ALPRAZOLAM TABLETS, USP, 0.25 mg, 0.5 mg, 1 mg and 2 mg

/ALPRAZOLAM TABLETS, USP, 0.25 mg, 0.5 mg, 1 mg and 2 mg
ALPRAZOLAM TABLETS, USP, 0.25 mg, 0.5 mg, 1 mg and 2 mg2018-09-06T09:12:40+00:00

Prescription Drug Name:

ALPRAZOLAM TABLETS, USP, 0.25 mg, 0.5 mg, 1 mg and 2 mg

ID:

dfa9fa44-a29c-4f1f-9249-23ecd9e2efdf

Code:

34391-3

DESCRIPTION


id: 6599d416-020d-4c31-9738-c75ac3c4e936
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Alprazolam Tablets, USP contain alprazolam which is a triazolo analog of the 1,4 benzodiazepine class of central nervous system-active compounds. The chemical name of alprazolam is 8-Chloro-1-methyl-6-phenyl-4Hs-triazolo[4,3-α][1,4] benzodiazepine. The structural formula is: Alprazolam is a white crystalline powder, which is soluble in methanol or ethanol but which has no appreciable solubility in water at physiological pH. Each alprazolam tablet, for oral administration, contains 0.25, 0.5, 1 or 2 mg of alprazolam. Alprazolam tablets, 2 mg, are multi-scored and may be divided as shown below: Inactive ingredients: Colloidal silicon dioxide, docusate sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium benzoate and sodium starch glycolate. In addition, the 0.5 mg tablet contains FD&C Yellow No. 6 Aluminum Lake and the 1 mg tablet contains FD&C Blue No. 1 Aluminum Lake.

CONTRAINDICATIONS


id: 22e6d1a8-f0e6-48dd-b874-d98213332cc7
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Alprazolam tablets are contraindicated in patients with known sensitivity to this drug or other benzodiazepines. Alprazolam tablets may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in patients with acute narrow angle glaucoma. Alprazolam tablets are contraindicated with ketoconazole and itraconazole, since these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP3A) (see  WARNINGS  and PRECAUTIONS-Drug Interactions ).

ADVERSE REACTIONS


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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Side effects to alprazolam tablets, if they occur, are generally observed at the beginning of therapy and usually disappear upon continued medication. In the usual patient, the most frequent side effects are likely to be an extension of the pharmacological activity of alprazolam, e.g., drowsiness or light-headedness. The data cited in the two tables below are estimates of untoward clinical event incidence among patients who participated under the following clinical conditions: relatively short duration (i.e., four weeks) placebo-controlled clinical studies with dosages up to 4 mg/day of alprazolam tablets (for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety) and short-term (up to ten weeks) placebo-controlled clinical studies with dosages up to 10 mg/day of alprazolam tablets in patients with panic disorder, with or without agoraphobia. These data cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics, and other factors often differ from those in clinical trials. These figures cannot be compared with those obtained from other clinical studies involving related drug products and placebo as each group of drug trials are conducted under a different set of conditions. Comparison of the cited figures, however, can provide the prescriber with some basis for estimating the relative contributions of drug and non-drug factors to the untoward event incidence in the population studied. Even this use must be approached cautiously, as a drug may relieve a symptom in one patient but induce it in others. (For example, an anxiolytic drug may relieve dry mouth [a symptom of anxiety] in some subjects but induce it [an untoward event] in others.) Additionally, for anxiety disorders the cited figures can provide the prescriber with an indication as to the frequency with which physician intervention (e.g., increased surveillance, decreased dosage or discontinuation of drug therapy) may be necessary because of the untoward clinical event.

Treatment-Emergent Adverse Events Reported in Placebo-Controlled Trials of Anxiety Disorders
  ANXIETY DISORDERS   
  Treatment-Emergent
Symptom Incidence 
Incidence of
Intervention
Because of
Symptom 
      ALPRAZOLAM TABLETS         PLACEBO         ALPRAZOLAM TABLETS    
Number of Patients
% of Patients Reporting:
565 505 565
Central Nervous System      
Drowsiness 41.0 21.6 15.1
Light-headedness 20.8 19.3 1.2
Depression 13.9 18.1 2.4
Headache 12.9 19.6 1.1
Confusion 9.9 10.0 0.9
Insomnia 8.9 18.4 1.3
Nervousness 4.1 10.3 1.1
Syncope 3.1 4.0
None reported
Dizziness 1.8 0.8 2.5
Akathisia 1.6 1.2
Tiredness/Sleepiness 1.8
Gastrointestinal      
Dry Mouth 14.7 13.3 0.7
Constipation 10.4 11.4 0.9
Diarrhea 10.1 10.3 1.2
Nausea/Vomiting 9.6 12.8 1.7
Increased Salivation 4.2 2.4
Cardiovascular      
Tachycardia/Palpitations 7.7 15.6 0.4
Hypotension 4.7 2.2
Sensory      
Blurred Vision 6.2 6.2 0.4
Musculoskeletal      
Rigidity 4.2 5.3
Tremor 4.0 8.8 0.4
Cutaneous      
Dermatitis/Allergy 3.8 3.1 0.6
Other      
Nasal Congestion 7.3 9.3
Weight Gain 2.7 2.7
Weight Loss 2.3 3.0
In addition to the relatively common (i.e., greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of benzodiazepines: dystonia, irritability, concentration difficulties, anorexia, transient amnesia or memory impairment, loss of coordination, fatigue, seizures, sedation, slurred speech, jaundice, musculoskeletal weakness, pruritus, diplopia, dysarthria, changes in libido, menstrual irregularities, incontinence and urinary retention.
Treatment-Emergent Adverse Events Reported in Placebo-Controlled Trials of Panic Disorders
PANIC DISORDERS
  Treatment-Emergent
Symptom Incidence
      ALPRAZOLAM TABLETS         PLACEBO    
Number of Patients
% of Patients Reporting:
1388 1231
Central Nervous System  
Drowsiness 76.8 42.7
Fatigue and Tiredness 48.6 42.3
Impaired Coordination 40.1 17.9
Irritability 33.1 30.1
Memory Impairment 33.1 22.1
Light-headedness/Dizziness 29.8 36.9
Insomnia 29.4 41.8
Headache 29.2 35.6
Cognitive Disorder 28.8 20.5
Dysarthria 23.3 6.3
Anxiety 16.6 24.9
Abnormal Involuntary Movement 14.8 21.0
Decreased Libido 14.4 8.0
Depression 13.8 14.0
Confusional State 10.4 8.2
Muscular Twitching 7.9 11.8
Increased Libido 7.7 4.1
Change in Libido (Not Specified) 7.1 5.6
Weakness 7.1 8.4
Muscle Tone Disorders 6.3 7.5
Syncope 3.8 4.8
Akathisia 3.0 4.3
Agitation 2.9 2.6
Disinhibition 2.7 1.5
Paresthesia 2.4 3.2
Talkativeness 2.2 1.0
Vasomotor Disturbances 2.0 2.6
Derealization 1.9 1.2
Dream Abnormalities 1.8 1.5
Fear 1.4 1.0
Feeling Warm 1.3 0.5
Gastrointestinal  
Decreased Salivation 32.8 34.2
Constipation 26.2 15.4
Nausea/Vomiting 22.0 31.8
Diarrhea 20.6 22.8
Abdominal Distress 18.3 21.5
Increased Salivation 5.6 4.4
Cardio-Respiratory  
Nasal Congestion 17.4 16.5
Tachycardia 15.4 26.8
Chest Pain 10.6 18.1
Hyperventilation 9.7 14.5
Upper Respiratory Infection 4.3 3.7
Sensory  
Blurred Vision 21.0 21.4
Tinnitus 6.6 10.4
Musculoskeletal  
Muscular Cramps 2.4 2.4
Muscle Stiffness 2.2 3.3
Cutaneous  
Sweating 15.1 23.5
Rash 10.8 8.1
Other  
Increased Appetite 32.7 22.8
Decreased Appetite 27.8 24.1
Weight Gain 27.2 17.9
Weight Loss 22.6 16.5
Micturition Difficulties 12.2 8.6
Menstrual Disorders 10.4 8.7
Sexual Dysfunction 7.4 3.7
Edema 4.9 5.6
Incontinence 1.5 0.6
Infection 1.3 1.7
In addition to the relatively common (i.e., greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of alprazolam tablets: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated bilirubin, elevated hepatic enzymes, and jaundice. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. (see PRECAUTIONS , General ). Adverse Events Reported as Reasons for Discontinuation in Treatment of Panic Disorder in Placebo-Controlled Trials In a larger database comprised of both controlled and uncontrolled studies in which 641 patients received alprazolam tablets, discontinuation-emergent symptoms which occurred at a rate of over 5% in patients treated with alprazolam tablets and at a greater rate than the placebo treated group were as follows:
DISCONTINUATION-EMERGENT SYMPTOM INCIDENCE
  Percentage of 641 Alprazolam Tablet-Treated Panic Disorder

Patients Reporting Events

Body System/Event 
 
 
Neurologic   
Insomnia  29.5 
Light-headedness  19.3 
Abnormal involuntary movement  17.3 
Headache  17.0 
Muscular twitching  6.9 
Impaired coordination  6.6 
Muscle tone disorders  5.9 
Weakness  5.8 
Psychiatric   
Anxiety  19.2 
Fatigue and Tiredness  18.4 
Irritability  10.5 
Cognitive disorder  10.3 
Memory impairment  5.5 
Depression  5.1 
Confusional state  5.0 
Gastrointestinal   
Nausea/Vomiting  16.5 
Diarrhea  13.6 
Decreased salivation 10.6 
Metabolic-Nutritional    
Weight loss  13.3 
Decreased appetite  12.8 
Dermatological   
Sweating  14.4 
Cardiovascular   
Tachycardia  12.2 
Special Senses    
Blurred vision  10.0 
From the studies cited, it has not been determined whether these symptoms are clearly related to the dose and duration of therapy with alprazolam tablets in patients with panic disorder. There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam tablets (see WARNINGS ). To discontinue treatment in patients taking alprazolam tablets, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam tablets be decreased by no more than 0.5 mg every three days (see DOSAGE AND ADMINISTRATION ). Some patients may benefit from an even slower dosage reduction. 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. As with all benzodiazepines, paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. 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. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that 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 discontinuation of alprazolam in patients with post-traumatic stress disorder. Post Introduction Reports: Various adverse drug reactions have been reported in association with the use of alprazolam tablets since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of alprazolam tablets cannot be readily determined. Reported events include: gastrointestinal disorder, hypomania, mania, liver enzyme elevations, hepatitis, hepatic failure, Stevens-Johnson syndrome, angioedema, peripheral edema, hyperprolactinemia, gynecomastia and galactorrhea (see PRECAUTIONS ).

DOSAGE AND ADMINISTRATION


id: 3c630f3e-69a5-4035-bdc9-99c8aa907297
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who require doses greater than 4 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.

HOW SUPPLIED


id: d887fabd-0fff-4c62-b10d-c5dc3b94b5b4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Alprazolam Tablets, USP are available as: 0.25 mg: White, oval, debossed “2087” over “V” on one side and scored on the reverse side. Bottles of 10    NDC 0603-2127-10    Bottles of 100    NDC 0603-2127-21
Bottles of 30    NDC 0603-2127-16    Bottles of 120    NDC 0603-2127-22
Bottles of 60    NDC 0603-2127-20    Bottles of 500    NDC 0603-2127-28
Bottles of 90    NDC 0603-2127-02    Bottles of 1000  NDC 0603-2127-32
0.5 mg: Peach, oval, debossed “2088” over “V” on one side and scored on the reverse side. Bottles of 10    NDC 0603-2128-10    Bottles of 100    NDC 0603-2128-21
Bottles of 30    NDC 0603-2128-16    Bottles of 120    NDC 0603-2128-22
Bottles of 60    NDC 0603-2128-20    Bottles of 500    NDC 0603-2128-28
Bottles of 90    NDC 0603-2128-02    Bottles of 1000  NDC 0603-2128-32
1 mg: Blue, oval, debossed “2089” over “V” on one side and scored on the reverse side. Bottles of 10    NDC 0603-2129-10    Bottles of 100    NDC 0603-2129-21
Bottles of 30    NDC 0603-2129-16    Bottles of 120    NDC 0603-2129-22
Bottles of 60    NDC 0603-2129-20    Bottles of 500    NDC 0603-2129-28
Bottles of 90    NDC 0603-2129-02    Bottles of 1000  NDC 0603-2129-32
2 mg: White, oblong, multi-scored, beveled edged, debossed “2090” on one side and debossed “V” on the reverse side. Bottles of 10    NDC 0603-2130-10    Bottles of 500    NDC 0603-2130-28
Bottles of 90    NDC 0603-2130-02    Bottles of 1000  NDC 0603-2130-32
Bottles of 100  NDC 0603-2130-21    

ANIMAL STUDIES


id: 585bd374-32f2-45ce-9e1a-001075d1ac74
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

When rats were treated with alprazolam at 3, 10, and 30 mg/kg/day (15 to 150 times the maximum recommended human dose) orally for 2 years, a tendency for a dose related increase in the number of cataracts was observed in females and a tendency for a dose related increase in corneal vascularization was observed in males. These lesions did not appear until after 11 months of treatment.

PRINCIPAL DISPLAY PANEL


id: faabd09c-62f4-4eb2-b17b-d2016369575f
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 66336-0932-XX
NDC 66336-0932-10
NDC 66336-0932-30
NDC 66336-0932-60
NDC 66336-0932-90