Zolpidem Tartrate (zolpidem tartrate 12.5 mg) Dailymed

9 Drug Abuse And Dependence

9.1 Controlled substance

Zolpidem tartrate is classified as a Schedule IV controlled substance by federal regulation.

9.2 Abuse

Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug effects over time. Tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects.

Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common.

Studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg effects were difficult to distinguish from placebo.

Because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic.

9.3 Dependence

Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. The following adverse events, which are considered to meet the DSM-III-R criteria for uncomplicated sedative/hypnotic withdrawal, were reported during U.S. clinical trials following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness, and abdominal discomfort. These reported adverse events occurred at an incidence of 1% or less. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Post-marketing reports of abuse, dependence and withdrawal have been received.

10 Overdosage

10.1 Signs and symptoms

In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS-depressant agents, impairment of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise and fatal outcomes have been reported.

10.2 Recommended treatment

General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Zolpidem's sedative hypnotic effect was shown to be reduced by flumazenil and therefore may be useful; however, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Sedating drugs should be withheld following zolpidem overdosage, even if excitation occurs. The value of dialysis in the treatment of overdosage has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable.

As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.

11description

Zolpidem Tartrate Extended-Release Tablets contain zolpidem tartrate, a non-benzodiazepine hypnotic of the imidazopyridine class. Zolpidem Tartrate Extended-Release Tablets are available in 6.25 mg and 12.5 mg strength tablets for oral administration.

Chemically, zolpidem is N,N,6-trimethyl-2-p-tolylimidazo[1,2-a] pyridine-3-acetamide L-(+)-tartrate (2:1). It has the following structure:

Zolpidem tartrate is a white to off-white crystalline powder that is sparingly soluble in water, alcohol, and propylene glycol. It has a molecular weight of 764.88.

Zolpidem Tartrate Extended-Release Tablet consists of a coated two-layer tablet: one layer that releases its drug content immediately and another layer that allows a slower release of additional drug content. The 6.25 mg Zolpidem Tartrate Extended-Release tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, red ferric oxide, sodium starch glycolate, and titanium dioxide. The 12.5 mg Zolpidem Tartrate Extended-Release tablet contains the following inactive ingredients: colloidal silicon dioxide, FD&C Blue #2, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate, titanium dioxide, and yellow ferric oxide.

12 Clinical Pharmacology

12.1 Mechanism of action

Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZ₁ receptor preferentially with a high affinity ratio of the α₁/α₅ subunits. This selective binding of zolpidem on the BZ₁ receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem tartrate at hypnotic doses.

12.3 Pharmacokinetics

Zolpidem Tartrate Extended-Release Tablets exhibit biphasic absorption characteristics, which results in rapid initial absorption from the gastrointestinal tract similar to zolpidem tartrate immediate-release, then provides extended plasma concentrations beyond three hours after administration. A study in 24 healthy male subjects was conducted to compare mean zolpidem plasma concentration-time profiles obtained after single oral administration of Zolpidem Tartrate Extended-Release Tablets 12.5 mg and of an immediate-release formulation of zolpidem tartrate (10 mg). The terminal elimination half-life observed with Zolpidem Tartrate Extended-Release Tablets (12.5 mg) was similar to that obtained with immediate-release zolpidem tartrate (10 mg). The mean plasma concentration-time profiles are shown in Figure 1. 

Figure 1: Mean plasma concentration-time profiles for Zolpidem Tartrate Extended-Release Tablets (12.5 mg) and immediate-release zolpidem tartrate (10 mg)

In adult and elderly patients treated with Zolpidem Tartrate Extended-Release Tablets, there was no evidence of accumulation after repeated once-daily dosing for up to two weeks.

Absorption:

Following administration of Zolpidem Tartrate Extended-Release Tablets, administered as a single 12.5 mg dose in healthy male adult subjects, the mean peak concentration (C_max) of zolpidem was 134 ng/mL (range: 68.9 to 197 ng/ml) occurring at a median time (T_max) of 1.5 hours. The mean AUC of zolpidem was 740 ng∙hr/mL (range: 295 to 1359 ng∙hr/mL).

A food-effect study in 45 healthy subjects compared the pharmacokinetics of Zolpidem Tartrate Extended-Release Tablets 12.5 mg when administered while fasting or within 30 minutes after a meal. Results demonstrated that with food, mean AUC and C_max were decreased by 23% and 30%, respectively, while median T_max was increased from 2 hours to 4 hours. The half-life was not changed. These results suggest that, for faster sleep onset, Zolpidem Tartrate Extended-Release Tablets should not be administered with or immediately after a meal.

Distribution:

Total protein binding was found to be 92.5 ± 0.1% and remained constant, independent of concentration between 40 and 790 ng/mL.

Metabolism:

Zolpidem is converted to inactive metabolites that are eliminated primarily by renal excretion.

Elimination:

When Zolpidem Tartrate Extended-Release Tablets were administered as a single 12.5 mg dose in healthy male adult subjects, the mean zolpidem elimination half-life was 2.8 hours (range: 1.62 to 4.05 hr).

Special Populations

Elderly:

In 24 elderly (≥ 65 years) healthy subjects administered a single 6.25 mg dose of Zolpidem Tartrate Extended-Release Tablets, the mean peak concentration (C_max) of zolpidem was 70.6 (range: 35.0 to 161) ng/mL occurring at a median time (T_max) of 2.0 hours. The mean AUC of zolpidem was 413 ng∙hr/mL (range: 124 to 1190 ng∙hr/mL) and the mean elimination half-life was 2.9 hours (range: 1.59 to 5.50 hours).

Hepatic Impairment:

Zolpidem Tartrate Extended-Release Tablets were not studied in patients with hepatic impairment. The pharmacokinetics of an immediate-release formulation of zolpidem tartrate in eight patients with chronic hepatic insufficiency were compared to results in healthy subjects. Following a single 20-mg oral zolpidem tartrate dose, mean C_max and AUC were found to be two times (250 vs. 499 ng/mL) and five times (788 vs. 4,203 ng∙hr/mL) higher, respectively, in hepatically compromised patients. T_max did not change. The mean half-life in cirrhotic patients of 9.9 hr (range: 4.1 to 25.8 hr) was greater than that observed in normal subjects of 2.2 hr (range: 1.6 to 2.4 hr). Dosing should be modified accordingly in patients with hepatic insufficiency [see Dosage and Administration (2.2) and Warnings and Precautions (5.6)].

Renal Impairment:

Zolpidem Tartrate Extended-Release Tablets were not studied in patients with renal impairment. The pharmacokinetics of an immediate-release formulation of zolpidem tartrate were studied in 11 patients with end-stage renal failure (mean Cl_Cr = 6.5 ± 1.5 mL/min) undergoing hemodialysis three times a week, who were dosed with zolpidem tartrate 10 mg orally each day for 14 or 21 days. No statistically significant differences were observed for C_max, T_max, half-life, and AUC between the first and last day of drug administration when baseline concentration adjustments were made. On day 1, C_max was 172 ± 29 ng/mL (range: 46 to 344 ng/mL). After repeated dosing for 14 or 21 days, C_max was 203 ± 32 ng/mL (range: 28 to 316 ng/mL). On day 1, T_max was 1.7 ± 0.3 hr (range: 0.5 to 3.0 hr); after repeated dosing T_max was 0.8 ± 0.2 hr (range: 0.5 to 2.0 hr). This variation is accounted for by noting that last-day serum sampling began 10 hours after the previous dose, rather than after 24 hours. This resulted in residual drug concentration and a shorter period to reach maximal serum concentration. On day 1, T_1/2 was 2.4 ± 0.4 hr (range: 0.4 to 5.1 hr). After repeated dosing, T_1/2 was 2.5 ± 0.4 hr (range: 0.7 to 4.2 hr). AUC was 796 ± 159 ng∙hr/mL after the first dose and 818 ± 170 ng∙hr/mL after repeated dosing. Zolpidem was not hemodialyzable. No accumulation of unchanged drug appeared after 14 or 21 days. Zolpidem pharmacokinetics were not significantly different in renally-impaired patients. No dosage adjustment is necessary in patients with compromised renal function. However, as a general precaution, these patients should be closely monitored.

13 Nonclinical Toxicology

13.1 Carcinogenesis, mutagenesis, impairment of fertility

Carcinogenesis: Zolpidem was administered to mice and rats for 2 years at dietary dosages of 4, 18, and 80 mg base/kg. In mice, these doses are approximately 2, 9, and 40 times the maximum recommended human dose (MRHD) of 12.5 mg/day (10 mg zolpidem base) on mg/m² basis. In rats, these doses are approximately 4, 18, and 80 times the MRHD on a mg/m² basis. No evidence of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid- and high doses.

Mutagenesis: Zolpidem was negative in in vitro (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and in vivo (mouse micronucleus) genetic toxicology assays.

Impairment of fertility: Oral administration of zolpidem (doses of 4, 20, and 100 mg base/kg or approximately 4, 20, and 100 times the MRHD on a mg/m² basis) to rats prior to and during mating, and continuing in females through postpartum day 25, resulted in irregular estrus cycles and prolonged precoital intervals. The no-effect dose for these findings is approximately 20 times the MRHD of Zolpidem Tartrate Extended-Release Tablets on a mg/m² basis. There was no impairment of fertility at any dose tested.

14 Clinical Studies

14.1 Controlled clinical trials

Zolpidem Tartrate Extended-Release Tablets were evaluated in three placebo-controlled studies for the treatment of patients with chronic primary insomnia (as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM IV).

Adult outpatients (18–64 years) with primary insomnia (N=212) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing Zolpidem Tartrate Extended-Release Tablets 12.5 mg and placebo. Zolpidem Tartrate Extended-Release Tablets 12.5 mg decreased wake time after sleep onset (WASO) for the first 7 hours during the first 2 nights and for the first 5 hours after 2 weeks of treatment. Zolpidem Tartrate Extended-Release Tablets 12.5 mg were superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasing latency to persistent sleep [LPS]) during the first 2 nights of treatment and after 2 weeks of treatment. Zolpidem Tartrate Extended-Release Tablets 12.5 mg were also superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment.

Elderly outpatients (≥ 65 years) with primary insomnia (N=205) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing Zolpidem Tartrate Extended-Release Tablets 6.25 mg and placebo. Zolpidem Tartrate Extended-Release Tablets 6.25 mg decreased wake time after sleep onset (WASO) for the first 6 hours during the first 2 nights and the first 4 hours after 2 weeks of treatment. Zolpidem Tartrate Extended-Release Tablets 6.25 mg were superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasing LPS) during the first 2 nights of treatment and after 2 weeks on treatment. Zolpidem Tartrate Extended-Release Tablets 6.25 mg were superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment.

In both studies, in patients treated with Zolpidem Tartrate Extended-Release Tablets, polysomnography showed increased wakefulness at the end of the night compared to placebo-treated patients.

In a 24-week double-blind, placebo controlled, randomized study in adult outpatients (18–64 years) with primary insomnia (N=1025), Zolpidem Tartrate Extended-Release Tablets 12.5 mg administered as needed (3 to 7 nights per week) were superior to placebo over 24 weeks, on patient global impression regarding aid to sleep, and on patient-reported specific sleep parameters for sleep induction and sleep maintenance with no significant increased frequency of drug intake observed over time.

14.2 Studies pertinent to safety concerns for sedative/hypnotic drugs

Next-day residual effects: In five clinical studies [three controlled studies in adults (18–64 years of age) administered Zolpidem Tartrate Extended-Release Tablets 12.5 mg and two controlled studies in the elderly (≥ 65 years of age) administered Zolpidem Tartrate Extended-Release Tablets 6.25 mg or 12.5 mg], the effect of Zolpidem Tartrate Extended-Release Tablets on vigilance, memory, or motor function were assessed using neurocognitive tests. In these studies, no significant decrease in performance was observed eight hours after a nighttime dose. In addition, no evidence of next-day residual effects was detected with Zolpidem Tartrate Extended-Release Tablets 12.5 mg and 6.25 mg using self-ratings of sedation.

During the 3-week studies, next-day somnolence was reported by 15% of the adult patients who received 12.5 mg Zolpidem Tartrate Extended-Release Tablets versus 2% of the placebo group; next-day somnolence was reported by 6% of the elderly patients who received 6.25 mg Zolpidem Tartrate Extended-Release Tablets versus 5% of the placebo group [see Adverse Reactions (6)]. In a 6-month study, the overall incidence of next-day somnolence was 5.7% in the Zolpidem Tartrate Extended-Release Tablets group as compared to 2% in the placebo group.

Rebound effects: Rebound insomnia, defined as a dose-dependent worsening in sleep parameters (latency, sleep efficiency, and number of awakenings) compared with baseline following discontinuation of treatment, is observed with short- and intermediate-acting hypnotics. In the two 3-week placebo-controlled studies in patients with primary insomnia, a rebound effect was only observed on the first night after abrupt discontinuation of Zolpidem Tartrate Extended-Release Tablets. On the second night, there was no worsening compared to baseline in the Zolpidem Tartrate Extended-Release Tablets group.

In a 6-month placebo-controlled study in which Zolpidem Tartrate Extended-Release Tablets were taken as needed (3 to 7 nights per week), within the first month a rebound effect was observed for Total Sleep Time (not for WASO) during the first night off medication. After this first month period, no further rebound insomnia was observed. After final treatment discontinuation no rebound was observed.

16 How Supplied/storage And Handling

Zolpidem Tartrate Extended-Release 12.5 mg tablets are composed of two layers1 and are coated, blue, round, bi-convex, debossed with ZCR on one side and supplied as:

Bottles of 10	NDC 54868-6215-1
Bottles of 30	NDC 54868-6215-0
Bottles of 60	NDC 54868-6215-2
Bottles of 90	NDC 54868-6215-3

1Layers are covered by the coating and are indistinguishable.

STORAGE AND HANDLING SECTION

Store between 15°–25° C (59°–77°F). Limited excursions permissible up to 30° C (86°F)

17 Patient Counseling Information

Prescribers or other healthcare professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with sedative-hypnotics, should counsel them in its appropriate use, and should instruct them to read the accompanying Medication Guide [see Medication Guide (17.4)].

17.1 Severe anaphylactic and anaphylactoid reactions

Inform patients that severe anaphylactic and anaphylactoid reactions have occurred with zolpidem. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if any of them occur.

17.2Sleep-driving and other complex behaviors

There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since "sleep-driving" can be dangerous. This behavior is more likely to occur when Zolpidem Tartrate Extended-Release Tablets are taken with alcohol or other central nervous system depressants [see Warnings and Precautions (5.3)]. 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.

In addition, patients should be advised to report all concomitant medications to the prescriber. Patients should be instructed to report events such as "sleep-driving" and other complex behaviors immediately to the prescriber.

17.3 Administration instructions

Patients should be counseled to take Zolpidem Tartrate right before they get into bed and only when they are able to stay in bed a full night (7–8 hours) before being active again. Zolpidem Tartrate Extended-Release Tablets should not be crushed, divided, or chewed, and should not be taken with or immediately after a meal. Advise patients NOT to take Zolpidem Tartrate Extended-Release Tablets when drinking alcohol.

17.4 Medication Guide

Spl Medguide Section

MEDICATION GUIDE ZOLPIDEM TARTRATE EXTENDED-RELEASE TABLETS C-IV

Read the Medication Guide that comes with ZOLPIDEM TARTRATE Extended-Release Tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment.

What is the most important information I should know about ZOLPIDEM TARTRATE Extended-Release Tablets?

After taking ZOLPIDEM TARTRATE Extended-Release Tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with ZOLPIDEM TARTRATE Extended-Release Tablets. Reported activities include:

• driving a car ("sleep-driving")
• making and eating food
• talking on the phone
• having sex
• sleep-walking

Call your doctor right away if you find out that you have done any of the above activities after taking ZOLPIDEM TARTRATE Extended-Release Tablets.

Important:

1.  Take ZOLPIDEM TARTRATE Extended-Release Tablets exactly as prescribed

• Do not take more ZOLPIDEM TARTRATE Extended-Release Tablets than prescribed.
• Take ZOLPIDEM TARTRATE Extended-Release Tablets right before you get in bed, not sooner.

2.  Do not take ZOLPIDEM TARTRATE Extended-Release Tablets if you:

• drink alcohol
• take other medicines that can make you sleepy. Talk to your doctor about all of your medicines. Your doctor will tell you if you can take ZOLPIDEM TARTRATE Extended-Release Tablets with your other medicines.
• cannot get a full night's sleep

What are ZOLPIDEM TARTRATE Extended-Release Tablets?

ZOLPIDEM TARTRATE Extended-Release Tablets is a sedative-hypnotic (sleep) medicine. ZOLPIDEM TARTRATE Extended-Release Tablets are used in adults for the treatment of a sleep problem called insomnia. Symptoms of insomnia include:

• trouble falling asleep
• waking up often during the night

ZOLPIDEM TARTRATE Extended-Release Tablets are not for children.

BOXED WARNING SECTION

ZOLPIDEM TARTRATE Extended Release Tablets are a federally controlled substance (C-IV) because they 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.

Who should not take ZOLPIDEM TARTRATE Extended-Release Tablets?

Do not take ZOLPIDEM TARTRATE Extended-Release Tablets if you are allergic to anything in it. See the end of this Medication Guide for a complete ul of ingredients in ZOLPIDEM TARTRATE Extended-Release Tablets.

ZOLPIDEM TARTRATE Extended-Release Tablets may not be right for you. Before starting ZOLPIDEM TARTRATE Extended-Release Tablets, tell your doctor about all of your health conditions, including if you:

• have a history of depression, mental illness, or suicidal thoughts
• have a history of drug or alcohol abuse or addiction
• have kidney or liver disease
• have a lung disease or breathing problems
• are pregnant, planning to become pregnant, or breastfeeding

Tell your doctor about all of the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Medicines can interact with each other, sometimes causing serious side effects. Do not take ZOLPIDEM TARTRATE Extended-Release Tablets with other medicines that can make you sleepy.

Know the medicines you take. Keep a ul of your medicines with you to show your doctor and pharmacist each time you get a new medicine.

How should I take ZOLPIDEM TARTRATE Extended-Release Tablets?

• Take ZOLPIDEM TARTRATE Extended-Release Tablets exactly as prescribed. Do not take more ZOLPIDEM TARTRATE Extended-Release Tablets than prescribed for you.
• Take ZOLPIDEM TARTRATE Extended-Release Tablets right before you get into bed.
• Do not take ZOLPIDEM TARTRATE Extended-Release Tablets unless you are able to stay in bed a full night (7–8 hours) before you must be active again.
• Swallow ZOLPIDEM TARTRATE Extended-Release Tablets whole. Do not chew or break the tablets. Tell your doctor if you cannot swallow tablets whole.
• For faster sleep onset, ZOLPIDEM TARTRATE Extended-Release Tablets should NOT be taken with or immediately after a meal.
• Call your doctor if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problems.
• If you take too much ZOLPIDEM TARTRATE Extended-Release Tablets or overdose, call your doctor or poison control center right away, or get emergency treatment.

What are the possible side effects of ZOLPIDEM TARTRATE Extended-Release Tablets?

Serious side effects of ZOLPIDEM TARTRATE Extended-Release Tablets include:

• getting out of bed while not being fully awake and do an activity that you do not know you are doing. (See "What is the most important information I should know about ZOLPIDEM TARTRATE Extended-Release Tablets?")
• abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions.
• memory loss
• anxiety
• severe allergic reactions. Symptoms include swelling of the tongue or throat, trouble breathing, and nausea and vomiting. Get emergency medical help if you get these symptoms after taking ZOLPIDEM TARTRATE Extended-Release Tablets.

Call your doctor right away if you have any of the above side effects or any other side effects that worry you while using ZOLPIDEM TARTRATE Extended-Release Tablets.

The most common side effects of ZOLPIDEM TARTRATE Extended-Release Tablets are:

• headache
• sleepiness
• dizziness
• You may still feel drowsy the next day after taking ZOLPIDEM TARTRATE Extended-Release Tablets. Do not drive or do other dangerous activities after taking ZOLPIDEM TARTRATE Extended-Release Tablets until you feel fully awake.

After you stop taking a sleep medicine, you may have symptoms for 1 to 2 days such as: trouble sleeping, nausea, flushing, lightheadedness, uncontrolled crying, vomiting, stomach cramps, panic attack, nervousness, and stomach area pain.

These are not all the side effects of ZOLPIDEM TARTRATE Extended-Release Tablets. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1–800–FDA–1088.

How should I store ZOLPIDEM TARTRATE Extended-Release Tablets?

• Store ZOLPIDEM TARTRATE Extended-Release Tablets at room temperature, 59° to 77°F (15° to 25° C).
• Keep ZOLPIDEM TARTRATE Extended-Release Tablets and all medicines out of reach of children.

General Information about ZOLPIDEM TARTRATE Extended-Release Tablets

• Medicines are sometimes prescribed for purposes other than those uled in a Medication Guide.
• Do not use ZOLPIDEM TARTRATE Extended-Release Tablets for a condition for which it was not prescribed.
• Do not share ZOLPIDEM TARTRATE Extended-Release Tablets with other people, even if you think they have the same symptoms that you have. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about ZOLPIDEM TARTRATE Extended-Release Tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about ZOLPIDEM TARTRATE Extended-Release Tablets that is written for healthcare professionals. For more information about ZOLPIDEM TARTRATE Extended-Release Tablets, call 1-800-633-1610.

What are the ingredients in ZOLPIDEM TARTRATE Extended-Release Tablets?

Active Ingredient: Zolpidem tartrate

Inactive Ingredients: The 6.25 mg tablets contain: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, red ferric oxide, sodium starch glycolate, and titanium dioxide. The 12.5 mg tablets contain: colloidal silicon dioxide, FD&C Blue #2, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate, titanium dioxide, and yellow ferric oxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Winthrop U.S.,a business of sanofi-aventis U.S. LLC

December, 2010

Relabeling and Repackaging by: Physicians Total Care, Inc.Tulsa, OK       74146

Package Label.principal Display Panel

PRINCIPAL DISPLAY PANEL - 12.5 mg Tablet Bottle Label

Zolpidem Tartrate Extended-ReleaseCIV

12.5 ^mg

Dispense with Medication Guide

Rx only