Alprazolam: Package Insert and Label Information (Page 4 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenic potential was observed during 2-year bioassay studies of alprazolam in rats at doses up to 30 mg/kg per day (30 times the maximum recommended human dose of 10 mg per day on a mg/m2 basis) and in mice at doses up to 10 mg/kg per day (5 times the maximum recommended human dose on a mg/m2).

Alprazolam also was not mutagenic in vitro in the DNA Damage/Alkaline Elution Assay or the Ames Assay, and was negative in the rat micronucleus test.

Alprazolam produced no impairment of fertility in rats at doses up to 5 mg/kg per day, which is 5 times the maximum recommended human dose of 10 mg per day on a mg/m2 basis.

13.2 Animal Toxicology and/or Pharmacology

When rats were treated with oral alprazolam doses of 3, 10, and 30 mg/kg per day (3 to 30 times the maximum recommended human dose of 10 mg per day on a mg/m2 basis) 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.

14 CLINICAL STUDIES

14.1 Anxiety Disorders

The efficacy of alprazolam in the treatment of anxiety symptoms was demonstrated in five short-term (4 weeks), randomized, double-blind, placebo-controlled studies. The studies included patients with a diagnosis of anxiety or anxiety with associated depressive symptomatology. Alprazolam doses ranged from 0.5 mg to 4 mg per day. The mean daily doses ranged from 1.6 mg to 2.4 mg. Treatment with alprazolam was statistically significantly superior to placebo treatment, as measured by the following psychometric instruments: Hamilton Anxiety Rating Scale, Physician’s Global Impressions, Target Symptoms, Patient’s Global Impressions and Self-Rating Symptom Scale.

14.2 Panic Disorder

The efficacy of alprazolam in the treatment of panic disorder was demonstrated in three short-term (up to 10 weeks), randomized, double-blind, placebo-controlled studies. Patients in the studies had diagnoses corresponding closely to DSM-III-R criteria for panic disorder (with or without agoraphobia).

The average dose of alprazolam was 5 mg to 6 mg per day in two of the studies, and the doses of alprazolam were fixed at 2 mg and 6 mg per day in the third study. In all three studies, alprazolam was superior to placebo on a variable defined as “the number of patients with zero panic attacks” (range, 37 to 83% met this criterion), as well as on a global improvement score. In two of the three studies, alprazolam was superior to placebo on a variable defined as “change from baseline on the number of panic attacks per week” (range, 3.3 to 5.2), and also on a phobia rating scale. A subgroup of patients who were improved on alprazolam during short-term treatment in one of these trials was continued on an open basis up to 8 months, without apparent loss of benefit.

16 HOW SUPPLIED/STORAGE AND HANDLING

Alprazolam orally disintegrating tablets, USP are supplied as follows:

0.25 mg — Each white to off-white, round tablet imprinted with imprinted on one side and 019 and bisect on the other side contains 0.25 mg of Alprazolam, USP. Tablets are supplied in bottles of 100 (NDC 0228-4019-11).

0.5 mg — Each white to off-white, round tablet imprinted with imprinted on one side and 022 and bisect on the other side contains 0.5 mg of Alprazolam, USP. Tablets are supplied in bottles of 100 (NDC 0228-4022-11).

1 mg — Each yellow, round tablet imprinted with imprinted on one side and 024 and bisect on the other side contains 1 mg of Alprazolam, USP. Tablets are supplied in bottles of 100 (NDC 0228-4024-11).

2 mg — Each yellow, round tablet imprinted with imprinted on one side and 025 and bisect on the other side contains 2 mg of Alprazolam, USP. Tablets are supplied in bottles of 100 (NDC 0228-4025-11).

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86ºF) [See USP Controlled Room Temperature]. Protect from moisture.

Dispense in tight, light-resistant containers as defined in the USP.

Keep container tightly closed.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Medication Guide).

Counseling Information for All Users of Alprazolam Orally Disintegrating Tablets

Inform patients and caregivers that potentially fatal additive effects may occur if alprazolam is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

To assure safe and effective use of benzodiazepines, all patients prescribed alprazolam orally disintegrating tablets should be provided with the following guidance.

  1. Do not remove Alprazolam orally disintegrating tablets from the bottle until just prior to dosing. With dry hands, open the bottle, remove the tablet, and immediately place on the tongue to dissolve and be swallowed with the saliva. The tablet may also be taken with water.
  2. Discard any cotton that was included in the bottle and reseal the bottle tightly to prevent introducing moisture that might cause the tablets to disintegrate.
  3. Store at room temperature in a dry place. Protect from moisture.
  4. Inform your physician about any alcohol consumption and medicine you are taking now, including medication you may buy without a prescription. Alcohol should generally not be used during treatment with benzodiazepines.
  5. Alprazolam orally disintegrating tablets are not recommended for use in pregnancy. Therefore, inform your physician if you are pregnant, if you are planning to have a child, or if you become pregnant while you are taking this medication.
  6. Inform your physician if you are nursing.
  7. Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.
  8. Do not increase the dose even if you think the medication “does not work anymore” without consulting your physician. Benzodiazepines, even after relatively short-term use at the doses recommended, may produce emotional and/or physical dependence.
  9. Do not stop taking this medication abruptly or decrease the dose without consulting your physician, since withdrawal symptoms can occur even after relatively short-term use at the doses recommended. You should follow a gradual dosage tapering schedule.

Additional Counseling Information for Panic Disorder Patients

The use of alprazolam orally disintegrating tablets at doses greater than 4 mg per day, often necessary to treat panic disorder, is accompanied by risks that you need to carefully consider. When used at doses greater than 4 mg per day, which may or may not be required for your treatment, alprazolam orally disintegrating tablets have the potential to cause severe psychological and physical dependence in some patients and these patients may find it exceedingly difficult to terminate treatment. In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 7 to 29% of patients treated with alprazolam orally disintegrating tablets did not completely taper off therapy. In a controlled postmarketing discontinuation study of panic disorder patients, the patients treated with doses of alprazolam orally disintegrating tablets greater than 4 mg per day had more difficulty tapering to zero dose than patients treated with less than 4 mg per day. In all cases, it is important that your physician help you discontinue this medication in a careful and safe manner to avoid overly extended use of alprazolam orally disintegrating tablets.

In addition, the extended use at doses greater than 4 mg per day appears to increase the incidence and severity of withdrawal reactions when alprazolam orally disintegrating tablets are discontinued. These are generally minor but seizure can occur, especially if you reduce the dose too rapidly or discontinue the medication abruptly. Seizure can be life-threatening.

Manufactured by:
Actavis Elizabeth LLC
Elizabeth, NJ 07207 USA

Distributed by:
Actavis Pharma, Inc.Parsippany, NJ 07054 USA

Rev. A 11/2019

MEDICATION GUIDE

Alprazolam (al-PRAE-zoe-lam) Orally Disintegrating Tablet (ODT), C-IV

Rx Only

What is the most important information I should know about alprazolam ODT?

  • Alprazolam ODT is a benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death.
  • Alprazolam ODT can make you sleepy or dizzy, and can slow your thinking and motor skills.
  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how alprazolam ODT affects you.
  • Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking alprazolam ODT without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, alprazolam ODT may make your sleepiness or dizziness much worse.
  • Do not take more alprazolam ODT than prescribed.

What is alprazolam ODT?

  • Alprazolam ODT is a prescription medicines used to treat:
  • generalized anxiety disorder
  • panic disorder with or without fear of places and situations that might cause panic, helplessness, or embarrassment (agoraphobia)
  • Alprazolam ODT is a federal controlled substance (C-IV) because it can be abused or lead to dependence. Keep alprazolam ODT in a safe place to prevent misuse and abuse. Selling or giving away alprazolam ODT may harm others, and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.
  • It is not known if alprazolam ODT is safe and effective in children.
  • It is not known if alprazolam ODT is safe and effective when to treat generalized anxiety disorder for longer than 4 months.
  • It is not known if alprazolam ODT is safe and effective when used treat panic disorder for longer than 10 weeks.

Do not take alprazolam ODT if you:

  • take an antifungal medicines including ketoconazole and itraconazole

Before you take alprazolam ODT, tell your healthcare provider about all of your medical conditions, including if you:

  • have or have had depression, mood problems, or suicidal thoughts or behavior
  • have liver or kidney problems
  • have lung disease or breathing problems
  • are pregnant or plan to become pregnant. Alprazolam may harm your unborn baby. You and your healthcare provider should decide if you should take alprazolam ODT while you are pregnant.
  • are breastfeeding or plan to breastfeed. Alprazolam passes into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take alprazolam ODT. You should not breastfeed while taking alprazolam ODT.

Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking alprazolam ODT with certain other medicines can cause side effects or affect how well alprazolam ODT or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider.

How should I take alprazolam ODT?

  • Take alprazolam ODT exactly as your healthcare provider tells you to take it. Your healthcare provider will tell you how much alprazolam ODT to take and when to take it.
  • Do not remove alprazolam ODT from the bottle until you are ready to take it. With dry hands, remove the alprazolam ODT, and immediately place on your tongue to dissolve and be swallowed with your saliva. The tablet may also be taken with water.
  • If you take too much alprazolam ODT, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking alprazolam ODT?

  • Alprazolam ODT can cause you to be drowsy. Do not drive a car or operate heavy machinery until you know how alprazolam ODT affects you.
  • You should not drink alcohol while taking alprazolam ODT. Drinking alcohol can increase your chances of having serious side effects.

What are the possible side effects of alprazolam ODT?

Alprazolam ODT may cause serious side effects, including:

  • See “What is the most important information I should know about alprazolam ODT?”
  • Abuse and dependence. Taking alprazolam ODT can cause physical and psychological dependence. Physical and psychological dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical and psychological dependence and drug addiction.
  • Withdrawal symptoms. You may have withdrawal symptoms if you stop taking alprazolam ODT suddenly. Withdrawal symptoms can be serious and include seizures. Mild withdrawal symptoms include a depressed mood and trouble sleeping. Talk to your healthcare provider about slowly stopping alprazolam ODT to avoid withdrawal symptoms.
  • Seizures. Stopping alprazolam ODT can cause seizures and seizures that will not stop (status epilepticus).
  • Mania. Alprazolam ODT may cause an increase in activity and talking (hypomania and mania) in people who have depression.

The most common side effects of alprazolam ODT include:

  • sedation
  • problems with coordination
  • speech problems (dysarthria)
  • increased libido
  • low blood pressure (hypotension)

These are not all the possible side effects of alprazolam ODT. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store alprazolam ODT?

  • Store alprazolam ODT at room temperature between 68°F to 77°F (20°C to 25°C).
  • Keep alprazolam ODT in a tightly closed container and keep dry.
  • Keep alprazolam ODT and all medicines out of the reach of children.

General information about the safe and effective use of alprazolam ODT.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use alprazolam ODT for a condition for which it was not prescribed. Do not give alprazolam ODT to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about alprazolam ODT that is written for health professionals. For more information call Actavis at 1-800-432-8534.

What are the ingredients in alprazolam ODT?
Active ingredient: alprazolam
Inactive ingredients: corn starch, crospovidone, magnesium stearate, mannitol, methacrylic acid copolymer (type C), microcrystalline cellulose, natural and artificial orange flavor, polysorbate 80, sodium lauryl sulfate, sucralose. In addition, the 1 mg and 2 mg tablets contain ferric oxide (yellow 10 synthetic yellow iron oxide).

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:
Actavis Elizabeth LLC
Elizabeth, NJ 07207 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

Rev. A 11/2019

PRINCIPAL DISPLAY PANEL

NDC 0228-4019 -11
Alprazolam Orally Disintegrating Tablets, USP CIV
0.25 mg
100 Tablets
Rx Only
Actavis
PHARMACIST: Dispense the accompanying Medication Guide to each patient.

0.25mglabel
(click image for full-size original)

PRINCIPAL DISPLAY PANEL

NDC 0228-4022 -11
Alprazolam Orally Disintegrating Tablets, USP CIV
0.5 mg
100 Tablets
Rx Only
ActavisPHARMACIST: Dispense the accompanying Medication Guide to each patient.

0.5mglabel
(click image for full-size original)

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