Need to evaluate for co-morbid diagnosis: Reevaluate if insomnia persists after 7 to 10 days

of use. (5.2)
Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. (5.3)
Sleep-driving and other complex behaviors while not fully awake. Risk increases with dose
and use with other CNS depressants and alcohol. Immediately evaluate any new onset
behavioral changes. (5.4)
Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least
amount of tablets feasible to avoid intentional overdose. (5.5)
Respiratory Depression: Consider this risk before prescribing in patients with compromised
respiratory function (5.6)
Withdrawal effects: Symptoms may occur with rapid dose reduction or discontinuation (5.7, 9.3)
Severe Injuries: Drowsiness may lead to fall including severe injuries (5.8)
ADVERSE REACTIONS
Most commonly observed adverse reactions were:
Short-term (< 10 nights): Drowsiness, dizziness, and diarrhea
Long-term (28 35 nights): Dizziness and drugged feelings (6.1)

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use AMBIEN safely and
effectively. See full prescribing information for AMBIEN
AMBIEN (zolpidem tartrate) tablets, for oral use, C-IV
Initial U.S. Approval: 1992
RECENT MAJOR CHANGES
Warnings and Precautions, Severe Injuries (5.8)

10/2014

INDICATIONS AND USAGE

AMBIEN, a gamma-aminobutyric acid (GABA) A agonist, is indicated for the short-term treatment
of insomnia characterized by difficulties with sleep initiation. AMBIEN has been shown to decrease
sleep latency for up to 35 days in controlled clinical studies. (1)
DOSAGE AND ADMINISTRATION
Use the lowest dose effective for the patient (2.1)
Recommended initial dose is 5 mg for women and 5 or 10 mg for men, immediately before
bedtime with at least 78 hours remaining before the planned time of awakening (2.1)
Geriatric patients and patients with hepatic impairment: Recommended dose is 5 mg for men
and women (2.2)
Lower doses of CNS depressants may be necessary when taken concomitantly with AMBIEN
(2.3)
The effect of AMBIEN may be slowed if taken with or immediately after a meal (2.4)

To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at

1-800-633-1610 or FDA at 1-800-FDA-1088, or http://www.fda.gov/medwatch
DRUG INTERACTIONS
CNS depressants, including alcohol: Possible adverse additive CNS-depressant effects (5.1,
7.1)
Imipramine: Decreased alertness observed (7.1)
Chlorpromazine: Impaired alertness and psychomotor performance observed (7.1)
Rifampin: Combination use may decrease effect (7.2)
Ketoconazole: Combination use may increase effect (7.2)
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm (8.1)
Pediatric use: Safety and effectiveness not established. Hallucinations (incidence rate 7%) and
other psychiatric and/or nervous system adverse reactions were observed frequently in a study
of pediatric patients with Attention-Deficit/Hyperactivity Disorder (5.4, 8.4)

DOSAGE FORMS AND STRENGTHS

5 mg and 10 mg tablets. Tablets not scored. (3)
CONTRAINDICATIONS
Known hypersensitivity to zolpidem (4)

WARNINGS AND PRECAUTIONS

CNS depressant effects: Impairs alertness and motor coordination. Instruct patients on correct
use. (5.1)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved Medication Guide

Revised: 10/2014

FULL PRESCRIBING INFORMATION: CONTENTS*

1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1
Dosage in Adults
2.2
Special Populations
2.3
Use with CNS Depressants
2.4
Administration
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
5.1
CNS Depressant Effects and Next-Day Impairment
5.2
Need to Evaluate for Co-morbid Diagnoses
5.3
Severe Anaphylactic and Anaphylactoid Reactions
5.4
Abnormal Thinking and Behavioral Changes
5.5
Use in Patients with Depression
5.6
Respiratory Depression
5.7
Withdrawal Effects
5.8
Severe Injuries
6
ADVERSE REACTIONS
6.1
Clinical Trials Experience
7
DRUG INTERACTIONS
7.1
CNS-active Drugs
7.2
Drugs that Affect Drug Metabolism via Cytochrome P450
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.2
Labor and Delivery

10

11
12

13
14

16
17

8.3
Nursing Mothers
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Gender Difference in Pharmacokinetics
DRUG ABUSE AND DEPENDENCE
9.1
Controlled Substance
9.2
Abuse
9.3
Dependence
OVERDOSAGE
10.1
Signs and Symptoms
10.2
Recommended Treatment
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
12.3
Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1
Transient Insomnia
14.2
Chronic Insomnia
14.3
Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs
HOW SUPPLIED/STORAGE AND HANDLING
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed

FULL PRESCRIBING INFORMATION

1
INDICATIONS AND USAGE
AMBIEN (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized by
difficulties with sleep initiation. AMBIEN has been shown to decrease sleep latency for up to 35 days
in controlled clinical studies [see Clinical Studies (14)].
The clinical trials performed in support of efficacy were 45 weeks in duration with the final formal
assessments of sleep latency performed at the end of treatment.
2
DOSAGE AND ADMINISTRATION
2.1 Dosage in Adults
Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and
either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 78 hours
remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be

increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose
increase the risk of next day impairment of driving and other activities that require full alertness [see
Warnings and Precautions (5.1)]. The total dose of AMBIEN should not exceed 10 mg once daily
immediately before bedtime.
The recommended initial doses for women and men are different because zolpidem clearance is lower
in women.
2.2 Special Populations
Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. Patients
with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose
of AMBIEN in both of these patient populations is 5 mg once daily immediately before bedtime [see
Warnings and Precautions (5.1); Use in Specific Populations (8.5)].
1

2.3 Use with CNS Depressants

Dosage adjustment may be necessary when AMBIEN is combined with other CNS depressant drugs
because of the potentially additive effects [see Warnings and Precautions (5.1)].
2.4 Administration
The effect of AMBIEN may be slowed by ingestion with or immediately after a meal.
3
DOSAGE FORMS AND STRENGTHS
AMBIEN is available in 5 mg and 10 mg strength tablets for oral administration. Tablets are not scored.
AMBIEN 5 mg tablets are capsule-shaped, pink, film coated, with AMB 5 debossed on one side and
5401 on the other.
AMBIEN 10 mg tablets are capsule-shaped, white, film coated, with AMB 10 debossed on one side
and 5421 on the other.
4
CONTRAINDICATIONS
AMBIEN is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions
include anaphylaxis and angioedema [see Warnings and Precautions (5.3)].
5
WARNINGS AND PRECAUTIONS
5.1 CNS Depressant Effects and Next-Day Impairment
AMBIEN, like other sedative-hypnotic drugs, has central nervous system (CNS) depressant effects.
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Dosage adjustments of AMBIEN and of other
concomitant CNS depressants may be necessary when AMBIEN is administered with such agents
because of the potentially additive effects. The use of AMBIEN with other sedative-hypnotics (including
other zolpidem products) at bedtime or the middle of the night is not recommended [see Dosage and
Administration (2.3)].
The risk of next-day psychomotor impairment, including impaired driving, is increased if AMBIEN is
taken with less than a full night of sleep remaining (7 to 8 hours); if a higher than the recommended
dose is taken; if co-administered with other CNS depressants; or if co-administered with other drugs
that increase the blood levels of zolpidem. Patients should be cautioned against driving and other
activities requiring complete mental alertness if AMBIEN is taken in these circumstances [see Dosage
and Administration (2) and Clinical Studies (14.3)].
5.2 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.
5.3 Severe Anaphylactic and Anaphylactoid Reactions
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.
5.4 Abnormal Thinking and Behavioral Changes
Abnormal thinking and behavior changes have been reported in patients treated with sedative/
hypnotics, including AMBIEN. Some of these changes included decreased inhibition (e.g., aggressiveness and extroversion that seemed out of character), bizarre behavior, agitation and depersonalization. Visual and auditory hallucinations have been reported.
In controlled trials of AMBIEN 10 mg taken at bedtime < 1% of adults with insomnia reported
hallucinations. In a clinical trial, 7% of pediatric patients treated with AMBIEN 0.25 mg/kg taken at
bedtime reported hallucinations versus 0% treated with placebo [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 in sedative-hypnotic-naive as well
as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving have
occurred with AMBIEN alone at therapeutic doses, the co-administration of AMBIEN with alcohol and
other CNS depressants increases the risk of such behaviors, as does the use of AMBIEN at doses
exceeding the maximum recommended dose. Due to the risk to the patient and the community,
discontinuation of AMBIEN 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 neuropsychiatric symptoms may also occur.
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.
5.5 Use in Patients with Depression
In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal
thoughts and actions (including completed suicides), have been reported. 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 lowest number of tablets that is feasible should be
prescribed for the patient at any one time.
5.6 Respiratory Depression
Although studies with 10 mg zolpidem tartrate did not reveal respiratory depressant effects at hypnotic
doses in healthy subjects 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 zolpidem compared to placebo. Since sedativehypnotics have the capacity to depress respiratory drive, precautions should be taken if AMBIEN is
prescribed to patients with compromised respiratory function. Post-marketing reports of respiratory
insufficiency in patients receiving 10 mg of zolpidem tartrate, most of whom had pre-existing respiratory
impairment, have been reported. The risk of respiratory depression should be considered prior to
prescribing AMBIEN in patients with respiratory impairment including sleep apnea and myasthenia
gravis.

5.7 Withdrawal Effects

There have been reports of withdrawal signs and symptoms following the rapid dose decrease or abrupt
discontinuation of zolpidem. Monitor patients for tolerance, abuse, and dependence [see Drug Abuse
and Dependence (9.2) and (9.3)].
5.8 Severe Injuries
Zolpidem can cause drowsiness and a decreased level of consciousness, which may lead to falls and
consequently to severe injuries. Severe injuries such as hip fractures and intracranial hemorrhage have
been reported.
6
ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
CNS-depressant effects and next-day impairment [see Warnings and Precautions (5.1)]
Serious anaphylactic and anaphylactoid reactions [see Warnings and Precautions (5.3)]
Abnormal thinking and behavior changes, and complex behaviors [see Warnings and Precautions
(5.4)]
Withdrawal effects [see Warnings and Precautions (5.7)]
6.1 Clinical Trials Experience
Associated with discontinuation of treatment: Approximately 4% of 1,701 patients who received
zolpidem at all doses (1.25 to 90 mg) in U.S. premarketing clinical trials discontinued treatment because
of an adverse reaction. Reactions most commonly associated with discontinuation from U.S. trials were
daytime drowsiness (0.5%), dizziness (0.4%), headache (0.5%), nausea (0.6%), and vomiting (0.5%).
Approximately 4% of 1,959 patients who received zolpidem at all doses (1 to 50 mg) in similar foreign
trials discontinued treatment because of an adverse reaction. Reactions most commonly associated
with discontinuation from these trials were daytime drowsiness (1.1%), dizziness/vertigo (0.8%),
amnesia (0.5%), nausea (0.5%), headache (0.4%), and falls (0.4%).
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 short-term treatment (up to 10
nights) with AMBIEN at doses up to 10 mg, the most commonly observed adverse reactions associated
with the use of zolpidem and seen at statistically significant differences from placebo-treated patients
were drowsiness (reported by 2% of zolpidem patients), dizziness (1%), and diarrhea (1%). During
longer-term treatment (28 to 35 nights) with zolpidem at doses up to 10 mg, the most commonly
observed adverse reactions associated with the use of zolpidem and seen at statistically significant
differences from placebo-treated patients were dizziness (5%) and drugged feelings (3%).
Adverse reactions observed at an incidence of 1% in controlled trials: The following tables enumerate
treatment-emergent adverse reactions frequencies that were observed at an incidence equal to 1% or
greater among patients with insomnia who received zolpidem tartrate and at a greater incidence than
placebo in U.S. placebo-controlled trials. Events reported by investigators were classified utilizing a
modified World Health Organization (WHO) dictionary of preferred terms 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 table was derived from results of 11 placebo-controlled short-term U.S. efficacy trials
involving zolpidem in doses ranging from 1.25 to 20 mg. The table is limited to data from doses up
to and including 10 mg, the highest dose recommended for use.
Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials
Lasting up to 10 Nights (Percentage of patients reporting)
Zolpidem
(10 mg)
Placebo
Body System/
(N=685)
(N=473)
Adverse Event*
Central and Peripheral Nervous System
Headache
7
6
Drowsiness
2
Dizziness
1
Gastrointestinal System
Diarrhea
1
*Reactions reported by at least 1% of patients treated with AMBIEN and at a greater frequency than
placebo.
The following table was derived from results of three placebo-controlled long-term efficacy trials
involving AMBIEN (zolpidem tartrate). These trials involved patients with chronic insomnia who were
treated for 28 to 35 nights with zolpidem at doses of 5, 10, or 15 mg. The table is limited to data from
doses up to and including 10 mg, the highest dose recommended for use. The table includes only
adverse events occurring at an incidence of at least 1% for zolpidem patients.
Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials
Lasting up to 35 Nights (Percentage of patients reporting)
Zolpidem
(10 mg)
Placebo
Body System/
*
(N=152)
(N=161)
Adverse Event
Autonomic Nervous System
Dry mouth
3
1
Body as a Whole
Allergy
4
1
Back Pain
3
2
Influenza-like symptoms
2
Chest pain
1
Cardiovascular System
Palpitation
2
2

Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials

Lasting up to 35 Nights (Percentage of patients reporting) (continued)
Zolpidem
(10 mg)
Placebo
Body System/
*
(N=152)
(N=161)
Adverse Event
Central and Peripheral Nervous System
Drowsiness
8
5
Dizziness
5
1
Lethargy
3
1
Drugged feeling
3
Lightheadedness
2
1
Depression
2
1
Abnormal dreams
1
Amnesia
1
Sleep disorder
1
Gastrointestinal System
Diarrhea
3
2
Abdominal pain
2
2
Constipation
2
1
Respiratory System
Sinusitis
4
2
Pharyngitis
3
1
Skin and Appendages
Rash
2
1

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.
7
DRUG INTERACTIONS
7.1 CNS-active Drugs
Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression [see
Warnings and Precautions (5.1)]. Zolpidem tartrate was evaluated in healthy volunteers in single-dose
interaction studies for several CNS drugs.
Imipramine, Chlorpromazine
Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20%
decrease in peak levels of imipramine, but there was an additive effect of decreased alertness.
Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but
there was an additive effect of decreased alertness and psychomotor performance [see Clinical
Pharmacology (12.3)].
Haloperidol
A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics
or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration
does not predict the absence of an effect following chronic administration [see Clinical Pharmacology
(12.3)].
Alcohol
An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was
demonstrated [see Warnings and Precautions (5.1)].
Sertraline
Concomitant administration of zolpidem and sertraline increases exposure to zolpidem [see Clinical
Pharmacology (12.3)].
Fluoxetine
After multiple doses of zolpidem tartrate and fluoxetine an increase in the zolpidem half-life (17%) was
observed. There was no evidence of an additive effect in psychomotor performance [see Clinical
Pharmacology (12.3)].
7.2 Drugs that Affect Drug Metabolism via Cytochrome P450
Some compounds known to inhibit CYP3A may increase exposure to zolpidem. The effect of drugs on
other P450 enzymes on the exposure to zolpidem is not known.
Rifampin
Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects
of zolpidem. Use of Rifampin in combination with zolpidem may decrease the efficacy of zolpidem.
Ketoconazole
Ketoconazole, a potent CYP3A4 inhibitor, increased the pharmacodynamic effects of zolpidem.
Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are
given together.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies of AMBIEN in pregnant women.
Studies in children to assess the effects of prenatal exposure to zolpidem have not been conducted;
however, cases of severe neonatal respiratory depression have been reported when zolpidem was
used at the end of pregnancy, especially when taken with other CNS-depressants. Children born to
mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal
period. Neonatal flaccidity has also been reported in infants born to mothers who received sedativehypnotic drugs during pregnancy. AMBIEN should be used during pregnancy only if the potential benefit
outweighs the potential risk to the fetus.
Administration of zolpidem to pregnant rats and rabbits resulted in adverse effects on offspring
development at doses greater than the AMBIEN maximum recommended human dose (MRHD) of 10
mg/day (approximately 8 mg/day zolpidem base); however, teratogenicity was not observed.
When zolpidem was administered at oral doses of 4, 20, and 100 mg base/kg/day to pregnant rats
during the period of organogenesis, dose-related decreases in fetal skull ossification occurred at all but
the lowest dose, which is approximately 5 times the MRHD on a mg/m2 basis. In rabbits treated during
organogenesis with zolpidem at oral doses of 1, 4, and 16 mg base/kg/day increased embryo-fetal
death and incomplete fetal skeletal ossification occurred at the highest dose tested. The no-effect dose
for embryo-fetal toxicity in rabbits is approximately 10 times the MRHD on a mg/m2 basis.
Administration of zolpidem to rats at oral doses of 4, 20, and 100 mg base/kg/day during the latter part
of pregnancy and throughout lactation produced decreased offspring growth and survival at all but the
lowest dose, which is approximately 5 times the MRHD on a mg/m2 basis.
8.2 Labor and Delivery
AMBIEN has no established use in labor and delivery [see Pregnancy (8.1)].
8.3 Nursing Mothers
Zolpidem is excreted in human milk. Caution should be exercised when AMBIEN is administered to a
nursing woman.
8.4 Pediatric Use
AMBIEN is not recommended for use in children. Safety and effectiveness of zolpidem in pediatric
patients below the age of 18 years have not been established.
In an 8-week study, in pediatric patients (aged 617 years) with insomnia associated with attentiondeficit/hyperactivity disorder (ADHD) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at
bedtime did not decrease sleep latency compared to placebo. Psychiatric and nervous system
disorders comprised the most frequent (> 5%) treatment emergent adverse reactions observed with
zolpidem versus placebo and included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and
hallucinations were reported in 7% of the pediatric patients who received zolpidem; none of the pediatric
patients who received placebo reported hallucinations [see Warnings and Precautions(5.4)]. Ten
patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction.
8.5 Geriatric Use
A total of 154 patients in U.S. controlled clinical trials and 897 patients in non-U.S. clinical trials who
received zolpidem were 60 years of age. For a pool of U.S. patients receiving zolpidem at doses
of 10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for
zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could
be considered drug related).

*Reactions reported by at least 1% of patients treated with AMBIEN and at a greater frequency than
placebo.
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.
Adverse event incidence across the entire preapproval database: AMBIEN 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 AMBIEN, 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: 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: edema, falling, fatigue, 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, euphoria, headache, insomnia,
vertigo Infrequent: agitation, anxiety, 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: dyspepsia, hiccup, nausea. Infrequent: anorexia, constipation,
dysphagia, flatulence, gastroenteritis, vomiting. 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: Frequent: arthralgia, myalgia. Infrequent: arthritis. Rare: arthrosis, muscle
weakness, sciatica, tendinitis.
Reproductive system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast
neoplasm, breast pain.
Respiratory system: Frequent: upper respiratory infection, lower respiratory infection. Infrequent:
bronchitis, coughing, dyspnea, rhinitis. Rare: bronchospasm, respiratory depression, epistaxis, hypoxia,
laryngitis, pneumonia.
3

Adverse Event
Dizziness
Drowsiness
Diarrhea

Zolpidem
3%
5%
3%

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.
Each AMBIEN tablet includes the following inactive ingredients: hydroxypropyl methylcellulose, lactose,
magnesium stearate, micro-crystalline cellulose, polyethylene glycol, sodium starch glycolate, and
titanium dioxide. The 5 mg tablet also contains FD&C Red No. 40, iron oxide colorant, and polysorbate
80.
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 1/5
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
The pharmacokinetic profile of AMBIEN is characterized by rapid absorption from the gastrointestinal
tract and a short elimination half-life (T1/2) in healthy subjects.
In a single-dose crossover study in 45 healthy subjects administered 5 and 10 mg zolpidem tartrate
tablets, the mean peak concentrations (Cmax) were 59 (range: 29 to 113) and 121 (range: 58 to 272)
ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both. The mean AMBIEN
elimination half-life was 2.6 (range: 1.4 to 4.5) and 2.5 (range: 1.4 to 3.8) hours, for the 5 and 10 mg
tablets, respectively. AMBIEN is converted to inactive metabolites that are eliminated primarily by renal
excretion. AMBIEN demonstrated linear kinetics in the dose range of 5 to 20 mg. Total protein binding
was found to be 92.5 0.1% and remained constant, independent of concentration between 40 and
790 ng/mL. Zolpidem did not accumulate in young adults following nightly dosing with 20 mg zolpidem
tartrate tablets for 2 weeks.
A food-effect study in 30 healthy male subjects compared the pharmacokinetics of AMBIEN 10 mg when
administered while fasting or 20 minutes after a meal. Results demonstrated that with food, mean AUC
and Cmax were decreased by 15% and 25%, respectively, while mean Tmax was prolonged by 60%
(from 1.4 to 2.2 hr). The half-life remained unchanged. These results suggest that, for faster sleep
onset, AMBIEN should not be administered with or immediately after a meal.
Special Populations
Elderly:
In the elderly, the dose for AMBIEN should be 5 mg [see Warnings and Precautions (5) and Dosage
and Administration (2)]. This recommendation is based on several studies in which the mean Cmax, T1/2,
and AUC were significantly increased when compared to results in young adults. In one study of eight
elderly subjects (> 70 years), the means for Cmax, T1/2, and AUC significantly increased by 50% (255
vs. 384 ng/mL), 32% (2.2 vs. 2.9 hr), and 64% (955 vs. 1,562 nghr/mL), respectively, as compared
to younger adults (20 to 40 years) following a single 20 mg oral dose. AMBIEN did not accumulate in
elderly subjects following nightly oral dosing of 10 mg for 1 week.
Hepatic Impairment:
The pharmacokinetics of AMBIEN in eight patients with chronic hepatic insufficiency were compared
to results in healthy subjects. Following a single 20 mg oral zolpidem tartrate dose, mean Cmax and
AUC were found to be two times (250 vs. 499 ng/mL) and five times (788 vs. 4,203 nghr/mL) higher,
respectively, in hepatically -compromised patients. Tmax 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)].
Renal Impairment:
The pharmacokinetics of zolpidem tartrate were studied in 11 patients with end-stage renal failure
(mean ClCr = 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 Cmax, Tmax, half-life, and AUC between the first and last day of drug administration when
baseline concentration adjustments were made. 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.
Drug Interactions
CNS-depressants
Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression [see
Warnings and Precautions (5.1)]. Zolpidem tartrate was evaluated in healthy volunteers in single-dose
interaction studies for several CNS drugs. Imipramine in combination with zolpidem produced no
pharmacokinetic interaction other than a 20% decrease in peak levels of imipramine, but there was an
additive effect of decreased alertness. Similarly, chlorpromazine in combination with zolpidem produced
no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance.
A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics
or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration
does not predict the absence of an effect following chronic administration.
An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was
demonstrated [see Warnings and Precautions (5.1)].
Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence
of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem
Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics
of sertraline and N-desmethylsertraline were unaffected by zolpidem.
A single-dose interaction study with zolpidem tartrate 10 mg and fluoxetine 20 mg at steady-state levels
in male volunteers did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic
interactions. When multiple doses of zolpidem and fluoxetine were given at steady state and the
concentrations evaluated in healthy females, an increase in the zolpidem half-life (17%) was observed.
There was no evidence of an additive effect in psychomotor performance.
Drugs that Affect Drug Metabolism via Cytochrome P450
Some compounds known to inhibit CYP3A may increase exposure to zolpidem. The effect of inhibitors
of other P450 enzymes on the pharmacokinetics of zolpidem is unknown.
A single-dose interaction study with zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state
levels in male volunteers resulted in a 34% increase in AUC0 of zolpidem tartrate. There were no
pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance.

Placebo
0%
2%
1%

A total of 30/1,959 (1.5%) non-U.S. patients receiving zolpidem reported falls, including 28/30 (93%)
who were 70 years of age. Of these 28 patients, 23 (82%) were receiving zolpidem doses >10 mg.
A total of 24/1,959 (1.2%) non-U.S. patients receiving zolpidem reported confusion, including 18/24
(75%) who were 70 years of age. Of these 18 patients, 14 (78%) were receiving zolpidem doses
>10 mg.
The dose of AMBIEN in elderly patients is 5 mg to minimize adverse effects related to impaired motor
and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs [see Warnings and
Precautions (5.1)].
8.6 Gender Difference in Pharmacokinetics
Women clear zolpidem tartrate from the body at a lower rate than men. Cmax and AUC parameters of
zolpidem were approximately 45% higher at the same dose in female subjects compared with male
subjects. Given the higher blood levels of zolpidem tartrate in women compared to men at a given dose,
the recommended initial dose of AMBIEN for adult women is 5 mg, and the recommended dose for
adult men is 5 or 10 mg.
In geriatric patients, clearance of zolpidem is similar in men and women. The recommended dose of
AMBIEN in geriatric patients is 5 mg regardless of gender.
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 was
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. Zolpidems 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.
11 DESCRIPTION
AMBIEN (zolpidem tartrate) is a gamma-aminobutyric acid (GABA) A agonist of the imidazopyridine
class and is available in 5 mg and 10 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:

A single-dose interaction study with zolpidem tartrate 10 mg and rifampin 600 mg at steady-state levels
in female subjects showed significant reductions of the AUC (-73%), Cmax (-58%), and T1/2 (-36 %) of
zolpidem together with significant reductions in the pharmacodynamic effects of zolpidem tartrate.
Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects
of zolpidem.
A single-dose interaction study with zolpidem tartrate 5 mg and ketoconazole, a potent CYP3A4
inhibitor, given as 200 mg twice daily for 2 days increased Cmax of zolpidem (30%) and the total AUC
of zolpidem (70%) compared to zolpidem alone and prolonged the elimination half-life (30 %) along
with an increase in the pharmacodynamic effects of zolpidem. Consideration should be given to using
a lower dose of zolpidem when ketoconazole and zolpidem are given together.
Other Drugs with No Interactions with Zolpidem
A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no
effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.
Zolpidem tartrate had no effect on digoxin pharmacokinetics and did not affect prothrombin time when
given with warfarin in healthy subjects.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Zolpidem was administered to mice and rats for 2 years at oral doses of 4, 18, and
80 mg base/kg. In mice, these doses are approximately 2.5, 10, and 50 times the maximum
recommended human dose (MRHD) of 10 mg/day (8 mg zolpidem base) on mg/m2 basis. In rats, these
doses are approximately 5, 20, and 100 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/day) to rats
prior to and during mating, and continuing in females through postpartum day 25, resulted in irregular
estrus cycles and prolonged precoital intervals at the highest dose tested. The no-effect dose for these
findings is approximately 24 times the MRHD on a mg/m2 basis. There was no impairment of fertility
at any dose tested.
14 CLINICAL STUDIES
14.1 Transient Insomnia
Normal adults experiencing transient insomnia (n = 462) during the first night in a sleep laboratory were
evaluated in a double-blind, parallel group, single-night trial comparing two doses of zolpidem (7.5 and
10 mg) and placebo. Both zolpidem doses were superior to placebo on objective (polysomnographic)
measures of sleep latency, sleep duration, and number of awakenings.
Normal elderly adults (mean age 68) experiencing transient insomnia (n = 35) during the first two nights
in a sleep laboratory were evaluated in a double-blind, crossover, 2-night trial comparing four doses
of zolpidem (5, 10, 15 and 20 mg) and placebo. All zolpidem doses were superior to placebo on the
two primary PSG parameters (sleep latency and efficiency) and all four subjective outcome measures
(sleep duration, sleep latency, number of awakenings, and sleep quality).
14.2 Chronic Insomnia
Zolpidem was evaluated in two controlled studies for the treatment of patients with chronic insomnia
(most closely resembling primary insomnia, as defined in the APA Diagnostic and Statistical Manual
of Mental Disorders, DSM-IV). Adult outpatients with chronic insomnia (n = 75) were evaluated in
a double-blind, parallel group, 5-week trial comparing two doses of zolpidem tartrate and placebo. On
objective (polysomnographic) measures of sleep latency and sleep efficiency, zolpidem 10 mg was
superior to placebo on sleep latency for the first 4 weeks and on sleep efficiency for weeks 2 and 4.
Zolpidem was comparable to placebo on number of awakenings at both doses studied.
Adult outpatients (n=141) with chronic insomnia were also evaluated, in a double-blind, parallel group,
4-week trial comparing two doses of zolpidem and placebo. Zolpidem 10 mg was superior to placebo
on a subjective measure of sleep latency for all 4 weeks, and on subjective measures of total sleep
time, number of awakenings, and sleep quality for the first treatment week.
Increased wakefulness during the last third of the night as measured by polysomnography has not been
observed in clinical trials with AMBIEN.
14.3 Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs
Next-day residual effects: Next-day residual effects of AMBIEN were evaluated in seven studies
involving normal subjects. In three studies in adults (including one study in a phase advance model
of transient insomnia) and in one study in elderly subjects, a small but statistically significant decrease
in performance was observed in the Digit Symbol Substitution Test (DSST) when compared to placebo.
Studies of AMBIEN in non-elderly patients with insomnia did not detect evidence of next-day residual
effects using the DSST, the Multiple Sleep Latency Test (MSLT), and patient ratings of alertness.
Rebound effects: There was no objective (polysomnographic) evidence of rebound insomnia at
recommended doses seen in studies evaluating sleep on the nights following discontinuation of
AMBIEN (zolpidem tartrate). There was subjective evidence of impaired sleep in the elderly on the first
post-treatment night at doses above the recommended elderly dose of 5 mg.
Memory impairment: Controlled studies in adults utilizing objective measures of memory yielded no
consistent evidence of next-day memory impairment following the administration of AMBIEN. However,
in one study involving zolpidem doses of 10 and 20 mg, there was a significant decrease in
next-morning recall of information presented to subjects during peak drug effect (90 minutes post-dose),
i.e., these subjects experienced anterograde amnesia. There was also subjective evidence from
adverse event data for anterograde amnesia occurring in association with the administration of
AMBIEN, predominantly at doses above 10 mg.
Effects on sleep stages: In studies that measured the percentage of sleep time spent in each sleep
stage, AMBIEN has generally been shown to preserve sleep stages. Sleep time spent in stages 3 and
4 (deep sleep) was found comparable to placebo with only inconsistent, minor changes in REM
(paradoxical) sleep at the recommended dose.
16 HOW SUPPLIED/STORAGE AND HANDLING
AMBIEN 5 mg tablets are capsule-shaped, pink, film coated, with AMB 5 debossed on one side and
5401 on the other and supplied as:
NDC Number
0024-5401-31

NDC Number
0024-5421-31
0024-5421-50

Size
bottle of 100
bottle of 500

Store at controlled room temperature 2025C (6877F).

17 PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Inform patients and their families about the benefits and risks of treatment with AMBIEN. Inform patients
of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating
treatment with AMBIEN and with each prescription refill. Review the AMBIEN Medication Guide with
every patient prior to initiation of treatment. Instruct patients or caregivers that AMBIEN should be taken
only as prescribed.
CNS Depressant Effects and Next-Day Impairment
Tell patients that AMBIEN has the potential to cause next-day impairment, and that this risk is increased
if dosing instructions are not carefully followed. Tell patients to wait for at least 8 hours after dosing
before driving or engaging in other activities requiring full mental alertness. Inform patients that
impairment can be present despite feeling fully awake.
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.
Sleep-driving and Other Complex Behaviors
Instruct patients and their families that sedative hypnotics can cause abnormal thinking and behavior
change, including sleep driving and other complex behaviors while not being fully awake (preparing
and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop
any of these symptoms.
Suicide
Tell patients to immediately report any suicidal thoughts.
Alcohol and Other Drugs
Ask patients about alcohol consumption, medicines they are taking, and drugs they may be taking
without a prescription. Advise patients not to use AMBIEN if they drank alcohol that evening or before
bed.
Tolerance, Abuse, and Dependence
Tell patients not to increase the dose of AMBIEN on their own, and to inform you if they believe the
drug does not work.
Administration Instructions
Patients should be counseled to take AMBIEN right before they get into bed and only when they are
able to stay in bed a full night (78 hours) before being active again. AMBIEN tablets should not be
taken with or immediately after a meal. Advise patients NOT to take AMBIEN if they drank alcohol that
evening.

MEDICATION GUIDE
AMBIEN (ambe-n)
(zolpidem tartrate)
Tablets C-IV
Read the Medication Guide that comes with AMBIEN 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
healthcare provider about your medical condition or treatment.
What is the most important information I should know about
AMBIEN?
Do not take more AMBIEN than prescribed.
Do not take AMBIEN unless you are able to stay in bed a full
night (7 to 8 hours) before you must be active again.
Take AMBIEN right before you get in bed, not sooner.
AMBIEN may cause serious side effects, including:
After taking AMBIEN, 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 AMBIEN. Reported activities include:
driving a car (sleep-driving)
making and eating food
talking on the phone
having sex
sleep-walking
Call your healthcare provider right away if you find out that you
have done any of the above activities after taking AMBIEN.
Do not take AMBIEN if you:
drank alcohol that evening or before bed
took another medicine to help you sleep.
What is AMBIEN?
AMBIEN is a sedative-hypnotic (sleep) medicine. AMBIEN is used in
adults for the short-term treatment of a sleep problem called insomnia
(trouble falling asleep).
It is not known if AMBIEN is safe and effective in children under the age
of 18 years.

Size
bottle of 100

AMBIEN 10 mg tablets are capsule-shaped, white, film coated, with AMB 10 debossed on one side
and 5421 on the other and supplied as:
5

Call your healthcare provider right away if you have any of the
above side effects or any other side effects that worry you while
using AMBIEN.
The most common side effects of AMBIEN are:
drowsiness
dizziness
diarrhea
grogginess or feeling as if you have been drugged
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
stomach area pain
These are not all the side effects of AMBIEN. Ask your healthcare
provider or pharmacist for more information.
Call your healthcare provider for medical advice about side effects. You
may report side effects to FDA at 1800FDA1088.
How should I store AMBIEN?
Store AMBIEN at room temperature, 68F to 77F (20C to 25C).
Keep AMBIEN and all medicines out of reach of children.
General Information about the safe and effective use of AMBIEN
Medicines are sometimes prescribed for purposes other than those
listed in a Medication Guide. Do not use AMBIEN for a condition for
which it was not prescribed. Do not share AMBIEN with other people,
even if 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 AMBIEN. If you would like more information, talk with your
healthcare provider. You can ask your healthcare provider or pharmacist
for information about AMBIEN that is written for healthcare professionals.
For more information, call 1-800-633-1610.
What are the ingredients in AMBIEN?
Active Ingredient: Zolpidem tartrate
Inactive Ingredients: hydroxypropyl methylcellulose, lactose, magnesium stearate, micro-crystalline cellulose, polyethylene glycol, sodium
starch glycolate, and titanium dioxide. In addition, the 5 mg tablet
contains FD&C Red No. 40, iron oxide colorant, and polysorbate 80.
This Medication Guide has been approved by the U.S. Food and Drug
Administration.

AMBIEN is a federally controlled substance (C-IV) because it can

be abused or lead to dependence. Keep AMBIEN in a safe place
to prevent misuse and abuse. Selling or giving away AMBIEN may
harm others, and is against the law. Tell your healthcare provider
if you have ever abused or have been dependent on alcohol,
prescription medicines or street drugs.
Who should not take AMBIEN?
Do not take AMBIEN if you are allergic to zolpidem or any other
ingredients in AMBIEN. See the end of this Medication Guide for a
complete list of ingredients in AMBIEN.
Do not take AMBIEN if you have had an allergic reaction to drugs
containing zolpidem, such as Ambien CR, Edluar, Zolpimist, or
Intermezzo.
Symptoms of a serious allergic reaction to zolpidem can include:
swelling of your face, lips, and throat that may cause difficulty
breathing or swallowing
What should I tell my healthcare provider before taking AMBIEN?
AMBIEN may not be right for you. Before starting AMBIEN, tell your
healthcare provider 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. It is not known if
AMBIEN will harm your unborn baby.
are breastfeeding or plan to breastfeed. AMBIEN can pass into your
breast milk. It is not known if AMBIEN will harm your baby. Talk to
your healthcare provider about the best way to feed your baby while
you take AMBIEN.
Tell your healthcare provider 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 AMBIEN with other medicines that can make
you sleepy unless your healthcare provider tells you to.
Know the medicines you take. Keep a list of your medicines with you to
show your healthcare provider and pharmacist each time you get a new
medicine.
How should I take AMBIEN?
See What is the most important information I should know
about AMBIEN?
Take AMBIEN exactly as prescribed. Only take 1 AMBIEN tablet a
night if needed.
Do not take AMBIEN if you drank alcohol that evening or before bed.
You should not take AMBIEN with or right after a meal. AMBIEN may
help you fall asleep faster if you take it on an empty stomach.
Call your healthcare provider if your insomnia worsens or is not
better within 7 to 10 days. This may mean that there is another
condition causing your sleep problem.
If you take too much AMBIEN or overdose, get emergency treatment.
What are the possible side effects of AMBIEN?
AMBIEN may cause serious side effects, including:
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 AMBIEN?
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, and trouble breathing. Get emergency medical
help if you get these symptoms after taking AMBIEN.
falls, which may lead to severe injuries

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807
A SANOFI COMPANY
October 2014
2014 sanofi-aventis U.S. LLC
ZOL-FPLR-SL-OCT14

Rx Only