Typical antipsychotics Chlorpromazine Thioridazine , etc. For excipients, see 6. Zolpidem Tartrate 10mg Tablets. Do not share this medication with others. The sedative effect may be enhanced when the product is used in combination with alcohol. Do not take it with or after a meal because it will not work as quickly.
Patients with mild to moderate hepatic impairment do not clear the drug as rapidly as normal subjects. Tablets are not scored. NDC Number Size bottle of NDC Number Size bottle of bottle of The following serious adverse reactions are discussed in greater detail in other sections of the labeling:. Reactions most commonly associated with discontinuation from U. Reactions most commonly associated with discontinuation from these trials were daytime drowsiness 1.
Events reported by investigators were classified utilizing a modified World Health Organization WHO dictionary of preferred terms for the purpose of establishing event frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in these clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted under a different set of conditions.
However, the cited figures provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied. The following table was derived from results of 11 placebo-controlled short-term U. The table is limited to data from doses up to and including 10 mg, the highest dose recommended for use. The following table was derived from results of three placebo-controlled long-term efficacy trials involving AMBIEN zolpidem tartrate.
These trials involved patients with chronic insomnia who were treated for 28 to 35 nights with zolpidem at doses of 5, 10, or 15 mg. There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse reactions associated with zolpidem use, particularly for certain CNS and gastrointestinal adverse events. Treatment-emergent adverse events associated with clinical trial participation were recorded by clinical investigators using terminology of their own choosing.
To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent adverse events, similar types of untoward events were grouped into a smaller number of standardized event categories and classified utilizing a modified World Health Organization WHO dictionary of preferred terms. The frequencies presented, therefore, represent the proportions of the 3, individuals exposed to zolpidem, at all doses, who experienced an event of the type cited on at least one occasion while receiving zolpidem.
All reported treatment-emergent adverse events are included, except those already listed in the table above of adverse events in placebo-controlled studies, those coding terms that are so general as to be uninformative, and those events where a drug cause was remote. It is important to emphasize that, although the events reported did occur during treatment with AMBIEN, they were not necessarily caused by it. Adverse events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Liver and biliary system: Concomitant use of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability. Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies for several CNS drugs. A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. Some compounds known to induce or inhibit CYP3A may affect exposure to zolpidem.
The effect of drugs that induce or inhibit other P enzymes on the exposure to zolpidem is not known. Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances.
Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug effects over time. Tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects. Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: Drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common.
Studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. Because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic.
These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Post-marketing reports of abuse, dependence and withdrawal have been received.
Co-administration with other CNS depressants e. The risk of next-day psychomotor impairment, including impaired driving, is increased if AMBIEN is taken with less than a full night of sleep remaining 7 to 8 hours ; if a higher than the recommended dose is taken; if co-administered with other CNS depressants or alcohol; or if co-administered with other drugs that increase the blood levels of zolpidem. In order to minimize this risk a full night of sleep 7—8 hours is recommended.
Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including zolpidem.
Some patients have had additional symptoms such as dyspnea , throat closing or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the throat, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug.
Some of these changes included decreased inhibition e. Visual and auditory hallucinations have been reported. Complex behaviors such as "sleep-driving" i. Due to the risk to the patient and the community, discontinuation of AMBIEN should be strongly considered for patients who report a "sleep-driving" episode. Other complex behaviors e.
As with "sleep-driving", patients usually do not remember these events. Amnesia, anxiety and other neuropsychiatric symptoms may also occur. 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. In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions including completed suicides , have been reported.
Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed for the patient at any one time. Since sedativehypnotics have the capacity to depress respiratory drive, precautions should be taken if AMBIEN is prescribed to patients with compromised respiratory function. Post-marketing 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. GABA agonists such as zolpidem tartrate have been associated with precipitation of hepatic encephalopathy in patients with hepatic insufficiency. In addition, patients with hepatic insufficiency do not clear zolpidem tartrate as rapidly as patients with normal hepatic function.
There have been reports of withdrawal signs and symptoms following the rapid dose decrease or abrupt discontinuation of zolpidem. Monitor patients for tolerance, abuse, and dependence [see Drug Abuse And Dependence ]. Zolpidem can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries. Severe injuries such as hip fractures and intracranial hemorrhage have been reported.
Tell patients that AMBIEN has the potential to cause next-day impairment, and that this risk is increased if dosing instructions are not carefully followed. Tell patients to wait for at least 8 hours after dosing before driving or engaging in other activities requiring full mental alertness. Inform patients that impairment can be present despite feeling fully awake.
Inform patients that severe anaphylactic and anaphylactoid reactions have occurred with zolpidem. Instruct patients and their families that sedative hypnotics can cause abnormal thinking and behavior change, including "sleep driving" and other complex behaviors while not being fully awake preparing and eating food, making phone calls, or having sex. Tell patients to call you immediately if they develop any of these symptoms. Ask patients about alcohol consumption, medicines they are taking, and drugs they may be taking without a prescription.
Tell patients not to increase the dose of AMBIEN on their own, and to inform you if they believe the drug "does not work". Patients should be counseled to take AMBIEN right before they get into bed and only when they are able to stay in bed a full night 7—8 hours before being active again. In mice, these doses are approximately 2.
No evidence of carcinogenic potential was observed in mice. In rats, renal tumors lipoma , liposarcoma were seen at the mid- and high doses. Zolpidem was negative in in vitro bacterial reverse mutation, mouse lymphoma , and chromosomal aberration and in vivo mouse micronucleus genetic toxicology assays. There was no impairment of fertility at any dose tested. Studies in children to assess the effects of prenatal exposure to zolpidem have not been conducted; however, cases of severe neonatal respiratory depression have been reported when zolpidem was used at the end of pregnancy, especially when taken with other CNS-depressants.
Children born to mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal period. Neonatal flaccidity has also been reported in infants born to mothers who received sedativehypnotic drugs during pregnancy. AMBIEN should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. The failure of insomnia to remit after a 7 — 14 day course of treatment may indicate the presence of a primary psychiatric or physical disorder, and the patient should be carefully re-evaluated at regular intervals.
The risk of next-day psychomotor impairment, including impaired driving ability, is increased if:. Zolpidem should be taken in a single intake immediately at bedtime and not be re-administered during the same night. As hypnotics have the capacity to depress respiratory drive, precautions should be observed if zolpidem is prescribed to patients with compromised respiratory function. Concomitant use of zolpidem and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as zolpidem with opioids should be reserved for patients for whom alternative treatment options are not possible.
If a decision is made to prescribe zolpidem concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible see also general dose recommendation in section 4. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their environment to be aware of these symptoms see section 4.
Extreme caution should be exercised when prescribing for patients with a history of drug or alcohol abuse. These patients should be under careful surveillance when receiving zolpidem tartrate or any other hypnotic, since they are at risk of habituation and psychological dependence. Suicidal tendencies may be present therefore the least amount of zolpidem that is feasible should be supplied to these patients to avoid the possibility of intentional overdose by the patient. Pre-existing depression may be unmasked during use of zolpidem.
Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists. General information relating to effects seen following administration of benzodiazepines and other hypnotic agents which should be taken into account by the prescribing physician are described below. Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines and benzodiazepine-like agents like zolpidem may develop after repeated use for a few weeks.
Use of benzodiazepines or benzodiazepine-like agents like zolpidem may lead to the development of physical and psychological dependence. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches or muscle pain, extreme anxiety and tension, restlessness, confusion and irritability.
In severe cases the following symptoms may occur: A transient syndrome whereby the symptoms that led to treatment with a benzodiazepine or benzodiazepine-like agent recur in an enhanced form, may occur on withdrawal of hypnotic treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. It is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur when the medicinal product is discontinued.
Since the risk of withdrawal phenomena or rebound has been shown to be greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually where clinically appropriate. There are indications that, in the case of benzodiazepines and benzodiazepine-like agents with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
Benzodiazepines or benzodiazepine-like agents such as zolpidem may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 8 hours see section 4. Other psychiatric and paradoxical reactions like restlessness, exacerbated insomnia, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, abnormal behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents.
Should this occur, use of the product should be discontinued. These reactions are more likely to occur in the elderly. The use of alcohol and other CNS-depressants with zolpidem appears to increase the risk of such behaviour, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of zolpidem should be strongly considered for patients who report such behaviour for example, sleep driving , due to the risk to the patient and others.
Due to its pharmacological properties, zolpidem can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines. Therefore, concomitant use of zolpidem with these drugs may increase drowsiness and next-day psychomotor impairment, including impaired driving ability see section 4. Also, isolated cases of visual hallucinations were reported in patients taking zolpidem with antidepressants including bupropion, desipramine, fluoxetine, sertraline and venlafaxine.
Co-administration of fluvoxamine may increase blood levels of zolpidem, concurrent use is not recommended. In the case of narcotic analgesics enhancement of euphoria may also occur leading to an increase in psychological dependence. The concomitant use of sedative medicines such as benzodiazepines or related drugs such as zolpidem with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited see section 4.
Co-administration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended. Compounds which inhibit certain hepatic enzymes particularly cytochrome P may enhance the activity of benzodiazepines and benzodiazepine-like agents. The pharmacodynamic effect of zolpidem is decreased when it is administered with a CYP3A4 inducer such as rifampicin and St. John's Wort has been shown to have a pharmacokinetic interaction with zolpidem.
Mean C max and AUC were decreased John's Wort compared to zolpidem administered alone. John's Wort may decrease blood levels of zolpidem, concurrent use is not recommended. However when zolpidem was administered with itraconazole a CYP3A4 inhibitor its pharmacokinetics and pharmacodynamics were not significantly modified. The clinical relevance of these results is unknown. Co-administration of zolpidem with ketoconazole mg twice daily , a potent CYP3A4 inhibitor, prolonged zolpidem elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to zolpidem plus placebo.
The total AUC for zolpidem, when co-administered with ketoconazole, increased by a factor of 1. A routine dosage adjustment of zolpidem is not considered necessary, but patients, should be advised that use of zolpidem with ketoconazole may enhance the sedative effects. Since CYP3A4 plays an important role in zolpidem metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered. When zolpidem was administered with ranitidine no significant pharmacokinetic interactions were observed.
For zolpidem tartrate, no or very limited amount of data on pregnant patients are available. Although animal studies have shown no teratogenic or embryotoxic effects, safety in pregnancy has not been established. As with all drugs zolpidem should be avoided in pregnancy particularly during the first trimester. If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the product if she intends to become or suspects that she is pregnant.
If, for compelling medical reasons, zolpidem is administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected due to the pharmacological action of the product. Cases of severe neonatal respiratory depression have been reported when zolpidem tartrate was used with other CNS depressants at the end of pregnancy.
Infants born to mothers who took benzodiazepines or benzodiazepine-like agents chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period. Small quantities of zolpidem appear in breast milk. The use of zolpidem in nursing mothers is therefore not recommended. In order to minimise this risk a resting period of at least 8 hours is recommended between taking zolpidem and driving, using machinery and working at heights.
Driving ability impairment and behaviours such as 'sleep-driving' have occurred with zolpidem alone at therapeutic doses. Furthermore, co-administration of zolpidem with alcohol and other CNS depressants increases the risk of such behaviours see sections 4. Patients should be warned not to use alcohol or other psychoactive substances when taking zolpidem. There is evidence of a dose-relationship for adverse effects associated with zolpidem use, particularly for certain CNS and gastrointestinal events.
As recommended in section 4. They occur most frequently in elderly patients. Liver enzymes elevated, hepatocellular, cholestatic or mixed liver injury see sections 4. Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: In cases of overdose, involving zolpidem alone or with other CNS-depressant agents including alcohol , impairment of consciousness ranging from somnolence to coma, and more severe symptomatology, including fatal outcomes have been reported.
General symptomatic and supportive measures should be used. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Sedating drugs should be withheld even if excitation occurs. Use of flumazenil may be considered where serious symptoms are observed. Flumazenil is reported to have an elimination half-life of about 40 — 80 minutes.
Patients should be kept under close observation because of this short duration of action; further doses of flumazenil may be necessary. However, flumazenil administration may contribute to the appearance of neurological symptoms convulsions. Zolpidem is not dialyzable. The value of dialysis in the treatment of an overdose has not been determined.
Dialysis in patients with renal failure receiving therapeutic doses of zolpidem has demonstrated no reduction in levels of zolpidem. In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken. Zolpidem is an imidazopyridine which selectively binds the omega-1 receptor subtype also known as the benzodiazepine-1 subtype which is the alpha unit of the GABA-A receptor complex.
Whereas benzodiazepines non-selectively bind all three omega receptor subtypes, zolpidem preferentially binds the omega-1 subtype.