DESCRIPTION
id: 6ce05971-48a8-3e04-e053-2991aa0a8052
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-4H-s-triazolo [4,3-α] [1,4] benzodiazepine.
The structural formula is represented to the right:
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, USP, for oral administration, contains 0.25, 0.5, 1 or 2 mg of alprazolam.
Inactive ingredients: crospovidone, docusate sodium, lactose, magnesium stearate, microcrystalline cellulose, silicon dioxide, sodium benzoate and starch 1500. In addition, the 0.5 mg tablet contains D&C Yellow No. 10 and the 1 mg and 2 mg tablet contains Green Lake Blend.
CONTRAINDICATIONS
id: 6ce05971-48b2-3e04-e053-2991aa0a8052
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Alprazolam Tablets are contraindicated in patients with known sensitivity to this drug or other benzodiazepines.
Alprazolam is 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
id: 6ce05971-48c9-3e04-e053-2991aa0a8052
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, eg, 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 (ie, four weeks) placebo-controlled clinical studies with dosages up to 4 mg/day of alprazolam (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 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 (eg, 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
|
PLACEBO
|
ALPRAZOLAM
|
| Number of Patients
% of Patients Reporting:
|
565 |
505 |
565 |
|
Central Nervous System
Drowsiness
Light-headedness
Depression
Headache
Confusion
Insomnia
Nervousness
Syncope
Dizziness
Akathisia
Tiredness/Sleepiness
|
41.0
20.8
13.9
12.9
9.9
8.9
4.1
3.1
1.8
1.6
†
|
21.6
19.3
18.1
19.6
10.0
18.4
10.3
4.0
0.8
1.2
†
|
15.1
1.2
2.4
1.1
0.9
1.3
1.1
†
2.5
†
1.8
|
|
Gastrointestinal
Dry Mouth
Constipation
Diarrhea
Nausea/Vomiting
Increased Salivation
|
14.7
10.4
10.1
9.6
4.2
|
13.3
11.4
10.3
12.8
2.4
|
0.7
0.9
1.2
1.7
†
|
|
Cardiovascular
Tachycardia/Palpitations
Hypotension
|
7.7
4.7
|
15.6
2.2
|
0.4
†
|
|
Sensory
Blurred Vision
|
6.2
|
6.2
|
0.4
|
|
Musculoskeletal
Rigidity
Tremor
|
4.2
4.0
|
5.3
8.8
|
†
0.4
|
|
Cutaneous
Dermatitis/Allergy
|
3.8
|
3.1
|
0.6
|
|
Other
Nasal Congestion
Weight Gain
Weight Loss
|
7.3
2.7
2.3
|
9.3
2.7
3.0
|
†
†
†
|
*
Events reported by 1% or more of alprazolam patients are included.
†
None reported
|
In addition to the relatively common (ie, 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 Disorder
PANIC DISORDER
|
| |
Treatment-Emergent
Symptom Incidence*
|
| |
ALPRAZOLAM
|
PLACEBO
|
| Number of Patients
% of Patients Reporting:
|
1388 |
1231 |
|
Central Nervous System
Drowsiness
Fatigue and Tiredness
Impaired Coordination
Irritability
Memory Impairment
Light-headedness/Dizziness
Insomnia
Headache
Cognitive Disorder
Dysarthria
Anxiety
Abnormal Involuntary Movement
Decreased Libido
Depression
Confusional State
Muscular Twitching
Increased Libido
Change in Libido (Not Specified)
Weakness
Muscle Tone Disorders
Syncope
Akathisia
Agitation
Disinhibition
Paresthesia
Talkativeness
Vasomotor Disturbances
Derealization
Dream Abnormalities
Fear
Feeling Warm
|
76.8
48.6
40.1
33.1
33.1
29.8
29.4
29.2
28.8
23.3
16.6
14.8
14.4
13.8
10.4
7.9
7.7
7.1
7.1
6.3
3.8
3.0
2.9
2.7
2.4
2.2
2.0
1.9
1.8
1.4
1.3
|
42.7
42.3
17.9
30.1
22.1
36.9
41.8
35.6
20.5
6.3
24.9
21.0
8.0
14.0
8.2
11.8
4.1
5.6
8.4
7.5
4.8
4.3
2.6
1.5
3.2
1.0
2.6
1.2
1.5
1.0
0.5
|
|
Gastrointestinal
Decreased Salivation
Constipation
Nausea/Vomiting
Diarrhea
Abdominal Distress
Increased Salivation
|
32.8
26.2
22.0
20.6
18.3
5.6
|
34.2
15.4
31.8
22.8
21.5
4.4
|
|
Cardio-Respiratory
Nasal Congestion
Tachycardia
Chest Pain
Hyperventilation
Upper Respiratory Infection
|
17.4
15.4
10.6
9.7
4.3
|
16.5
26.8
18.1
14.5
3.7
|
|
Sensory
Blurred Vision
Tinnitus
|
21.0
6.6
|
21.4
10.4
|
|
Musculoskeletal
Muscular Cramps
Muscle Stiffness
|
2.4
2.2
|
2.4
3.3
|
|
Cutaneous
Sweating
Rash
|
15.1
10.8
|
23.5
8.1
|
|
Other
Increased Appetite
Decreased Appetite
Weight Gain
Weight Loss
Micturition Difficulties
Menstrual Disorders
Sexual Dysfunction
Edema
Incontinence
Infection
|
32.7
27.8
27.2
22.6
12.2
10.4
7.4
4.9
1.5
1.3
|
22.8
24.1
17.9
16.5
8.6
8.7
3.7
5.6
0.6
1.7
|
|
* Events reported by 1% or more of alprazolam patients are included.
|
In addition to the relatively common (ie, greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of alprazolam: 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).
DOSAGE AND ADMINISTRATION
id: 6ce05971-48d1-3e04-e053-2991aa0a8052
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: 6ce19f3d-80a5-89e8-e053-2991aa0a949d
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Alprazolam Tablets, USP are available as follows:
0.25 mg (white, oval, scored on one side: S left of bisect 900 to right)
NDC 68071-4447-2 BOTTLES OF 20
NDC 68071-4447-3 BOTTLES OF 30
NDC 68071-4447-6 BOTTLES OF 60
NDC 68071-4447-9 BOTTLES OF 90
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Rx only
ANIMAL STUDIES
id: 6ce05971-48d5-3e04-e053-2991aa0a8052
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
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 – 0.25 mg
id: 6ce05971-48fa-3e04-e053-2991aa0a8052
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
