. Low dose ritonavir administered for short periods causes a consistent weakening of triazolam clearance (less than 4% of control values ), a prolongation of the elimination half-life and an enhancement of clinical effects. Concomitant administration of triazolam and HIV protease inhibitors is contraindicated (see section "Contraindications");
- concomitant administration of triazolam with other azole antifungals is not recommended;
- it is recommended to use caution and to consider a dose reduction when triazolam is administered concomitantly with cimetidine or macrolide antibiotics, such as erythromycin, clarithromycin and troleandomycin;
- Caution is advised when triazolam is administered concomitantly with isoniazid, fluvoxamine, sertraline, paroxetine, diltiazem and verapamil;
- oral contraceptives and imatinib may potentiate the clinical effects of triazolam due to inhibition of the CYP3A4 isoenzyme. Caution is advised in case of concomitant use with triazolam;
- rifampicin and carbamazepine cause induction of CYP3A4, therefore the effects of triazolam may decrease significantly during rifampicin or carbamazepine therapy. Patients should be switched to alternative hypnotic drugs which are predominantly eliminated as glucuronides.
- Efavirenz inhibits the oxidative metabolism of triazolam and can cause fatal effects such as prolonged sedation and respiratory depression. As a precaution, concomitant treatment is contraindicated.
- Apripitant: Potentiation of clinical effects may occur in case of concomitant use with triazolam due to inhibition of the CYP34A enzyme. This interaction may require a reduction in the dose of triazolam.
- Benzodiazepines produce an additive effect when given together with alcohol or other sedatives. Concomitant alcohol intake is not recommended. Triazolam should be used with caution when taken in combination with other sedative substances. Enhancement of central depressive effects may occur in case of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressant agents, narcotic analgesics, anti-epileptic products, anesthetics and sedative antihistamines. Potentiation of euphoria leading to increased psychic dependence may occur in the case of narcotic analgesics (see section Special warnings and Precautions for use).
- An increase in bioavailability has been noted when triazolam is taken at the same time as grapefruit juice.
Warnings It is important to know that:
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Data on teratogenicity and effects on postnatal development and behavior following treatment with benzodiazepines are inconsistent. Some early studies with other benzodiazepines have shown that in utero exposure may be associated with malformations. Subsequent studies with benzodiazepines have provided no clear evidence of malformations. Babies exposed to benzodiazepines during the last trimester of pregnancy or during labor have experienced both flaccid baby syndrome and neonatal withdrawal symptoms. If triazolam is used during pregnancy or the patient becomes pregnant while taking triazolam, the parents should be informed. potential danger to the fetus Triazolam should not be used by mothers who are breastfeeding.
Effects on ability to drive and use machines
Triazolam can greatly affect the ability to drive or use machines. Patients should be advised not to drive or operate machinery during treatment until daytime sleepiness or dizziness has been ruled out. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section Special warnings and Precautions for use).
Dosage and method of use How to use Halcion: Dosage
Treatment should be as short as possible. The duration of treatment usually ranges from a few days to two weeks up to a maximum of four weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without reassessment of the patient's condition. Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
Dosage
- Adults: 125 - 250 micrograms
- Elderly: 125 micrograms
- Patients with impaired liver function: Halcion 125 micrograms should be taken just before bedtime.
Overdose What to do if you have taken too much Halcion
Symptoms of triazolam overdose are amplifications of its pharmacological action and include somnolence, speech disturbances, motor coordination disorders, coma and respiratory depression. Serious consequences are rare unless other drugs and / or ethanol have been ingested concomitantly.
Treatment of overdose mainly consists of supporting respiratory and cardiovascular functions. The value of dialysis has not been determined. Flumazenil can be used as an adjunct to cardiovascular and respiratory support treatments associated with overdose.
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. improvement with stomach emptying, activated charcoal should be given to reduce absorption.
Benziodiazepine overdose usually presents with 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 as and very rarely death.
In case of accidental ingestion / intake of an excessive dose of Halcion, notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of HALCION, ask your doctor or pharmacist.
Side Effects What are the side effects of Halcion
Table 1: Adverse reactions
Frequency of adverse events observed in placebo-controlled clinical trials and "post marketing experience with frequency" not known
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see "Special warnings and precautions for" use ")
Depression
A pre-existing depressive state can be unmasked during the use of benzodiazepines.
Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe. They are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see "Special warnings and precautions for use"). Psychic dependence can occur.
Abuse of benzodiazepines has been reported.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Like all medicines, HALCION can cause side effects, although not everybody gets them.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
This medicine does not require any special storage conditions.
WARNING: do not use the medicine after the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
COMPOSITION
HALCION 125 micrograms tablets
Each tablet (lavender) contains: 125 micrograms triazolam.
Excipients: lactose, microcrystalline cellulose, colloidal silica, dioctyl sodium sulfosuccinate, sodium benzoate, corn starch, magnesium stearate, color E 132, color E 127, hydrated alumina.
HALCION 250 micrograms tablets
Each tablet (light blue) contains: 250 micrograms triazolam.
Excipients: lactose, microcrystalline cellulose, colloidal silica, dioctyl sodium sulfosuccinate, sodium benzoate, corn starch, magnesium stearate, color E 132, hydrated alumina.
PHARMACEUTICAL FORM AND CONTENT
Tablets
10 - 20 tablets of 125 micrograms
10 - 20 tablets of 250 micrograms
ORAL USE
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
HALCION TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
HALCION 125 mcg tablets
One tablet contains: active ingredient:
triazolam 125 mcg
HALCION 250 mcg tablets
One tablet contains: active ingredient: triazolam 250 mcg
Excipient with known effect: lactose
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets
125 mcg tablets: lavender color.
250 mcg tablets: light blue color.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Short-term treatment of insomnia.
Benzodiazepines are indicated only when the insomnia is severe, disabling or subjecting the subject to severe distress.
04.2 Posology and method of administration
Dosage
Treatment should be as short as possible. The duration of treatment usually ranges from a few days to two weeks up to a maximum of four weeks, including a gradual withdrawal period.
In certain cases, it may be necessary to extend beyond the maximum treatment period; if so, it should not take place without reassessment of the patient's condition.
Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
Dosage
Adults: 125 - 250 mcg
Elderly: 125 mcg
Patients with impaired hepatic and / or renal function: 125 mcg
Halcion should be taken just before bedtime.
Treatment should be started at the lowest recommended dose.
04.3 Contraindications
Halcion is contraindicated in patients with: known hypersensitivity to benzodiazepines, triazolam, or to any of the excipients of Halcion listed in section 6.1.
Halcion is also contraindicated in patients with myasthenia gravis, severe respiratory failure, sleep apnea syndrome and severe hepatic insufficiency.
Concomitant administration of triazolam with ketoconazole, itraconazole, nefazodone, efavirenz and HIV protease inhibitors is contraindicated (see section 4.5 Interactions with other medicinal products and other forms of interaction).
04.4 Special warnings and appropriate precautions for use
Caution should be used in patients with mild to moderate hepatic impairment receiving triazolam.
In patients with impaired respiratory function, respiratory depression and apnea have been reported infrequently.
Benzodiazepines produce an additive effect when administered concomitantly with alcohol or other CNS depressants. Concomitant alcohol intake is not recommended. Triazolam should be used with caution when taken in combination with other CNS depressants (see section 4.5 Interactions with other medicinal products and other forms of interaction).
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Tolerance
Some loss of the hypnotic effect 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.
Triazolam should be used primarily for the occasional short-term treatment of insomnia, usually for up to 7-10 days, up to a maximum of 4 weeks (see section 4.2. "Posology and method of administration" ). Use for longer than two weeks requires a complete reassessment of the patient.
Withdrawal Symptoms: Once addiction has developed, abrupt discontinuation 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: Rebound insomnia is a transient syndrome in which the indication for treatment (insomnia), which led to treatment with benzodiazepines, is more severely interrupted than in the initial phase. It may be accompanied by other reactions, including mood changes, anxiety, sleep disturbances and restlessness. Since the risk of withdrawal or rebound phenomena is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is recommended.
Although benzodiazepines are not depressogenic, they can be associated with mental depression which may or may not be associated with suicidal thoughts or actual suicide attempts. This happens in a rare and unpredictable way. Therefore, triazolam should be used with caution and the quantity of the prescription should be limited in patients with signs and symptoms of depressive disorders or suicidal tendencies.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2 Posology and method of administration), but should not exceed four 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.
There is evidence that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses.
Amnesia
Benzodiazepines can induce antegrade amnesia. This most often occurs several hours after ingestion of the drug and, therefore, to reduce the risk, patients must ensure that they can have uninterrupted sleep for 7 to 8 hours.
Caution should be exercised in elderly and debilitated patients.
In elderly and / or debilitated patients, it is recommended that triazolam treatment be initiated with 0.125 mg to decrease the possibility of excessive sedation, dizziness or impaired coordination. In other adult patients a dose of 0.25 mg is recommended (see section 4.2 Posology and method of administration).
Triazolam is not recommended in children and adolescents below 18 years of age as there are insufficient data on safety and efficacy.
Psychiatric and paradoxical reactions
Reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, inappropriate behavior and other behavioral disturbances are known to occur when using benzodiazepines. Should this occur, the use of the medicinal product should be discontinued. These reactions occur more frequently in children and the elderly.
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 Posology and method of administration). 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.
Complex events related to sleep behavioral disturbances, such as "sleepiness while driving" (that is, when driving and not fully alert after taking a hypnotic-sedative, with amnesia of the event) have been reported in patients who were not fully alert after taking a sedative-hypnotic, including triazolam. These and other complex events related to sleep behavioral disturbances can occur with hypnotic-sedatives, including triazolam taken alone in therapeutic doses. Alcohol consumption and others. substances that depress the central nervous system together with hypnotic-sedatives seem to increase the risk of such behaviors, as do hypnotic-sedatives taken at doses higher than the maximum recommended dose. Due to the risk to the patient and the community, discontinuation treatment with hypnotic-sedatives should be strongly considered in patients who report such events (see par rafo 4.8 Undesirable effects)
Serious anaphylactoid reactions and anaphylactic reactions, including rare fatal cases of anaphylaxis, have been reported in patients receiving triazolam. Cases of angioedema of the tongue, glottis, or larynx have been reported in patients who received the first or subsequent doses of hypnotic-sedatives, including triazolam (see section 4.8 Undesirable effects).
The medicine contains lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacokinetic interactions can occur when triazolam is administered with medicinal products that interfere with its metabolism. Compounds that inhibit certain liver enzymes (particularly cytochrome P4503A4) can increase the concentration of triazolam and enhance its activity. Data from clinical trials with triazolam, in vitro studies with triazolam and clinical trials with drugs metabolized similarly to triazolam , have provided evidence of varying levels of interaction and possible interactions with triazolam in a large number of drugs. Based on the level of interaction and the type of data available, the following recommendations should be followed:
• concomitant administration of triazolam with ketoconazole, itraconazole and nefazodone is contraindicated;
• interactions involving HIV protease inhibitors (eg ritonavir) and triazolam are complex and time-dependent. Low dose ritonavir administered for short periods causes a substantial weakening of the clearance of triazolam (less than 4% of the control), a prolongation of the elimination half-life and a potentiation of clinical effects. Concomitant administration of triazolam and HIV protease inhibitors is contraindicated (see section 4.3 Contraindications);
• concomitant administration of triazolam with other azole antifungals is not recommended;
• it is recommended to use caution and to consider a dose reduction when triazolam is administered concomitantly with cimetidine or macrolide antibiotics, such as erythromycin, clarithromycin and troleandomycin;
• Caution is advised when triazolam is co-administered with isoniazid, fluvoxamine, sertraline, paroxetine, diltiazem and verapamil;
• oral contraceptives and imatinib may potentiate the clinical effects of triazolam due to inhibition of the CYP3A4 isoenzyme. Caution is advised in case of concomitant use with triazolam;
• rifampicin and carbamazepine cause induction of CYP3A4, therefore the effects of triazolam may significantly decrease during rifampicin or carbamazepine therapy. Patients should be switched to alternative hypnotic drugs which are predominantly eliminated as glucuronides.
• Efavirenz inhibits the oxidative metabolism of triazolam and can cause fatal effects such as prolonged sedation and respiratory depression. As a precaution, concomitant treatment is therefore contraindicated.
• Apripitant: Potentiation of clinical effects may occur in case of concomitant use with triazolam due to inhibition of the CYP34A enzyme. This interaction may require a reduction in the dose of triazolam.
• Benzodiazepines produce an additive effect when given together with alcohol or other CNS depressants. Concomitant alcohol intake is not recommended. Triazolam should be used with caution when taken in combination with other CNS depressants. Enhancement of central depressive effects may occur in case of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressant agents, narcotic analgesics, anti-epileptic products, anesthetics and sedative antihistamines. Potentiation of euphoria leading to increased psychic dependence may occur in the case of narcotic analgesics (see section 4.4 Special warnings and precautions for use).
• An increase in bioavailability has been noted when triazolam is taken at the same time as grapefruit juice.
04.6 Pregnancy and lactation
Data on teratogenicity and effects on postnatal development and behavior following treatment with benzodiazepines are inconsistent. Some early studies with other benzodiazepines have shown that in utero exposure may be associated with malformations. Subsequent studies with benzodiazepines have provided no clear evidence of malformations. Babies exposed to benzodiazepines during the last trimester of pregnancy or during labor have experienced both flaccid baby syndrome and neonatal withdrawal symptoms. If triazolam is used during pregnancy or the patient becomes pregnant while taking triazolam, the parents should be informed. patients of the potential danger to the fetus.
Triazolam should not be used by mothers who are breastfeeding.
04.7 Effects on ability to drive and use machines
Triazolam can greatly affect the ability to drive or use machines. Patients should be advised not to drive or operate machinery during treatment until daytime sleepiness or dizziness has been ruled out. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section 4.4 Special warnings and precautions for use).
04.8 Undesirable effects
Table 1: Adverse reactions
Frequency of adverse events observed in placebo-controlled clinical trials and "post marketing experience with frequency" not known
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see "Special warnings and precautions for use")
Depression
A pre-existing depressive state can be unmasked during the use of benzodiazepines.
Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe. They are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see section 4.4). Psychic dependence may occur.
Abuse of benzodiazepines has been reported.
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. "Street address: www.aifa.gov.it/responsabili
04.9 Overdose
Symptoms of triazolam overdose are amplifications of its pharmacological action and include somnolence, speech disturbances, motor coordination disorders, coma and respiratory depression. Serious consequences are rare unless other drugs and / or ethanol have been ingested concomitantly. Treatment of overdose mainly consists of supporting respiratory and cardiovascular functions. The value of dialysis has not been determined. Flumazenil can be used as an adjunct to cardiovascular and respiratory support treatments associated with overdose.
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. improvement with stomach emptying, activated charcoal should be given to reduce absorption.
Benziodiazepine overdose usually presents with 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 as and very rarely death.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: sedative hypnotics; benzodiazepine derivatives.
ATC code: N05CD05.
Triazolam is a benzodiazepine with anxiolytic, sedative and hypno-inducing properties as well as with possible muscle-relaxing and anticonvulsant characteristics.
05.2 Pharmacokinetic properties
In adults, following a single dose of 0.25 mg, a Cmax of 2.02 ± 0.15 ng / ml is achieved at a Tmax of 0.96 ± 0.1 h. The elimination half-life is 1.5 - 5.5 hours.
In the elderly, Cmax increases by approximately 50%. Tmax and t1 / 2 remain unchanged. In healthy volunteers the volume of distribution was approximately 0.67 L / kg (range 0.57 - 0.86 L / kg after a dose of 0.125 - 1 mg).
Triazolam binds to plasma proteins, with a free fraction ranging from 9.9 to 25.7%. The fraction remains unchanged in the elderly.
Triazolam is metabolised by cytochrome P450. There is an active metabolite, alpha-hydroxybenzodiazepine, which has a t1 / 2 of 3.9 hours.
05.3 Preclinical safety data
The toxicological data relating to the experimental animal are as follows:
LD50, intraperitoneal administration - mouse, 2,473 mg / kg.
LD50, intraperitoneal administration - rat, greater than 5,000 mg / kg.
LD50, oral administration - rat, greater than 5,000 mg / kg.
Chronic toxicity studies conducted on Wistar rats at doses of 10 and 30 mg / kg / day and on Beagle dogs at a dose of 10 mg / kg / day, treated for 25 weeks by oral administration did not reveal any toxicological effects. Teratogenesis studies conducted on pregnant rats and rabbits from day 6 to 18 of pregnancy, treated at doses of 0 - 10 and 30 mg / kg / day for oral administration, did not reveal any changes in the reproductive parameters observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
One 125 mcg tablet contains:
Excipients : Lactose; Microcrystalline cellulose; Colloidal silica; Dioctyl sodium sulfosuccinate; Sodium benzoate; Cornstarch; Magnesium stearate; E 132; E 127; Alumina hydrates.
One 250 mcg tablet contains:
Excipients: Lactose; Microcrystalline cellulose; Colloidal silica; Dioctyl sodium sulfosuccinate; Sodium benzoate; Cornstarch; Magnesium stearate; E 132; Alumina hydrates.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 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
Opaque PVC / Aluminum blister.
Box of 10-20 tablets of 125 mcg.
Box of 10-20 tablets of 250 mcg.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l. Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
HALCION 125 mcg tablets: 10 tablets, AIC
024713048
HALCION 125 mcg tablets: 20 tablets, AIC
024713063
HALCION 250 mcg tablets: 10 tablets, AIC
024713051
HALCION 250 mcg tablets: 20 tablets, AIC
024713075
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Halcion 125 mcg tablets - 10 tablets
Date of first authorization: 28 March 1992
Date of last renewal: May 31, 2010
Halcion 125 mcg tablets - 20 tablets
Date of first authorization: 10 April 1995
Date of last renewal: May 31, 2010
Halcion 250 mcg tablets - 10 tablets
Date of first authorization: 28 March 1992
Date of last renewal: May 31, 2010
Halcion 250 mcg tablets - 20 tablets
Date of first authorization: 10 April 1995
Date of last renewal: May 31, 2010
