Frequently Asked Questions

Pharmacokinetics

Q:	What are the pharmacokinetic characteristics of AMBIEN CR compared to zolpidem tartrate?
Q:	Do AMBIEN CR blood level accumulate over time?
Q:	How rapidly is AMBIEN CR absorbed?
Q:	What is the half-life of AMBIEN CR?
Q:	How are pharmacokinetics affected in elderly patients (≥65 years of age)?

Indication and Efficacy

Q:	What is the indication for AMBIEN CR?
Q:	How quickly does AMBIEN CR work?

Safety and Tolerability

Q:	What are the most common adverse events seen with AMBIEN CR?
Q:	How does AMBIEN CR affect next-day psychomotor performance?
Q:	Is rebound insomnia associated with AMBIEN CR?

Pharmacokinetics

Q:	What are the pharmacokinetic characteristics of AMBIEN CR compared to zolpidem tartrate?
A:	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 4 hours after administration.

Q:	Do AMBIEN CR blood level accumulate over time?
A:	No. AMBIEN CR has not been shown to accumulate in adult and elderly subjects following nightly oral dosing for up to 2 weeks.

Q:	How rapidly is AMBIEN CR absorbed?
A:	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 [C_max ] of zolpidem was 134 ng/mL, occurring at a mean time [T_max ] of 1.5 hours.

Q:	What is the half-life of AMBIEN CR?
A:	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.

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. The mean values for T T AUC, and half-life for AMBIEN CR 6.25 mg in elderly subjects compared to AMBIEN CR 12.5 mg in adults are shown in Table 1.

Indication and Efficacy

Q:	What is the indication for AMBIEN CR?
A:	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).

How quickly does AMBIEN CR work?

A 3-week placebo-controlled efficacy study of AMBIEN CR 12.5 mg in 212 adult patients with primary insomnia (110 placebo, 102 AMBIEN CR) demonstrated a mean onset of action within 20 minutes of ingestion as determined by polysomnography (PSG) on nights 1 and 2. Similar results were observed in a 3-week, placebo controlled efficacy study of AMBIEN CR 6.25 mg in 203 elderly patients (≥65 years of age) with primary insomnia (placebo, 114; AMBIEN CR, 99).

Safety and Tolerability

Q:	What are the most common adverse events seen with AMBIEN CR?
A:	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.

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.

Q:	Is rebound insomnia associated with AMBIEN CR?
A:	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 as no worsening compared to baseline in the AMBIEN CR group.

Important safety information:

AMBIEN CR is indicated for the treatment of insomnia.

In elderly or debilitated patients, or patients with hepatic insufficiency, the recommended dose is 6.25 mg and patients should be closely monitored. Due to its rapid onset of action, patients should take AMBIEN CR right before going to bed and when ready for sleep.

Patients should not take AMBIEN CR unless they are prepared to get a full night's sleep (7 to 8 hours) to avoid residual effects.

Until they know how it will affect their physical or mental performance upon awakening, patients should not drive or operate hazardous machinery after taking AMBIEN CR or any other sleep medication. Complex behaviors such as somnambulism, including driving or eating while not fully awake, with amnesia for the event, have been reported in patients who have taken a sedative hypnotic. Discontinuation of AMBIEN CR should be strongly considered for patients reporting such complex behaviors. Rare cases of angioedema have been reported in patients after taking sedative hypnotics. Patients who develop angioedema should not be rechallenged. The most commonly observed adverse effects in controlled clinical trials were headache, somnolence, and dizziness. Because individuals with a history of addiction or substance abuse are at increased risk of habituation and dependence, they should be under careful surveillance when receiving AMBIEN CR or any o ther hypnotic. AMBIEN CR is a Schedule IV controlled substance. US clinical trial experience from zolpidem does not reveal any clear evidence for withdrawal syndrome.

Please refer to the full prescribing information.