FDA label d78b1cc4-be67-44b8-820a-8dc91d0eec05

WARNINGS

ADVERSE REACTIONS Side effects to alprazolam, if they occur, are generally observed at the beginning of therapy and usually disappear upon continued medication. In the usual patient, the most frequent side effects are likely to be an extension of the pharmacological activity of alprazolam, eg, drowsiness or light-headedness. The data cited in the two tables below are estimates of untoward clinical event incidence among patients who participated under the following clinical conditions: relatively short duration (ie, four weeks) placebo-controlled clinical studies with dosages up to 4 mg/day of alprazolam (for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety) and short-term (up to ten weeks) placebo-controlled clinical studies with dosages up to 10 mg/day of alprazolam in patients with panic disorder, with or without agoraphobia. These data cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics, and other factors often differ from those in clinical trials. These figures cannot be compared with those obtained from other clinical studies involving related drug products and placebo as each group of drug trials are conducted under a different set of conditions. Comparison of the cited figures, however, can provide the prescriber with some basis for estimating the relative contributions of drug and non-drug factors to the untoward event incidence in the population studied. Even this use must be approached cautiously, as a drug may relieve a symptom in one patient but induce it in others. (For example, an anxiolytic drug may relieve dry mouth [a symptom of anxiety] in some subjects but induce it [an untoward event] in others.) Additionally, for anxiety disorders the cited figures can provide the prescriber with an indication as to the frequency with which physician intervention (eg, increased surveillance, decreased dosage or discontinuation of drug therapy) may be necessary because of the untoward clinical event. ANXIETY DISORDERS Treatment-Emergent Symptom Incidence† Incidence of Intervention Because of Symptom *None reported †Events reported by 1% or more of alprazolam patients are included Alprazolam Placebo Alprazolam Number of Patients 565 505 565 % of Patients Reporting: CENTRAL NERVOUS SYSTEM Drowsiness 41.0 21.6 15.1 Light-headedness 20.8 19.3 1.2 Depression 13.9 18.1 2.4 Headache 12.9 19.6 1.1 Confusion 9.9 10.0 0.9 Insomnia 8.9 18.4 1.3 Nervousness 4.1 10.3 1.1 Syncope 3.1 4.0 * Dizziness 1.8 0.8 2.5 Akathisia 1.6 1.2 * Tiredness/Sleepiness * * 1.8 GASTROINTESTINAL Dry Mouth 14.7 13.3 0.7 Constipation 10.4 11.4 0.9 Diarrhea 10.1 10.3 1.2 Nausea/Vomiting 9.6 12.8 1.7 Increased Salivation 4.2 2.4 * CARDIOVASCULAR Tachycardia/Palpitations 7.7 15.6 0.4 Hypotension 4.7 2.2 * SENSORY Blurred Vision 6.2 6.2 0.4 MUSCULOSKELETAL Rigidity 4.2 5.3 * Tremor 4.0 8.8 0.4 CUTANEOUS Dermatitis/Allergy 3.8 3.1 0.6 OTHER Nasal Congestion 7.3 9.3 * Weight Gain 2.7 2.7 * Weight Loss 2.3 3.0 * In addition to the relatively common (ie, greater than 1%) untoward events enumerated in the table above, the following adverse events 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. PANIC DISORDER Treatment-Emergent Symptom Incidence* *Events reported by 1% or more of alprazolam patients are included. Alprazolam Placebo Number of Patients 1388 1231 % of Patients Reporting: Central Nervous System Drowsiness 76.8 42.7 Fatigue and Tiredness 48.6 42.3 Impaired Coordination 40.1 17.9 Irritability 33.1 30.1 Memory Impairment 33.1 22.1 Light-headedness/Dizziness 29.8 36.9 Insomnia 29.4 41.8 Headache 29.2 35.6 Cognitive Disorder 28.8 20.5 Dysarthria 23.3 6.3 Anxiety 16.6 24.9 Abnormal Involuntary Movement 14.8 21.0 Decreased Libido 14.4 8.0 Depression 13.8 14.0 Confusional State 10.4 8.2 Muscular Twitching 7.9 11.8 Increased Libido 7.7 4.1 Change in Libido (Not Specified) 7.1 5.6 Weakness 7.1 8.4 Muscle Tone Disorders 6.3 7.5 Syncope 3.8 4.8 Akathisia 3.0 4.3 Agitation 2.9 2.6 Disinhibition 2.7 1.5 Paresthesia 2.4 3.2 Talkativeness 2.2 1.0 Vasomotor Disturbances 2.0 2.6 Derealization 1.9 1.2 Dream Abnormalities 1.8 1.5 Fear 1.4 1.0 Feeling Warm 1.3 0.5 Gastrointestinal Decreased Salivation 32.8 34.2 Constipation 26.2 15.4 Nausea/Vomiting 22.0 31.8 Diarrhea 20.6 22.8 Abdominal Distress 18.3 21.5 Increased Salivation 5.6 4.4 Cardio-Respiratory Nasal Congestion 17.4 16.5 Tachycardia 15.4 26.8 Chest Pain 10.6 18.1 Hyperventilation 9.7 14.5 Upper Respiratory Infection 4.3 3.7 Sensory Blurred Vision 21.0 21.4 Tinnitus 6.6 10.4 Musculoskeletal Muscular Cramps 2.4 2.4 Muscle Stiffness 2.2 3.3 Cutaneous Sweating 15.1 23.5 Rash 10.8 8.1 Other Increased 32.7 22.8 Decreased Appetite 27.8 24.1 Weight Gain 27.2 17.9 Weight Loss 22.6 16.5 Micturition Difficulties 12.2 8.6 Menstrual Disorders 10.4 8.7 Sexual Dysfunction 7.4 3.7 Edema 4.9 5.6 Incontinence 1.5 0.6 Infection 1.3 1.7 In addition to the relatively common (ie, greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of alprazolam: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated bilirubin, elevated hepatic enzymes, and jaundice. There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam (see ). WARNINGS To discontinue treatment in patients taking alprazolam, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every three days (see ). Some patients may benefit from an even slower dosage reduction. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. DOSAGE AND ADMINISTRATION Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Therefore, the same precaution must be exercised when using doses of alprazolam greater than 4 mg/day in treating patients with panic disorders as is exercised with the use of any psychotropic drug in treating depressed patients or those in whom there is reason to expect concealed suicidal ideation or plans. As with all benzodiazepines, 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. Laboratory analyses were performed on all patients participating in the clinical program for alprazolam. The following incidences of abnormalities shown below were observed in patients receiving alprazolam and in patients in the corresponding placebo group. Few of these abnormalities were considered to be of physiological significance. Placebo LOW HIGH LOW HIGH *Less Than 1% HEMATOLOGY Hematocrit * * * * Hemoglobin * * * * Total WBC Count 1.4 2.3 1.0 2.0 Neutrophil Count 2.3 3.0 4.2 1.7 Lymphocyte Count 5.5 7.4 5.4 9.5 Monocyte Count 5.3 2.8 6.4 * Eosinophil Count 3.2 9.5 3.3 7.2 Basophil Count * * * * URINALYSIS Albumin -- * -- * Sugar -- * -- * RBC/HPF -- 3.4 -- 5.0 WBC/HPF -- 25.7 -- 25.9 BLOOD CHEMISTRY Creatinine 2.2 1.9 3.5 1.0 Bilirubin * 1.6 * * SGOT * 3.2 1.0 1.8 Alkaline Phosphatase * 1.7 * 1.8 When treatment with alprazolam is protracted, periodic blood counts, urinalysis and blood chemistry analyses are advisable. Minor changes in EEG patterns, usually low-voltage fast activity have been observed in patients during therapy with alprazolam and are of no known significance. Various adverse drug reactions have been reported in association with the use of alprazolam since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of alprazolam cannot be readily determined. Reported events include: liver enzyme elevations, hepatitis, hepatic failure, Stevens-Johnson syndrome, hyperprolactinemia, gynecomastia and galactorrhea. Post Introduction Reports:

<table frame="void"><caption>ANXIETY DISORDERS</caption><col/><col/><col/><col/><col/><thead><tr><td valign="top"> </td><th align="center" valign="top" colspan="2"><content styleCode="bold">Treatment-Emergent Symptom Incidence&#x2020;</content></th><td valign="top"> </td><td align="center" valign="top"> <content styleCode="bold">Incidence of Intervention</content><content styleCode="bold"> </content><content styleCode="bold">Because of Symptom</content></td></tr></thead><tfoot><tr><td valign="top" colspan="5"> *None reported</td></tr><tr><td valign="top" colspan="5"> &#x2020;Events reported by 1% or more of alprazolam patients are included</td></tr></tfoot><tbody><tr><td align="center" valign="top"> </td><td align="center" valign="top"> <content styleCode="bold"><content styleCode="underline">Alprazolam</content></content></td><td align="center" valign="top"> <content styleCode="bold"><content styleCode="underline">Placebo</content></content></td><td align="center" valign="top"> </td><td align="center" valign="top"> <content styleCode="bold"><content styleCode="underline">Alprazolam</content></content></td></tr><tr><td valign="top"> Number of Patients</td><td align="center" valign="top"> 565</td><td align="center" valign="top"> 505</td><td align="center" valign="top"> </td><td align="center" valign="top"> 565</td></tr><tr><td valign="top"> % of Patients Reporting:</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> CENTRAL NERVOUS SYSTEM</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Drowsiness</td><td align="center" valign="top"> 41.0</td><td align="center" valign="top"> 21.6</td><td align="center" valign="top"> </td><td align="center" valign="top"> 15.1</td></tr><tr><td valign="top"> Light-headedness</td><td align="center" valign="top"> 20.8</td><td align="center" valign="top"> 19.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.2</td></tr><tr><td valign="top"> Depression</td><td align="center" valign="top"> 13.9</td><td align="center" valign="top"> 18.1</td><td align="center" valign="top"> </td><td align="center" valign="top"> 2.4</td></tr><tr><td valign="top"> Headache</td><td align="center" valign="top"> 12.9</td><td align="center" valign="top"> 19.6</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.1</td></tr><tr><td valign="top"> Confusion</td><td align="center" valign="top"> 9.9</td><td align="center" valign="top"> 10.0</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.9</td></tr><tr><td valign="top"> Insomnia</td><td align="center" valign="top"> 8.9</td><td align="center" valign="top"> 18.4</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.3</td></tr><tr><td valign="top"> Nervousness</td><td align="center" valign="top"> 4.1</td><td align="center" valign="top"> 10.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.1</td></tr><tr><td valign="top"> Syncope</td><td align="center" valign="top"> 3.1</td><td align="center" valign="top"> 4.0</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Dizziness</td><td align="center" valign="top"> 1.8</td><td align="center" valign="top"> 0.8</td><td align="center" valign="top"> </td><td align="center" valign="top"> 2.5</td></tr><tr><td valign="top"> Akathisia</td><td align="center" valign="top"> 1.6</td><td align="center" valign="top"> 1.2</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Tiredness/Sleepiness</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.8</td></tr><tr><td valign="top"> GASTROINTESTINAL</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Dry Mouth</td><td align="center" valign="top"> 14.7</td><td align="center" valign="top"> 13.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.7</td></tr><tr><td valign="top"> Constipation</td><td align="center" valign="top"> 10.4</td><td align="center" valign="top"> 11.4</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.9</td></tr><tr><td valign="top"> Diarrhea</td><td align="center" valign="top"> 10.1</td><td align="center" valign="top"> 10.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.2</td></tr><tr><td valign="top"> Nausea/Vomiting</td><td align="center" valign="top"> 9.6</td><td align="center" valign="top"> 12.8</td><td align="center" valign="top"> </td><td align="center" valign="top"> 1.7</td></tr><tr><td valign="top"> Increased Salivation</td><td align="center" valign="top"> 4.2</td><td align="center" valign="top"> 2.4</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> CARDIOVASCULAR</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Tachycardia/Palpitations</td><td align="center" valign="top"> 7.7</td><td align="center" valign="top"> 15.6</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.4</td></tr><tr><td valign="top"> Hypotension</td><td align="center" valign="top"> 4.7</td><td align="center" valign="top"> 2.2</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> SENSORY</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Blurred Vision</td><td align="center" valign="top"> 6.2</td><td align="center" valign="top"> 6.2</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.4</td></tr><tr><td valign="top"> MUSCULOSKELETAL</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Rigidity</td><td align="center" valign="top"> 4.2</td><td align="center" valign="top"> 5.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Tremor</td><td align="center" valign="top"> 4.0</td><td align="center" valign="top"> 8.8</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.4</td></tr><tr><td valign="top"> CUTANEOUS</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Dermatitis/Allergy</td><td align="center" valign="top"> 3.8</td><td align="center" valign="top"> 3.1</td><td align="center" valign="top"> </td><td align="center" valign="top"> 0.6</td></tr><tr><td valign="top"> OTHER</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Nasal Congestion</td><td align="center" valign="top"> 7.3</td><td align="center" valign="top"> 9.3</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Weight Gain</td><td align="center" valign="top"> 2.7</td><td align="center" valign="top"> 2.7</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Weight Loss</td><td align="center" valign="top"> 2.3</td><td align="center" valign="top"> 3.0</td><td align="center" valign="top"> </td><td align="center" valign="top"> *</td></tr></tbody></table>

<table frame="void"><caption>PANIC DISORDER</caption><col/><col/><col/><col/><thead><tr><td valign="top"> </td><td valign="top"> </td><th align="center" valign="top" colspan="2"><content styleCode="bold">Treatment-Emergent</content><content styleCode="bold"> </content><content styleCode="bold">Symptom Incidence*</content></th></tr></thead><tfoot><tr><td valign="top" colspan="4"> <content styleCode="italics">*Events reported by 1% or more of alprazolam patients are included.</content></td></tr></tfoot><tbody><tr><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> Alprazolam</td><td align="center" valign="top"> Placebo</td></tr><tr><td valign="top"> Number of Patients</td><td valign="top"> </td><td align="center" valign="top"> 1388</td><td align="center" valign="top"> 1231</td></tr><tr><td valign="top"> % of Patients Reporting:</td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> <content styleCode="underline">Central Nervous System</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Drowsiness</td><td valign="top"> </td><td align="center" valign="top"> 76.8</td><td align="center" valign="top"> 42.7</td></tr><tr><td valign="top"> Fatigue and Tiredness</td><td valign="top"> </td><td align="center" valign="top"> 48.6</td><td align="center" valign="top"> 42.3</td></tr><tr><td valign="top"> Impaired Coordination</td><td valign="top"> </td><td align="center" valign="top"> 40.1</td><td align="center" valign="top"> 17.9</td></tr><tr><td valign="top"> Irritability</td><td valign="top"> </td><td align="center" valign="top"> 33.1</td><td align="center" valign="top"> 30.1</td></tr><tr><td valign="top"> Memory Impairment</td><td valign="top"> </td><td align="center" valign="top"> 33.1</td><td align="center" valign="top"> 22.1</td></tr><tr><td valign="top"> Light-headedness/Dizziness</td><td valign="top"> </td><td align="center" valign="top"> 29.8</td><td align="center" valign="top"> 36.9</td></tr><tr><td valign="top"> Insomnia</td><td valign="top"> </td><td align="center" valign="top"> 29.4</td><td align="center" valign="top"> 41.8</td></tr><tr><td valign="top"> Headache</td><td valign="top"> </td><td align="center" valign="top"> 29.2</td><td align="center" valign="top"> 35.6</td></tr><tr><td valign="top"> Cognitive Disorder</td><td valign="top"> </td><td align="center" valign="top"> 28.8</td><td align="center" valign="top"> 20.5</td></tr><tr><td valign="top"> Dysarthria</td><td valign="top"> </td><td align="center" valign="top"> 23.3</td><td align="center" valign="top"> 6.3</td></tr><tr><td valign="top"> Anxiety</td><td valign="top"> </td><td align="center" valign="top"> 16.6</td><td align="center" valign="top"> 24.9</td></tr><tr><td valign="top"> Abnormal Involuntary Movement</td><td valign="top"> </td><td align="center" valign="top"> 14.8 </td><td align="center" valign="top"> 21.0 </td></tr><tr><td valign="top"> Decreased Libido</td><td valign="top"> </td><td align="center" valign="top"> 14.4</td><td align="center" valign="top"> 8.0</td></tr><tr><td valign="top"> Depression</td><td valign="top"> </td><td align="center" valign="top"> 13.8</td><td align="center" valign="top"> 14.0</td></tr><tr><td valign="top"> Confusional State</td><td valign="top"> </td><td align="center" valign="top"> 10.4</td><td align="center" valign="top"> 8.2</td></tr><tr><td valign="top"> Muscular Twitching</td><td valign="top"> </td><td align="center" valign="top"> 7.9</td><td align="center" valign="top"> 11.8</td></tr><tr><td valign="top"> Increased Libido</td><td valign="top"> </td><td align="center" valign="top"> 7.7</td><td align="center" valign="top"> 4.1</td></tr><tr><td valign="top"> Change in Libido (Not Specified) </td><td valign="top"> </td><td align="center" valign="top"> 7.1 </td><td align="center" valign="top"> 5.6 </td></tr><tr><td valign="top"> Weakness</td><td valign="top"> </td><td align="center" valign="top"> 7.1</td><td align="center" valign="top"> 8.4</td></tr><tr><td valign="top"> Muscle Tone Disorders</td><td valign="top"> </td><td align="center" valign="top"> 6.3</td><td align="center" valign="top"> 7.5</td></tr><tr><td valign="top"> Syncope</td><td valign="top"> </td><td align="center" valign="top"> 3.8</td><td align="center" valign="top"> 4.8</td></tr><tr><td valign="top"> Akathisia</td><td valign="top"> </td><td align="center" valign="top"> 3.0</td><td align="center" valign="top"> 4.3</td></tr><tr><td valign="top"> Agitation</td><td valign="top"> </td><td align="center" valign="top"> 2.9</td><td align="center" valign="top"> 2.6</td></tr><tr><td valign="top"> Disinhibition</td><td valign="top"> </td><td align="center" valign="top"> 2.7</td><td align="center" valign="top"> 1.5</td></tr><tr><td valign="top"> Paresthesia</td><td valign="top"> </td><td align="center" valign="top"> 2.4</td><td align="center" valign="top"> 3.2</td></tr><tr><td valign="top"> Talkativeness</td><td valign="top"> </td><td align="center" valign="top"> 2.2</td><td align="center" valign="top"> 1.0</td></tr><tr><td valign="top"> Vasomotor Disturbances</td><td valign="top"> </td><td align="center" valign="top"> 2.0</td><td align="center" valign="top"> 2.6</td></tr><tr><td valign="top"> Derealization</td><td valign="top"> </td><td align="center" valign="top"> 1.9</td><td align="center" valign="top"> 1.2</td></tr><tr><td valign="top"> Dream Abnormalities</td><td valign="top"> </td><td align="center" valign="top"> 1.8</td><td align="center" valign="top"> 1.5</td></tr><tr><td valign="top"> Fear</td><td valign="top"> </td><td align="center" valign="top"> 1.4</td><td align="center" valign="top"> 1.0</td></tr><tr><td valign="top"> Feeling Warm</td><td valign="top"> </td><td align="center" valign="top"> 1.3</td><td align="center" valign="top"> 0.5</td></tr><tr><td valign="top"> <content styleCode="underline">Gastrointestinal</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Decreased Salivation</td><td valign="top"> </td><td align="center" valign="top"> 32.8</td><td align="center" valign="top"> 34.2</td></tr><tr><td valign="top"> Constipation</td><td valign="top"> </td><td align="center" valign="top"> 26.2</td><td align="center" valign="top"> 15.4</td></tr><tr><td valign="top"> Nausea/Vomiting</td><td valign="top"> </td><td align="center" valign="top"> 22.0</td><td align="center" valign="top"> 31.8</td></tr><tr><td valign="top"> Diarrhea</td><td valign="top"> </td><td align="center" valign="top"> 20.6</td><td align="center" valign="top"> 22.8</td></tr><tr><td valign="top"> Abdominal Distress</td><td valign="top"> </td><td align="center" valign="top"> 18.3</td><td align="center" valign="top"> 21.5</td></tr><tr><td valign="top"> Increased Salivation</td><td valign="top"> </td><td align="center" valign="top"> 5.6</td><td align="center" valign="top"> 4.4</td></tr><tr><td valign="top"> <content styleCode="underline">Cardio-Respiratory</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Nasal Congestion</td><td valign="top"> </td><td align="center" valign="top"> 17.4</td><td align="center" valign="top"> 16.5</td></tr><tr><td valign="top"> Tachycardia</td><td valign="top"> </td><td align="center" valign="top"> 15.4</td><td align="center" valign="top"> 26.8</td></tr><tr><td valign="top"> Chest Pain</td><td valign="top"> </td><td align="center" valign="top"> 10.6</td><td align="center" valign="top"> 18.1</td></tr><tr><td valign="top"> Hyperventilation</td><td valign="top"> </td><td align="center" valign="top"> 9.7</td><td align="center" valign="top"> 14.5</td></tr><tr><td valign="top"> Upper Respiratory Infection</td><td valign="top"> </td><td align="center" valign="top"> 4.3</td><td align="center" valign="top"> 3.7</td></tr><tr><td valign="top"> <content styleCode="underline">Sensory</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Blurred Vision</td><td valign="top"> </td><td align="center" valign="top"> 21.0</td><td align="center" valign="top"> 21.4</td></tr><tr><td valign="top"> Tinnitus</td><td valign="top"> </td><td align="center" valign="top"> 6.6</td><td align="center" valign="top"> 10.4</td></tr><tr><td valign="top"> <content styleCode="underline">Musculoskeletal</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Muscular Cramps</td><td valign="top"> </td><td align="center" valign="top"> 2.4</td><td align="center" valign="top"> 2.4</td></tr><tr><td valign="top"> Muscle Stiffness</td><td valign="top"> </td><td align="center" valign="top"> 2.2</td><td align="center" valign="top"> 3.3</td></tr><tr><td valign="top"> <content styleCode="underline">Cutaneous</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Sweating</td><td valign="top"> </td><td align="center" valign="top"> 15.1</td><td align="center" valign="top"> 23.5</td></tr><tr><td valign="top"> Rash</td><td valign="top"> </td><td align="center" valign="top"> 10.8</td><td align="center" valign="top"> 8.1</td></tr><tr><td valign="top"> <content styleCode="underline">Other</content></td><td valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Increased</td><td valign="top"> </td><td align="center" valign="top"> 32.7</td><td align="center" valign="top"> 22.8</td></tr><tr><td valign="top"> Decreased Appetite</td><td valign="top"> </td><td align="center" valign="top"> 27.8</td><td align="center" valign="top"> 24.1</td></tr><tr><td valign="top"> Weight Gain</td><td valign="top"> </td><td align="center" valign="top"> 27.2</td><td align="center" valign="top"> 17.9</td></tr><tr><td valign="top"> Weight Loss</td><td valign="top"> </td><td align="center" valign="top"> 22.6</td><td align="center" valign="top"> 16.5</td></tr><tr><td valign="top"> Micturition Difficulties</td><td valign="top"> </td><td align="center" valign="top"> 12.2</td><td align="center" valign="top"> 8.6</td></tr><tr><td valign="top"> Menstrual Disorders</td><td valign="top"> </td><td align="center" valign="top"> 10.4</td><td align="center" valign="top"> 8.7</td></tr><tr><td valign="top"> Sexual Dysfunction</td><td valign="top"> </td><td align="center" valign="top"> 7.4</td><td align="center" valign="top"> 3.7</td></tr><tr><td valign="top"> Edema</td><td valign="top"> </td><td align="center" valign="top"> 4.9</td><td align="center" valign="top"> 5.6</td></tr><tr><td valign="top"> Incontinence</td><td valign="top"> </td><td align="center" valign="top"> 1.5</td><td align="center" valign="top"> 0.6</td></tr><tr><td valign="top"> Infection</td><td valign="top"> </td><td align="center" valign="top"> 1.3</td><td align="center" valign="top"> 1.7</td></tr></tbody></table>

<table frame="void"><col/><col/><col/><col/><col/><thead><tr><td valign="top"> </td><th align="center" valign="top" colspan="2"/><th align="center" valign="top" colspan="2"><content styleCode="bold">Placebo</content></th></tr><tr><td align="center" valign="top"> </td><td align="center" valign="top"> <content styleCode="bold">LOW</content></td><td align="center" valign="top"> <content styleCode="bold">HIGH</content></td><td align="center" valign="top"> <content styleCode="bold">LOW</content></td><td align="center" valign="top"> <content styleCode="bold">HIGH</content></td></tr></thead><tfoot><tr><td valign="top" colspan="5"> *Less Than 1%</td></tr></tfoot><tbody><tr><td valign="top"> HEMATOLOGY</td><td valign="top"> </td><td valign="top"> </td><td valign="top"> </td><td valign="top"> </td></tr><tr><td valign="top"> Hematocrit</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Hemoglobin</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Total WBC Count</td><td align="center" valign="top"> 1.4</td><td align="center" valign="top"> 2.3</td><td align="center" valign="top"> 1.0</td><td align="center" valign="top"> 2.0</td></tr><tr><td valign="top"> Neutrophil Count</td><td align="center" valign="top"> 2.3</td><td align="center" valign="top"> 3.0</td><td align="center" valign="top"> 4.2</td><td align="center" valign="top"> 1.7</td></tr><tr><td valign="top"> Lymphocyte Count</td><td align="center" valign="top"> 5.5</td><td align="center" valign="top"> 7.4</td><td align="center" valign="top"> 5.4</td><td align="center" valign="top"> 9.5</td></tr><tr><td valign="top"> Monocyte Count</td><td align="center" valign="top"> 5.3</td><td align="center" valign="top"> 2.8</td><td align="center" valign="top"> 6.4</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Eosinophil Count</td><td align="center" valign="top"> 3.2</td><td align="center" valign="top"> 9.5</td><td align="center" valign="top"> 3.3</td><td align="center" valign="top"> 7.2</td></tr><tr><td valign="top"> Basophil Count</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> URINALYSIS</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Albumin</td><td align="center" valign="top"> --</td><td align="center" valign="top"> *</td><td align="center" valign="top"> --</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> Sugar</td><td align="center" valign="top"> --</td><td align="center" valign="top"> *</td><td align="center" valign="top"> --</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> RBC/HPF</td><td align="center" valign="top"> --</td><td align="center" valign="top"> 3.4</td><td align="center" valign="top"> --</td><td align="center" valign="top"> 5.0</td></tr><tr><td valign="top"> WBC/HPF</td><td align="center" valign="top"> --</td><td align="center" valign="top"> 25.7</td><td align="center" valign="top"> --</td><td align="center" valign="top"> 25.9</td></tr><tr><td valign="top"> BLOOD CHEMISTRY</td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td></tr><tr><td valign="top"> Creatinine</td><td align="center" valign="top"> 2.2</td><td align="center" valign="top"> 1.9</td><td align="center" valign="top"> 3.5</td><td align="center" valign="top"> 1.0</td></tr><tr><td valign="top"> Bilirubin</td><td align="center" valign="top"> *</td><td align="center" valign="top"> 1.6</td><td align="center" valign="top"> *</td><td align="center" valign="top"> *</td></tr><tr><td valign="top"> SGOT</td><td align="center" valign="top"> *</td><td align="center" valign="top"> 3.2</td><td align="center" valign="top"> 1.0</td><td align="center" valign="top"> 1.8</td></tr><tr><td valign="top"> Alkaline Phosphatase</td><td align="center" valign="top"> *</td><td align="center" valign="top"> 1.7</td><td align="center" valign="top"> *</td><td align="center" valign="top"> 1.8</td></tr></tbody></table>