Zolpidem Tartrate

Check Drug InteractionsCheck known drug interactions.

Zolpidem Tartrate Prescribing Information

Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of Zolpidem tartrate extended-release tablets. Some of these events may result in serious injuries, including death. Discontinue Zolpidem tartrate extended-release tablets immediately if a patient experiences a complex sleep behavior

[see

4 CONTRAINDICATIONS

Zolpidem tartrate extended-release tablets are contraindicated in patients

who have experienced complex sleep behaviors after taking zolpidem tartrate extended-release tablets
[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 Zolpidem tartrate extended-release tablets
Known hypersensitivity to zolpidem

and

5.1 Complex Sleep Behaviors

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 zolpidem tartrate extended-release tablets. 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 zolpidem tartrate extended-release tablets alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants

[see Drug Interactions (7.1)]

. Discontinue Zolpidem tartrate extended-release tablets immediately if a patient experiences a complex sleep behavior

[see Contraindications (4)]

Indications and Usage ( 1 INDICATIONS AND USAGE Zolpidem tartrate extended-release tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). The clinical trials performed in support of efficacy were up to 3 weeks (using polysomnography measurement up to 2 weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in adult patients only) in duration [see Clinical Studies (14)]. Zolpidem tartrate extended-release tablets, a gamma-aminobutyric acid (GABA) A receptor positive modulator, is indicated for the short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. )	2/2022
Dosage and Administration ( 2.1 Dosage in Adults Use the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 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 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 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 zolpidem tartrate extended-release tablets should not exceed 12.5 mg once daily immediately before bedtime. Zolpidem tartrate extended-release tablets 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. Treatment with zolpidem tartrate extended-release tablets should be as short as possible. Extended treatment should not take place without re-evaluation of the patient's status, since the risk of abuse and dependence increases with duration of treatment [see Drug Abuse and Dependence (9.3)] . )	2/2022
Warnings and Precautions ( 5.5 Abnormal Thinking and Behavioral Changes Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including zolpidem tartrate extended-release tablets. 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, <1% of adults with insomnia reported hallucinations. In a clinical trial, 7% of pediatric patients treated with zolpidem tartrate extended-release tablets 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 ( 5.7 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 sedative-hypnotics have the capacity to depress respiratory drive, precautions should be taken if zolpidem tartrate extended-release tablets are 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 zolpidem tartrate extended-release tablets 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

Zolpidem tartrate extended-release tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset).

The clinical trials performed in support of efficacy were up to 3 weeks (using polysomnography measurement up to 2 weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in adult patients only) in duration

[see

14 CLINICAL STUDIES

14.1 Controlled Clinical Trials

Zolpidem tartrate extended-release tablets were evaluated in three placebo-controlled studies for the treatment of patients with chronic primary insomnia (as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM IV™).

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

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

In both studies, in patients treated with zolpidem tartrate extended-release tablets, polysomnography showed increased wakefulness at the end of the night compared to placebo-treated patients.

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

14.2 Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs

Next-Day Residual Effects

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

During the 3-week studies, next-day somnolence was reported by 15% of the adult patients who received 12.5 mg zolpidem tartrate extended-release tablets versus 2% of the placebo group; next-day somnolence was reported by 6% of the elderly patients who received 6.25 mg zolpidem tartrate extended-release tablets versus 5% of the placebo group

[see Adverse Reactions (6)].

In a 6-month study, the overall incidence of next-day somnolence was 5.7% in the zolpidem tartrate extended-release tablets group as compared to 2% in the placebo group.

Rebound Effects

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

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

Use the lowest dose effective for the patient and must not exceed a total of 12.5 mg daily (
2.1 Dosage in Adults
Use the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 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 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 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 zolpidem tartrate extended-release tablets should not exceed 12.5 mg once daily immediately before bedtime. Zolpidem tartrate extended-release tablets 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.
Treatment with zolpidem tartrate extended-release tablets should be as short as possible. Extended treatment should not take place without re-evaluation of the patient's status, since the risk of abuse and dependence increases with duration of treatment
[see Drug Abuse and Dependence (9.3)]
.
)
Treatment should be as short as possible (
2.1 Dosage in Adults
Use the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 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 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 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 zolpidem tartrate extended-release tablets should not exceed 12.5 mg once daily immediately before bedtime. Zolpidem tartrate extended-release tablets 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.
Treatment with zolpidem tartrate extended-release tablets should be as short as possible. Extended treatment should not take place without re-evaluation of the patient's status, since the risk of abuse and dependence increases with duration of treatment
[see Drug Abuse and Dependence (9.3)]
.
)
Recommended initial dose is a single dose of 6.25 mg for women and a single dose of 6.25 or 12.5 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening (
2.1 Dosage in Adults
Use the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 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 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 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 zolpidem tartrate extended-release tablets should not exceed 12.5 mg once daily immediately before bedtime. Zolpidem tartrate extended-release tablets 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.
Treatment with zolpidem tartrate extended-release tablets should be as short as possible. Extended treatment should not take place without re-evaluation of the patient's status, since the risk of abuse and dependence increases with duration of treatment
[see Drug Abuse and Dependence (9.3)]
.
)
Geriatric patients and patients with mild to moderate hepatic impairment: Recommended dose is 6.25 mg for men and women (
2.2 Special Populations
Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. The recommended dose of zolpidem tartrate extended-release tablets in these patients is 6.25 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 zolpidem tartrate extended-release tablets in these patients is 6.25 mg once daily immediately before bedtime. Avoid zolpidem tartrate extended-release tablets 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 Zolpidem tartrate extended-release tablets (
2.3 Use with CNS Depressants
Dosage adjustment may be necessary when zolpidem tartrate extended-release tablets are combined with other CNS-depressant drugs because of the potentially additive effects
[see Warnings and Precautions (5.2, 5.7)]
.
)
Tablets to be swallowed whole, not to be crushed, divided or chewed (
2.4 Administration
Zolpidem tartrate extended-release tablets should be swallowed whole, and not be divided, crushed, or chewed. The effect of zolpidem tartrate extended-release tablets may be slowed by ingestion with or immediately after a meal.
)
The effect of Zolpidem tartrate extended release tablets may be slowed if taken with or immediately after a meal (
2.4 Administration
Zolpidem tartrate extended-release tablets should be swallowed whole, and not be divided, crushed, or chewed. The effect of zolpidem tartrate extended-release tablets may be slowed by ingestion with or immediately after a meal.
)

Zolpidem tartrate extended-release tablets, USP are available as extended-release tablets containing 6.25 mg or 12.5 mg of zolpidem tartrate for oral administration. Tablets are not scored.

Zolpidem tartrate extended-release tablets, USP 6.25 mg are pink, round, coated tablets debossed with "T" on one side and plain on other side.

Zolpidem tartrate extended-release tablets, USP 12.5 mg are blue, round, coated tablets debossed with "Z" on one side and plain on other side.

Pregnancy: May cause respiratory depression and sedation in neonates with exposure late in the third trimester. (
8.1 Pregnancy
Risk Summary
Neonates 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 Considerations
Fetal/neonatal adverse reactions
Zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to zolpidem tartrate extended-release tablets during pregnancy and labor for signs of excess sedation, hypotonia, and respiratory depression and manage accordingly.
Data
Human 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 4, 20, and 100 times the maximum recommended human dose (MRHD) of 12.5 mg/day (10 mg zolpidem base) based on mg/m²body surface area, caused delayed fetal development (incomplete fetal skeletal ossification) at maternally toxic (ataxia) doses 20 and 100 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, 8, and 30 times the MRHD of 12.5 mg/day (10 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 30 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 4, 20, and 100 times the MRHD of 12.5 mg/day (10 mg zolpidem base) based on a mg/m²body surface area, delayed offspring growth and decreased survival at doses 20 and 100 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 Zolpidem tartrate extended-release tablets administration. (
8.2 Lactation
Risk Summary
Limited 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 zolpidem tartrate extended-release tablets and any potential adverse effects on the breastfed infant from zolpidem tartrate extended-release tablets or from the underlying maternal condition.
Clinical Considerations
Infants exposed to zolpidem tartrate extended-release tablets 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 zolpidem tartrate extended-release tablets 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 Changes
Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including zolpidem tartrate extended-release tablets. 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, <1% of adults with insomnia reported hallucinations. In a clinical trial, 7% of pediatric patients treated with zolpidem tartrate extended-release tablets 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 Use
Zolpidem tartrate extended-release tablets are 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.
FDA has not required pediatric studies of zolpidem tartrate extended-release tablets in the pediatric population based on these efficacy and safety findings.
)

Report Adverse Event

Zolpidem Tartrate

Zolpidem Tartrate Prescribing Information

Zolpidem Tartrate PubMed™ News