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  • Xanax XR
    / Pfizer

    Active Ingredient
    Alprazolam 0.5, 1, 2 mg

    Status in Israel

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Sustained-Release Tablets

    30 × 0.5 MG

    not in the basket chart 2495 24019

    Sustained-Release Tablets

    30 X 1 mg

    not in the basket chart 2496 24020

    Sustained-Release Tablets

    30 X 2 mg

    not in the basket chart 2497 24021

    Related information


    Tablets may be administered once daily, preferably in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.
    Anxiety: Usual init. Dose  1 mg daily in one or two doses,  usual dose range-0.5 to 4 mg daily, in one or two doses.
    Depression: Usual init. Dose 1 mg daily in one or two doses,  usual dose range-0.5 to 4.5 mg daily, in one or two doses.
    Panic Disorders: Usual init. dose – 0.5 to 1.0 mg given at bedtime or 0.5 mg two times daily,  usual uose range-dose should be adjusted to patient response, with increments no greater than 1 mg/day every 3 to 4 days.
    [In clinical trials the mean maintenance dose was between 5 and 6 mg/day, given as a single daily dose or divided into two doses daily, with occasional patients needing up to 10 mg/day].
    Dosage should be individualized for maximum beneficial effect. While the suggested total daily dosages given will meet the needs of most patients, there will be some patients who require doses greater than 6 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.
    Dose Titration
    Treatment with XANAX XR may be initiated with a dose of 0.5 mg to 1 mg once daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg/day. Slower titration to the dose levels may be advisable to allow full expression of the pharmacodynamic effect of XANAX XR.
    Generally, therapy should be initiated at a low dose to minimize the risk of adverse responses in patients especially sensitive to the drug. Dose should be advanced until an acceptable therapeutic response (ie, a substantial reduction in or total elimination of panic attacks) is achieved, intolerance occurs, or the maximum recommended dose is attained.
    Dose Maintenance
    In controlled trials conducted to establish the efficacy of XANAX XR Tablets in panic disorder, doses in the range of 1 to 10 mg/day were used. Most patients showed efficacy in the dose range of 3 to 6 mg/day. Occasional patients required as much as 10 mg/day to achieve a successful response. The necessary duration of treatment for panic disorder patients responding to XANAX XR is unknown. However, periodic reassessment is advised.
    After a period of extended freedom from attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena.
    Discontinuation or Dosage Reduction of XANAX XR
    Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided. In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.
    In any case, reduction of dose must be undertaken under close supervision and must be gradual. If significant withdrawal symptoms develop, the previous dosing schedule should be reinstituted and, only after stabilization, should a less rapid schedule of discontinuation be attempted. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. It is suggested that the dose be reduced by no more than 0.5 mg every three days, with the understanding that some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens.
    Dosage Recommendations in Geriatric Patients
    In elderly patients the usual starting dosage of XANAX XR is 0.5 mg once daily. This may be gradually increased if needed and tolerated (see Dose Titration).The elderly may be especially sensitive to the effects of benzodiazepines.
    In patients with hepatic impairment or in patients with debilitating disease, the usual starting dosage of XANAX XR is 0.5 mg once daily. This may be gradually increased if needed and tolerated. See prescribing information for full details.




    Treatment of anxiety associated with depression.
    Treatment of panic disorder, with or without phobic avoidance.
    XANAX XR are indicated for the management of anxiety disorder (a condition corresponding most closely to the APA Diagnostic and Statistical Manual (DSM-III-R) diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
    Generalized anxiety disorder is characterized by unrealistic or excessive anxiety and worry (apprehensive expectation) about two or more life circumstances, for a period of six months or longer, during which the person has been bothered more days than not by these concerns. At least 6 of the following 18 symptoms are often present in these patients: MOTOR TENSION (trembling, twitching, or feeling shaky, muscle tension, aches, or soreness; restlessness, easy fatigability); AUTONOMIC HYPERACTIVITY (shortness of breath or smothering sensations, palpitations or accelerated heart rate, sweating, or cold clammy hands; dry mouth; dizziness or light-headedness; nausea, diarrhea, or other abdominal distress, flushes or chills; frequent urination, trouble swallowing or ‘lump in throat’); VIGILANCE AND SCANNING (feeling keyed up or on edge, exaggerated startle response, difficulty concentrating or ‘mind going blank” because of anxiety, trouble falling or staying asleep, irritability). These symptoms must not be secondary to another psychiatric disorder or caused by some organic factor.
    This claim is supported on the basis of two positive studies with XANAX XR conducted in patients whose diagnoses corresponded closely to the DSM-III-R/IV criteria for panic disorder [see CLINICAL STUDIES (14].
    Panic disorder (DSM-IV) is an illness characterized by recurrent panic attacks. The panic attacks, at least initially, are unexpected. Later in the course of this disturbance certain situations, e.g., driving a car or being in a crowded place, may become associated with having a panic attack. These panic attacks are not triggered by situations in which the person is the focus of others’ attention (as in social phobia). The diagnosis requires four such attacks within a four week period, or one or more attacks followed by at least a month of persistent fear of having another attack The panic attacks must be characterized by at least four of the following symptoms: dyspnea or smothering sensations, dizziness, unsteady feelings, or faintness; palpitations or tachycardia; trembling or shaking; sweating; choking, nausea or abdominal distress; depersonalization or derealization; paresthesias, hot flashes or chills; chest pain or discomfort; fear of dying; fear of going crazy or of doing something uncontrolled. At least some of the panic attack symptoms must develop suddenly, and the panic attack symptoms must not be attributable to some known organic factors. Panic disorder is frequently associated with some symptoms of agoraphobia.
    The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician who elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.


    Patients with known sensitivity to this drug or other benzodiazepines.
    Patients taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir. See prescribing information for full details.


    Special Precautions

    Risks from concomitant use with opioids
    Concomitant use of benzodiazepines, including Alprazolam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe Alprazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of Alprazolam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking Alprazolam, prescribe a lower initial dose of the opioid and titrate based upon clinical response. Advise both patients and caregivers about the risks of respiratory depression and sedation when Alprazolam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.
    Abuse, Misuse, and Addiction
    The use of benzodiazepines, including this drug, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death.
    Before prescribing this drug and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of this drug, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of this drug along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.
    Dependence and Withdrawal Reactions
    To reduce the risk of withdrawal reactions, use a gradual taper to discontinue this drug or reduce the dosage (a patient-specific plan should be used to taper the dose). Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.
    Acute Withdrawal Reactions

    The continued use of benzodiazepines, including this drug, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of this drug after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures).
    Protracted Withdrawal Syndrome
    In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.
    Effects on Driving and Operating Machinery
    Because of its CNS depressant effects, patients receiving this drug should be cautioned against engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle. For the same reason, patients should be cautioned about the concomitant use of alcohol and other CNS depressant drugs during treatment with this drug.
    Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A
    The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam.
    Strong CYP3A Inhibitors: This medicinal product is contraindicated in patients receiving strong inhibitors of CYP3A such as azole antifungal agents. Ketoconazole and itraconazole have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively.
    Dosage adjustment is necessary when this drug and ritonavir are initiated concomitantly or when ritonavir is added to a stable dosage of this drug.
    Drugs demonstrated to be CYP3A inhibitors on the basis of clinical studies involving alprazolam: nefazodone, fluvoxamine, and cimetidine. Use caution and consider dose reduction of this drug, as appropriate, during co-administration with these drugs.
    Patients with Depression
    Benzodiazepines may worsen depression. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered in patients with depression.
    Episodes of hypomania and mania have been reported in association with the use of alprazolam tablets in patients with depression.
    Neonatal Sedation and Withdrawal Syndrome
    Use of this drug late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to this drug during pregnancy or labor for signs of sedation and monitor neonates exposed to this drug during pregnancy for signs of withdrawal; manage these neonates accordingly.
    Risks in Patients with Impaired Respiratory Function
    There have been reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with alprazolam. Closely monitor patients with impaired respiratory function. If signs and symptoms of respiratory depression, hypoventilation, or apnea occur, discontinue this drug.
    Each 0.5 mg, 1 mg & 2 mg sustained release tablet contains 221.7 mg lactose
    Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption should not take this drug.
    See prescribing information for full details. 

    Side Effects

    Sedation, somnolence, dysarthria, memory impairment, dysarthria.
    See prescribing information for full details.

    Drug interactions

    Concomitant use  with drugs that inhibit metabolism via Cytochrome P450 3A: The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam. Consequently, alprazolam should be avoided in patients receiving very potent inhibitors of CYP3A. With drugs inhibiting CYP3A to a lesser but still significant degree, alprazolam should be used only with caution and consideration of appropriate dosage reduction. For some drugs, an interaction with alprazolam has been quantified with clinical data; for other drugs, interactions are predicted from in vitro data and/or experience with similar drugs in the same pharmacologic class. The following are examples of drugs known to inhibit the metabolism of alprazolam and/or related benzodiazepines, presumably through inhibition of CYP3A.
    Potent CYP3A Inhibitors: Azole antifungal agents — Ketoconazole and itraconazole are potent CYP3A inhibitors and have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively. The coadministration of alprazolam with these agents is not recommended. Other azole-type antifungal agents should also be considered potent CYP3A inhibitors and the coadministration of alprazolam with them is contraindicatednot recommended.
    See prescribing information for full details. 

    Pregnancy and Lactation

    Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects.

    The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
    Clinical Considerations:
    Fetal/Neonatal adverse reactions: Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to this drug during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to this drug during pregnancy for signs of withdrawal. Manage these neonates accordingly.
    Human Data:
    Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco, and other medications, have not confirmed these findings.

    Limited data from published literature reports the presence of alprazolam in human breast milk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. The effects of alprazolam on lactation are unknown. Because of the potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed infants, advise patients that breastfeeding is not recommended during treatment.          


    Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal. Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage.
    In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information.

    Important notes

    Storage: Store at 15-25°C.

    Pfizer Italy