Zolpidem

Hypnotics/sedatives have been associated with abnormal thinking and behavior changes including decreased inhibition (eg, aggressiveness and extroversion that seemed out of character), bizarre behavior, agitation, visual and auditory hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving). An increased risk of next-day psychomotor impairment is increased if patient is unable to stay in bed for a full night of sleep (7 to 8 hours); if coadministered with other CNS depressants and/or taken with other drugs that increase blood levels of zolpidem; or if a higher than recommended dose is taken. Dose adjustment may be necessary if taking concomitant CNS depressants; use with alcohol is not recommended.

Hypersensitivity reactions, including anaphylaxis as well as angioedema, have been reported after taking the first or subsequent doses. Do not rechallenge patient if such reactions occur.

An increased risk for hazardous sleep-related activities such as sleep-driving, preparing and eating food, making phone calls, or having sex while asleep have also been noted; amnesia, anxiety, and other neuropsychiatric symptoms may also occur. Patients usually do not remember these events. The use of alcohol, other CNS depressants, and exceeding the recommended maximum dose may increase the risk of these activities. Discontinue treatment in patients who report any sleep-driving episodes. Disease-related concerns:

Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.

Use with caution in patients with a history of drug dependence. Risk of abuse is increased in patients with a history or family history of alcohol or drug abuse or mental illness.

GABA agonists, including zolpidem, have been associated with precipitation of hepatic encephalopathy in patients with hepatic impairment. Patients with hepatic impairment do not clear zolpidem as rapidly as patients with normal hepatic function. Use with caution in patients with mild to moderate hepatic impairment; dose adjustment recommended. Avoid use of immediate and extended-release tablets in patients with severe hepatic impairment; may result in encephalopathy.

Use with caution in patients with myasthenia gravis.

Use with caution in patients with respiratory compromise, COPD, or sleep apnea. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in debilitated patients; potential for oversedation, impaired coordination, and confusion with use; dosage adjustment recommended.

Use with caution in elderly patients; dose adjustment recommended. Monitor for impaired cognitive and/or motor performance, confusion, and potential for falling.

Dosage adjustment is recommended for females; pharmacokinetic studies involving zolpidem showed a significant increase in maximum concentration and exposure in females compared to males at the same dose.

When studied for the unapproved use of insomnia associated with ADHD in children, a higher incidence (~7%) of hallucinations was reported. In addition, sleep latency did not decrease compared to placebo. Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate the need for psychiatric and/or medical illness reevaluation.

Because of the rapid onset of action, administer Intermezzo immediately prior to bedtime, after the patient has gone to bed and is having difficulty falling asleep, or during the middle of the night when at least 4 hours are left before waking.

Abrupt discontinuance or rapid dose decrease may lead to withdrawal symptoms.