ALPRAZOLAM tablet, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ALPRAZOLAM (UNII: YU55MQ3IZY) (ALPRAZOLAM - UNII:YU55MQ3IZY)

Available from:

Amneal Pharmaceuticals LLC

INN (International Name):

ALPRAZOLAM

Composition:

ALPRAZOLAM 0.5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Alprazolam extended-release tablets are indicated for the treatment of panic disorder with or without agoraphobia, in adults. Alprazolam extended-release tablets are contraindicated in patients: - with known hypersensitivity to alprazolam or other benzodiazepines. Angioedema has been reported [see Adverse Reactions (6.2)]. - taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.5), Warnings and Precautions (5.5), Drug Interactions (7.1)] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including alprazolam extended-release tablets during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/pregnancyregistry/. Risk Summary Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8), and Clinical Considerations)]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to alprazolam extended-release tablets during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to alprazolam extended-release tablets during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)]. Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco, and other medications, have not confirmed these findings. Risk Summary Limited data from published literature reports the presence of alprazolam in human breast milk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. The effects of alprazolam on lactation are unknown. Because of the potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed infants, advise patients that breastfeeding is not recommended during treatment with alprazolam extended-release tablets. Safety and effectiveness of alprazolam extended-release tablets have not been established in pediatric patients. Alprazolam extended-release tablets-treated geriatric patients had higher plasma concentrations of alprazolam (due to reduced clearance) compared to younger adults receiving the same doses. Therefore, dosage reduction of alprazolam extended-release tablets is recommended in geriatric patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)] . Patients with alcoholic liver disease exhibit a longer elimination half-life (19.7 hours), compared to healthy subjects (11.4 hours). This may be caused by decreased clearance of alprazolam extended-release tablets in patients with alcoholic liver disease. Dosage reduction of alprazolam is recommended in patients with hepatic impairment [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)] . Alprazolam extended-release tablets contains alprazolam, which is a Schedule IV controlled substance. Alprazolam extended-release tablets are benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions (5.2)] . The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol). Physical Dependence Alprazolam extended-release tablets may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions (5.3)] . To reduce the risk of withdrawal reactions, use a gradual taper to discontinue alprazolam extended-release tablets or reduce the dosage [see Dosage and Administration (2.3), Warnings and Precautions (5.3)] . Acute Withdrawal Signs and Symptoms Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. Protracted Withdrawal Syndrome Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. Tolerance Tolerance to alprazolam extended-release tablets may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of alprazolam extended-release tablets may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

Product summary:

Alprazolam Extended-Release Tablets, USP are available as follows: 0.5 mg (green, round, biconvex tablets, debossed "IP 9" on one side) Bottles of 30:              NDC 65162-809-03 Bottles of 60:              NDC 65162-809-06 Bottles of 500:            NDC 65162-809-50 1 mg (yellow, round, biconvex tablets, debossed "IP 10" on one side) Bottles of 30:              NDC 65162-810-03 Bottles of 60:              NDC 65162-810-06 Bottles of 500:            NDC 65162-810-50 2 mg (blue, round, biconvex tablets, debossed "IP 12" on one side) Bottles of 30:              NDC 65162-812-03 Bottles of 60:              NDC 65162-812-06 Bottles of 500:            NDC 65162-812-50 3 mg (white, round, biconvex tablets, debossed "IP 13" on one side) Bottles of 30:              NDC 65162-813-03 Bottles of 60:              NDC 65162-813-06 Bottles of 500:            NDC 65162-813-50 Store at 20o  to 25o C (68o  to 77o F); excursions permitted between 15o to 30o C (59o to 86o F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Amneal Pharmaceuticals LLC
----------
MEDICATION GUIDE
Alprazolam (al pra’ zoe lam) Extended-Release Tablets USP, C-IV
What is the most important information I should know about alprazolam
extended-release tablets?
•
Alprazolam extended-release tablets are a benzodiazepine medicine.
Taking benzodiazepines with
opioid medicines, alcohol, or other central nervous system (CNS)
depressants (including street
drugs) can cause severe drowsiness, breathing problems (respiratory
depression), coma and death.
Get emergency help right away if any of the following happens:
•
shallow or slowed breathing
•
breathing stops (which may lead to the heart stopping)
•
excessive sleepiness (sedation)
Do not drive or operate heavy machinery until you know how taking
alprazolam extended-release tablets
with opioids affects you.
•
Risk of abuse, misuse, and addiction. There is a risk of abuse,
misuse, and addiction with
benzodiazepines including alprazolam extended-release tablets which
can lead to overdose and
serious side effects including coma and death.
•
Serious side effects including coma and death have happened in people
who have abused or
misused benzodiazepines, including alprazolam extended-release
tablets. These serious side
effects may also include delirium, paranoia, suicidal thoughts or
actions, seizures, and difficulty
breathing. Call your healthcare provider or go to the nearest hospital
emergency room right away
if you get any of these serious side effects.
•
You can develop an addiction even if you take alprazolam
extended-release tablets as prescribed
by your healthcare provider.
•
Take alprazolam extended-release tablets exactly as your healthcare
provider prescribed.
•
Do not share your alprazolam extended-release tablets with other
people.
•
Keep alprazolam extended-release tablets in a safe place and away from
children.
•
Physical dependence and withdrawal reactions. Alprazolam
extended-release tablets can cause
physical dependence and withdrawal reactions.
•
Do not suddenly stop taking al

Summary of Product characteristics

ALPRAZOLAM- ALPRAZOLAM TABLET, EXTENDED RELEASE
AMNEAL PHARMACEUTICALS LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALPRAZOLAM EXTENDED-
RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR ALPRAZOLAM
EXTENDED-RELEASE TABLETS.
ALPRAZOLAM EXTENDED-RELEASE TABLETS, FOR ORAL USE, CIV
INITIAL U.S. APPROVAL: 1981
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND
ADDICTION; AND DEPENDENCE AND WITHDRAWAL REACTIONS
SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING.
CONCOMITANT USE OF BENZODIAZEPINES AND OPIOIDS MAY RESULT IN PROFOUND
SEDATION,
RESPIRATORY DEPRESSION, COMA, AND DEATH. RESERVE CONCOMITANT
PRESCRIBING OF THESE
DRUGS FOR USE IN PATIENTS FOR WHOM ALTERNATIVE TREATMENT OPTIONS ARE
INADEQUATE.
LIMIT DOSAGES AND DURATIONS TO THE MINIMUM REQUIRED. FOLLOW PATIENTS
FOR SIGNS AND
SYMPTOMS OF RESPIRATORY DEPRESSION AND SEDATION. (5.1, 7.1)
THE USE OF BENZODIAZEPINES, INCLUDING ALPRAZOLAM EXTENDED-RELEASE
TABLETS,
EXPOSES USERS TO RISKS OF ABUSE, MISUSE, AND ADDICTION, WHICH CAN LEAD
TO OVERDOSE
OR DEATH. BEFORE PRESCRIBING ALPRAZOLAM EXTENDED-RELEASE TABLETS AND
THROUGHOUT
TREATMENT, ASSESS EACH PATIENT’S RISK FOR ABUSE, MISUSE, AND
ADDICTION. (5.2)
ABRUPT DISCONTINUATION OR RAPID DOSAGE REDUCTION OF ALPRAZOLAM
EXTENDED-RELEASE
TABLETS AFTER CONTINUED USE MAY PRECIPITATE ACUTE WITHDRAWAL
REACTIONS, WHICH CAN
BE LIFE-THREATENING. TO REDUCE THE RISK OF WITHDRAWAL REACTIONS, USE A
GRADUAL TAPER
TO DISCONTINUE ALPRAZOLAM EXTENDED-RELEASE TABLETS OR REDUCE THE
DOSAGE. (2.2, 5.3)
RECENT MAJOR CHANGES
Warnings and Precautions (5.8) 1/2023
INDICATIONS AND USAGE
Alprazolam extended-release tablets are a benzodiazepine indicated for
the treatment of panic disorder
with or without agoraphobia, in adults. (1)
DOSAGE AND ADMINISTRATION
Recommended starting oral dosage is 0.5 mg to 1 mg once daily
(preferably in the morning).
Depending on the response, the dose may be increased at intervals of 3
to 4 day