Alprazolam: uses, appearance and warnings

Alprazolam orally disintegrating tablets are a benzodiazepine indicated for: The treatment of generalized anxiety disorder ( 1.1 ). The efficacy of alprazolam was demonstrated in 5 short-term, placebo-controlled trials ( 14 ). The treatment of panic disorder, with or without agoraphobia ( 1.2 ). The efficacy of alprazolam in the treatment of panic disorder was established in 2 short-term, placebo-controlled trials ( 14 ). 1.1 Generalized Anxiety Disorder Alprazolam orally disintegrating tablets, USP are indicated for the treatment of generalized anxiety disorder. The efficacy of alprazolam in the treatment of generalized anxiety disorder was demonstrated in 5 short-term, placebo-controlled trials [see Clinical Studies ( 14.1 )] . 1.2 Panic Disorder Alprazolam orally disintegrating tablets, USP are also indicated for the treatment of panic disorder, with or without agoraphobia. The efficacy of alprazolam in the treatment of panic disorder was established in 2 short-term, placebo-controlled trials [see Clinical Studies ( 14.2 )] . Demonstrations of the effectiveness of alprazolam by systematic clinical study are limited to 4 months in duration for generalized anxiety disorder and 4 to 10 weeks duration for panic disorder; however, patients with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit. The physician should periodically reassess the usefulness of the drug for the individual patient.

0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg scored orally disintegrating tablets, USP. 0.25 mg, 0.5 mg, 1 mg, or 2 mg scored orally disintegrating tablets USP ( 3 )

Alprazolam orally disintegrating tablets, USP 0.25 mg are white to off-white, round, scored, flat face, beveled edge tablets debossed ‘110’ on the scored side and plain on the other. They are supplied as follows: Blisters of 10 x 10 NDC 49884-110-74 Alprazolam orally disintegrating tablets, USP 0.5 mg are white to off-white, round, scored, flat face, beveled edge tablets debossed ‘111’ on the scored side and plain on the other. They are supplied as follows: Blisters of 10 x 10 NDC 49884-111-74 Alprazolam orally disintegrating tablets, USP 1 mg are white to off-white, round, scored, flat face, beveled edge tablets debossed ‘213’ on the scored side and plain on the other. They are supplied as follows: Blisters of 10 x 10 NDC 49884-213-74 Alprazolam orally disintegrating tablets, USP 2 mg are white to off-white, round, scored, flat face, beveled edge tablets debossed ‘214’ on the scored side and plain on the other. They are supplied as follows: Blisters of 10 x 10 NDC 49884-214-74 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.

Alprazolam orally disintegrating tablets are contraindicated in patients with acute narrow angle glaucoma. Alprazolam orally disintegrating tablets can exacerbate narrow angle closure. Alprazolam orally disintegrating tablets may be used in patients with open angle glaucoma who are receiving appropriate therapy. Alprazolam orally disintegrating tablets are contraindicated in patients treated with potent CYP3A4 inhibitors (e.g., ketoconazole and itraconazole), because these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP3A) and can increase alprazolam exposures [see Clinical Pharmacology ( 12.3 ), Warnings and Precautions ( 5.9 ), and Drug Interactions ( 7.4 )]. Acute narrow angle glaucoma. Alprazolam can exacerbate narrow angle closure ( 4 ). Concomitant Use with potent CYP3A inhibitors (e.g., ketoconazole and itraconazole). Can increase the serum concentration of alprazolam ( 4 ).

Suicide: As with other psychotropic medications, use precautions with respect to administration of the drug and size of the prescription, especially in patients who are severely depressed or in patients where there is reason to expect concealed suicidal ideation or plans ( 5.4 ). Status Epilepticus and Seizure: can occur during discontinuation of alprazolam ( 5.5 ). CNS Depression and Impaired Cognitive and Motor Performance: caution patients against engaging in hazardous occupations or activities requiring complete mental alertness, until they are reasonably certain that alprazolam treatment does not affect them adversely. Caution patients about the use of alcohol and other CNS depressant drugs during treatment with alprazolam ( 5.7 ). Neonatal Sedation and Withdrawal Syndrome: Alprazolam use during pregnancy can result in neonatal sedation and/or neonatal withdrawal ( 5.8 , 8.1 ). Interdose anxiety symptoms: can occur at prescribed maintenance doses. Consider dividing the daily dose into more frequent administrations ( 5.10 ). Patients with Concomitant Illness: In the elderly or debilitated patients, the smallest effective dose is recommended to preclude the development of ataxia or oversedation. There have been rare reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with alprazolam ( 5.12 ). 5.1 Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including alprazolam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe alprazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of alprazolam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking alprazolam, prescribe a lower initial dose of the opioid and titrate based upon clinical response. Advise both patients and caregivers about the risks of respiratory depression and sedation when alprazolam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined [see Drug Interactions ( 7.1 )]. 5.2 Abuse, Misuse, and Addiction The use of benzodiazepines, including Alprazolam orally disintegrating tablets, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. 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 [see Drug Abuse and Dependence ( 9.2 )]. Before prescribing Alprazolam orally disintegrating tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of alprazolam orally disintegrating tablets, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of alprazolam orally disintegrating tablets along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. 5.3 Dependence and Withdrawal Reactions To reduce the risk of withdrawal reactions, use a gradual taper to discontinue Alprazolam orally disintegrating tablets or reduce the dosage (a patient-specific plan should be used to taper the dose) [see Dosage and Administration ( 2.3 ) ] . Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. Acute Withdrawal Reactions The continued use of benzodiazepines, including Alprazolam orally disintegrating tablets, lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of Alprazolam orally disintegrating tablets after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) [see Drug Abuse and Dependence ( 9.3 )]. Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months [see Drug Abuse and Dependence ( 9.3 )] . Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to alprazolam. These include a spectrum of withdrawal symptoms; the most important is seizure [see Drug Abuse and Dependence ( 9.3 )] . Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg per day and for long periods (more than 12 weeks). …

Anxiety Disorder : The most common adverse reactions (greater than or equal to 5% and ~twice the rate of placebo) were sedation, and hypotension. Panic Disorder : The most common adverse reactions included sedation, impaired coordination, dysarthria, and increased libido ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience The most commonly reported (greater than or equal to 5% and ~ twice the rate of placebo) adverse reactions with alprazolam treatment are: sedation, impaired coordination, dysarthria, and increased libido. …

Alprazolam produces additive CNS depressant effects when coadministered with other psychotropic medications, anticonvulsants, antihistaminics, alcohol and other drugs that produce CNS depression ( 7.1 ). The formulation requires an acidic environment to dissolve; therefore, drugs or diseases that cause dry mouth or raise stomach pH may slow disintegration or dissolution, resulting in decreased absorption ( 7.2 ). Drugs which inhibit the hydroxylation catalyzed by cytochrome P450 3A (CYP3A) metabolic pathway can decrease the clearance of alprazolam and increase the serum concentration ( 7.4 ). 7.1 Use with Other CNS Depressants 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. …