CNS depressant effects and next day impairment: Zolpidem tartrate, like other sedative-hypnotic drugs, has central nervous system (CNS) depressant effects. Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Dosage adjustment of zolpidem tartrate and of other concomitant CNS depressants may be necessary when zolpidem tartrate is administered with such agents because of the potentially additive effects. The use of zolpidem tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or in the middle of the night is not recommended.
The risk of next-day psychomotor impairment, including impaired driving, is increased if zolpidem tartrate 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 coadministered with other CNS depressants; or if coadministered with other drugs that increase the blood levels of zolpidem tartrate. Patients should be cautioned against driving and other activities requiring complete mental alertness if zolpidem tartrate is taken in these circumstances.
Abnormal thinking and behavioral changes: Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including zolpidem tartrate. 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.
Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as "sleep-driving" have occurred with zolpidem tartrate alone at therapeutic doses, the concomitant use of zolpidem tartrate with alcohol and other CNS depressants increases the risk of such behaviors, as does the use of zolpidem tartrate at doses exceeding the maximum recommended dose. Discontinuation of zolpidem tartrate should be strongly considered for patients who report a "sleep-driving" episode due to the risk to the patient and the community.
Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. 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 previously is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. However, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
Evaluation for co-morbid diagnoses: Symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient since sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. These findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem tartrate.
Use in patients with depression: There have been reports of worsening of depression, and suicidal thoughts and actions (including completed suicides), in primarily depressed patients treated with sedative-hypnotics. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in these patients; thus, the lowest number of tablets that is feasible should be prescribed for the patient at any one time.
Respiratory depression: Since sedative-hypnotics have the capacity to depress respiratory drive, precautions should be taken if zolpidem tartrate is prescribed to patients with compromised respiratory function. There have been postmarketing reports of respiratory insufficiency in patients receiving 10 mg of zolpidem tartrate, most of whom had pre-existing respiratory impairment. The risk of respiratory depression should be considered prior to prescribing zolpidem tartrate in patients with respiratory impairment including sleep apnea and myasthenia gravis.
Severe anaphylactic and anaphylactoid reactions: Rare cases of angioedema involving the tongue, glottis or larynx have been observed in patients after the first or subsequent doses of sedative-hypnotics, including zolpidem tartrate. Additional symptoms are dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Airway obstruction may occur and may be fatal if angioedema involves the throat, glottis or larynx. If patient develops angioedema, discontinue zolpidem tartrate and do not attempt to reinitiate treatment.
Tolerance: Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines and benzodiazepine-like agents may develop after repeated use for a few weeks.
Drug Abuse and Dependence: Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Patients with history of addiction to or abuse of drugs or alcohol and/or concomitant psychiatric illness are at increased risk for misuse, abuse and addiction of zolpidem tartrate. Therefore, these patients should be closely monitored during zolpidem tartrate therapy.
Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. 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.
Amnesia: Benzodiazepines or benzodiazepine-like agents may induce anterograde amnesia. This condition occurs most often several hours after ingesting the product; therefore, to reduce the risk, patients should ensure that they will be able to have an uninterrupted sleep of 7 to 8 hours.
Psychiatric and "paradoxical" reactions: Reactions such as restlessness, aggravated insomnia, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behavior and other adverse behavioral effects are known to occur when using benzodiazepines or benzodiazepine-like agents. Should this occur, zolpidem tartrate should be discontinued. These reactions are more likely to occur in the elderly.
Rebound insomnia: 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 such as mood changes, anxiety and restlessness.
Patient should be informed of the possibility of rebound phenomena, thus minimizing anxiety over such symptoms should they occur when the drug 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 manifest within the dosage interval, particularly when the dosage is high.
Patients with concomitant illness: Caution should be exercised in giving zolpidem tartrate in patients with diseases or conditions that could affect the metabolism or hemodynamic responses such as sleep apnea syndrome or myasthenia gravis.
Use in Children: Safety and effectiveness of zolpidem tartrate in pediatric patients under 18 years old have not been established. Thus, zolpidem tartrate should not be prescribed in this population.
Use in Elderly: Adverse effects of zolpidem tartrate tend to be dose related, particularly in the elderly. The initial dose of zolpidem tartrate should be reduced to decrease the possibility of adverse effects. These patients also should be monitored closely.