Alprazolam

FDA Drug Information • Also known as: Alprazolam, Alprazolam Extended Release, Alprazolam Xr, Xanax, Xanax Xr

Brand Names: Alprazolam, Alprazolam Extended Release, Alprazolam Xr, Xanax, Xanax Xr
Drug Class: Benzodiazepine [EPC]
Route: ORAL
Dosage Form: TABLET
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for 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 [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . The use of benzodiazepines, including alprazolam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing alprazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction [see Warnings and Precautions (5.2) ] . The continued use of benzodiazepines, including alprazolam, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of alprazolam 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 or reduce the dosage [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) ] . 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 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, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing alprazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction. ( 5.2 ) Abrupt discontinuation or rapid dosage reduction of alprazolam 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 or reduce the dosage. ( 2.2 , 5.3 )

Description

11 DESCRIPTION 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: Alprazolam USP is a white to off-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 mg, 0.5 mg, 1 mg, or 2 mg of alprazolam USP. Inactive ingredients: colloidal silicon dioxide, corn starch, docusate sodium 85% with sodium benzoate 15%, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. In addition, the 0.5 mg tablet contains FD&C Yellow # 6 aluminum lake and the 1 mg tablet contains FD&C Blue No. 2 lake. Chemical Structure

What Is Alprazolam Used For?

1 INDICATIONS AND USAGE Alprazolam tablets are indicated for the: acute treatment of generalized anxiety disorder (GAD) in adults. treatment of panic disorder (PD), with or without agoraphobia in adults. Alprazolam is a benzodiazepine indicated for the: Acute treatment of generalized anxiety disorder in adults. ( 1 ) Treatment of panic disorder with or without agoraphobia in adults. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Generalized Anxiety Disorder : ( 2.1 ) Recommended starting oral dosage is 0.25 mg to 0.5 mg three times daily. Dosage may be increased, at intervals of every 3 to 4 days, to a maximum recommended daily dose of 4 mg, given in divided doses. Use the lowest possible effective dose and frequently assess the need for continued treatment. Panic Disorder : Recommended starting oral dosage is 0.5 mg three times daily. The dosage may be increased at intervals of every 3 to 4 days in increments of no more than 1 mg per day. ( 2.2 ) When tapering, decrease dosage by no more than 0.5 mg every 3 days. Some patients may require an even slower dosage reduction. ( 2.3 , 5.2 ) See the Full Prescribing Information for the recommended dosage in geriatric patients, patients with hepatic impairment, and with use with ritonavir. ( 2.4 , 2.5 , 2.6 ) 2.1 Dosage in Generalized Anxiety Disorder The recommended starting oral dosage of alprazolam tablets for the acute treatment of patients with GAD is 0.25 mg to 0.5 mg administered three times daily. Depending upon the response, the dosage may be adjusted at intervals of every 3 to 4 days. The maximum recommended dosage is 4 mg daily (in divided doses). Use the lowest possible effective dose and frequently assess the need for continued treatment [see Warnings and Precautions (5.2) ] . 2.2 Dosage in Panic Disorder The recommended starting oral dosage of alprazolam tablets for the treatment of PD is 0.5 mg three times daily. Depending on the response, the dosage may be increased at intervals of every 3 to 4 days in increments of no more than 1 mg per day. Controlled trials of alprazolam tablets in the treatment of panic disorder included dosages in the range of 1 mg to 10 mg daily. The mean dosage was approximately 5 mg to 6 mg daily. Occasional patients required as much as 10 mg per day. For patients receiving doses greater than 4 mg per day, periodic reassessment and consideration of dosage reduction is advised. In a controlled postmarketing dose-response study, patients treated with doses of alprazolam tablets greater than 4 mg per day for 3 months were able to taper to 50% of their total maintenance dose without apparent loss of clinical benefit. The necessary duration of treatment for PD in patients responding to alprazolam tablets are unknown. After a period of extended freedom from panic attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena [see Dosage and Administration (2.3) ]. 2.3 Discontinuation or Dosage Reduction of Alprazolam Tablets To reduce the risk of withdrawal reactions, use a gradual taper to discontinue alprazolam tablets or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1) ] Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2) ] Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3) ] Effects on Driving and Operating Machinery [see Warnings and Precautions (5.4) ] Patients with Depression [see Warnings and Precautions (5.6) ] Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.8) ] Risks in Patients with Impaired Respiratory Function [see Warnings and Precautions (5.9) ] The most common adverse reactions reported in clinical trials for generalized anxiety disorder and panic disorder (incidence > 5% and at least twice that of placebo) include: impaired coordination, hypotension, dysarthria, and increased libido. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the two tables below are estimates of adverse reaction incidence among adult patients who participated in: 4-week placebo-controlled clinical studies with alprazolam dosages up to 4 mg per day for the acute treatment of generalized anxiety disorder (Table 1) Short-term (up to 10 weeks) placebo-controlled clinical studies with alprazolam dosages up to 10 mg per day for panic disorder, with or without agoraphobia (Table 2). Table 1: Adverse Reactions Occurring in ≥1% in Alprazolam-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials for Generalized Anxiety Alprazolam n=565 Placebo n=505 Nervous system disorders Drowsiness Light-headedness Dizziness Akathisia Gastrointestinal disorders Dry mouth Increased salivation 41% 21% 2% 2% 15% 4% 22% 19% 1% 1% 13% 2% Cardiovascular disorders Hypotension Skin and subcutaneous tissue disorders Dermatitis/allergy 5% 4% 2% 3% In addition to the adverse reactions (i.e., greater than 1%) enumerated in the table above for patients with generalized anxiety disorder, the following adverse reactions 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. Table 2: Adverse Reactions Occuring in ≥1% in Alprazolam-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials (Up to 10 Weeks) for Panic Disorder Alprazolam n=1388 Placebo n=1231 Drowsiness Fatique and Tiredness Impaired Coordination Irritability Memory Impairment Cognitive Disorder Decreased Libido Dysartharia Confusional state Increased libido Change in libido (not specified) Disinhibition Talkativeness Derealization 77% 49% 40% 33% 33% 29% 14% 23% 10% 8% 7% 3% 2% 2% 43% 42% 18% 30% 22% 21% 8% 6% 8% 4% 6% 2% 1% 1% Gastrointestinal disorders Constipation Increased salivation 26% 6% 15% 4% Skin and subcutaneous tissue disorders Rash 11% 8% Other Increased appetite Decreased appetite Weight gain Weight loss Micturition difficulties Menstrual disorders Sexual dysfunction Incontinence 33% 28% 27% 23% 12% 11% 7% 2% 23% 24% 18% 17% 9% 9% 4% 1% In addition to the reactions (i.e., greater than 1%) enumerated in the table above for patients with panic disorder, the following adverse reactions have been reported in association with the use of alprazolam: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated...

Drug Interactions

7 DRUG INTERACTIONS Use with Opioids: Increase the risk of respiratory depression. ( 7.1 ) Use with Other CNS Depressants: Produces additive CNS depressant effects. ( 7.1 ) Use with Digoxin: Increase the risk of digoxin toxicity. ( 7.1 ) Use with CYP3A Inhibitors (except ritonavir): Increase the risk of adverse reactions of alprazolam. ( 4 , 5.5 , 7.1 ) Use with CYP3A Inducers: Increase the risk of reduced efficacy of alprazolam. ( 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Alprazolam Table 4 includes clinically significant drug interactions with alprazolam [see Clinical Pharmacology (12.3) ] . Table 4: Clinically Significant Drug Interactions with Alprazolam Opioids Clinical implication The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at gamma-aminobutyric acid(GABA A ) sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Prevention or management Limit dosage and duration of concomitant use of alprazolam and opioids, and monitor patients closely for respiratory depression and sedation [see Warnings and Precautions (5.1) ]. Examples Morphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine, dihydrocodeine, meperidine, pentazocine, remifentanil, sufentanil, tapentadol, tramadol. CNS Depressants Clinical implication The benzodiazepines, including alprazolam, produce additive CNS depressant effects when coadministered with other CNS depressants. Prevention or management Limit dosage and duration of alprazolam during concomitant use with CNS depressants [see Warnings and Precautions (5.3) ] . Examples Psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression. Strong Inhibitors of CYP3A (except ritonavir) Clinical implication Concomitant use of alprazolam with strong CYP3A inhibitors has a profound effect on the clearance of alprazolam, resulting in increased concentrations of alprazolam and increased risk of adverse reactions [see Clinical Pharmacology (12.3) ]. Prevention or management Concomitant use of alprazolam with a strong CYP3A4 inhibitor (except ritonavir) is contraindicated [see Contraindications (4) , Warnings and Precautions (5.5) ]. Examples Ketoconazole, itraconazole, clarithromycin Moderate or Weak Inhibitors of CYP3A Clinical implication Concomitant use of alprazolam with CYP3A inhibitors may increase the concentrations of alprazolam, resulting in increased risk of adverse reactions of alprazolam [see Clinical Pharmacology (12.3) ]. Prevention or management Avoid use and consider appropriate dose reduction when alprazolam is coadministered with a moderate or weak CYP3A inhibitor [see...

Contraindications

4 CONTRAINDICATIONS Alprazolam 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 (2.6) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] Known hypersensitivity to alprazolam or other benzodiazepines. ( 4 ) Concomitant use with strong cytochrome P450 3A (CYP3A) inhibitors, except ritonavir. ( 4 , 5.5 , 7.1 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including alprazolam, 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/research/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 during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to alprazolam 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...

Overdosage

10 OVERDOSAGE Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [see Warnings and Precautions (5.2) ] . Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting the Poison Help Line...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Alprazolam Tablets USP, 0.25 mg are white, oval shaped, uncoated tablets with breakline on one side debossed with ‘1’ and ‘8’ on either sides of the breakline and ‘Y’ on the other side. Bottles of 6 NDC 68071-3481-6

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.