XANOR Alprazolam 500mcg Tablet 100's
RXDRUG-DR-XY14607
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Alprazolam is indicated for the treatment of: Anxiety; Depression (usage has not been established in depression with psychotic features, in bipolar disorders, or in "endogenous" depression); Mixed anxiety-depression; Anxiety, mixed anxiety-depression, or depression associated with other functional or organic disease; Panic disorders.
Dosage/Direction for Use
Alprazolam (Xanor) Tablets (all formulations): The optimum dose should be individualized based upon the severity of the symptoms and individual patient response. In patients who require higher doses, dosage should be increased cautiously to avoid adverse effects. In general, patients who have not previously received psychotropic medications will require somewhat lower doses than those previously treated with minor tranquilizers, antidepressants, or hypnotics. It is recommended that the general principle of using the lowest effective dose be followed, especially in elderly or debilitated patients to preclude the development of ataxia or oversedation.
Alprazolam (Xanor XR) Controlled-release Tablets: If alprazolam (Xanor XR): controlled-release tablets are to be given once daily, it is preferable to administer the dose in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.
Dosing recommendations for alprazolam XR tablets are based on a comparable pharmacokinetic profile in normal subjects given alprazolam tablets three or four times daily and in those given alprazolam XR tablets twice daily.
Duration of Treatment: Data are available to support usage for up to 6 months for anxiety and depression and for up to 8 months in the treatment of panic disorder. The risk of dependence may increase with dose and duration of treatment, therefore, the lowest possible effective dose and duration should be used and the need for continued treatment reassessed frequently. (See Precautions.)
Discontinuation of Treatment: To discontinue alprazolam treatment, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 500 mcg every 3 days. Some patients may require an even slower dosage reduction. (See Precautions.)
Pediatric Use: Safety and efficacy have not been established in children under 18 years of age. (See Table 1.)
Alprazolam (Xanor XR) Controlled-release Tablets: If alprazolam (Xanor XR): controlled-release tablets are to be given once daily, it is preferable to administer the dose in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.
Dosing recommendations for alprazolam XR tablets are based on a comparable pharmacokinetic profile in normal subjects given alprazolam tablets three or four times daily and in those given alprazolam XR tablets twice daily.
Duration of Treatment: Data are available to support usage for up to 6 months for anxiety and depression and for up to 8 months in the treatment of panic disorder. The risk of dependence may increase with dose and duration of treatment, therefore, the lowest possible effective dose and duration should be used and the need for continued treatment reassessed frequently. (See Precautions.)
Discontinuation of Treatment: To discontinue alprazolam treatment, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 500 mcg every 3 days. Some patients may require an even slower dosage reduction. (See Precautions.)
Pediatric Use: Safety and efficacy have not been established in children under 18 years of age. (See Table 1.)
Overdosage
Symptoms of overdose with alprazolam are extensions of its pharmacological action and include drowsiness, slurred speech, motor incoordination, coma and respiratory depression. Serious sequela are rare unless other drugs and/or ethanol are concomitantly ingested. Treatment of overdosage is primarily supportive of respiratory and cardiovascular function. The value of dialysis has not been determined. Flumazenil may be used as an adjunct to the management of respiratory and cardiovascular function associated with overdose.
Administration
May be taken with or without food: Side effects eg, sleepiness/drowsiness may be reduced if taken immediately after meals. Xanor XR Swallow whole, do not chew/crush/break.
Contraindications
Alprazolam (Xanor) is contraindicated in patients with known hypersensitivity to benzodiazepines, alprazolam, or to any components, namely: lactose monohydrate, microcrystalline cellulose, docusate sodium, sodium benzoate, colloidal anhydrous silica, magnesium stearate, maize starch, F.D. & C. Blue no. 2 Aluminum Lake, F.D. & C. Yellow no. 6 Aluminum Lake, methylhydroxypropylcellulose.
Special Precautions
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required.
Caution is recommended when treating patients with impaired renal or hepatic function.
Habituation and emotional/physical dependence may occur with benzodiazepines, including alprazolam. As with all benzodiazepines, the risk of dependence increases with higher doses and long-term use and is further increased in patients with a history of alcoholism or drug abuse. Drug abuse is a known risk for alprazolam and other benzodiazepines, and patients should be monitored accordingly when receiving alprazolam. Alprazolam may be subject to diversion. There have been reports of overdose-related deaths when alprazolam is abused with other central nervous system (CNS) depressants including opioids, other benzodiazepines, and alcohol. These risks should be considered when prescribing or dispensing alprazolam. To reduce these risks the smallest appropriate quantity should be used and patients should be advised on the proper storage and disposal of unused drug. (See Dosage & Administration, Adverse Reactions, and Overdosage.)
Withdrawal symptoms have occurred following rapid decrease or abrupt discontinuance of benzodiazepines including alprazolam. These can range from mild dysphoria and insomnia to a major syndrome which may include abdominal and muscle cramps, vomiting, sweating, tremor, and convulsions. In addition, withdrawal seizures have occurred upon rapid decrease or abrupt discontinuation of therapy with alprazolam. (See Discontinuation of Treatment under Dosage & Administration and Adverse Reactions.)
Panic disorders have been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Therefore, the same precaution must be exercised when using the higher doses of alprazolam (Xanor) in treating patients with panic disorders as is exercised with the use of any psychotropic drug in treating depressed patients or those in whom there is reason to expect concealed suicidal ideation or plans.
Administration to severely depressed or suicidal patients should be done with appropriate precautions and appropriate size of the prescription.
Episodes of hypomania and mania have been reported in association with the use of alprazolam in patients with depression.
The use of alprazolam has not been established in certain types of depression. (See Indications.)
Effects on Ability to Drive and Use Machines: Patients should be cautioned about using alprazolam while operating motor vehicles or engaging in other dangerous activities until it is established that they do not become impaired while receiving the drug.
Caution is recommended when treating patients with impaired renal or hepatic function.
Habituation and emotional/physical dependence may occur with benzodiazepines, including alprazolam. As with all benzodiazepines, the risk of dependence increases with higher doses and long-term use and is further increased in patients with a history of alcoholism or drug abuse. Drug abuse is a known risk for alprazolam and other benzodiazepines, and patients should be monitored accordingly when receiving alprazolam. Alprazolam may be subject to diversion. There have been reports of overdose-related deaths when alprazolam is abused with other central nervous system (CNS) depressants including opioids, other benzodiazepines, and alcohol. These risks should be considered when prescribing or dispensing alprazolam. To reduce these risks the smallest appropriate quantity should be used and patients should be advised on the proper storage and disposal of unused drug. (See Dosage & Administration, Adverse Reactions, and Overdosage.)
Withdrawal symptoms have occurred following rapid decrease or abrupt discontinuance of benzodiazepines including alprazolam. These can range from mild dysphoria and insomnia to a major syndrome which may include abdominal and muscle cramps, vomiting, sweating, tremor, and convulsions. In addition, withdrawal seizures have occurred upon rapid decrease or abrupt discontinuation of therapy with alprazolam. (See Discontinuation of Treatment under Dosage & Administration and Adverse Reactions.)
Panic disorders have been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Therefore, the same precaution must be exercised when using the higher doses of alprazolam (Xanor) in treating patients with panic disorders as is exercised with the use of any psychotropic drug in treating depressed patients or those in whom there is reason to expect concealed suicidal ideation or plans.
Administration to severely depressed or suicidal patients should be done with appropriate precautions and appropriate size of the prescription.
Episodes of hypomania and mania have been reported in association with the use of alprazolam in patients with depression.
The use of alprazolam has not been established in certain types of depression. (See Indications.)
Effects on Ability to Drive and Use Machines: Patients should be cautioned about using alprazolam while operating motor vehicles or engaging in other dangerous activities until it is established that they do not become impaired while receiving the drug.
Use In Pregnancy & Lactation
Pregnancy: The data concerning teratogenicity and effects on postnatal development and behavior following benzodiazepine treatment are inconsistent. There is evidence from some early studies with other members of the benzodiazepine class that in utero exposure may be associated with malformations. Later studies with the benzodiazepine class of drugs have provided no clear evidence of any type of defect. Infants exposed to benzodiazepines during late third trimester of pregnancy or during labor have been reported to exhibit either the floppy infant syndrome or neonatal withdrawal symptoms. If alprazolam is used during pregnancy, or if the patient becomes pregnant while taking alprazolam, the patient should be apprised of the potential hazard to the fetus.
Breastfeeding: Levels of benzodiazepines, including alprazolam, in breast milk are low. However, nursing should not be undertaken while using benzodiazepines.
Breastfeeding: Levels of benzodiazepines, including alprazolam, in breast milk are low. However, nursing should not be undertaken while using benzodiazepines.
Adverse Reactions
Adverse events, if they occur, are generally observed at the beginning of therapy and usually disappear upon continued medication or decreased dosage.
Undesirable effects associated with alprazolam therapy in patients participating in controlled clinical studies and with post-marketing experience were as follows: See Table 2.
Undesirable effects associated with alprazolam therapy in patients participating in controlled clinical studies and with post-marketing experience were as follows: See Table 2.
In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility and intrusive thoughts have been reported during discontinuance of alprazolam in patients with post-traumatic stress disorder.
Drug Interactions
Benzodiazepines produce additive CNS depressant effects, including respiratory depression, when co-administered with opioids, alcohol or other drugs producing CNS depression. (See Precautions.)
Pharmacokinetic interactions can occur when alprazolam is administered along with drugs that interfere with its metabolism. Compounds which inhibit certain hepatic enzymes (particularly cytochrome P4503A4) may increase the concentration of alprazolam and enhance its activity. Data from clinical studies with alprazolam, in vitro studies with alprazolam, and clinical studies with drugs metabolized similarly to alprazolam provide evidence for varying degrees of interaction and possible interaction with alprazolam for a number of drugs. Based on the degree of interaction and the type of data available, the following recommendations are made: The coadministration of alprazolam with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.
Caution and consideration of dose reduction is recommended when alprazolam is coadministered with nefazodone, fluvoxamine, and cimetidine.
Caution is recommended when alprazolam is co-administered with fluoxetine, propoxyphene, oral contraceptives, diltiazem, or macrolide antibiotics such as erythromycin and troleandomycin.
Interactions involving human immunodeficiency virus (HIV) protease inhibitors (e.g., ritonavir) and alprazolam are complex and time dependent. Low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam.
Increased digoxin concentrations have been reported when alprazolam was given, especially in elderly (>65 years of age). Patients who receive alprazolam and digoxin should therefore be monitored for signs and symptoms related to digoxin toxicity.
Pharmacokinetic interactions can occur when alprazolam is administered along with drugs that interfere with its metabolism. Compounds which inhibit certain hepatic enzymes (particularly cytochrome P4503A4) may increase the concentration of alprazolam and enhance its activity. Data from clinical studies with alprazolam, in vitro studies with alprazolam, and clinical studies with drugs metabolized similarly to alprazolam provide evidence for varying degrees of interaction and possible interaction with alprazolam for a number of drugs. Based on the degree of interaction and the type of data available, the following recommendations are made: The coadministration of alprazolam with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.
Caution and consideration of dose reduction is recommended when alprazolam is coadministered with nefazodone, fluvoxamine, and cimetidine.
Caution is recommended when alprazolam is co-administered with fluoxetine, propoxyphene, oral contraceptives, diltiazem, or macrolide antibiotics such as erythromycin and troleandomycin.
Interactions involving human immunodeficiency virus (HIV) protease inhibitors (e.g., ritonavir) and alprazolam are complex and time dependent. Low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam.
Increased digoxin concentrations have been reported when alprazolam was given, especially in elderly (>65 years of age). Patients who receive alprazolam and digoxin should therefore be monitored for signs and symptoms related to digoxin toxicity.
Storage
Alprazolam (Xanor) 250 mcg, 500 mcg and 1 mg Tablets: Store at temperatures not exceeding 25°C.
Alprazolam (Xanor XR) 500 mcg Controlled-Release Tablet: Store at temperatures not exceeding 30°C.
Alprazolam (Xanor XR) 500 mcg Controlled-Release Tablet: Store at temperatures not exceeding 30°C.
Action
Pharmacologic Category: Anxiolytic.
Pharmacology: Pharmacodynamics: CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis.
Clinical Studies: Alprazolam (Xanor) tablets were compared to placebo in double blind clinical trials in patients with a diagnosis of anxiety or anxiety with associated depressive symptomatology. Alprazolam (Xanor) was significantly better than placebo at each of the evaluation periods of these four week studies as judged by the following psychometric instruments: Physician's Global Impressions, Hamilton Anxiety Rating Scale, Target Symptoms, Patient's Global Impressions and Self-Rating Symptom Scale.
Pharmacokinetics: Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in one to two hours following administration. Plasma levels are proportions to the dose given over the dose range of 0.5 to 3.0 mg. Peak levels of 8.0 to 37 mg/mL were observed. The mean elimination half-life of alprazolam is 12-15 hours. The predominant metabolites are α-hydroxy-alprazolam and a benzophenone derived from alprazolam. The biological activity of α-hydroxy-alprazolam is approximately one-half that of alprazolam. The benzophenone metabolites is essentially inactive. Plasma levels of these metabolites are extremely low, thus, precluding precise pharmacokinetic description. However, their half-lives appear to be of the same order of magnitude as alprazolam. Alprazolam and its metabolites are excreted primarily in the urine.
The ability of alprazolam to induce human hepatic enzyme systems has not yet been determined. However, this is not a property of benzodiazepines in general. Further, alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally.
In vitro, alprazolam is bound (80 percent) to human serum protein.
Changes in the absorption, distribution, metabolism and excretion of benzodiazepines have been reported in a variety of disease states including alcoholism, impaired hepatic function and impaired renal function changes have also been demonstrated in geriatric patients. It has not yet been determined if similar changes occur in the pharmacokinetics of alprazolam.
Because of its similarity to other benzodiazepines, it is assumed that alprazolam undergoes transplacental passage and is excreted in human milk.
Toxicology: Preclinical Safety Data: Mutagenesis: Alprazolam was not mutagenic in the in vitro Ames test. Alprazolam did not produce chromosomal aberrations in the in vivo micronucleus assay in rats up to the highest dose tested of 100 mg/kg, which is 500 times greater than the maximum recommended daily human dose of 10 mg/day.
Carcinogenesis: No evidence of carcinogenic potential was observed during 2-year bioassay studies of alprazolam in rats at doses up to 30 mg/kg/day (150 times the maximum recommended daily human dose of 10 mg/day) and in mice at doses up to 10 mg/kg/day (50 times the maximum recommended daily human dose of 10 mg/day).
Fertility: Alprazolam did not impair fertility in rats up to the highest dose tested of 5 mg/kg/day, which is 25 times the maximum recommended daily human dose of 10 mg/day.
Ocular Effects: When rats were treated orally with alprazolam at 3, 10, and 30 mg/kg/day (15 to 150 times the maximum recommended daily human dose of 10 mg/day) for 2 years, a tendency for a dose related increase in the number of cataracts (females) and corneal vascularization (males) was observed. These lesions did not appear until after 11 months of treatment.
Effect of anesthetic and sedative drugs: Nonclinical research has shown that administration of anesthetic and sedation drugs that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity can increase neuronal cell death in the brain and result in long term deficits in cognition and behavior of juvenile animals when administered during the period of peak brain development. Based on comparisons across nonclinical species, the window of vulnerability of the brain to these effects is believed to correlate with human exposures in the third trimester of pregnancy through the first year of life, but may extend to approximately 3 years of age. While there is limited information of this effect with alprazolam, since the mechanism of action includes potentiation of GABA activity, a similar effect may occur. The relevance of these nonclinical findings to human use is unknown.
Pharmacology: Pharmacodynamics: CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis.
Clinical Studies: Alprazolam (Xanor) tablets were compared to placebo in double blind clinical trials in patients with a diagnosis of anxiety or anxiety with associated depressive symptomatology. Alprazolam (Xanor) was significantly better than placebo at each of the evaluation periods of these four week studies as judged by the following psychometric instruments: Physician's Global Impressions, Hamilton Anxiety Rating Scale, Target Symptoms, Patient's Global Impressions and Self-Rating Symptom Scale.
Pharmacokinetics: Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in one to two hours following administration. Plasma levels are proportions to the dose given over the dose range of 0.5 to 3.0 mg. Peak levels of 8.0 to 37 mg/mL were observed. The mean elimination half-life of alprazolam is 12-15 hours. The predominant metabolites are α-hydroxy-alprazolam and a benzophenone derived from alprazolam. The biological activity of α-hydroxy-alprazolam is approximately one-half that of alprazolam. The benzophenone metabolites is essentially inactive. Plasma levels of these metabolites are extremely low, thus, precluding precise pharmacokinetic description. However, their half-lives appear to be of the same order of magnitude as alprazolam. Alprazolam and its metabolites are excreted primarily in the urine.
The ability of alprazolam to induce human hepatic enzyme systems has not yet been determined. However, this is not a property of benzodiazepines in general. Further, alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally.
In vitro, alprazolam is bound (80 percent) to human serum protein.
Changes in the absorption, distribution, metabolism and excretion of benzodiazepines have been reported in a variety of disease states including alcoholism, impaired hepatic function and impaired renal function changes have also been demonstrated in geriatric patients. It has not yet been determined if similar changes occur in the pharmacokinetics of alprazolam.
Because of its similarity to other benzodiazepines, it is assumed that alprazolam undergoes transplacental passage and is excreted in human milk.
Toxicology: Preclinical Safety Data: Mutagenesis: Alprazolam was not mutagenic in the in vitro Ames test. Alprazolam did not produce chromosomal aberrations in the in vivo micronucleus assay in rats up to the highest dose tested of 100 mg/kg, which is 500 times greater than the maximum recommended daily human dose of 10 mg/day.
Carcinogenesis: No evidence of carcinogenic potential was observed during 2-year bioassay studies of alprazolam in rats at doses up to 30 mg/kg/day (150 times the maximum recommended daily human dose of 10 mg/day) and in mice at doses up to 10 mg/kg/day (50 times the maximum recommended daily human dose of 10 mg/day).
Fertility: Alprazolam did not impair fertility in rats up to the highest dose tested of 5 mg/kg/day, which is 25 times the maximum recommended daily human dose of 10 mg/day.
Ocular Effects: When rats were treated orally with alprazolam at 3, 10, and 30 mg/kg/day (15 to 150 times the maximum recommended daily human dose of 10 mg/day) for 2 years, a tendency for a dose related increase in the number of cataracts (females) and corneal vascularization (males) was observed. These lesions did not appear until after 11 months of treatment.
Effect of anesthetic and sedative drugs: Nonclinical research has shown that administration of anesthetic and sedation drugs that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity can increase neuronal cell death in the brain and result in long term deficits in cognition and behavior of juvenile animals when administered during the period of peak brain development. Based on comparisons across nonclinical species, the window of vulnerability of the brain to these effects is believed to correlate with human exposures in the third trimester of pregnancy through the first year of life, but may extend to approximately 3 years of age. While there is limited information of this effect with alprazolam, since the mechanism of action includes potentiation of GABA activity, a similar effect may occur. The relevance of these nonclinical findings to human use is unknown.
MedsGo Class
Anxiolytics
Features
Brand
Xanor
Full Details
Dosage Strength
500 mcg
Drug Ingredients
- Alprazolam
Drug Packaging
Tablet 100's
Generic Name
Alprazolam
Dosage Form
Tablet
Registration Number
DR-XY14607
Drug Classification
Prescription Drug (RX)
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