Frequently Asked Questions
Pharmacokinetics
Indication and Efficacy
Safety and Tolerability
Pharmacokinetics
What are the pharmacokinetic characteristics
of AMBIEN CR compared to zolpidem tartrate?
AMBIEN CR exhibits 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 3 hours after administration.4,9
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Do AMBIEN CR blood levels accumulate
over time?
No. AMBIEN CR has not been shown to accumulate in adult and elderly subjects following
nightly oral dosing for up to 2 weeks.4
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How rapidly is AMBIEN CR absorbed?
Zolpidem tartrate is characterized by rapid absorption from the gastrointestinal
tract. Following administration of AMBIEN CR as a single 12.5-mg dose in healthy
male adult subjects, the mean peak concentration [Cmax] of zolpidem was
134 ng/mL, occurring at a mean time [Tmax] of 1.5 hours.4
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What is the half-life of AMBIEN
CR?
In healthy adult subjects, AMBIEN CR has a half-life of 2.8 hours at the 12.5-mg
dose. In elderly patients, AMBIEN CR has a half-life of 2.9 hours at the 6.25-mg
dose.4
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How are pharmacokinetics affected
in elderly patients (≥65 years of age)?
Elderly subjects may be more sensitive to the effects of zolpidem. Compared to young
adults, elderly subjects had higher values for C half-life and AUC (area under the
curve) following a single oral dose of immediate-release zolpidem. The lower dose
of 6.25 mg is recommended for elderly patients.4,28
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Indication and Efficacy
What is the indication for AMBIEN
CR?
AMBIEN CR is indicated for the treatment of insomnia characterized by difficulties
with sleep onset and/or sleep maintenance (as measured by wake-time after sleep
onset).4
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Safety and Tolerability
What are the most common adverse
events seen with AMBIEN CR?
During treatment with AMBIEN CR in adults and the elderly at doses of 12.5 mg and
6.25 mg, respectively, each for 3 weeks, the most commonly observed adverse events
associated with the use of AMBIEN CR were headache, somnolence and dizziness.4
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What are some uncommon adverse
events seen with AMBIEN CR?
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.
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-naive as well as in sedative-hypnotic-experienced persons.
Although behaviors such as "sleep-driving" may occur with AMBIEN CR alone
at therapeutic doses, the use of alcohol and other CNS depressants with AMBIEN CR
appears to increase the risk of such behaviors, as does the use of AMBIEN CR at
doses exceeding the maximum recommended dose. Due to the risk to the patient and
the community, discontinuation of AMBIEN CR 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.4
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How does AMBIEN CR affect next-day
psychomotor performance?
In 5 clinical studies, 3 controlled studies in adults (18 to 64 years of age) administered
AMBIEN CR 12.5 mg and 2 controlled studies in the elderly (≥65 years of age) administered
AMBIEN CR 6.25 mg or 12.5 mg, the effect of AMBIEN CR on vigilance, memory or motor
function was assessed using neurocognitive tests. In these studies, no significant
decrease in performance was observed 8 hours after a nighttime dose.4
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Is rebound insomnia associated
with AMBIEN CR?
In the 2 placebo-controlled studies in patients with primary insomnia, a rebound
effect was only observed in the first night after abrupt discontinuation of AMBIEN
CR. On the second night, there was no worsening compared to baseline in the AMBIEN
CR group.4
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