FDA label e676a130-e340-05ae-e053-2a95a90a491b

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 )

5 WARNINGS AND PRECAUTIONS Effects on Driving and Operating Machinery: Patients receiving Alprazolam should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs. ( 5.4 ) Neonatal Sedation and Withdrawal Syndrome (NOWS): Use of Alprazolam during pregnancy can result in neonatal sedation and neonatal withdrawal syndrome. ( 5.5 , 8.1 ) Patients with Depression: Exercise caution in patients with signs or symptoms of depression. Prescribe the least number of tablets feasible to avoid intentional overdosage. ( 5.7 ) 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, 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 and throughout treatment, assess each patient's risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of Alprazolam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of Alprazolam 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 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, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of Alprazolam 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) ] . Even after relatively short-term use at doses of ≤4 mg/day, there is some risk of dependence. 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/day and for long periods (more than 12 weeks). However, in a controlled postmarketing discontinuation study of panic disorder patients who received Alprazolam, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose. In contrast, patients treated with doses of Alprazolam greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day. In a controlled clinical trial in which 63 patients were randomized to Alprazolam and where withdrawal symptoms were specifically sought, the following were identified as symptoms of withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss. Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal. Interdose Symptoms Early morning anxiety and emergence of anxiety symptoms between doses of Alprazolam have been reported in patients with panic disorder taking prescribed maintenance doses. These symptoms may reflect the development of tolerance or a time interval between doses which is longer than the duration of clinical action of the administered dose. In either case, it is presumed that the prescribed dose is not sufficient to maintain plasma levels above those needed to prevent relapse, rebound, or withdrawal symptoms over the entire course of the interdosing interval. 5.4 Effects on Driving and Operating Machinery Because of its CNS depressant effects, patients receiving Alprazolam 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 concomitant use of alcohol and other CNS depressant drugs during treatment with Alprazolam [see Drug Interactions (7.1) ] . 5.5 Neonatal Sedation and Withdrawal Syndrome Use of Alprazolam during later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Observe newborns for signs of sedation and neonatal withdrawal syndrome and manage accordingly [see Use in Specific Populations (8.1) ] . 5.6 Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A The initial step in Alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of Alprazolam. Strong CYP3A Inhibitors Alprazolam is contraindicated in patients receiving strong inhibitors of CYP3A (such as azole antifungal agents), except ritonavir [see Contraindications (4) ]. Ketoconazole and itraconazole have been shown in vivo to increase plasma Alprazolam concentrations 3.98 fold and 2.70 fold, respectively. Dosage adjustment is necessary when Alprazolam and ritonavir are initiated concomitantly or when ritonavir is added to a stable dosage of Alprazolam [see Dosage and Administration (2.6) , Drug Interactions (7.1) ]. Drugs demonstrated to be CYP3A inhibitors on the basis of clinical studies involving Alprazolam: nefazodone, fluvoxamine, and cimetidine [see Drug Interaction (7.1) , Clinical Pharmacology (12.3) ]. Use caution and consider dose reduction of Alprazolam, as appropriate, during co-administration with these drugs. 5.7 Patients with Depression 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. 5.8 Mania Episodes of hypomania and mania have been reported in association with the use of Alprazolam in patients with depression [see Adverse Reactions (6.2) ] . 5.9 Risk in Patients with Impaired Respiratory Function There have been reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with alprazolam. Closely monitor patients with impaired respiratory function. If signs and symptoms of respiratory depression, hypoventilation, or apnea occur, discontinue alprazolam.

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) ] Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.5) ] Patients with Depression [see Warnings and Precautions (5.7) ] 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 Greenstone LLC at 1-800-438-1985 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 41% 22% Light-headedness 21% 19% Dizziness 2% 1% Akathisia 2% 1% Gastrointestinal disorders Dry mouth 15% 13% Increased salivation 4% 2% Cardiovascular disorders Hypotension 5% 2% Skin and subcutaneous tissue disorders Dermatitis/allergy 4% 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 77% 43% Fatique and Tiredness 49% 42% Impaired Coordination 40% 18% Irritability 33% 30% Memory Impairment 33% 22% Cognitive Disorder 29% 21% Decreased Libido 14% 8% Dysartharia 23% 6% Confusional state 10% 8% Increased libido 8% 4% Change in libido (not specified) 7% 6% Disinhibition 3% 2% Talkativeness 2% 1% Derealization 2% 1% Gastrointestinal disorders Constipation 26% 15% Increased salivation 6% 4% Skin and subcutaneous tissue disorders Rash 11% 8% Other Increased appetite 33% 23% Decreased appetite 28% 24% Weight gain 27% 18% Weight loss 23% 17% Micturition difficulties 12% 9% Menstrual disorders 11% 9% Sexual dysfunction 7% 4% Incontinence 2% 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 bilirubin, elevated hepatic enzymes, and jaundice. Adverse Reactions Reported as Reasons for Discontinuation in Treatment of Panic Disorder in Placebo-Controlled Trials In a larger database comprised of both controlled and uncontrolled studies in which 641 patients received alprazolam, discontinuation-emergent symptoms which occurred at a rate of over 5% in patients treated with alprazolam and at a greater rate than the placebo-treated group are shown in Table 3. Table 3: Discontinuation-Emergent Symptom Incidence Reported in ≥5% of Alprazolam-treated Patients and > Placebo-treated Patients Alprazolam-treated Patients n=641 n=number of patients. Nervous system disorders Insomnia 29.5% Light-headedness 19.3% Abnormal involuntary movement 17.3% Headache 17.0% Muscular twitching 6.9% Impaired coordination 6.6% Muscle tone disorders 5.9% Weakness 5.8% Psychiatric disorders Anxiety 19.2% Fatigue and Tiredness 18.4% Irritability 10.5% Cognitive disorder 10.3% Memory impairment 5.5% Depression 5.1% Confusional state 5.0% Gastrointestinal disorders Nausea/Vomiting 16.5% Diarrhea 13.6% Decreased salivation 10.6% Metabolism and nutrition disorders Weight loss 13.3% Decreased appetite 12.8% Dermatological disorders Sweating 14.4% Cardiovascular disorders Tachycardia 12.2% Special Senses Blurred vision 10.0% There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam [see Warning and Precautions (5.2) and Drug Abuse and Dependence (9.3) ]. Paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations, and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with posttraumatic stress disorder. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Alprazolam. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Endocrine disorders: Hyperprolactinemia General disorders and administration site conditions: Edema peripheral Hepatobiliary disorders: Hepatitis, hepatic failure Investigations: Liver enzyme elevations Psychiatric disorders: Hypomania, mania Reproductive system and breast disorders: Gynecomastia, galactorrhea Skin and subcutaneous tissue disorders: Photosensitivity reaction, angioedema, Stevens-Johnson syndrome

<table width="75%" ID="table1"><caption>Table 1: Adverse Reactions Occurring in &#x2265;1% in ALPRAZOLAM-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials for Generalized Anxiety</caption><col width="34%" align="left" valign="top"/><col width="33%" align="center" valign="top"/><col width="33%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">alprazolam n=565 </th><th styleCode="Rrule">Placebo n=505 </th></tr></thead><tbody><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Nervous system disorders </content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Drowsiness</td><td styleCode="Rrule">41%</td><td styleCode="Rrule">22%</td></tr><tr><td styleCode="Lrule Rrule"> Light-headedness</td><td styleCode="Rrule">21%</td><td styleCode="Rrule">19%</td></tr><tr><td styleCode="Lrule Rrule"> Dizziness</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr><tr><td styleCode="Lrule Rrule"> Akathisia</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Dry mouth</td><td styleCode="Rrule">15%</td><td styleCode="Rrule">13%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Increased salivation</td><td styleCode="Rrule">4%</td><td styleCode="Rrule">2%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Cardiovascular disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Hypotension</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">2%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Dermatitis/allergy</td><td styleCode="Rrule">4%</td><td styleCode="Rrule">3%</td></tr></tbody></table>

<table width="75%" ID="table2"><caption>Table 2: Adverse Reactions Occuring in &#x2265;1% in Alprazolam-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials (Up to 10 Weeks) for Panic Disorder</caption><col width="34%" align="left" valign="top"/><col width="33%" align="center" valign="top"/><col width="33%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">Alprazolam n=1388 </th><th styleCode="Rrule">Placebo n=1231 </th></tr></thead><tbody><tr><td styleCode="Lrule Rrule"> Drowsiness</td><td styleCode="Rrule">77%</td><td styleCode="Rrule">43%</td></tr><tr><td styleCode="Lrule Rrule"> Fatique and Tiredness</td><td styleCode="Rrule">49%</td><td styleCode="Rrule">42%</td></tr><tr><td styleCode="Lrule Rrule"> Impaired Coordination</td><td styleCode="Rrule">40%</td><td styleCode="Rrule">18%</td></tr><tr><td styleCode="Lrule Rrule"> Irritability</td><td styleCode="Rrule">33%</td><td styleCode="Rrule">30%</td></tr><tr><td styleCode="Lrule Rrule"> Memory Impairment</td><td styleCode="Rrule">33%</td><td styleCode="Rrule">22%</td></tr><tr><td styleCode="Lrule Rrule"> Cognitive Disorder</td><td styleCode="Rrule">29%</td><td styleCode="Rrule">21%</td></tr><tr><td styleCode="Lrule Rrule"> Decreased Libido</td><td styleCode="Rrule">14%</td><td styleCode="Rrule">8%</td></tr><tr><td styleCode="Lrule Rrule"> Dysartharia</td><td styleCode="Rrule">23%</td><td styleCode="Rrule">6%</td></tr><tr><td styleCode="Lrule Rrule"> Confusional state</td><td styleCode="Rrule">10%</td><td styleCode="Rrule">8%</td></tr><tr><td styleCode="Lrule Rrule"> Increased libido</td><td styleCode="Rrule">8%</td><td styleCode="Rrule">4%</td></tr><tr><td styleCode="Lrule Rrule"> Change in libido (not specified)</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">6%</td></tr><tr><td styleCode="Lrule Rrule"> Disinhibition</td><td styleCode="Rrule">3%</td><td styleCode="Rrule">2%</td></tr><tr><td styleCode="Lrule Rrule"> Talkativeness</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Derealization</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Constipation</td><td styleCode="Rrule">26%</td><td styleCode="Rrule">15%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Increased salivation</td><td styleCode="Rrule">6%</td><td styleCode="Rrule">4%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash</td><td styleCode="Rrule">11%</td><td styleCode="Rrule">8%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Other</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Increased appetite</td><td styleCode="Rrule">33%</td><td styleCode="Rrule">23%</td></tr><tr><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">28%</td><td styleCode="Rrule">24%</td></tr><tr><td styleCode="Lrule Rrule"> Weight gain</td><td styleCode="Rrule">27%</td><td styleCode="Rrule">18%</td></tr><tr><td styleCode="Lrule Rrule"> Weight loss</td><td styleCode="Rrule">23%</td><td styleCode="Rrule">17%</td></tr><tr><td styleCode="Lrule Rrule"> Micturition difficulties </td><td styleCode="Rrule">12%</td><td styleCode="Rrule">9%</td></tr><tr><td styleCode="Lrule Rrule"> Menstrual disorders</td><td styleCode="Rrule">11%</td><td styleCode="Rrule">9%</td></tr><tr><td styleCode="Lrule Rrule"> Sexual dysfunction</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">4%</td></tr><tr><td styleCode="Lrule Rrule"> Incontinence</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr></tbody></table>

<table width="75%" ID="table3"><caption>Table 3: Discontinuation-Emergent Symptom Incidence Reported in &#x2265;5% of Alprazolam-treated Patients and &gt; Placebo-treated Patients</caption><col width="50%" align="left" valign="top"/><col width="50%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">Alprazolam-treated Patients n=641 </th></tr></thead><tfoot><tr><td align="left" colspan="2">n=number of patients.</td></tr></tfoot><tbody><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Nervous system disorders </content></td><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Insomnia</td><td styleCode="Rrule">29.5%</td></tr><tr><td styleCode="Lrule Rrule">Light-headedness</td><td styleCode="Rrule">19.3%</td></tr><tr><td styleCode="Lrule Rrule">Abnormal involuntary movement</td><td styleCode="Rrule">17.3%</td></tr><tr><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">17.0%</td></tr><tr><td styleCode="Lrule Rrule">Muscular twitching</td><td styleCode="Rrule">6.9%</td></tr><tr><td styleCode="Lrule Rrule">Impaired coordination </td><td styleCode="Rrule">6.6%</td></tr><tr><td styleCode="Lrule Rrule">Muscle tone disorders</td><td styleCode="Rrule">5.9%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Weakness</td><td styleCode="Rrule">5.8%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Psychiatric disorders</content></td><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Anxiety</td><td styleCode="Rrule">19.2%</td></tr><tr><td styleCode="Lrule Rrule">Fatigue and Tiredness</td><td styleCode="Rrule">18.4%</td></tr><tr><td styleCode="Lrule Rrule">Irritability</td><td styleCode="Rrule">10.5%</td></tr><tr><td styleCode="Lrule Rrule">Cognitive disorder</td><td styleCode="Rrule">10.3%</td></tr><tr><td styleCode="Lrule Rrule">Memory impairment</td><td styleCode="Rrule">5.5%</td></tr><tr><td styleCode="Lrule Rrule">Depression</td><td styleCode="Rrule">5.1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Confusional state</td><td styleCode="Rrule">5.0%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Nausea/Vomiting</td><td styleCode="Rrule">16.5%</td></tr><tr><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">13.6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased salivation</td><td styleCode="Rrule">10.6%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Weight loss</td><td styleCode="Rrule">13.3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased appetite</td><td styleCode="Rrule">12.8%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Dermatological disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Sweating</td><td styleCode="Rrule">14.4%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Cardiovascular disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Tachycardia</td><td styleCode="Rrule">12.2%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Special Senses</content></td><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Blurred vision</td><td styleCode="Rrule">10.0%</td></tr></tbody></table>