Xanor/Xanor XR

Xanor/Xanor XR

alprazolam

Manufacturer:

Sanico NV/Pfizer Italia

Distributor:

PF OFG
Full Prescribing Info
Contents
Alprazolam.
Description
Alprazolam (Xanor) tablets: Each tablet contains 250 mcg alprazolam.
Each tablet contains 500 mcg alprazolam.
Each tablet contains 1 mg alprazolam.
Alprazolam (Xanor XR) controlled-release tablets: Each controlled-release tablet contains 500 mcg of alprazolam.
Each controlled-release tablet contains 1 mg of alprazolam.
Xanor Tablets contain alprazolam which is a triazolo analog of the 1,4 benzodiazepine class of central nervous system active compound.
The chemical name of the alprazolam is 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-α] [1,4] benzodiazepine.
Alprazolam is a white crystalline powder, soluble in methanol or ethanol but with no appreciable solubility in water at physiological pH.
Action
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, Carcinogenesis, Fertility, and Ocular Effects: 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.
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).
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.
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.
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 in elderly or debilitated patients to preclude the development of ataxia or oversedation.
Alprazolam (Xanor XR) controlled-release Tablets: If alprazolam (Xanor XR) extended-release tablet is 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. (See Table 1.)

Click on icon to see table/diagram/image

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.
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 0.5 mg 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.
Overdosage
Symptoms of overdose with alprazolam are extensions of its pharmacological action and include drowsiness, slurred speech, motor incoordination, coma and respiratory depression. Serious sequelae 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.
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
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.
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 Dosage & Administration.)
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 post-natal 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.
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.

Click on icon to see table/diagram/image

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 when co-administered with alcohol or other drugs producing CNS depression.
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 co-administration of alprazolam with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.
Caution and consideration of dose reduction is recommended when alprazolam is co-administered 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 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 Tablet and Alprazolam 500 mcg (Xanor XR) Controlled-Release Tablet: Store at temperatures not exceeding 30°C.
Alprazolam (Xanor) 500 mcg and 1 mg Tablets: Store at temperatures not exceeding 25°C.
MIMS Class
ATC Classification
N05BA12 - alprazolam ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.
Presentation/Packing
Xanor: Tab 250 mcg (white, elliptical, full oval, scored) x 100's. 500 mcg (light orange, elliptical, full oval, scored, with "Upjohn 55" or "F" on one side and a score on the other side) x 100's. 1 mg (blue, elliptical, full oval, scored, with "Upjohn 90" or "F" on one side and a score on the other side) x 100's.
Xanor XR: CR tab 500 mcg (round, blue, convex, with "P&U 57" on one side and plain on the other side) x 100's. 1 mg x 100's.
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