Zolpidem

5 WARNINGS AND PRECAUTIONS CNS-Depressant Effects: Impairs alertness and motor coordination including risk of morning impairment. Risk increases with dose and use with other CNS depressants and alcohol. Caution patients against driving and other activities requiring mental alertness the morning after use. Instruct patients on correct use. ( 5.2 ) Need to Evaluate for Comorbid Diagnoses: Re-evaluate if insomnia persists after 7 to 10 days of use. ( 5.3 ) Severe Anaphylactic/Anaphylactoid Reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. ( 5.4 ) Abnormal Thinking and Behavioral Changes: Changes including decreased inhibition, bizarre behavior, agitation, and depersonalization have been reported. Immediately evaluate any new onset behavioral changes. ( 5.5 ) Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least amount of tablets feasible to avoid intentional overdose. ( 5.6 ) Respiratory Depression: Consider this risk before prescribing in patients with compromised respiratory function. ( 5.7 ) Hepatic Impairment: Avoid Zolpidem Tartrate Tablets use in patients with severe hepatic impairment. ( 5.8 ) Withdrawal Effects: Symptoms may occur with rapid dose reduction or discontinuation. ( 5.9 , 9.3 ) 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 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 Tablets alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants [see Drug Interaction ( 7.1 )]. Discontinue Zolpidem Tartrate Tablets immediately if a patient experiences a complex sleep behavior [see Contraindications ( 4 )]. 5.2 CNS-Depressant Effects and Next-Day Impairment Zolpidem Tartrate Tablets, like other sedative-hypnotic drugs, has CNS-depressant effects. Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression [see Drug Interaction ( 7.1 )]. Dosage adjustments of Zolpidem Tartrate Tablets and of other concomitant CNS depressants may be necessary when Zolpidem Tartrate Tablets is administered with such agents because of the potentially additive effects. The use of Zolpidem Tartrate Tablets with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended [see Dosage and Administration ( 2.3 )] The risk of next-day psychomotor impairment, including impaired driving, is increased if Zolpidem Tartrate Tablets 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 alcohol; or if coadministered with other drugs that increase the blood levels of zolpidem. Patients should be warned against driving and other activities requiring complete mental alertness if Zolpidem Tartrate Tablets is taken in these circumstances [see Dosage and Administration ( 2 ), Clinical Studies ( 14.3 )] Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness, and impaired driving the morning after therapy. In order to minimize this risk a full night of sleep (7–8 hours) is recommended. Because Zolpidem Tartrate Tablets can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls. 5.3 Need to Evaluate for Comorbid Diagnoses Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. 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. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem. 5.4 Severe Anaphylactic and Anaphylactoid Reactions 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. 5.5 Abnormal Thinking and Behavioral Changes Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including Zolpidem Tartrate 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 of Zolpidem Tartrate Tablets 10 mg taken at bedtime <1% of adults with insomnia reported hallucinations. In a clinical trial, 7% of pediatric patients treated with Zolpidem Tartrate 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 [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. 5.6 Use in Patients with Depression 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. 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 Tablets 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 Zolpidem Tartrate 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 )]. 5.8 Precipitation of Hepatic Encephalopathy Drugs affecting GABA receptors, 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. Avoid Zolpidem Tartrate Tablets use in patients with severe hepatic impairment as it may contribute to encephalopathy [see Dosage and Administration ( 2.2 ), Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )] 5.9 Withdrawal Effects 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 ( 9.2 , 9.3 )]