Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor right away if any of these unlikely but serious side effects occur: Rarely, after taking this drug, people have gotten out of bed and driven vehicles while not fully awake " sleep -driving".
Often, these people do not remember these events. This problem can be dangerous to you or to others. If you find out that you have done any of these activities after taking this medication, tell your doctor right away. Your risk is increased if you use alcohol or other medications that can make you drowsy while taking zolpidem. A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction , including: This is not a complete list of possible side effects.
If you notice other effects not listed above, contact your doctor or pharmacist. Call your doctor for medical advice about side effects. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at Before taking zolpidem, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication , tell your doctor or pharmacist your medical history, especially of: Do not drive, use machinery, or do any activities that require clear thinking after you take this medication and the next day. You may feel alert, but this medication may continue to affect your thinking, making such activities unsafe. This medication may also increase the risk of falls. Alcohol or marijuana can make you more dizzy or drowsy. Do not drink alcoholic beverages.
Talk to your doctor if you are using marijuana. Children may be more sensitive to the side effects of this drug, especially dizziness and hallucinations. Older adults may be more sensitive to the side effects of this drug, especially dizziness, confusion, unsteadiness, and excessive drowsiness. These side effects can increase the risk of falling. Before having surgery, tell your doctor or dentist about all the products you use including prescription drugs , nonprescription drugs, and herbal products.
During pregnancy , this medication should be used only when clearly needed. Infants born to mothers who have taken sedative-hypnotics near the time of delivery may have undesirable effects such as breathing problems or withdrawal symptoms. Discuss the risks and benefits with your doctor. A small amount of this medication passes into breast milk.
Consult your doctor before breast -feeding. Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Do not start, stop, or change the dosage of any medicines without your doctor's approval. A product that may interact with this drug is: Other medications can affect the removal of zolpidem from your body, which may affect how zolpidem works.
Examples include azole antifungals such as ketoconazole , rifampin , St. John's Wort, among others. Tell your doctor or pharmacist if you are taking other products such as opioid pain or cough relievers such as codeine, hydrocodone , alcohol, marijuana , other drugs for sleep or anxiety such as alprazolam , lorazepam , zopiclone , muscle relaxants such as carisoprodol , cyclobenzaprine , or antihistamines such as cetirizine , diphenhydramine.
Check the labels on all your medicines such as allergy or cough -and-cold products because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely. If someone has overdosed and has serious symptoms such as passing out or trouble breathing , call Otherwise, call a poison control center right away. US residents can call their local poison control center at Canada residents can call a provincial poison control center.
Symptoms of overdose may include slowed breathing or a deep sleep from which you cannot be awakened. Do not share this medication with others. It is against the law. As you get older, your sleep pattern may naturally change and your sleep may be interrupted several times during the night. Consult your doctor or pharmacist for ways to improve your sleep without medication, such as avoiding caffeine and alcohol close to bedtime , avoiding daytime naps, and going to bed at the same time each night.
If you miss a dose, do not take it unless you have time to sleep for 7 to 8 hours afterwards. Store at room temperature away from light and moisture. Do not store in the bathroom. Multicenter, week, phase IIIb, randomized, double-blind, placebo-controlled, parallel-group. Single-dose zolpidem extended-release At week 12, PGI, Item 1 aid to sleep , the primary endpoint, was scored as favorable i. Most frequent adverse events for zolpidem extended-release were headache, anxiety and somnolence.
No rebound effect was observed during the first 3 nights of discontinuation. These findings establish the efficacy of 3 to 7 nights per week dosing of zolpidem extended-release Treatment provided sustained and significant improvements in sleep onset and maintenance and also improved next-day concentration and morning sleepiness. An important methodological point is that, in the few long-term pharmacotherapy studies that have been done, patients with insomnia received nightly medication dosing throughout the treatment period.
As the duration of treatment increases, the costs and risks of adverse effects associated with taking a medication nightly become increasingly important considerations. There is good reason to believe that, for many insomnia patients, it may be possible to achieve effective treatment while decreasing risks and costs by employing non-nightly medication dosing. The efficacy and safety of optional dosing of a hypnotic within a prespecified range has thus far only been demonstrated for zolpidem tartrate, a short-acting nonbenzodiazepine agent indicated for the short-term treatment of insomnia, 18 in clinical trials of 8 and 12 weeks' duration.
Zolpidem tartrate extended-release The efficacy and safety of zolpidem extended release Polysomnographic evaluation showed that, in comparison with placebo, treatment with zolpidem extended-release The present study expands upon this finding by examining the long-term efficacy and safety of zolpidem extended-release The primary objective of the study was to evaluate the efficacy of 6 months of treatment with zolpidem extended-release Additional objectives included evaluation of the safety and tolerability of zolpidem extended-release Next-day functioning, including the ability to concentrate and level of sleepiness in the morning, was also subjectively assessed throughout the treatment period.
This was a national United States , multicenter, phase IIIb, randomized, double-blind, placebo-controlled, two-parallel-group study in adult patients with chronic primary insomnia. The week study was divided into the following three phases: During the treatment period, patients received either zolpidem extended-release Patients were instructed to take the medication on those nights when they judged it to be necessary, with the caveat that they were required to self-administer study medication at least 3 nights per week.
Patients were given sleep hygiene instructions, which included a directive to refrain from alcohol. Patients were scheduled to report to their study center every 4 weeks for clinical evaluation; those who completed the trial were evaluated at a total of 9 study center visits Figure 1. Each patient signed an informed consent form before the conduct of any study-related procedure. The appropriate Institutional Review Board at each investigative site approved the protocol.
Eligible study participants included male and female patients, 18 to 64 years of age, who met criteria for chronic primary insomnia from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition DSM-IV. Women of childbearing potential were required to have a negative serum pregnancy test at the screening visit and to agree to use an acceptable form of contraception throughout the study.
Patients were excluded if they were shift workers or if they napped more than 3 times per week. Also excluded were patients who consumed more than 5 xanthine-containing beverages per day, as well as patients who had been using over-the-counter sleep remedies or prescription sleep medications within 2 weeks or 5 half-lives whichever was longer before screening.
In addition, patients were ineligible if they had primary hypersomnia, narcolepsy, breathing-related sleep disorders, circadian-rhythm sleep disorders, parasomnia, or dyssomnia not otherwise specified i. Patients who had a current severe neuropsychiatric disorder i. Women who were lactating or pregnant were also excluded, as were any patients who had participated in another clinical trial within the 2 months prior to screening.
After successful completion of the screening visit and run-in period, eligible patients were randomly assigned to receive either zolpidem extended-release Placebo tablets were the same size, shape, color, and taste as zolpidem extended-release tablets and were therefore indistinguishable from active treatment. Patients were instructed to take no more than 1 tablet per night of study medication immediately before bedtime with a glass of water, for a minimum of 3 tablets and a maximum of 7 tablets per week.
The 3-tablet minimum was judged to be necessary to produce a minimum drug-treatment effect in this chronically ill population. During week 25, the run-out period, patients took no medication. Patient kits contained blister packages of the study medication sufficient for 4 weeks of treatment. At each visit, patients returned the packet from the previous 4 weeks, and the study staff recorded the number of remaining tablets along with the dates on which the patient omitted dosing, as noted on the questionnaire that patients completed each morning.
The investigator reviewed the patient questionnaire at each study visit to determine drug compliance and the recording of daily sleep parameters. Patients were considered compliant with treatment if they took between 3 and 7 tablets per week. Patients could withdraw from the study at any time and for any reason. Study staff recorded the reasons for withdrawal or early discontinuation and made every effort to have the patients complete an early termination visit.
The PGI is a 4-item, subjective, patient self-report that assesses treatment aid to sleep Item 1 , treatment benefit to sleep induction Item 2 , treatment benefit to sleep duration Item 3 , and appropriateness of study medication strength Item 4. Each patient completed the PGI at every 4-week study center visit during the week treatment period and at the final visit at week 25 during the run-out period.
PGI assessments at each visit were based on the patient's global perception of the effects of treatment on sleep during that treatment period including nights with and without dosing , as compared to their sleep prior to entering the study. The CGI is a clinician-rated scale composed of two subscales that measure disease severity and degree of improvement, respectively. CGI-Severity CGI-S is a single-item, global scale of disease severity that requires the investigator to compare the patient's symptoms with those of all other patients who have the disorder.
It is scored from 1 normal to 7 among the most extremely ill. CGI-S was assessed at the baseline visit. CGI-Improvement CGI-I is a single-item scale of symptomatic improvement or worsening that requires the investigator to compare the patient's status at the time of assessment with baseline severity baseline CGI-S. CGI-I is scored from 1 very much improved to 7 very much worsened.
CGI-I was assessed at each 4-week study center visit during the week treatment period and at the final visit at week 25 during the run-out period. Patients completed the PMQ each morning upon awakening and recorded their responses via the interactive voice response system or Internet. The PMQ asks the respondent whether he or she took the study medication the previous evening and assesses the following subjective sleep measures: QOS was measured using a 4-point categorical scale scored as excellent 1 , good 2 , fair 3 , and poor 4.
In addition, each respondent assessed the level of next-day functioning by rating the level of morning sleepiness using numerical values from 0 very sleepy to 10 not at all sleepy and by rating ability to concentrate using a 4-point categorical scale scored as excellent 1 , good 2 , fair 3 , and poor 4. The PMQ was completed daily beginning after the screening visit and continuing through to study termination. Data from this questionnaire were used in various assessments: The ESS was used to determine daytime sleepiness and was completed by each patient at each 4-week study center visit during the week treatment period and at the final visit at week 25 of the run-out period.
The scale consisted of 8 items assessing the degree of sleepiness during the performance of everyday activities, each item being scored from 0 would never fall asleep to 3 high chance of falling asleep. The primary efficacy variable was the score on the PGI Item 1, treatment aid to sleep, assessed at week 12 of the treatment period in the intent-to-treat ITT population.
The ITT population consisted of all randomized patients who had received at least one dose of study medication and had undergone at least one post-baseline efficacy assessment. The PGI Item 1 included three ordered categories related to the patient's impression that treatment 1 helped me sleep, 2 did not affect my sleep, or 3 worsened my sleep. The main secondary efficacy variables were the scores on the following additional assessments performed every fourth week during the treatment period: Tablet-taking behavior was analyzed over each 4-week period of treatment.
Measures of daytime ability to function and sleepiness in the morning, provided daily as part of the PMQ, were analyzed on a monthly basis. Safety was assessed by physical examination during screening and at the last visit, by measurement of vital signs heart rate, supine and standing systolic and diastolic blood pressure during each visit, and by documentation of spontaneously reported or observed adverse events AEs throughout the study.
A rebound insomnia effect was defined as a worsening of sleep from baseline values. Rebound effect was assessed by patients' TST and WASO scores as recorded in the patient's daily questionnaire during the run-out period. A sample size of patients was required in a ratio of 2: Efficacy assessments were analyzed in the ITT population. Safety assessments were analyzed in the population of randomized patients who had received at least one dose of study medication.
In the event of missing assessments of the primary endpoint at week 12, data from the week 16 assessments were used, and for missing assessments of the main secondary PMQ endpoints at month 3, data from the month 4 assessments were used. If assessments were not available for week 12 and week 16, then week 8 values were used, and for missing assessments for month 3 and month 4, month 2 values were used. No other replacements were performed. Unless otherwise noted, all statistical analyses were performed at the 0.
For PGI Item 4, a chi-square test on proportion favorable ratings was used. On the PMQ, for all measurements, the change from baseline was averaged over each month each 4-week period during the treatment period up to week The change from baseline for each PMQ measurement and ESS total score was assessed using analysis of covariance ANCOVA , with treatment group as a fixed factor and the baseline value centered on the grand mean for each group as covariate.
Analysis for a rebound effect was conducted on data from patients who took at least one tablet on the last night of the treatment period. Rebound was also assessed for patients who permanently discontinued the study during the treatment period i. There were no post-baseline data for 2 randomized patients in the zolpidem extended-release group, and thus the ITT population totaled patients.
In the zolpidem extended-release group, patients In the placebo group, patients Demographic characteristics of the 2 treatment groups were similar Table 1. The patients ranged in age from 18 to 64 years, and the majority were white and female. Mean weight of all patients was Baseline disease characteristics were comparable between treatment groups.
Mean baseline CGI-S score was 4. Baseline insomnia characteristics recorded from the PMQ during the run-in period were similar between groups Table 2. In the zolpidem extended-release group, The percentage of patients who reported a treatment benefit on the PGI was higher in the zolpidem extended-release group than in the placebo group for all four PGI items at the conclusion of the first 4-week treatment period, and this difference was sustained throughout the entire study. The percentage of patients who obtained a positive evaluation on the CGI-I scale i.
The magnitude of these improvements generally increased over the week treatment period. At baseline, both groups had a mean baseline ESS of 7. ESS was overall statistically significantly lower in the zolpidem extended-release group than the placebo group during the double-blind treatment period. Univariate analyses indicated that the groups were statistically significantly different at all time points except month 6 and month 1 trend for significance Table 4. Over the 6-month period, the mean number of nights per month that tablets were reported as taken was stable in each treatment group.
The mean value was slightly higher for patients in the zolpidem extended-release group than for those in the placebo group Table 5. Of note, each patient's average tablet intake per month was based on a minimum required dosing of 3 tablets per week, with the option to take up to a maximum of 7 tablets per week.
Of the patients who received at least one dose of study drug, treatment-emergent AEs were reported by patients The majority of AEs were mild or moderate in severity. The most common AEs occurring at a slightly higher frequency in the zolpidem extended-release group than in the placebo group were headache, anxiety, somnolence, dizziness, fatigue, disturbance in attention, irritability, nausea, and sinusitis Table 6.
These AEs were similar in nature to those reported in previous studies and to the known safety profile of zolpidem extended-release. Overall, 57 patients 8. The AEs most commonly leading to discontinuation in the zolpidem extended-release and placebo groups were psychiatric disorders 3. A total of 30 serious AEs occurred in 25 patients in 2. Potential rebound insomnia was assessed by examining the mean change in TST and WASO scores from baseline on each of the first 3 nights after abrupt discontinuation of study medication during the run-out period.
In neither the zolpidem extended-release group nor the placebo group was any worsening from baseline i. However, no differences between these groups were observed on nights 2 and 3.