What are the potential side effects of Zoley?

Zolpidem (Zoley) Side Effects

Zolpidem carries significant risks including complex sleep behaviors (sleep-driving, sleepwalking), next-day cognitive impairment, falls and fractures (especially in elderly), and potential for dependency—it should only be used short-term (≤4 weeks) at the lowest effective dose with careful patient counseling about these serious adverse effects. 1, 2

Serious and Life-Threatening Side Effects

Complex Sleep Behaviors

• Sleep-driving, sleepwalking, sleep-eating, and engaging in sexual activity while not fully awake are documented serious adverse effects that can occur regardless of dose, medical history, or prior sleepwalking history 1, 3
• The FDA has issued warnings about these complex behaviors, which may be life-threatening 1
• Patients should be cautioned about allowing appropriate sleep time and avoiding combination with alcohol or other sedatives 1

Cognitive and Neurological Effects

• Memory impairment, amnesia, confusion, and disorientation occur at 5-fold higher rates compared to placebo in older patients 1
• Next-morning driving impairment is a significant concern, with drugs remaining at levels high enough to interfere with morning driving 1
• Hallucinations, anxiety, depression, and other psychiatric adverse effects are reported more frequently than with placebo 1
• Anterograde amnesia can occur, particularly when combined with other medications like imipramine 4

Falls and Fractures

• Zolpidem increases fall risk with an odds ratio of 4.28 (P<0.001) in hospitalized patients 3
• Hip fracture risk is elevated with a relative risk of 1.92 (95% CI 1.65-2.24), making this a critical concern especially in elderly patients 1, 2, 3
• Dizziness, loss of balance, and falls occur at 3-fold higher rates versus placebo in older adults 1

Mortality and Cancer Risk

• Observational studies suggest associations between zolpidem use and increased all-cause mortality, though confounding factors must be considered 1, 2
• Some studies have found associations with incident cancers, though the relationship requires cautious interpretation 1

Common Side Effects

Central Nervous System Effects

• Residual morning sedation occurs at 4-fold higher rates than placebo 1
• Daytime somnolence, drowsiness, and decreased alertness are frequently reported 1, 5, 3
• Headache and dizziness are common adverse events 5, 3

Gastrointestinal Effects

• Nausea and vomiting occur more frequently than with placebo 5
• Dysgeusia (altered taste) has been reported 1

Other Common Effects

• Confusion and disorientation, particularly in elderly patients (80.8% of adverse drug reactions in patients ≥50 years were CNS-related) 3
• Vertigo and diplopia (double vision) have been documented 1

Dependency and Withdrawal Risks

Tolerance and Dependence

• Approximately half of patients prescribed zolpidem continue treatment for at least 12 months despite recommendations against long-term use 6, 2
• While most evidence suggests minimal tolerance development at recommended doses (10mg/day for <1 month), tolerance has been described in patients taking high dosages for extended periods 5, 7

Withdrawal Effects

• Seizures following zolpidem withdrawal have been reported, most commonly at daily dosages of 450-600mg/day, but documented as low as 160mg/day 3
• Rebound insomnia can occur, with sleep onset latency significantly increased on the first night after stopping (13.0 minutes increase; 95% CI 4.3-21.7; P<0.01) 3
• Rapid discontinuation may produce withdrawal symptoms similar to benzodiazepines 1

Special Population Considerations

Women

• Women metabolize zolpidem more slowly than men, resulting in higher plasma concentrations and greater next-day impairment 2, 3
• After 8 hours, women had higher mean plasma concentrations than men for both 10mg immediate-release (28 vs. 20 ng/mL) and 12.5mg modified-release (33 vs. 28 ng/mL) formulations 3
• The FDA recommends lower starting doses in women (5mg for immediate-release) due to slower drug clearance 2, 8

Elderly Patients

• Elderly patients are at substantially higher risk for adverse effects including memory loss, confusion, falls, and fractures 1, 2
• Dose reduction to 5mg is advised in elderly or debilitated adults due to slower drug metabolism 1, 2
• Clearance is lower in very elderly people compared to young adults 4

Pregnancy and Breastfeeding

• Zolpidem is FDA pregnancy category C based on adverse outcomes in animal studies 3
• Maternal exposure is associated with increased incidence of low birth weight (OR=1.39), preterm delivery (OR=1.49), small for gestational age babies (OR=1.34), and cesarean deliveries (OR=1.74) 3
• Not recommended during pregnancy or nursing 1

Hepatic Impairment

• Dose reduction to 5mg is recommended in patients with hepatic impairment 1, 4
• Caution should be exercised when prescribing to elderly patients with hepatic impairment 4

Psychiatric and Behavioral Risks

Suicidality

• Suicide attempts and completion have been linked with zolpidem use (OR 2.08; 95% CI 1.83-2.63) regardless of the presence of comorbid psychiatric illness 3
• Worsening of depression and suicidal thinking may occur in individuals with depression 1

Other Psychiatric Effects

• Depression incidence is increased among individuals using nonbenzodiazepine hypnotics including zolpidem 1
• Anxiety and other neuropsychiatric symptoms are documented 1
• Sleep paralysis and hypnagogic/hypnopompic hallucinations can occur 1

Additional Safety Concerns

Infections and Injuries

• Pooled RCT data found increased infection incidence with zolpidem 1, 2
• Accidental injury rates are higher compared to placebo 1
• Major head injury or fracture requiring hospitalization shows increased risk (adjusted hazard ratio 1.67; CI 1.19-2.34) 1

Respiratory Considerations

• Caution is advised in patients with compromised respiratory function including asthma, COPD, or sleep apnea 1

Drug Interactions

• Additive effects on psychomotor performance occur with concomitant CNS depressants and/or alcohol use 1
• Combination with alcohol, other sedatives, and sleep restriction increases risk of adverse effects 1

Clinical Management Recommendations

Dosing Guidelines

• Standard adult dose is 10mg at bedtime; maximum 10mg 1
• Reduce to 5mg in elderly, debilitated, women, or those with hepatic impairment 1, 2
• Administration on an empty stomach is advised to maximize effectiveness 1, 6

Duration of Treatment

• Zolpidem should only be used for short-term treatment (≤4 weeks) to minimize risk of dependency and adverse effects 6, 2, 5
• If discontinuing after long-term use, gradual tapering is recommended to minimize withdrawal symptoms 2

Monitoring and Precautions

• Patients should be counseled about the potential for complex sleep behaviors and the importance of allowing adequate sleep time 1
• Avoid use in patients with signs/symptoms of depression, compromised respiratory function, or hepatic/heart failure 1
• Safety and effectiveness in patients <18 years not established 1