ALPRAZIG <0.25 mg Tabletka

Treść ulotki

1. ALPRAZIG 0.25 mg tablets, 0.50 mg tablets, 1 mg tablets, 0.75 mg/ml oral drops, solution

ALPRAZIG 0.25 mg tablets, 0.50 mg tablets, 1 mg tablets, 0.75 mg/ml oral drops, solution

alprazolam

PHARMACOTHERAPEUTIC CATEGORY
Anxiolytics, benzodiazepine derivatives.

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
individual to severe distress.

CONTRAINDICATIONS
Alprazig is contraindicated in patients with known hypersensitivity to benzodiazepines, alprazolam or to any
of the excipients contained in the tablets and/or drops.
Benzodiazepines, including Alprazig, are also contraindicated in patients with myasthenia gravis,
severe respiratory insufficiency, sleep apnea syndrome, severe hepatic insufficiency.
In patients with acute angle-closure glaucoma. The product can be used in patients with
open-angle glaucoma who are receiving appropriate therapy.
Acute intoxication caused by alcohol or other drugs active on the CNS (hypnotic, analgesic
or psychotropic drugs). In the first trimester of pregnancy and during breastfeeding (see Pregnancy and
breastfeeding).
Patients under the age of 18 (see Precautions for use).

PRECAUTIONS FOR USE
Duration of treatment
The duration of treatment should be as short as possible (see Dosage, method and time of
administration) based on the therapeutic indications; however, in the case of anxiety, it should not exceed
8-12 weeks, including the period of gradual discontinuation.
Extending the therapy beyond these periods should not occur without re-evaluation of the clinical
situation
(prolongation of the duration of treatment is only possible after re-evaluating the patient's condition).
At the beginning of treatment, it is important to inform the patient that the duration of the treatment
itself will be limited and to explain precisely how the dosage must be gradually reduced
progressively.
Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, in order to
minimize the anxiety reaction that the eventual occurrence of such symptoms could trigger upon
discontinuation of the medicine.
When using benzodiazepines with a short half-life, there is a possibility that withdrawal symptoms occur
within the interval between administrations, especially when high doses are administered. When
benzodiazepines with a long half-life are used, it is important to warn the patient that it is not advisable to
change abruptly to a benzodiazepine with a short half-life, as withdrawal symptoms may occur.

Discontinuation of treatment
As with any other benzodiazepine, the dosage of ALPRAZIG must be reduced gradually
from the moment that abrupt or too rapid discontinuation can lead to the appearance of withdrawal symptoms.
Withdrawal symptoms may include mild dysphoria and insomnia or present as major syndromes
with muscle and abdominal cramps, vomiting, sweating, tremors.
Occasionally, withdrawal seizures may occur following rapid reduction or
abrupt discontinuation of alprazolam therapy.
These symptoms, especially the most serious ones, are generally more common in those patients who have been
treated with excessive doses for prolonged periods of time. However, withdrawal symptoms have been
reported even after abrupt discontinuation of therapeutic doses of
benzodiazepines. Therefore, abrupt discontinuation must be avoided and a
gradual reduction of the dosage must be prescribed (see “Dosage, method and time of administration”).
During the suspension of the drug in patients suffering from panic disorder, sometimes, symptoms related to the recurrence of panic attacks can be observed that mimic those typical of
withdrawal

Amnesia
Like other benzodiazepines, alprazolam can induce anterograde amnesia. This usually happens
several hours after taking the drug (see “Undesirable effects” section).

Psychiatric and paradoxical reactions
It is known that the use of benzodiazepines can induce reactions such as restlessness, agitation, irritability,
aggressiveness, delusion, anger, nightmares, severe insomnia, hallucinations, psychosis, inappropriate behaviors
and other alterations in behavior, sleepwalking and other behavioral disorders typical of treatment with
benzodiazepines. If this should happen, the use of the medicine
must be discontinued. Paradoxical reactions occur more frequently in children and the
elderly.
Particular caution must be used when prescribing benzodiazepines to patients with personality disorders.

Specific patient groups
Pediatric patients
Alprazolam should not be administered to children and adolescents under the age of 18,
as the safety and efficacy of the medicine have not been demonstrated in this category of
patients (see “Contraindications” section).

Elderly and/or debilitated patients
It is recommended to follow the general principle of using the minimum effective dose in elderly and/or debilitated patients
to avoid the development of ataxia or oversedation (see “Dosage, method and time of administration”).

Patients with chronic respiratory insufficiency
In patients with chronic respiratory insufficiency, a reduced dose should be administered, due to
the risk of respiratory depression (see Contraindications).

Patients with severe hepatic insufficiency
ALPRAZIG should be administered with caution in patients with mild to
moderate hepatic insufficiency.
Benzodiazepines are not indicated in the treatment of patients with severe hepatic insufficiency
because treatment with benzodiazepines can facilitate the development of encephalopathy (see
Contraindications).

Patients with renal insufficiency
ALPRAZIG should be administered with caution in patients with impaired
renal function.

Patients with psychosis
Benzodiazepines are not effective in the primary treatment of psychotic illnesses.

Patients with depression
In patients with latent depression, cases of manic episodes have been reported.
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
Benzodiazepines and benzodiazepine-like agents should not be used alone for the
treatment of depression in patients with major depression or anxiety associated with
depression, as they can precipitate or increase the risk of suicide. Therefore, alprazolam
should be used with caution and the prescription should be limited in those patients who present
signs and symptoms of depressive disorder or suicidal tendencies.
Panic disorder has been associated with primary and secondary major depressive disorders
and an increase in cases of suicide among untreated patients. Therefore, the same precautions must
be taken when using higher doses of ALPRAZIG for the treatment of patients with
panic disorder similarly to the use of any psychotropic drug in the
treatment of depressed patients or those in whom suicidal ideation or attempt is suspected.
ALPRAZIG should not be used in those patients in whom depression is characterized by
psychomotor retardation; in patients with endogenous depression, bipolar disorder or with psychotic symptoms.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the doctor
to avoid unexpected interaction effects.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse (see Interactions).
Patients who habitually abuse alcohol and/or drugs, when treated with
benzodiazepines must be kept under strict medical supervision, due to the predisposition of such
subjects to addiction and dependence.
For the same reason, patients must be warned of the dangers associated with the simultaneous
consumption of alcohol or other drugs with a depressant effect on the CNS.
ALPRAZIG can cause sedation. This effect is potentiated by alcohol (see Effects on ability to drive and operate machinery).
Benzodiazepines should be used with extreme caution in patients with acute angle-closure glaucoma or in patients who may be predisposed due to the possible anticholinergic effects
(see Contraindications).

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, even those
available over the counter.
Alcohol: benzodiazepines develop an additive effect when administered with alcohol or other
substances with a depressant effect on the Central Nervous System (CNS). Concomitant use with
alcohol is not recommended. This negatively affects the ability to drive and operate machinery
(see Effects on ability to drive and operate machinery).
Particular attention should be paid with medicines that depress breathing such as opioids
(analgesics, antitussives, substitution treatments), especially in elderly patients.
Alprazolam should be administered with caution when associated with CNS depressants.
The depressant effect on the central nervous system can be increased in the case of concomitant use with antipsychotics
(neuroleptics), anxiolytics/sedatives, some antidepressant agents, opioids, anticonvulsants,
anti-H1 sedating antihistamines, hypnotics, narcotic analgesics, anesthetics.
In the case of narcotic analgesics, an increase in the euphoric effect of the narcotic and an
increase in psychological dependence may occur.
Pharmacokinetic interactions may occur when alprazolam is administered in association with
medicines that inhibit the hepatic enzyme CYP3A4, thus increasing plasma levels of alprazolam.
The concomitant administration of alprazolam with potent CYP3A4 inhibitors, such as azole antifungals
(ketoconazole, itraconazole, posaconazole, voriconazole), protease inhibitors or some macrolides
(erythromycin, clarithromycin, telithromycin) should be carried out with caution and a substantial reduction in the dose should be considered.
Nefazodone, Fluvoxamine and Cimetidine: in consideration of pharmacokinetic interactions (cytochrome
P-450), in case of taking such agents (inhibitors of cytochrome P-450 3A4) in concomitance with
Alprazolam, caution is advised and possibly a reduction of the dosage of ALPRAZIG.

SPECIAL WARNINGS
Tolerance
After repeated use for a few weeks, a loss of efficacy of the
benzodiazepines may occur with respect to hypnotic effects.

Dependence
The use of benzodiazepines can lead to the development of physical and psychological dependence on these drugs. The risk of dependence increases with the dose and duration of treatment; it is also higher in patients with a history of drug or alcohol abuse or in patients with marked personality disorders. Pharmacodependence can occur at therapeutic doses and/or in patients without an individual risk factor. A greater risk of pharmacodependence has been observed with the concomitant use of numerous benzodiazepines, regardless of anxiolytic or hypnotic indications. Cases of abuse have also been reported.
Once physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, severe anxiety, tension, restlessness, confusion, and irritability. In severe cases, the following symptoms may manifest: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures. Withdrawal symptoms may also appear several days after the end of treatment.

Rebound Anxiety
Upon discontinuation of treatment, a transient syndrome may occur in which the symptoms that led to treatment with benzodiazepines recur in an aggravated form. The syndrome may be accompanied by other reactions, including mood changes, anxiety, restlessness, or sleep disturbances.
Because the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual reduction of the dosage is recommended.

Amnesia
Like other benzodiazepines, alprazolam can induce anterograde amnesia. This usually happens several hours after ingestion of the drug (see section “Undesirable Effects”).

Psychiatric and Paradoxical Reactions
It is known that the use of benzodiazepines can induce reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behavior, and other behavioral alterations, sleepwalking, and other behavioral disorders. If this should occur, the use of the medicine should be discontinued. Paradoxical reactions occur more frequently in children and the elderly. Particular caution must be used when prescribing benzodiazepines to patients with personality disorders.

Patients under the age of 18 years
ALPRAZIG should not be used in this specific group of patients as safety and efficacy have not been established.

Pregnancy and Breastfeeding
Due to potential risks of congenital malformations, already observed with other benzodiazepines, do not administer ALPRAZIG in the first trimester of pregnancy.
If the product is prescribed to a woman of childbearing potential, the patient should be warned of the opportunity to contact her doctor to discontinue taking the product if she intends to become pregnant or suspects she is pregnant.

Pregnancy
A large amount of data based on cohort studies indicates that exposure to benzodiazepines during the first trimester of pregnancy is not associated with an increased risk of major malformations. However, some previous case-control epidemiological studies have shown an increased risk of labioschisis. The results indicate that the risk of giving birth to a newborn with cleft lip and palate following maternal exposure to benzodiazepines is less than 2/1000 compared to the expected risk of about 1/1000 for these defects in the general population.
Treatment with benzodiazepines at high doses during the second and/or third trimester of pregnancy has shown a decrease in active fetal movements and variability in fetal heart rate.
When the medicine is administered for medical reasons during the last period of pregnancy, even at low doses, the “floppy infant” syndrome may manifest, consisting of axial hypotonia, difficulty sucking with consequent reduced weight gain. These signs are reversible but may last from one to three weeks, depending on the half-life of the medicinal product.
High doses can cause effects in the newborn such as respiratory depression or apnea and hypothermia. In addition, withdrawal symptoms may appear a few days after birth, such as hyperexcitability, agitation, and tremor, even if a “floppy infant” syndrome has not occurred. The development of withdrawal symptoms after birth depends on the half-life of the substance.
Considering these data, the use of alprazolam during pregnancy can be considered if the therapeutic indications and dosage are strictly respected.
If treatment with alprazolam is necessary during the last part of pregnancy, high doses should be avoided, and withdrawal symptoms and/or the “floppy infant” syndrome should be monitored in the newborn.

Breastfeeding
Alprazolam is excreted in breast milk at low concentrations. However, the use of alprazolam is not recommended during breastfeeding.

Effects on ability to drive and operate machinery
Sedation, amnesia, altered concentration and muscle function can negatively affect the ability to drive or operate machinery. If the duration of sleep has been insufficient, the likelihood that alertness is altered may be increased (see Interactions). Given the depressant effect on the CNS of alprazolam, patients treated with the drug should be warned that it may be dangerous for them to engage in activities requiring complete mental attention, such as operating dangerous machinery or driving vehicles. These effects are enhanced by alcohol.

Important information about some excipients of ALPRAZIG
ALPRAZIG tablets contain lactose: if your doctor has diagnosed you with intolerance to some sugars, contact him before taking this medicine.
APRAZIG oral drops, solution contains only small amounts of ethyl alcohol (ethanol): less than 100 mg per dose of 0.50 mg, equivalent to 20 drops.

For those who play sports
The use of medicines containing ethyl alcohol can result in positive doping tests in relation to the blood alcohol concentration limits indicated by some sports federations.

DOSAGE, ADMINISTRATION AND DURATION OF TREATMENT
The period of treatment should be as short as possible. In each patient, the need for treatment with ALPRAZIG and the appropriate dose should be reviewed periodically.
The optimal dosage of ALPRAZIG should be individualized according to the severity of the symptoms and the patient's subjective response.
The dosage guidelines reported below cover the needs of most patients. If a higher dosage is necessary, the doses should be increased gradually, according to the doctor's opinion, to avoid the risk of side effects. In these cases, it is advisable to increase the evening dose before the daytime dose.
In general, patients never treated with psychotropic drugs require lower doses than those patients previously treated with anxiolytics or sedatives, antidepressants, hypnotics, or chronic alcoholics.
It is advisable to always use the lowest dose to avoid the risk of residual sedation or ataxia.
If side effects occur at the initial administration, it is advisable to reduce the dosage.

Anxiety
Treatment should be as short as possible.
The patient should be re-evaluated regularly and the need for continued treatment should be carefully assessed, especially if the patient is symptom-free.
The initial dose ranges from 0.25 to 0.50 mg 3 times a day.
This dosage may be increased by the doctor according to the patient's needs up to a maximum of 4 mg per day in divided doses. The maximum dose should not be exceeded.
The total duration of treatment generally should not exceed 8-12 weeks, including the period of gradual discontinuation.
In certain cases, extension beyond the maximum treatment period may be necessary; in such cases, this should not occur without reassessment of the patient's condition.
In elderly patients, in patients with severe liver disease or altered renal function, or in the presence of debilitating organic diseases, it is advisable to start with 0.25 mg 2-3 times a day and to increase if necessary, only if tolerated.

Agoraphobia and panic disorder
In patients with agoraphobia associated with panic attacks or with panic disorder, the initial dose is 0.5-1 mg, administered before bedtime, for one or two days. The dose should then be adjusted according to the individual patient's response. Dosage increments should not exceed 1 mg every 3 or 4 days. Dosage increments may be made first at noon, then in the morning and finally in the afternoon/evening until reaching a dosage schedule 3 or 4 times a day for a duration not exceeding 8 months.
In an international multicenter study involving a large number of patients, the average daily dose was 5.7 mg/day; only in a few rare cases was it necessary to reach 10 mg/day.
Treatment with ALPRAZIG can also be carried out using the drop formulation: 10 drops correspond to 0.25 mg of alprazolam, 20 drops to 0.50 mg.

Discontinuation of therapy
As a good clinical rule, administration should be discontinued slowly. It is suggested to reduce the daily dosage by no more than 0.5 mg every 3 days. Some patients may require an even more gradual reduction.

OVERDOSE
Symptoms of overdose manifest as an increase in its pharmacological activity, especially ataxia and drowsiness.
As with other benzodiazepines, an excessive dose should not be life-threatening, unless there is concomitant intake of other CNS depressants (including alcohol).
In the treatment of overdose of any drug, the possibility of concomitant intake of other substances should be considered.
Following an excessive dose of benzodiazepines by oral route, if the patient is conscious, vomiting should be induced (within one hour) or alternatively, if the patient is unconscious, gastric lavage should be performed with protection of the airways.
If no improvement is observed with gastric emptying, activated charcoal should be administered to reduce absorption. In emergency therapy, particular attention should be paid to respiratory and cardiovascular functions.
Benzodiazepine overdose usually manifests with varying degrees of CNS depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotension, respiratory depression, rarely coma, and very rarely death.
Flumazenil may be useful as an antidote.
Flumazenil has an elimination half-life ranging from 40 to 80 minutes. Patients should be kept under close observation due to its short duration of action; additional doses of flumazenil may be necessary. The antagonism caused by Flumazenil to the effects of benzodiazepines can increase the risk of neurological disorders (seizures), especially in patients with epilepsy.
In patients in a coma, treatment is primarily symptomatic. Measures should be taken to prevent potential complications such as asphyxia due to blockage of the airways caused by the patient's tongue or aspiration of gastric contents. Intravenous administration of fluids may be helpful in preventing dehydration.
Especially in the case of association with other sedatives, it is important to support vital functions, particularly breathing.
Experiments performed in animals indicate that after a massive dose by intravenous route of alprazolam (over 195 mg/Kg; more than 975 times the maximum daily dose in humans) cardiovascular collapse may occur. The animals were treated with mechanical ventilation and intravenous administration of norepinephrine. Other experiments on animals have shown that hemodialysis and forced diuresis are of little use in the treatment of overdose.

UNDESIRABLE EFFECTS
The following undesirable effects have been observed and reported during treatment with alprazolam at the
following frequencies: Very common: (≥1/10)

Common: ( ≥1/100, <1/10)

Uncommon: ( ≥1/1000, <1/100)

Rare: ( ≥1/10.000, <1/1000)

Very rare: (<1/10.000)

Frequency not known(the frequency cannot be defined on the basis of available data).
Somnolence, sedation, mood changes, reduced attention, confusion, fatigue, headache, dizziness, vertigo, muscle weakness, ataxia, double or blurred vision, insomnia,
nervousness / anxiety, tremor, weight change. These phenomena usually occur mainly
at the beginning of therapy and usually disappear with repeated administration.
As with other benzodiazepines, paradoxical reactions can occur in rare cases, such as: excitement,
agitation, difficulty concentrating, confusion, hallucinations and other alterations in
behavior. In addition, the following may be observed: emotional blunting, reduced vigilance,
reactions affecting the skin.
Endocrine disorders
Uncommon: hyperprolactinemia
Blood and lymphatic system disorders
Uncommon: dyscrasias, peripheral edema.
Cardiac disorders
Not known: hypotension, tachycardia.
Eye disorders
Common: blurred vision
Uncommon: double vision.
Gastrointestinal disorders
Common: nausea, constipation
Uncommon: vomiting, diarrhea
Rare: dry mouth
Not known: increased salivation, dysphagia
Systemic disorders and conditions related to the site of administration
Common: asthenia, irritability
Not known: peripheral edema
Hepatobiliary disorders
Uncommon: alteration of liver function, jaundice
Not known: hepatitis
Diagnostic tests
Uncommon: weight changes, increased intraocular pressure.
Metabolism and nutrition disorders
Common: decreased appetite
Not known: weight gain, anorexia
Musculoskeletal and connective tissue disorders
Uncommon: muscle weakness
Nervous system disorders
Very common: sedation, somnolence
Common: ataxia, coordination problems, memory impairment, poor articulation
of speech, difficulty concentrating, dizziness, headache, mental dullness,
Uncommon: amnesia, tremor, dystonia
Not known: blunted emotions, reduced vigilance, autonomic nervous system disorders
Psychiatric disorders
Common: Concentration disorders, confusion, depression, dependence
Uncommon: anger, psychiatric problems, paradoxical reactions, hallucinations, aggressive behaviors, hostile behaviors, anxiety, agitation, altered libido, insomnia, abnormal thoughts, nervousness, psychomotor hyperactivity
Renal and urinary disorders
Uncommon: urinary incontinence, urinary retention.
Reproductive system and breast disorders
Uncommon: sexual dysfunction, menstrual irregularities.
Respiratory, thoracic and mediastinal disorders
Not known: nasal congestion.
Skin and subcutaneous tissue disorders
Uncommon: Skin reactions, dermatitis.
Not known: angioedema

Amnesia
Anterograde amnesia may occur even 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 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, delusion, anger, nightmares, hallucinations, psychosis, alterations in
behavior.
Such reactions can be quite severe: they are more frequent in children and the elderly. Patients
who have borderline personality disorder, or a history of violent or aggressive behavior, or
patients who abuse alcohol or drugs, may be at risk of such events.

Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause withdrawal or rebound phenomena (see
section 4.4 Special warnings and precautions for use). Psychological dependence can occur. Abuse of benzodiazepines has been reported (see section “Special warnings”).

Reporting of undesirable effects
If you experience any side effects, including those not listed in this leaflet, please inform your
doctor or pharmacist. You can also report side effects directly through the national reporting system at www.agenziafarmaco.gov.it/it/responsabili”. By reporting side effects you can contribute to providing more information on the safety of this medicine.

EXPIRY DATE AND STORAGE
Expiry date: see the expiry date printed on the packaging.

WARNING:do not use the medicine after the expiry date printed on the packaging.
The expiry date refers to the product in intact packaging, stored correctly.
Alprazig oral drops: validity after first opening of the bottle: 3 months.
Store at a temperature not exceeding 30°C, store in the original packaging to protect
the medicine from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

KEEP THE MEDICINE OUT OF THE REACH AND SIGHT OF CHILDREN
COMPOSITION
ALPRAZIG 0.25 mg tablets

Each tablet contains:
Active ingredient:
Alprazolam 0.25 mg

Excipients:
lactose monohydrate, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, corn starch,
magnesium stearate.
ALPRAZIG 0.50 mg tablets

Each tablet contains:
Active ingredient:
Alprazolam 0.50 mg

Excipients:
lactose monohydrate, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, corn starch,
magnesium stearate, sunset yellow (E110) aluminium lake.
ALPRAZIG 1 mg tablets

Each tablet contains:
Active ingredient:
Alprazolam 1 mg

Excipients:
lactose monohydrate, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, corn starch,
magnesium stearate, indigotine (E132) aluminium lake.
ALPRAZIG 0.75 mg/ml oral drops, solution

100 ml of solution contain:

Active ingredient:
Alprazolam 75 mg

Excipients:
ethanol, propylene glycol, sodium saccharin, cherry aroma, purified water.

PHARMACEUTICAL FORM AND CONTENT
Tablets: packs of 20 tablets of 0.25, 0.50 and 1 mg.
Oral drops, solution: bottle of 20 ml.

MARKETING AUTHORISATION HOLDER
LABORATORI BALDACCI S.p.A.
Via San Michele degli Scalzi 73
Pisa

PRODUCER

Tablets :
DOPPEL Farmaceutici s.r.l.-Via Volturno,48-Quinto dè Stampi-Rozzano (MI)

Oral drops, solution:
DOPPEL Farmaceutici s.r.l. - Via Martiri delle Foibe,1-29016 Cortemaggiore (PC)