Active ingredients: Alprazolam
ALPRAZOLAM ABC 0.25 mg tablets
ALPRAZOLAM ABC 0.50 mg tablets
ALPRAZOLAM ABC 1 mg tablets
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution
Why is Alprazolam ABC used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Benzodiazepine anxiolytic derivative
THERAPEUTIC INDICATIONS
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome.
Panic attacks with or without agoraphobia.
Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
Contraindications When Alprazolam ABC should not be used
ALPRAZOLAM ABC is contraindicated in patients with a known hypersensitivity to benzodiazepines, to alprazolam or to any of the excipients and in patients with acute angle-closure glaucoma. The product can be used in patients with open-angle glaucoma receiving therapy Benzodiazepines are also contraindicated in patients with myasthenia gravis, severe respiratory failure, sleep apnea syndrome, severe hepatic insufficiency.
Do not administer in the first trimester of pregnancy and during lactation.
Precautions for use What you need to know before taking Alprazolam ABC
Duration of treatment
The duration of treatment should be as short as possible (see Dose, method and time of administration) and in the case of anxiety should not exceed 8-12 weeks, including the gradual withdrawal period. The extension of therapy beyond these periods it must not take place without a thorough 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.
When using benzodiazepines with a long duration of action, it is important to warn the patient that abrupt change to a benzodiazepine with a short duration of action is not recommended, as withdrawal symptoms may appear.
Discontinuation of treatment
Like any other benzodiazepine, the dosage of ALPRAZOLAM ABC should be reduced gradually as abrupt or too fast discontinuation can lead to withdrawal symptoms.
Withdrawal symptoms may include mild dysphoria and insomnia or present as major syndromes with muscle and abdominal cramps, vomiting, sweating, tremors and convulsions. In addition, withdrawal crises may occur following a rapid decrease or abrupt discontinuation of alprazolam therapy (see Dose, method and time of administration - Discontinuation of therapy).
These symptoms, especially the more severe ones, are generally more common in those patients who have been treated with excessive doses for prolonged periods of time. However, withdrawal symptoms have also been reported following abrupt discontinuation of therapeutic doses of benzodiazepines. Therefore abrupt discontinuation should be avoided and a gradual reduction of the dosage should be prescribed (see Dose, method and time of administration).
During drug withdrawal in patients with panic disorder, symptoms related to the reappearance of panic attacks that mimic those typical of withdrawal can sometimes be observed.
Amnesia
Benzodiazepines can induce antegrade amnesia. This happens most frequently several hours after ingestion of the drug.
Psychiatric and paradoxical reactions
When using benzodiazepines it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes can occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in children and the elderly.
Specific groups of patients
Children and adolescents
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.
In elderly and / or debilitated patients it is recommended to always use the lowest dose to avoid the risk of residual sedation or ataxia. Elderly people should take a reduced dose (see Dose, method and time of administration). Likewise, a lower dose is recommended for patients with chronic respiratory failure because of the risk of respiratory depression.
The usual precautions are recommended in the treatment of patients with impaired renal function and mild or moderate hepatic insufficiency, while in patients with severe hepatic insufficiency benzodiazepines are not indicated as they can precipitate encephalopathy. Benzodiazepines are not recommended for the primary treatment of psychotic illness Benzodiazepines should not be used alone to treat severe depression or anxiety associated with depression (suicide may have precipitated in such patients).
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected effects from interaction.
As with other psychotropic drugs, alprazolam in severely depressed or suicidal patients should be administered with due precautions and prescribed in appropriate packaging.
A concomitant depressive disorder (primary or secondary) is associated with panic attack disorder with increased cases of suicide in untreated patients. Therefore the same precaution should be taken both when using the higher doses of ALPRAZOLAM ABC for the treatment of patients with panic disorder and when using any psychotropic drug in the treatment of depressed patients or those in whom ideation is suspected. or attempted suicide.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Patients who habitually abuse alcohol and / or drugs, when being treated with benzodiazepines should be kept under close medical supervision, due to the predisposition of these subjects to addiction and dependence. Cases of hypomania and mania have been reported in association with "use of alprazolam in patients with depression.
Interactions Which drugs or foods can modify the effect of Alprazolam ABC
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
For the same reason, patients must be warned of the dangers associated with the simultaneous intake of alcohol or other drugs with CNS depressant action.
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. Particular caution, especially in elderly patients, should be used with respiratory depressant drugs such as opioids (analgesics, cough suppressants, replacement treatments) Alprazolam should be used with caution in combination with other CNS depressants.
Association with CNS depressants: the central depressive effect may be enhanced in the case of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and antihistamines-H1 sedatives.
In the case of narcotic analgesics, an increase in euphoria can occur, leading to an increase in psychic dependence.
Pharmacokinetic interactions can occur when alprazolam is co-administered with drugs that interfere with its metabolism.
Molecules that inhibit certain liver enzymes (especially cytochrome P 45003A4) can increase the plasma concentration of alprazolam and enhance its activity.
Azole antifungal agents - ketoconazole and itraconazole are potent inhibitors of CYP3A and have been shown in vivo to increase alprazolam concentrations 3.98-fold and 2.70-fold, respectively. Concomitant administration of alprazolam with these two drugs is not recommended. Other azole-type antifungal agents should be considered potent inhibitors of CYP3A and their co-administration with alprazolam is not recommended.
Co-administration of alprazolam with potent CYP3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), protease inhibitors or certain macrolides (erythromycin, clarithromycin, telithromycin) should be substantial dose reduction.
Clinical and in vitro studies with alprazolam and clinical studies with metabolised drugs such as alprazolam show a possible interaction at varying degrees of alprazolam with a number of drugs. Based on the degree of interaction and the type of data available, the following recommendations should be considered:
- The concomitant administration of ALPRAZOLAM ABC with ketoconazole, itroconazole or other antifungals of the azole group is not recommended.
- Caution and caution in decreasing the dose is recommended when ALPRAZOLAM ABC is concomitantly administered with nefazodone, fluvoxamine and cimetidine.
- Caution is advised when ALPRAZOLAM ABC is concomitantly administered with fluoxetine, propoxyphene, oral contraceptives, diltiazem or macrolide antibiotics such as erythromycin and troleandomycin.
- Interactions between HIV protease inhibitors (eg ritonavir) and alprazolam are complex and time dependent. Low dose ritonavir causes a reduction in alprazolam clearance, prolongs its elimination half-life, and increases clinical effects. of prolonged exposure to ritonavir, induction of CYP3A compensates for this inhibition. This interaction will require a dose adjustment or "discontinuation of treatment with ALPRAZOLAM ABC.
- Increases in digoxin concentrations have been reported with administration of alprazolam, particularly in the elderly (> 65 years of age. Therefore elderly patients receiving alprazolam and digoxin should be monitored for signs and symptoms of digoxin toxicity.
To a lesser extent, this also applies to benzodiazepines metabolized only by conjugation. Steady state plasma concentrations of imipramine and desipramine increase by 31% and 20%, respectively, following concomitant administration of alprazolam in doses up to 4 mg / day. Kinetic interactions between benzodiazepines and other drugs have been described. For example, clearance of alprazolam and some other benzodiazepines may be decreased by concomitant administration of cimetidine or macrolide antibiotics. The clinical significance of these effects has not been established.
Warnings It is important to know that:
Tolerance
Some loss of the hypnotic effect of benzodiazepines may develop after repeated use for a few weeks.
Dependence
The use of benzodiazepines, including alprazolam, can lead to the development of physical and mental dependence on these drugs. As with all benzodiazepines, the risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse.
Dependence can occur at therapeutic doses and / or in patients with no individual risk factors. The risk of dependence increases with the concomitant use of several benzodiazepines regardless of the anxiolytic or hypnotic indication. Cases of abuse have also been reported.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms.
These can consist of headaches, body aches, anxiety of extreme severity, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or jolts.
Rebound insomnia and anxiety
A transient syndrome in which symptoms leading to benzodiazepine treatment 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, it is recommended to gradually decrease the dosage.
Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive or use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see Interactions).
Given the CNS depressant effect of alprazolam, patients taking the drug should be warned that it may be dangerous for them to engage in activities that require full mental attention, such as working on hazardous machinery or driving cars, until it is possible to exclude an impairment of attention and reflexes following the intake of the drug.
Use in case of pregnancy and lactation
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Data on teratogenicity and effects on postnatal development and behavior following benzodiazepine treatment are inconsistent.
There is evidence from some early studies with other benzodiazepine class compounds showing that in utero exposure may be associated with malformations. Subsequent studies with benzodiazepine class drugs have provided no clear evidence of any type of defect.
A large amount of data based on cohort studies indicate that benzodiazepine exposure during the first trimester is not associated with an increased risk of major malformations.
However, some early epidemiological case-control studies have shown an increased risk of oral cleft. The data indicated that the risk of having a baby with an oral cleft after maternal exposure to benzodiazepines is less than 2/1000 compared to an expected rate for such defects of about 1/1000 in the general population. Benzodiazepines at high doses, during the second and / or third trimester of pregnancy, has detected a decrease in active fetal movements and a variability of the fetal heart rhythm. It has been reported that newborns exposed to benzodiazepines during the end of the third trimester of pregnancy or during labor show floppy infant syndrome or neonatal withdrawal symptoms. When treatment is to be administered for medical reasons during the latter part of pregnancy, even at low doses, symptoms of floppy infant syndrome such as axial hypotonia may be observed and sucking problems leading to reduced weight gain. These signs are reversible, but can last from 1 to 3 weeks, depending on the half-life of the product. High doses, during the last period of pregnancy or during labor, can cause effects in the newborn such as respiratory depression or apnea and hypothermia, due to pharmacological action of the drug. If treatment with alprazolam is necessary during the latter part of pregnancy, high doses should be avoided, and withdrawal symptoms and / or floppy infant syndrome should be monitored in the neonate. In addition, neonatal withdrawal syndrome such as hyperexcitability, agitation and tremor can be observed a few days after birth, although "floppy infant" syndrome is not observed. The appearance of withdrawal symptoms after birth depends on the half-life of the product.
Due to the potential risk of congenital malformations already seen with other benzodiazepines, do not administer the drug in the first trimester of pregnancy. If the product is prescribed to a woman of childbearing age, she should contact her doctor both if she intends to become pregnant and if she suspects that she is pregnant regarding discontinuation of the medicine.
If ALPRAZOLAM ABC is administered during pregnancy or if the patient discovers that she is pregnant during treatment with ALPRAZOLAM ABC, the patient should be informed of the potential danger to the fetus.
Taking these data into account, the use of alprazolam during pregnancy can only be considered if the therapeutic indications and posology are strictly respected.
Feeding time
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.
Important information about some of the ingredients of ALPRAZOLAM ABC
ALPRAZOLAM ABC tablets contain lactose; in case of ascertained intolerance to sugars contact your doctor before taking this medicine.
The oral drops contain ethyl alcohol (about 13%); 10 drops equal to 0.25 mg of alprazolam contain over 43 mg of ethyl alcohol. . It can be harmful to alcoholics. To be taken into consideration in pregnant or lactating women, children and high-risk groups such as people with liver disease or epilepsy.
For those who carry out sports activities (only for drops) 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 Alprazolam ABC: Dosage
The optimal dosage of ALPRAZOLAM ABC should be individualized according to the severity of the symptoms and the subjective response of the patient. The dosage indications given should cover the needs of most patients. If a higher dosage is necessary, the doses should be gradually increased to avoid the risk of side effects. In these cases it is advisable to increase the evening dose earlier than the day dose, except in patients suffering from agoraphobia and / or panic disorder. In this case, see the dedicated paragraph.
In general, patients never treated with psychotropic drugs require lower doses than those previously treated with anxiolytics or sedatives, antidepressants, hypnotics or chronic alcoholic patients.
It is recommended to always use the lowest dose to avoid the risk of residual sedation or ataxia. In case of side effects already with the initial administration it is recommended to decrease the dosage.
The maximum dose should not be exceeded.
The evening dose of the drug should be taken just before going to bed. Treatment should be as short as possible. Patients should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free.
Anxiety:
The starting dose ranges from 0.25 to 0.50 mg 3 times a day. This dosage will be increased according to the patient's needs up to a maximum of 4 mg per day in divided doses for a duration not exceeding 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.
In elderly patients, in patients with severe liver disease and / or impaired renal function or in the presence of debilitating organic diseases it is recommended to start with 0.25 mg 2-3 times a day and to increase if necessary, only if tolerated. The treatment can also be carried out using the package in drops: 10 drops correspond to 0.25 mg of alprazolam, 20 drops to 0.50 mg. The recommended doses are the same as for the tablets. The concentration of the formulation in drops is 0.75 mg / ml.
Agoraphobia and panic disorder:
In patients with agoraphobia associated with panic attacks or with panic disorder with or without phobic avoidance, the starting dose is 0.5-1 mg, given at bedtime, for one to two days. The dose should therefore be adjusted according to the individual patient's response. Dosage increases should not exceed 1 mg every three to four days. Dosage increases can be made first at noon, then in the morning and finally in the afternoon / evening until a dosing schedule 3 or 4 times a day is achieved for a duration of no more than 8 months.
In an international multicenter study involving a large number of patients, the mean daily dose was 5.7 mg / day; only in some rare cases it was necessary to reach 10 mg / day.
Discontinuation of therapy
As a good clinical rule, administration should be withdrawn slowly. It is suggested to reduce the daily dosage by no more than 0.5 mg every three days. Some patients may require an even more gradual reduction (see "Special warnings" and "Precautions for" use ").
Children and adolescents
The safety and efficacy of alprazolam have not been established in children and adolescents below 18 years, therefore the use of alprazolam is not recommended.
Overdose What to do if you have taken too much Alprazolam ABC
Symptoms of overdose with ALPRAZOLAM ABC manifest as an increase in its pharmacological activity and include mainly ataxia and somnolence, dysarthria, motor incoordination, coma and respiratory depression. Treatment in cases of overdose is primarily to support respiratory and cardiovascular functions. The efficacy of dialysis has not been determined.
As with other benzodiazepines, an overdose is not expected to be life-threatening unless concomitant intake of other CNS depressants and ethanol (alcohol).
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
Following an overdose of oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious.
If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Benzodiazepine overdose usually presents with varying degrees of central nervous system depression ranging from drowsiness 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. Flumazenil additionally may be used in the management of respiratory and cardiovascular function associated with overdose.
Animal experiments indicate that after a massive intravenous dose of ALPRAZOLAM (over 195 mg / kg; more than 975 times the maximum daily dose in humans) cardiovascular collapse can occur.
The animals were treated with mechanical ventilation and intravenous infusion of norepinephrine.
Other animal experiments have shown that hemodialysis and forced diuresis are of little use in the treatment of overdose.
In case of accidental ingestion / intake of an excessive dose of ALPRAZOLAM ABC, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of ALPRAZOLAM ABC, ask your doctor or pharmacist.
Side Effects What are the side effects of Alprazolam ABC
Like all medicines, ALPRAZOLAM ABC can cause side effects, although not everybody gets them. Any undesirable effects of ALPRAZOLAM ABC are usually seen at the start of treatment and usually resolve with continued therapy or reduced doses.
Patients who participated in controlled clinical trials have reported the following undesirable effects associated with alprazolam therapy.
The following undesirable effects have been observed and reported during treatment with alprazolam with the following frequencies: very common (≥1 / 10), common (≥ 1/100,
(≥ 1/100,
(≥ 1/10000 a
* Undesirable effects identified post-marketing In many of the spontaneous reports for adverse behavioral effects, patients were treated concomitantly with other CNS medications and / or had pre-existing mental health problems. Patients with borderline personality problems, with a history of aggressive or violent behavior, or who abuse alcohol or other substances, may be at risk for such events. Reactions of irritability, hostility and invasive thoughts have been reported following discontinuation of Alprazolam treatment in patients with PTSD.
Amnesia:
Although no reports have been received for Alprazolam to date, benzodiazepines can cause anterograde amnesia. This can also occur at therapeutic doses and the risk increases at higher doses. Amnesic effects may be associated with behavioral changes (see "Special Warnings" and "Precautions for" use ").
Depression:
A pre-existing depressive state may be unmasked during the use of benzodiazepines.
Psychiatric and paradoxical reactions
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 serious: they are more frequent in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of dependence: discontinuation of therapy can cause rebound phenomena from withdrawal (see "Special warnings" and "precautions for use"). Abuse of drug has been reported. benzodiazepines.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting undesirable effects you can help provide more information on safety of this medicine.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
This date is intended for the product in intact packaging, properly stored.
Store in the original packaging to protect the product from light.
Shelf life after first opening the bottle: 3 months.
Warning: do not use the medicine after the expiry date indicated on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
OPENING THE DROPS BOTTLE
To open, press on the plastic cap and at the same time unscrew
To close, screw the cap back on completely.
Keep this medicine out of the sight and reach of children
Composition and pharmaceutical form
COMPOSITION
ALPRAZOLAM ABC 0.25 mg tablets
One tablet contains:
Active ingredient: alprazolam 0.25 mg
Excipients: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, corn starch, magnesium stearate.
ALPRAZOLAM ABC 0.50 mg tablets
One tablet contains:
Active ingredient: alprazolam 0.50 mg
Excipients: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, corn starch, magnesium stearate, sunset yellow (E110).
ALPRAZOLAM ABC 1 mg tablets
One tablet contains:
Active ingredient: alprazolam mg 1
Excipients: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, corn starch, magnesium stearate, Indigo carmine (E132).
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution
1 ml of solution contains:
Active ingredient: alprazolam 0.75 mg
Excipients: ethyl alcohol, propylene glycol, sodium saccharinate, black cherry flavor, purified water
PHARMACEUTICAL FORM AND CONTENT
tablets: box containing 20 tablets of 0.25 mg; 0.5 mg; 1 mg
tablets: box containing 30 tablets of 0.25 mg; 0.5 mg;
oral drops, solution: bottle of 20 ml and 30 ml
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
ALPRAZOLAM ABC
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
ALPRAZOLAM ABC 0.25 mg tablets
One tablet contains:
Active principle: alprazolam 0.25 mg
ALPRAZOLAM ABC 0.50 mg tablets
One tablet contains:
Active principle: alprazolam 0.50 mg
ALPRAZOLAM ABC 1 mg tablets
One tablet contains:
Active principle: alprazolam mg 1
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution
1 ml of solution contains:
Active principle: alprazolam 0.75 mg
10 drops correspond to 0.25 mg of alprazolam.
For excipients see point 6.1
03.0 PHARMACEUTICAL FORM
Tablets; oral drops, solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome.
Panic attacks with or without agoraphobia.
Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe discomfort
04.2 Posology and method of administration
The optimal dosage of ALPRAZOLAM ABC should be individualized according to the severity of the symptoms and the subjective response of the patient.
The dosage indications given should cover the needs of most patients. If a higher dosage is necessary, the doses should be gradually increased to avoid the risk of side effects. In these cases it is advisable to increase the evening dose earlier than the day one.
In general, patients never treated with psychotropic drugs require lower doses than those previously treated with anxiolytics or sedatives, antidepressants, hypnotics or chronic alcoholic patients.
It is recommended to always use the lowest dose to avoid the risk of residual sedation or ataxia.
In case of side effects already with the initial administration it is recommended to decrease the dosage.
Treatment should be as short as possible. Patients should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free.
The maximum dose should not be exceeded.
The drug should be taken just before going to bed.
Pediatric population
The safety and efficacy of alprazolam have not been established in children and adolescents below 18 years, therefore the use of alprazolam is not recommended.
Anxiety:
The starting dose ranges from 0.25 to 0.50 mg 3 times a day. This dosage will be increased according to the patient's needs up to a maximum of 4 mg per day in divided doses for a duration not exceeding 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.
In elderly patients, in patients with severe liver disease and / or impaired renal function or in the presence of debilitating organic diseases, it is recommended to start with 0.25 mg 2-3 times a day and increase if necessary, only if tolerated. The treatment can also be carried out using the package in drops: 10 drops correspond to 0.25 mg of alprazolam, 20 drops to 0.50 mg.
Agoraphobia and panic disorder:
In patients with agoraphobia associated with panic attacks or with panic disorder with or without phobic avoidance, the starting dose is 0.5-1 mg, given at bedtime, for one to two days. The dose should therefore be adjusted according to the individual patient's response. Dosage increases should not exceed 1 mg every three to four days. Dosage increases can be made first at noon, then in the morning and finally in the afternoon / evening until a dosing schedule 3 or 4 times a day is achieved for a duration of no more than 8 months.
In an international multicenter study involving a large number of patients, the mean daily dose was 5.7 mg / day; only in some rare cases it was necessary to reach 10 mg / day.
Discontinuation of therapy
As a good clinical rule, administration should be withdrawn slowly.
It is suggested to reduce the daily dosage by no more than 0.5 mg every three days. Some patients may require an even more gradual reduction.
04.3 Contraindications
Myasthenia gravis.
Hypersensitivity to benzodiazepines and their derivatives or to any of the excipients of the product.
Severe respiratory insufficiency.
Severe hepatic insufficiency.
Sleep apnea syndrome.
Acute angle-closure glaucoma.
The product can be used in patients with open angle glaucoma receiving appropriate therapy.
Do not administer to children (see par. 4.4), in the first trimester of pregnancy and during lactation (see par. 4.6).
04.4 Special warnings and appropriate precautions for use
Benzodiazepines are indicated only when the symptoms are severe, disabling or subjecting the subject to severe malaise.
Anxious or tense situations associated with daily stress usually do not require treatment with anxiolytics.
Tolerance
After repeated use for a few weeks, a loss of efficacy of benzodiazepines with respect to hypnotic effects may occur.
Dependence
The use of benzodiazepines can lead to the development of physical and mental dependence on these drugs. The risk of dependence increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse.
Once physical dependence has developed, abrupt cessation of treatment will be accompanied by withdrawal symptoms.
These can consist of headaches, body aches, anxiety of extreme severity, 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.
Insomnia and rebound anxiety: transient syndrome in which the symptoms that led to treatment with benzodiazepines recur in an aggravated form; it can occur when treatment is stopped.
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 cessation of treatment, it is recommended to gradually decrease the dosage.
Duration of treatment
The duration of treatment must be as short as possible (see par. 4.2) and in the case of anxiety it must not exceed 8-12 weeks, including the gradual suspension period. The extension of therapy beyond this period must not occur without a thorough 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, in order to minimize the anxious reaction that the possible appearance of such symptoms could trigger when the drug is discontinued.
It is recognized that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may appear in the interval between doses, particularly at high doses.
When using benzodiazepines with a long duration of action it is important to warn the patient that abrupt change to a short-acting benzodiazepine is inadvisable, as withdrawal symptoms may appear.
Discontinuation of treatment
Like any other benzodiazepine, the dosage of alprazolam should be gradually reduced as stopping abruptly or too quickly can lead to withdrawal symptoms.
Withdrawal symptoms may include mild dysphoria and insomnia or present as major syndromes with muscle and abdominal cramps, vomiting, sweating, tremors.
Seizures of withdrawal may occasionally occur following a rapid decrease or abrupt discontinuation of alprazolam therapy.
These symptoms, especially the more severe ones, are generally more common in those patients who have been treated with excessive doses for prolonged periods of time. However, withdrawal symptoms have also been reported following abrupt discontinuation of therapeutic doses of benzodiazepines. Therefore abrupt interruption must be avoided and a gradual reduction of the dosage must be prescribed (see par. 4.2).
During drug withdrawal in patients with panic disorder, symptoms related to the reappearance of panic attacks that mimic those typical of withdrawal can sometimes be observed.
Amnesia
Benzodiazepines can induce antegrade amnesia. This happens more often several hours after ingestion of the drug and, therefore, to reduce the risk the patient should ensure that he has an uninterrupted period of 7-8 hours to spend in sleep (see section 4.8).
Psychiatric and paradoxical reactions
The use of benzodiazepines is known to induce reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes. If this occurs, use of the drug should be discontinued. Such reactions are more frequent in children and the elderly.
Specific groups of patients
Pediatric population
The safety and efficacy of alprazolam have not been established in children and adolescents below 18 years of age; therefore the use of alprazolam is not recommended.
The dosages indicated for the elderly are lower than those for adults (see section 4.2). Likewise, reduced dosages are indicated in patients with chronic respiratory failure due to the risk of respiratory depression.
The usual precautions are recommended in the treatment of patients with impaired hepatic and / or renal function, while benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy. Benzodiazepines are not indicated as primary treatment of psychotic illness. Benzodiazepines should not be used as the only treatment for depression or anxiety associated with depression (they increase the risk of suicide in these patients).
Alprazolam should not be used in those patients whose depression is characterized by psychomotor slowing; in patients with endogenous depression, bipolar or with psychotic symptoms.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected effects from interaction.
As with other psychotropic drugs, alprazolam in severely depressed or suicidal patients should be administered with due precautions and prescribed in appropriate packaging.
Since concomitant depressive disease (primary or secondary) with increased cases of suicide in untreated patients is observed in panic disorder, it is important that the same precaution is taken when alprazolam is used to treat patients. with panic disorder similar to the use of any psychotropic drug in the treatment of depressed patients or those in whom suicidal ideation or attempt is suspected.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Patients who habitually abuse alcohol and / or drugs, when being treated with benzodiazepines must be kept under strict medical supervision, due to the predisposition of these subjects to addiction and dependence.
For the same reason, patients must be warned of the dangers associated with the simultaneous intake of alcohol or other drugs having a depressant action on the CNS.
The oral drops contain ethyl alcohol (about 13%): ten drops equal to 0.25 mg of alprazolam contain over 43 mg of ethyl alcohol: therefore, the product can be dangerous for subjects with liver diseases, alcoholics, epileptic subjects or with pathologies brain, pregnant women and children. Ethyl alcohol may change or enhance the effect of other medicines.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant alcohol intake should be avoided. The sedative effect may be enhanced when the medicinal product is taken together with alcohol. This adversely affects the ability to drive or use machines.
Combination with CNS depressant drugs: the central depressive effect may increase in cases of concomitant use of antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, analgesic narcotics, antiepileptics, anesthetics and sedative antihistamines.
In the case of analgesic narcotics, an increase in the euphoric effect of the narcotic may occur.
Compounds that inhibit certain liver enzymes (especially cytochrome P 450) may increase the activity of benzodiazepines.
To a lesser extent, this also applies to benzodiazepines metabolized only by conjugation.
Steady state plasma concentrations of imipramine and desipramine increase by 31% and 20%, respectively, following concomitant administration of alprazolam in doses up to 4 mg / day.
Kinetic interactions between benzodiazepines and other drugs have been described. For example, the clearance of alprazolam and some other benzodiazepines may be decreased by concomitant administration of cimetidine or macrolide antibiotics.
The clinical significance of these effects has not been defined.
04.6 Pregnancy and lactation
Due to the potential risk of congenital malformations already seen with other benzodiazepines, do not administer alprazolam in the first trimester of pregnancy.
If the product is prescribed to a woman of childbearing potential, the patient should be advised of the opportunity to contact her doctor to stop taking the product if she intends to become pregnant or suspects 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 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 of developing withdrawal symptoms in the postnatal period. Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.
04.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired ability to concentrate and impaired muscle function can adversely affect the ability to drive or use machines. par. 4.5).
Given the CNS depressant effect of alprazolam, patients taking the drug should be warned that it may be dangerous for them to engage in activities that require full mental attention, such as working on hazardous machinery or driving cars, until the onset of drowsiness or dizziness can be excluded for each patient.
04.8 Undesirable effects
Any side effects of alprazolam are usually seen at the start of treatment and usually resolve with continued therapy or by reducing doses.
In patients being treated for anxiety or anxiety associated with depression, the most frequently reported side effects are somnolence, dizziness / lightheadedness.
Blurred vision, headache, depression, insomnia, nervousness, tremor, weight changes, memory disturbances / amnesia, coordination disturbances, ataxia, gastrointestinal symptoms and autonomic nervous system hyperactivity have been reported less frequently.
As with other benzodiazepines, paradoxical reactions such as excitement, agitation, difficulty concentrating, confusion, hallucinations and other behavioral alterations can occur in rare cases.
In addition, the following can be observed: reduction of emotional responses and alertness, skin reactions.
In rare cases, increased intraocular pressure has been reported. Associated with the use of benzodiazepine anxiolytics, including alprazolam, the following adverse reactions have also been reported: dystonia, irritability, anorexia, fatigue, speech difficulties, diplopia, jaundice, muscle weakness, libido changes, menstrual irregularities, incontinence or urinary retention and changes in liver function.
The most common side effects in patients being treated for panic disorder are sedation / sleepiness, fatigue, ataxia / incoordination and speech difficulties.
Less common side effects are: mood changes, gastrointestinal symptoms, dermatitis, memory disturbances, sexual dysfunction, intellectual impairment and confusion.
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)
Depression
A pre-existing depressive state can be unmasked during prolonged use of benzodiazepines.
Psychiatric and paradoxical reactions
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 serious: they are more frequent in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see 4.4).
Abuse of benzodiazepines has been reported.
04.9 Overdose
Symptoms of overdose are manifested as an increase in its pharmacological activity, especially ataxia and somnolence.
An overdose of benzodiazepines is not expected to pose a risk to life unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
Following an overdose of oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage with respiratory protection given if the patient is unconscious.
If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Particular attention should be paid to respiratory and cardiovascular functions in the ICU. Benzodiazepine overdose usually results in varying degrees of CNS depression ranging from somnolence to coma. In mild cases, symptoms include drowsiness, confusion and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.
Flumazenil can be a useful antidote.
Animal experiments indicate that after a massive intravenous dose of ALPRAZOLAM (over 195 mg / kg; more than 975 times the maximum daily dose in humans) cardiovascular collapse can occur.
The animals were treated with mechanical ventilation and intravenous infusion of norepinephrine. Other animal experiments have shown that hemodialysis and forced diuresis are of little use in the treatment of overdose.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anxiolytic.
A.T.C.code N05BA12
Alprazolam is a triazolobenzodiazepine belonging to the anxiolytic-hypnotic-sedative therapeutic group.
Alprazolam binds to the GABAergic site of benzodiazepines by synergizing the activity of GABA, an inhibitory neurotransmitter, thus causing a reduction in neuronal excitation. This characteristic gives the molecule anxiolytic - hypnotic - sedative properties.
Clinical studies in healthy volunteers have shown that single doses up to 4 mg produce effects which can be considered extensions of its pharmacological activity.
No significant effects on the cardiovascular or respiratory systems were observed.
05.2 Pharmacokinetic properties
After oral administration, alprazolam is rapidly absorbed. Maximum plasma concentrations are achieved 1 to 2 hours after drug administration. Plasma levels are proportional to dose;
in the range of doses between 0.5 and 3 mg, plasma peaks of 8 to 37 ng / ml are observed. The mean half-life of alprazolam in the healthy adult is 11.2 hours (range: 6.3-26 , 9 hours).
The major metabolites are alpha-hydroxialprazolam and a benzophenone. The biological activity of hydroxialprazolam is approximately half that of alprazolam. Benzophenone is inactive. The plasma levels of these metabolites are extremely low, however their half-lives are of the same order of magnitude as that of alprazolam.
Alprazolam and its metabolites are mainly excreted in the urine.
Alprazolam did not affect prothrombin time or plasma warfarin levels in volunteers to whom warfarin was administered orally.
In vitro, about 80% of alprazolam is bound to serum proteins.
After administration of 14 C alprazolam to the pregnant female mouse, the radioactivity was uniformly distributed in the fetuses in concentrations of 14 C approximately equal to those present in the mother's blood and skeletal muscle.
Differences in benzodiazepine kinetics and metabolism have been observed in various pathological conditions, including alcoholism and liver and kidney function abnormalities, as well as in the geriatric patient. In healthy elderly subjects, the mean half-life of alprazolam is 16.3 hours (range: 9-26.9 hours). In healthy women, concomitant oral contraceptives prolong the half-life of alprazolam (mean half-life: 12.4 hours). Concomitant intake of cimetidine also prolongs the mean half-life of alprazolam (16.6 hours). with alcoholic liver disease the half-life of alprazolam ranges from 5.8 to 65.3 hours, with an average of 19.7 hours.
In obese subjects, the half-life range of the drug varies from 9.9 to 40.4 hours, on average 21.8 hours.
In view of the similarity of alprazolam to other benzodiazepines, it is hypothesized that the drug crosses the placenta and is excreted in breast milk.
05.3 Preclinical safety data
The acute toxicity data relating to the experimental animal are as follows:
In chronic toxicity studies conducted in rats treated orally for 2 years with alprazolam at doses of 3, 10, 30 mg / kg / day (15 to 150 times the maximum dose used in humans), a tendency to increase dose-related incidence of cataracts in females and a tendency for corneal vascularization, also dose-related, in males. These lesions appeared only 11 months after the start of treatment. Studies conducted on experimental animals (rats and rabbits) indicated that alprazolam is not teratogenic and does not affect fertility. The carcinogenesis and mutagenesis tests were negative. .
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
ALPRAZOLAM ABC 0.25 mg tablets: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, corn starch, magnesium stearate.
ALPRAZOLAM ABC 0.50 mg tablets: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, corn starch, magnesium stearate, sunset yellow (E110).
ALPRAZOLAM ABC 1 mg tablets: lactose, microcrystalline cellulose, sodium docusate, colloidal silica, maize starch, magnesium stearate, indigo carmine (E132).
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution: ethyl alcohol, propylene glycol, sodium saccharinate, black cherry flavor, purified water.
06.2 Incompatibility
No data are known in this regard.
06.3 Period of validity
Tablets: 4 years.
Solution for oral drops: 3 years.
06.4 Special precautions for storage
Store in the original packaging to protect the product from light.
Shelf life after first opening the bottle: 3 months.
06.5 Nature of the immediate packaging and contents of the package
Tablets: lithographed box containing 20 tablets in blister packs
Oral drops: lithographed box containing a 20 ml and 30 ml glass bottle
06.6 Instructions for use and handling
See par. 4.2.
07.0 MARKETING AUTHORIZATION HOLDER
ABC FARMACEUTICI S.p.A.
Corso Vittorio Emanuele II, 72
TURIN
08.0 MARKETING AUTHORIZATION NUMBER
ALPRAZOLAM ABC 0.25 mg tablets - 20 tablets AIC n. 035415013
ALPRAZOLAM ABC 0.50 mg tablets - 20 tablets AIC n. 035415025
ALPRAZOLAM ABC 1 mg tablets - 20 tablets AIC n. 035415037
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution - 20 ml bottle AIC n. 035415049
ALPRAZOLAM ABC 0.75 mg / ml oral drops, solution - bottle 30 ml AIC n. 035415076
ALPRAZOLAM ABC 0.25 mg tablets - 30 tablets AIC n. 035415052
ALPRAZOLAM ABC 0.50 mg tablets - 30 tablets AIC n. 035415064
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
10/02/03
10.0 DATE OF REVISION OF THE TEXT
September 2012
