Indicated for:

Anxiety Disorders:

• The management of anxiety disorder (a condition corresponding most closely to the APA Diagnostic and Statistical Manual [DSM-III-R] diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

Anxiety associated with depression is responsive to XANAX.

Panic Disorder:

• The treatment of panic disorder, with or without agoraphobia.

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 GABAA 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. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation.

The use of benzodiazepines, including XANAX, 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 XANAX and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

The continued use of benzodiazepines, including XANAX, 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 XANAX 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 XANAX or reduce the dosage.

Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to XANAX. These include a spectrum of withdrawal symptoms; the most important is seizure. Even after relatively short-term use at the doses recommended for the treatment of transient anxiety and anxiety disorder (ie, 0.75 to 4.0 mg per day), there is some risk of dependence.

Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.

Because the management of panic disorder often requires the use of average daily doses of XANAX above 4 mg, the risk of dependence among panic disorder patients may be higher than that among those treated for less severe anxiety.

Withdrawal reactions may occur when dosage reduction occurs for any reason. This includes purposeful tapering, but also inadvertent reduction of dose (eg, the patient forgets, the patient is admitted to a hospital). Therefore, the dosage of XANAX should be reduced or discontinued gradually.

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher doses, and those who have had longer durations of use.

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. 

Because of its CNS depressant effects, patients receiving XANAX should be cautioned against engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle. For the same reason, patients should be cautioned about the simultaneous ingestion of alcohol and other CNS depressant drugs during treatment with XANAX.

Episodes of hypomania and mania have been reported in association with the use of XANAX in patients with depression.

As with other psychotropic medications, the usual precautions with respect to administration of the drug and size of the prescription are indicated for severely depressed patients or those in whom there is reason to expect concealed suicidal ideation or plans. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients.

There have been rare reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with XANAX. A decreased systemic alprazolam elimination rate (eg, increased plasma half-life) has been observed in both alcoholic liver disease patients and obese patients receiving XANAX.

Benzodiazepines may worsen depression. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered in patients with depression.

Episodes of hypomania and mania have been reported in association with the use of XANAX XR in patients with depression.

XANAX is contraindicated with ketoconazole and itraconazole, since these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP3A). Alprazolam should be avoided in patients receiving very potent inhibitors of CYP3A.

The co-administration of alprazolam with azole antifungal agents is not recommended.

Co-administration of nefazodone increased alprazolam concentration two-fold.

Co-administration of fluvoxamine approximately doubled the maximum plasma concentration of alprazolam, decreased clearance by 49%, increased half-life by 71%, and decreased measured psychomotor performance.

Co-administration of cimetidine increased the maximum plasma concentration of alprazolam by 86%, decreased clearance by 42%, and increased half-life by 16%.

Interactions involving HIV protease inhibitors (eg, ritonavir) and alprazolam are complex and time dependent. Low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam.

Increased digoxin concentrations have been reported when alprazolam was given, especially in elderly (>65 years of age).

Co-administration of oral contraceptives increased the maximum plasma concentration of alprazolam by 18%, decreased clearance by 22%, and increased half-life by 29%.

Co-administration of propoxyphene decreased the maximum plasma concentration of alprazolam by 6%, decreased clearance by 38%, and increased half-life by 58%.

Benzodiazepines can potentially cause fetal harm when administered to pregnant women. If XANAX is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Because use of these drugs is rarely a matter of urgency, their use during the first trimester should almost always be avoided.

Benzodiazepines are known to be excreted in human milk. As a general rule, nursing should not be undertaken by mothers who must use XANAX.

GoToSource

• Use in patients under the age of 18 years of age. GoToSource

• Depression. GoToSource

• Social phobias. GoToSource

• Obsessive-compulsive disorder. GoToSource

• Post-traumatic stress disorder. GoToSource

• Premenstrual dysphoric disorder. GoToSource

• Chronic pain. GoToSource

• Primary fibrositis/fibromyalgia syndrome. GoToSource

• Insomnia. GoToSource 

• Restless legs syndrome. GoToSource

Seizures, psychosis and death following Xanax withdrawal. GoToSource

Suicidal ideation and behavior. GoToSource

Addiction. GoToSource

Sexual dysfunction. GoToSource

Sedation and abuse. GoToSource 

Gynecomastia (increased size of male breast tissue). GoToSource

Dysarthria (speech disorder), memory impairment and depression. GoToSource

Fetal harm. GoToSource

Lawsuits filed for addiction, withdrawal symptoms and death.