Ambien Prescribing Information
AMBIEN is contraindicated in patients
- who have experienced complex sleep behaviors after taking AMBIEN[see Warnings and Precautions (5.1)].
- with known hypersensitivity to zolpidem. Observed reactions include anaphylaxis and angioedema[see Warnings and Precautions (5.4)].
- Patients who have experienced complex sleep behaviors after taking AMBIEN
- Known hypersensitivity to zolpidem
Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake, may occur following the first or any subsequent use of AMBIEN. Patients can be seriously injured or injure others during complex sleep behaviors. Such injuries may result in a fatal outcome. Other complex sleep behaviors (e.g., preparing and eating food, making phone calls, or having sex) have also been reported. Patients usually do not remember these events. Postmarketing reports have shown that complex sleep behaviors may occur with AMBIEN alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants
Dosage and Administration (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 7–8 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 (5.2)] . The total dose of AMBIEN should not exceed 10 mg once daily immediately before bedtime. AMBIEN should be taken as a single dose and should not be readministered during the same night.The recommended initial doses for women and men are different because zolpidem clearance is lower in women. Long-term use of AMBIEN is not recommended. Treatment should be as short as possible. Extended treatment should not take place without re-evaluation of the patient’s status because the risk of abuse and dependence increases with the duration of treatment [see Drug Abuse and Dependence (9.3) ]. | 2/2022 |
Warnings and Precautions (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)] . There have been postmarketing reports of delirium with zolpidem use[see Adverse Reactions (6.2)]. 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. | 2/2022 |
Warnings and Precautions (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 sedative-hypnotics have the capacity to depress respiratory drive, precautions should be taken if AMBIEN is prescribed to patients with compromised respiratory function or concomitant use with opioids or other CNS depressants. Postmarketing 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 or with concomitant opioid use [see Dosage and Administration (2.3), Drug Interactions (7.1)] . | 2/2022 |
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
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).
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.
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.
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.
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.
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.
The clinical trials performed in support of efficacy were 4–5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment.
- Use the lowest dose effective for the patient and must not exceed a total of 10 mg daily ()
2.1 Dosage in AdultsUse 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 7–8 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 (5.2)]. The total dose of AMBIEN should not exceed 10 mg once daily immediately before bedtime. AMBIEN should be taken as a single dose and should not be readministered during the same night.The recommended initial doses for women and men are different because zolpidem clearance is lower in women.
Long-term use of AMBIEN is not recommended. Treatment should be as short as possible. Extended treatment should not take place without re-evaluation of the patient’s status because the risk of abuse and dependence increases with the duration of treatment [see
Drug Abuse and Dependence (9.3)]. - Treatment should be as short as possible ()
2.1 Dosage in AdultsUse 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 7–8 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 (5.2)]. The total dose of AMBIEN should not exceed 10 mg once daily immediately before bedtime. AMBIEN should be taken as a single dose and should not be readministered during the same night.The recommended initial doses for women and men are different because zolpidem clearance is lower in women.
Long-term use of AMBIEN is not recommended. Treatment should be as short as possible. Extended treatment should not take place without re-evaluation of the patient’s status because the risk of abuse and dependence increases with the duration of treatment [see
Drug Abuse and Dependence (9.3)]. - Recommended initial dose is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7–8 hours remaining before the planned time of awakening ()
2.1 Dosage in AdultsUse 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 7–8 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 (5.2)]. The total dose of AMBIEN should not exceed 10 mg once daily immediately before bedtime. AMBIEN should be taken as a single dose and should not be readministered during the same night.The recommended initial doses for women and men are different because zolpidem clearance is lower in women.
Long-term use of AMBIEN is not recommended. Treatment should be as short as possible. Extended treatment should not take place without re-evaluation of the patient’s status because the risk of abuse and dependence increases with the duration of treatment [see
Drug Abuse and Dependence (9.3)]. - Geriatric patients and patients with mild to moderate hepatic impairment: Recommended dose is 5 mg for men and women ()
2.2 Special PopulationsElderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. The recommended dose of AMBIEN in these patients is 5 mg once daily immediately before bedtime
[see Warnings and Precautions (5.2),Use in Specific Populations (8.5)].Patients with mild to moderate hepatic impairment do not clear the drug as rapidly as normal subjects. The recommended dose of AMBIEN in these patients is 5 mg once daily immediately before bedtime. Avoid AMBIEN use in patients with severe hepatic impairment as it may contribute to encephalopathy
[see Warnings and Precautions (5.8), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. - Lower doses of CNS depressants may be necessary when taken concomitantly with AMBIEN ()
2.3 Use with CNS DepressantsDosage adjustment may be necessary when AMBIEN is combined with other CNS-depressant drugs because of the potentially additive effects
[see Warnings and Precautions (5.2, 5.7)]. - The effect of AMBIEN may be slowed if taken with or immediately after a meal ()
2.4 AdministrationThe effect of AMBIEN may be slowed by ingestion with or immediately after a meal.
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.
- Pregnancy: May cause respiratory depression and sedation in neonates with exposure late in the third trimester. ()
8.1 PregnancyRisk SummaryNeonates born to mothers using zolpidem late in the third trimester of pregnancy have been reported to experience symptoms of respiratory depression and sedation
[see Clinical Considerationsand Data]. Published data on the use of zolpidem during pregnancy have not reported a clear association with zolpidem and major birth defects[see Data].Oral administration of zolpidem to pregnant rats and rabbits did not indicate a risk for adverse effects on fetal development at clinically relevant doses[see Data].The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.
Clinical ConsiderationsFetal/neonatal adverse reactions
Zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to AMBIEN during pregnancy and labor for signs of excess sedation, hypotonia, and respiratory depression and manage accordingly.
DataHuman data
Published data from observational studies, birth registries, and case reports on the use of zolpidem during pregnancy do not report a clear association with zolpidem and major birth defects.
There are limited postmarketing reports of severe to moderate cases of respiratory depression that occurred after birth in neonates whose mothers had taken zolpidem during pregnancy. These cases required artificial ventilation or intratracheal intubation. The majority of neonates recovered within hours to a few weeks after birth once treated.
Zolpidem has been shown to cross the placenta.
Animal data
Oral administration of zolpidem to pregnant rats during the period of organogenesis at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the maximum recommended human dose (MRHD) of 10 mg/day (8 mg zolpidem base) based on mg/m2body surface area, caused delayed fetal development (incomplete fetal skeletal ossification) at maternally toxic (ataxia) doses 25 and 120 times the MRHD based on mg/m2body surface area.
Oral administration of zolpidem to pregnant rabbits during the period of organogenesis at 1, 4, and 16 mg base/kg/day, which are approximately 2.5, 10, and 40 times the MRHD of 10 mg/day (8 mg zolpidem base) based on mg/m2body surface area caused embryo-fetal death and delayed fetal development (incomplete fetal skeletal ossification) at a maternally toxic (decreased body weight gain) dose 40 times the MRHD based on mg/m2body surface area.
Oral administration of zolpidem to pregnant rats from day 15 of gestation through lactation at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the MRHD of 10 mg/day (8 mg zolpidem base) based on mg/m2body surface area, delayed offspring growth and decreased survival at doses 25 and 120 times, respectively, the MRHD based on mg/m2body surface area.
- Lactation: A lactating woman may pump and discard breast milk during treatment and for 23 hours after AMBIEN administration. ()
8.2 LactationRisk SummaryLimited data from published literature report the presence of zolpidem in human milk. There are reports of excess sedation in infants exposed to zolpidem through breastmilk
[see Clinical Considerations].There is no information on the effects of zolpidem on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AMBIEN and any potential adverse effects on the breastfed infant from AMBIEN or from the underlying maternal condition.Clinical ConsiderationsInfants exposed to AMBIEN through breastmilk should be monitored for excess sedation, hypotonia, and respiratory depression. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 23 hours (approximately 5 elimination half-lives) after AMBIEN administration in order to minimize drug exposure to a breast fed infant.
- 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. (,
5.5 Abnormal Thinking and Behavioral ChangesAbnormal 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)]. There have been postmarketing reports of delirium with zolpidem use[see Adverse Reactions (6.2)].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.
)8.4 Pediatric UseAMBIEN 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 6–17 years) with insomnia associated with attention-deficit/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 (5.5)]. Ten patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction.