Alprazolam is in a group of drugs called benzodiazepines (ben-zoe-dye-AZE-eh-peens). It works by slowing down the movement of chemicals in the brain that may become unbalanced. This results in a reduction in nervous tension (anxiety).
Alprazolam is used to treat anxiety disorders, panic disorders, and anxiety caused by depression.
Alprazolam may also be used for purposes other than those listed in this medication guide.
NAME OF THE MEDICINAL PRODUCT
QUALITATIVE AND QUANTITATIVE COMPOSITION
Alprazolam is chemically 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-a] [1,4] benzodiazepine.
Each immediate-release (IR) tablet contains 0.25 mg, 0.5 mg or 1 mg of alprazotam.
Alprazolam is indicated for the treatment-of:
POSOLOGY AND METHOD OF ADMINISTRATION
Alprazolam Tablets: The optimum dose should be individualized based upon the severity of the symptoms and individual patient response. )n 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 over sedation.
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 section Special Warnings and Precautions for Use).
Pediatric Use: Safety and efficacy have not been established in children under 18 years of age-
|Alprazolam IR Tablets
|Indication or Population
|Usual Starting Dose
(if side effects occur,
dose should be lowered)
|Usual Dose Range
|0.75 to 1.5 mg daily given in divided doses
|0.5 to 4 mg given in divided doses
|1.5 mg daily given in divided doses
|1.5 to 4.5 mg given in divided doses
|0.5 to 1.0 mg given at bedtime or 0.5mg three times daily
|Dose should be adjusted to patient response with increments no greater thai 1 mg/day every 3 to 4 days. Additional doses can be added until a schedule of three or four times daily is achieved.
[The mean dose in a large multi-clinic study was 5.7 ± 2.27 mg, with occasional patients requiring a maximum of 10 mg/day.]
|0.5 to 0.75 mg daily given in divided doses
|0.5 to 0.75 mg/day, given in divided doses; may be
gradually increased if needed and tolerated.
Xanax® is contraindicated in patients with known sensitivity to the benzodiazepines, Alprazolam,.or to any component of these products’ formulations
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
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 section Posology and Method of Administration -Discontinuation of Treatment).
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 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 idealization or plans.
Administration to severely depressed or suicidal patients should be done with appropriate precautions and appropriate size of the prescription.
Episodes of hypo mania 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 section Therapeutic Indications).
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
Benzodiazepines produce additive CNS depressant effects when co-administered with alcohol or other drugs producing CNS depression.
Pharmacol kinetic interactions of benzodiazepines with other drugs have been reported. For example, the clearance of Alprazolam and certain other benzodiazepines can be delayed by the co-administration of cimetidine or macrolide. antibiotics. The clinical significance of this is unclear.
Pharmacol kinetic 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:
FERTILITY, PREGNANCY AND LACTATION
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.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
As with other CNS active drugs, patients receiving Xanax® should be advised not to operate motor vehicles or dangerous machinery until it is established that they do not become drowsy or dizzy while receiving Xanax®.
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 are were as
|MedDRA System Organ Class||Very Common =1/10||Common =1/100 to<1/1o||Uncommon =1/1 000 to <1/100||Rare =1/1 0 000 to <1/1 000||xa <1/1 0 000||Frequency not known (cannot be estimated arable data)|
|Metabolism and Nutrition Disorders||Decreased appetite|
|Psychiatric Disorders||Depression||Confusional Slate, libido decreased, nervousness||Hypomania’,, section Special Warnings and Precautions for Use). hallucination’, anger*, aggression*. hostiirty*. agitation”, libido disorder”, thinking psyctiofnotor hyperadivity’|
|Nervous System Disorders||Sedation, somnolence. impairment. dysartliria, headache||Balance disorder, coordination abnormal i disturbance in attention. flypersomnia, lethargy, tremor||Amnesia, dystonia’||Autonomic nervous system imbalance*
|Eye Disorders||Vision blurred|
|Gastrointestinal Disorders||Constipation. dry mouth||Nausea||Gastrointestinal disorder”|
|Hepalobiliafy Disorders||Hepatitis- hepatic 1 unction abnormal’, jaundice*|
|Skin and Subcutaneous Tissue Disorders||Dermatitis’||Angioedema ‘,ptiotosenslt iuityreaction’|
|Musculoskelatal. Connective Tissue and Bone Disorders||Muscular weakness|
|Renal and Urinary Disorders||Incontinence’, urinary retention’|
|Reproductive System and Breast Disorders||Sexual dysfunction-||Menstruation irregular’|
|General Disorders and Administration SHe Conditions||Fatigue. I rn lability|
|Investigations||Weight decreased. weigh! increased||Intraocular Increased’|
same order of magnitude as that of Alprazolam. The benzophenone metabolite is essentially inactive.
Alprazolam and its metabolites are excreted primarily in the urine. In vitro, Alprazoiam is bound (80%) to human serum protein.
PRECLINICAL SAFETY DATA
Mutaoenesis, 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 Hie 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 atprazolam 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 cornea! vascularization (males) was observed. These lesions did not appear until after 11 months of treatment.
SPECIAL PRECAUTIONS FOR STORAGE
Store below 30°C.
Protect from light and moisture.
Keep all medicines out of the reach of children.
NATURE AND CONTENTS OF CONTAINER
Xanax® tablets are supplied in blister pack of 30’s.
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.
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 over dosage 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.
Xanax® tablets contain a tri-azolo-benzodiazepam. The benzodiazepines have qualitatively similar properties: anxiolysis, hypnosedation, myo re taxation, anti convulsion. There are, however, quantitative differences in their pharmacol dynamic properties that have led to varying patterns of therapeutic application. Currently, there is a general agreement that the action of benzodiazepines is a result of the potenliation of the neural inhibition that is mediated by gamma-amino-butyric acid (GABA).
Following oral administration, peak concentrations in the plasma occur in 1 to 2 hours following administration. The mean half-life of Alprazolam is 12-15 hours.
Alprazolam is mainly oxidized. The predominant metabolites are alpha-hydroxy- Alprazolam and a benzophenone derived from Alprazolam. Plasma levels of these metabolites are extremely low. The biological activity of alpha-hydroxy-Alprazolam is approximately one-half that of Alprazolam.
Pfizer Pakistan Ltd.
B-2, S.i.T.E., Karachi, Pakistan.