FDA label e5d3b2c1-fd39-4369-bce0-4db9ea8b3183

Zolpidem tartrate extended-release tablets are a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep zolpidem tartrate extended-release tablets in a safe place to prevent misuse and abuse. Selling or giving away zolpidem tartrate extended-release tablets may harm others, and is against the law. Tell your doctor if you have ever abused or have been dependent on alcohol, prescription medicines or street drugs.

5 WARNINGS AND PRECAUTIONS Need to evaluate for co-morbid diagnoses: Revaluate if insomnia persists after 7 to 10 days of use ( 5.1 ) Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur ( 5.2 ) Abnormal thinking, behavioral changes, complex behaviors: May include “sleep-driving” and hallucinations. Immediately evaluate any new onset behavioral changes ( 5.3 ) Depression: Worsening of depression or, suicidal thinking may occur. Prescribe the least amount feasible to avoid intentional overdose ( 5.3 , 5.6 ) Withdrawal effects: Symptoms may occur with rapid dose reduction or discontinuation ( 5.4 , 9.2 ) CNS depressant effects: Use can impair alertness and motor coordination. If used in combination with other CNS depressants, dose reductions may be needed due to additive effects. Do not use with alcohol ( 2.3 , 5.5 ) Elderly/debilitated patients: Use lower dose due to impaired motor, cognitive performance and increased sensitivity ( 2.2 , 5.6 ) Patients with hepatic impairment, mild to moderate COPD, impaired drug metabolism or hemodynamic responses, mild to moderate sleep apnea: Use with caution and monitor closely ( 5.6 ) 5.1 Need to evaluate for co-morbid diagnoses Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem. 5.2 Severe anaphylactic and anaphylactoid reactions Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the throat, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug. 5.3 Abnormal thinking and behavioral changes A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of sedative/hypnotics. Some of these changes may be characterized by decreased inhibition (e.g. aggressiveness and extroversion that seemed out of character), similar to effects produced by alcohol and other CNS depressants. Visual and auditory hallucinations have been reported as well as behavioral changes such as bizarre behavior, agitation and depersonalization. In controlled trials, <1% of adults with insomnia who received zolpidem reported hallucinations. In a clinical trial, 7.4% of pediatric patients with insomnia associated with attention-deficit/hyperactivity disorder (ADHD), who received zolpidem reported hallucinations [see Use in Specific Populations (8.4) ]. Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported with sedative-hypnotics, including zolpidem. These events can occur in sedative-hypnotic-naïve as well as sedative-hypnotic-experienced persons. Although behaviors such as “sleep-driving” may occur with zolpidem tartrate extended-release tablets alone at therapeutic doses, the use of alcohol and other CNS depressants with zolpidem tartrate extended-release tablets appears to increase the risk of such behaviors, as does the use of zolpidem tartrate extended-release tablets at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of zolpidem tartrate extended-release tablets should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with “sleep-driving”, patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), have been reported in association with the use of sedative/hypnotics. It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation. 5.4 Withdrawal effects Following the rapid dose decrease or abrupt discontinuation of sedative/hypnotics, there have been reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs [see Drug Abuse and Dependence (9)] . 5.5 CNS depressant effects Zolpidem tartrate extended-release tablets, like other sedative/hypnotic drugs, has CNS-depressant effects. Due to the rapid onset of action, zolpidem tartrate extended-release tablets should only be taken immediately prior to going to bed. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of Zolpidem Tartrate Extended-Release Tablets. Zolpidem tartrate extended-release tablets showed additive effects when combined with alcohol and should not be taken with alcohol. Patients should also be cautioned about possible combined effects with other CNS-depressant drugs. Dosage adjustments may be necessary when zolpidem tartrate extended-release tablets are administered with such agents because of the potentially additive effects. 5.6 Special populations Use in the elderly and/or debilitated patients: Impaired motor and/or cognitive performance after repeated exposure or unusual sensitivity to sedative/hypnotic drugs is a concern in the treatment of elderly and/or debilitated patients. Therefore, the recommended zolpidem tartrate extended-release tablets dosage is 6.25 mg in such patients to decrease the possibility of side effects [see Dosage and Administration (2.2) ]. These patients should be closely monitored. Use in patients with concomitant illness: Clinical experience with zolpidem tartrate extended-release tablets in patients with concomitant systemic illness is limited. Caution is advisable in using zolpidem tartrate extended-release tablets in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Although studies did not reveal respiratory depressant effects at hypnotic doses of zolpidem in normals or in patients with mild to moderate chronic obstructive pulmonary disease (COPD), a reduction in the Total Arousal Index together with a reduction in lowest oxygen saturation and increase in the times of oxygen desaturation below 80% and 90% was observed in patients with mild-to-moderate sleep apnea when treated with an immediate-release formulation of zolpidem tartrate (10 mg) when compared to placebo. Since sedative/hypnotics have the capacity to depress respiratory drive, precautions should be taken if zolpidem tartrate extended-release tablets are prescribed to patients with compromised respiratory function. Post-marketing reports of respiratory insufficiency, most of which involved patients with pre-existing respiratory impairment, have been received. Zolpidem tartrate extended-release tablets should be used with caution in patients with sleep apnea syndrome or myasthenia gravis. Data in end-stage renal failure patients repeatedly treated with an immediate-release formulation of zolpidem tartrate (10 mg) did not demonstrate drug accumulation or alterations in pharmacokinetic parameters. No dosage adjustment in renally impaired patients is required; however, these patients should be closely monitored [see Clinical Pharmacology (12.3) ]. A study in subjects with hepatic impairment did reveal prolonged elimination in this group; therefore, treatment should be initiated with zolpidem tartrate extended-release tablets 6.25 mg in patients with hepatic compromise, and they should be closely monitored [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ]. Use in patients with depression: As with other sedative/hypnotic drugs, zolpidem tartrate extended-release tablets should be administered with caution to patients exhibiting signs or symptoms of depression. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients; therefore, the least amount of drug that is feasible should be prescribed for the patient at any one time. Use in pediatric patients: Safety and effectiveness of zolpidem has not been established in pediatric patients. In an 8-week study in pediatric patients (age 6-17 years) with insomnia associated with ADHD given an immediate-release oral solution of zolpidem tartrate, zolpidem did not decrease sleep latency compared to placebo. Hallucinations were reported in 7.4% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations [see Use in Specific Populations (8.4) ].

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious anaphylactic and anaphylactoid reactions [see Warnings and Precautions (5.2) ] Abnormal thinking, behavior changes, and complex behaviors [see Warnings and Precautions (5.3) ] Withdrawal effects [see Warnings and Precautions (5.4) ] CNS-depressant effects [see Warnings and Precautions (5.5) ] Most commonly observed adverse reactions (> 10% in either elderly or adult patients) are: headache, next-day somnolence and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical trials experience Associated with discontinuation of treatment: In 3-week clinical trials in adults and elderly patients (>65 years), 3.5% (7/201) patients receiving zolpidem tartrate extended-release tablets 6.25 or 12.5 mg discontinued treatment due to an adverse reaction as compared to 0.9% (2/216) of patients on placebo. The reaction most commonly associated with discontinuation in patients treated with zolpidem tartrate extended-release tablets was somnolence (1%). In a 6-month study in adult patients (18-64 years of age), 8.5% (57/669) of patients receiving zolpidem tartrate extended-release tablets 12.5 mg as compared to 4.6% on placebo (16/349) discontinued treatment due to an adverse reaction. Reactions most commonly associated with discontinuation of zolpidem tartrate extended-release tablets included anxiety (anxiety, restlessness or agitation) reported in 1.5% (10/669) of patients as compared to 0.3% (1/349) of patients on placebo, and depression (depression, major depression or depressed mood) reported in 1.5% (10/669) of patients as compared to 0.3% (1/349) of patients on placebo. Data from a clinical study in which selective serotonin reuptake inhibitor- (SSRI-) treated patients were given zolpidem revealed that four of the seven discontinuations during double-blind treatment with zolpidem (n=95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction; one patient treated with placebo (n =97) was discontinued after an attempted suicide. Most commonly observed adverse reactions in controlled trials: During treatment with zolpidem tartrate extended-release tablets in adults and elderly at daily doses of 12.5 mg and 6.25 mg, respectively, each for three weeks, the most commonly observed adverse reactions associated with the use of zolpidem tartrate extended-release tablets were headache, next-day somnolence, and dizziness. In the 6-month trial evaluating zolpidem tartrate extended-release tablets 12.5 mg, the adverse reaction profile was consistent with that reported in short-term trials, except for a higher incidence of anxiety (6.3% for zolpidem tartrate extended-release tablets versus 2.6% for placebo). Adverse reactions observed at an incidence of ≥1% in controlled trials: The following tables enumerate treatment-emergent adverse reaction frequencies that were observed at an incidence equal to 1% or greater among patients with insomnia who received zolpidem tartrate extended-release tablets in placebo-controlled trials. Events reported by investigators were classified utilizing the MedDRA dictionary for the purpose of establishing event frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in these clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted under a different set of conditions. However, the cited figures provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied. The following tables were derived from results of two placebo-controlled efficacy trials involving zolpidem tartrate extended-release tablets. These trials involved patients with primary insomnia who were treated for 3 weeks with zolpidem tartrate extended-release tablets at doses of 12.5 mg (Table 1) or 6.25 mg (Table 2), respectively. The tables include only adverse reactions occurring at an incidence of at least 1% for zolpidem tartrate extended-release tablets patients and with an incidence greater than that seen in the placebo patients. Table 1. Incidence of Treatment-Emergent Adverse Reactions in a 3-week Placebo-Controlled Clinical Trial in Adults (percentage of patients reporting) Zolpidem Tartrate Body System/Adverse Extended-Release Reaction* Tablets 12.5 mg Placebo (N = 102) (N = 110) *Reactions reported by at least 1% of patients treated with zolpidem tartrate extended-release tablets and at greater frequency than in the placebo group. **Hallucinations included hallucinations NOS as well as visual and hypnogogic hallucinations. ***Memory disorders include: memory impairment, amnesia, anterograde amnesia. Infections and infestations Influenza 3 0 Gastroenteritis 1 0 Labyrinthitis 1 0 Metabolism and nutrition disorders Appetite disorder 1 0 Psychiatric disorders Hallucinations** 4 0 Disorientation 3 2 Anxiety 2 0 Depression 2 0 Psychomotor retardation 2 0 Binge eating 1 0 Depersonalization 1 0 Disinhibition 1 0 Euphoric mood 1 0 Mood swings 1 0 Stress symptoms 1 0 Nervous system disorders Headache 19 16 Somnolence 15 2 Dizziness 12 5 Memory disorders*** 3 0 Balance disorder 2 0 Disturbance in attention 2 0 Hypoesthesia 2 1 Ataxia 1 0 Paresthesia 1 0 Eye disorders Visual disturbance 3 0 Eye redness 2 0 Vision blurred 2 1 Altered visual depth perception 1 0 Asthenopia 1 0 Ear and labyrinth disorders Vertigo 2 0 Tinnitus 1 0 Respiratory, thoracic and mediastinal disorders Throat irritation 1 0 Gastrointestinal disorders Nausea 7 4 Constipation 2 0 Abdominal discomfort 1 0 Abdominal tenderness 1 0 Frequent bowel movements 1 0 Gastroesophageal reflux disease 1 0 Vomiting 1 0 Skin and subcutaneous tissue disorders Rash 1 0 Skin wrinkling 1 0 Urticaria 1 0 Musculoskeletal and connective tissue disorders Back pain 4 3 Myalgia 4 0 Neck pain 1 0 Reproductive system and breast disorders Menorrhagia 1 0 General disorders and administration site conditions Fatigue 3 2 Asthenia 1 0 Chest discomfort 1 0 Investigations Blood pressure increased 1 0 Body temperature increased 1 0 Injury, poisoning and procedural complications Contusion 1 0 Social circumstances Exposure to poisonous plant 1 0 Table 2. Incidence of Treatment-Emergent Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial in Elderly (percentage of patients reporting) Zolpidem Tartrate Body System/Adverse Extended-Release Reaction* Tablets 6.25 mg Placebo (N=99) (N=106) *Reactions reported by at least 1% of patients treated with zolpidem tartrate extended-release tablets and at greater frequency than in the placebo group. **Memory disorders include: memory impairment, amnesia, anterograde amnesia. Infections and infestations Nasopharyngitis 6 4 Lower respiratory tract infection 1 0 Otitis externa 1 0 Upper respiratory tract infection 1 0 Psychiatric disorders Anxiety 3 2 Psychomotor retardation 2 0 Apathy 1 0 Depressed mood 1 0 Nervous system disorders Headache 14 11 Dizziness 8 3 Somnolence 6 5 Burning sensation 1 0 Dizziness postural 1 0 Memory disorders** 1 0 Muscle contractions involuntary 1 0 Paresthesia 1 0 Tremor 1 0 Cardiac disorders Palpitations 2 0 Respiratory, thoracic and mediastinal disorders Dry throat 1 0 Gastrointestinal disorders Flatulence 1 0 Vomiting 1 0 Skin and subcutaneous tissue disorders Rash 1 0 Urticaria 1 0 Musculoskeletal and connective tissue disorders Arthralgia 2 0 Muscle cramp 2 1 Neck pain 2 0 Renal and urinary disorders Dysuria 1 0 Reproductive system and breast disorders Vulvovaginal dryness 1 0 General disorders and administration site conditions Influenza like illness 1 0 Pyrexia 1 0 Injury, poisoning and procedural complications Neck injury 1 0 Dose relationship for adverse reactions: There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse reactions associated with zolpidem use, particularly for certain CNS and gastrointestinal adverse events. Other adverse reactions observed during the premarketing evaluation of Zolpidem Tartrate Extended-Release Tablets: Other treatment-emergent adverse reactions associated with participation in zolpidem tartrate extended-release tablets studies (those reported at frequencies of <1%) were not different in nature or frequency to those seen in studies with immediate-release zolpidem tartrate, which are listed below. Adverse Events Observed During the Premarketing Evaluation of Immediate-Release Zolpidem Tartrate: Immediate-release zolpidem tartrate was administered to 3,660 subjects in clinical trials throughout the U.S., Canada, and Europe. Treatment-emergent adverse events associated with clinical trial participation were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent adverse events, similar types of untoward events were grouped into a smaller number of standardized event categories and classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms. The frequencies presented, therefore, represent the proportions of the 3,660 individuals exposed to zolpidem, at all doses, who experienced an event of the type cited on at least one occasion while receiving zolpidem. All reported treatment-emergent adverse events are included, except those already listed in the table above of adverse events in placebo-controlled studies, those coding terms that are so general as to be uninformative, and those events where a drug cause was remote. It is important to emphasize that, although the events reported did occur during treatment with zolpidem tartrate tablets, they were not necessarily caused by it. Adverse events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in greater than 1/100 subjects; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in less than 1/1,000 patients. Autonomic nervous system: Frequent: dry mouth. Infrequent: increased sweating, pallor, postural hypotension, syncope. Rare: abnormal accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus. Body as a whole: Frequent : asthenia. Infrequent : chest pain, edema, falling, fever, malaise, trauma. Rare: allergic reaction, allergy aggravated, anaphylactic shock, face edema, hot flashes, increased ESR, pain, restless legs, rigors, tolerance increased, weight decrease. Cardiovascular system: Infrequent: cerebrovascular disorder, hypertension, tachycardia. Rare: angina pectoris, arrhythmia, arteritis, circulatory failure, extrasystoles, hypertension aggravated, myocardial infarction, phlebitis, pulmonary embolism, pulmonary edema, varicose veins, ventricular tachycardia. Central and peripheral nervous system: Frequent: ataxia, confusion, drowsiness, drugged feeling, euphoria, insomnia, lethargy, lightheadedness, vertigo. Infrequent: agitation, decreased cognition, detached, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, sleeping (after daytime dosing), speech disorder, stupor, tremor. Rare: abnormal gait, abnormal thinking, aggressive reaction, apathy, appetite increased, decreased libido, delusion, dementia, depersonalization, dysphasia, feeling strange, hypokinesia, hypotonia, hysteria, intoxicated feeling, manic reaction, neuralgia, neuritis, neuropathy, neurosis, panic attacks, paresis, personality disorder, somnambulism, suicide attempts, tetany, yawning. Gastrointestinal system: Frequent: diarrhea, dyspepsia, hiccup. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis. Rare: enteritis, eructation, esophagospasm, gastritis, hemorrhoids, intestinal obstruction, rectal hemorrhage, tooth caries. Hematologic and lymphatic system: Rare: anemia, hyperhemoglobinemia, leukopenia, lymphadenopathy, macrocytic anemia, purpura, thrombosis. Immunologic system: Infrequent: infection. Rare: abscess herpes simplex herpes zoster, otitis externa, otitis media. Liver and biliary system: Infrequent: abnormal hepatic function, increased SGPT. Rare: bilirubinemia, increased SGOT. Metabolic and nutritional: Infrequent: hyperglycemia, thirst. Rare: gout, hypercholesteremia, hyperlipidemia, increased alkaline phosphatase, increased BUN, periorbital edema. Musculoskeletal system: Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis. Reproductive system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain. Respiratory system: Frequent: sinusitis. Infrequent: bronchitis, coughing, dyspnea. Rare: bronchospasm, epistaxis, hypoxia, laryngitis, pneumonia. Skin and appendages: Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria. Special senses: Frequent: diplopia, vision abnormal. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia. Urogenital system: Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention.

<table frame="void" width="660" ID="i020ecb6f-9ed4-44c1-8194-76f71a296e16"> <caption> Table 1. Incidence of Treatment-Emergent Adverse Reactions in a 3-week Placebo-Controlled Clinical Trial in Adults (percentage of patients reporting)</caption> <thead> <tr> <td align="center" valign="middle"/> <td align="center" valign="top"> <content styleCode="bold">Zolpidem Tartrate</content> </td> <td align="center" valign="middle"/> </tr> <tr> <td align="center" valign="middle"> <content styleCode="bold">Body System/Adverse </content> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release </content> </td> <td align="center" valign="middle"/> </tr> <tr> <td align="center" valign="middle"> <content styleCode="bold">Reaction*</content> </td> <td align="center" valign="top"> <content styleCode="bold">Tablets 12.5 mg</content> </td> <td align="center" valign="middle"> <content styleCode="bold">Placebo</content> </td> </tr> <tr> <td align="center" valign="middle"/> <td align="center" valign="top"> <content styleCode="bold">(N = 102)</content> </td> <td align="center" valign="middle"> <content styleCode="bold">(N = 110)</content> </td> </tr> </thead> <tfoot> <tr> <td align="left" valign="top" colspan="3"> *Reactions reported by at least 1% of patients treated with zolpidem tartrate extended-release tablets and at greater frequency than in the placebo group. </td> </tr> <tr> <td align="left" valign="top" colspan="3"> **Hallucinations included hallucinations NOS as well as visual and hypnogogic hallucinations. </td> </tr> <tr> <td align="left" valign="top" colspan="3">***Memory disorders include: memory impairment, amnesia, anterograde amnesia.</td> </tr> </tfoot> <tbody> <tr> <td align="left" valign="top"> <content styleCode="bold">Infections and infestations</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Influenza</td> <td align="center" valign="top">3</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Gastroenteritis</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Labyrinthitis</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Metabolism and nutrition disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Appetite disorder</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Psychiatric disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Hallucinations**</td> <td align="center" valign="top">4</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Disorientation</td> <td align="center" valign="top">3</td> <td align="center" valign="top">2</td> </tr> <tr> <td align="left" valign="top">Anxiety</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Depression</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Psychomotor retardation</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Binge eating</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Depersonalization</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Disinhibition</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Euphoric mood</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Mood swings</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Stress symptoms</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Nervous system disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Headache</td> <td align="center" valign="top">19</td> <td align="center" valign="top">16</td> </tr> <tr> <td align="left" valign="top">Somnolence</td> <td align="center" valign="top">15</td> <td align="center" valign="top">2</td> </tr> <tr> <td align="left" valign="top">Dizziness</td> <td align="center" valign="top">12</td> <td align="center" valign="top">5</td> </tr> <tr> <td align="left" valign="top">Memory disorders***</td> <td align="center" valign="top">3</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Balance disorder</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Disturbance in attention</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Hypoesthesia</td> <td align="center" valign="top">2</td> <td align="center" valign="top">1</td> </tr> <tr> <td align="left" valign="top">Ataxia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Paresthesia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Eye disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Visual disturbance</td> <td align="center" valign="top">3</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Eye redness</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Vision blurred</td> <td align="center" valign="top">2</td> <td align="center" valign="top">1</td> </tr> <tr> <td align="left" valign="top">Altered visual depth perception</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Asthenopia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Ear and labyrinth disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Vertigo</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Tinnitus</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Throat irritation</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Gastrointestinal disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Nausea</td> <td align="center" valign="top">7</td> <td align="center" valign="top">4</td> </tr> <tr> <td align="left" valign="top">Constipation</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Abdominal discomfort</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Abdominal tenderness</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Frequent bowel movements</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Gastroesophageal reflux disease</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Vomiting</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Rash</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Skin wrinkling</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Urticaria</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Back pain</td> <td align="center" valign="top">4</td> <td align="center" valign="top">3</td> </tr> <tr> <td align="left" valign="top">Myalgia</td> <td align="center" valign="top">4</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Neck pain</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Reproductive system and breast disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Menorrhagia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">General disorders and administration site conditions</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Fatigue</td> <td align="center" valign="top">3</td> <td align="center" valign="top">2</td> </tr> <tr> <td align="left" valign="top">Asthenia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Chest discomfort</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Investigations</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Blood pressure increased</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Body temperature increased</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Injury, poisoning and procedural complications</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Contusion</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Social circumstances</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Exposure to poisonous plant</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> </tbody> </table>

<table frame="void" width="680" ID="i3ad0e288-aa15-4b54-8653-8783645b3168"> <caption> Table 2. Incidence of Treatment-Emergent Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial in Elderly (percentage of patients reporting)</caption> <thead> <tr> <td align="center" valign="middle"/> <td align="center" valign="top"> <content styleCode="bold">Zolpidem Tartrate</content> </td> <td align="center" valign="middle"/> </tr> <tr> <td align="center" valign="middle"> <content styleCode="bold">Body System/Adverse</content> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release</content> </td> <td align="center" valign="middle"/> </tr> <tr> <td align="center" valign="middle"> <content styleCode="bold">Reaction*</content> </td> <td align="center" valign="top"> <content styleCode="bold">Tablets 6.25 mg</content> </td> <td align="center" valign="middle"> <content styleCode="bold">Placebo</content> </td> </tr> <tr> <td align="center" valign="middle"/> <td align="center" valign="top"> <content styleCode="bold">(N=99)</content> </td> <td align="center" valign="middle"> <content styleCode="bold">(N=106)</content> </td> </tr> </thead> <tfoot> <tr> <td align="left" valign="top" colspan="3"> *Reactions reported by at least 1% of patients treated with zolpidem tartrate extended-release tablets and at greater frequency than in the placebo group. </td> </tr> <tr> <td align="left" valign="top" colspan="3"> **Memory disorders include: memory impairment, amnesia, anterograde amnesia. </td> </tr> </tfoot> <tbody> <tr> <td align="left" valign="top"> <content styleCode="bold">Infections and infestations</content> </td> <td align="left" valign="top"/> <td align="left" valign="top"/> </tr> <tr> <td align="left" valign="top">Nasopharyngitis</td> <td align="center" valign="top">6</td> <td align="center" valign="top">4</td> </tr> <tr> <td align="left" valign="top">Lower respiratory tract infection</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Otitis externa</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Upper respiratory tract infection</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Psychiatric disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Anxiety </td> <td align="center" valign="top">3</td> <td align="center" valign="top">2</td> </tr> <tr> <td align="left" valign="top">Psychomotor retardation</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Apathy</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Depressed mood</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Nervous system disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Headache </td> <td align="center" valign="top">14</td> <td align="center" valign="top">11</td> </tr> <tr> <td align="left" valign="top">Dizziness</td> <td align="center" valign="top">8</td> <td align="center" valign="top">3</td> </tr> <tr> <td align="left" valign="top">Somnolence</td> <td align="center" valign="top">6</td> <td align="center" valign="top">5</td> </tr> <tr> <td align="left" valign="top">Burning sensation</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Dizziness postural</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Memory disorders**</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Muscle contractions involuntary</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Paresthesia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Tremor</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Cardiac disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Palpitations</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Respiratory, thoracic and mediastinal disorders </content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Dry throat</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Gastrointestinal disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Flatulence</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Vomiting</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Rash</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Urticaria</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Arthralgia</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Muscle cramp</td> <td align="center" valign="top">2</td> <td align="center" valign="top">1</td> </tr> <tr> <td align="left" valign="top">Neck pain</td> <td align="center" valign="top">2</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Renal and urinary disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Dysuria</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Reproductive system and breast disorders</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Vulvovaginal dryness</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">General disorders and administration site conditions</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Influenza like illness</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top">Pyrexia</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> <tr> <td align="left" valign="top"> <content styleCode="bold">Injury, poisoning and procedural complications</content> </td> <td align="center" valign="top"/> <td align="center" valign="top"/> </tr> <tr> <td align="left" valign="top">Neck injury</td> <td align="center" valign="top">1</td> <td align="center" valign="top">0</td> </tr> </tbody> </table>