Zolpidem

• Insomnia
• Sleep Onset Insomnia
• Sleep Maintenance Insomnia
• Short-Term Insomnia Treatment

Zolpidem is a non-benzodiazepine sedative-hypnotic (imidazopyridine class) widely used to treat insomnia. It is one of the most commonly prescribed sleep medications and is available in multiple formulations for different sleep problems.

Mechanism of Action

Zolpidem works through GABAergic modulation:

• GABA-A receptor positive modulation: Binds to benzodiazepine binding site on GABA-A receptors
• Selective for alpha-1 subunit: Preferentially affects sedative/hypnotic function over anxiolytic/muscle relaxant
• Enhances inhibitory neurotransmission: Increases chloride conductance
• Rapid onset: Quickly induces sleep
• Various durations: Different formulations provide different duration of action

Available Formulations

• Immediate-release tablets: 5 mg, 10 mg (Ambien)
• Extended-release tablets: 6.25 mg, 12.5 mg (Ambien CR)
• Sublingual tablets (low dose): 1.75 mg, 3.5 mg (Intermezzo - for middle-of-night awakening)
• Sublingual tablets: 5 mg, 10 mg (Edluar)
• Oral spray: 5 mg/actuation, 10 mg/actuation (Zolpimist)

Medical Uses

FDA-Approved Indication:

• Short-term treatment of insomnia characterized by difficulty with sleep initiation (IR, sublingual, spray)
• Insomnia with difficulty falling asleep and/or staying asleep (ER)
• Middle-of-night awakening with difficulty returning to sleep (Intermezzo)

Dosing Guidelines

Immediate-Release:

• Women: 5 mg immediately before bedtime
• Men: 5-10 mg immediately before bedtime
• Maximum: 10 mg/night

Extended-Release:

• Women: 6.25 mg immediately before bedtime
• Men: 6.25-12.5 mg immediately before bedtime
• Maximum: 12.5 mg/night

Sublingual (Middle-of-Night - Intermezzo):

• Women: 1.75 mg
• Men: 3.5 mg
• Take only if 4+ hours remain before planned awakening

Important Safety Information

Controlled Substance:

• Schedule IV

Boxed Warning (2019):

• Complex sleep behaviors including sleep-walking, sleep-driving, and other activities while not fully awake that may result in serious injury or death

Contraindications:

• Known hypersensitivity to zolpidem
• History of complex sleep behaviors with zolpidem

Warnings and Precautions:

• Complex sleep behaviors: Discontinue immediately if occurs
• CNS depression: Additive with other CNS depressants
• Next-day impairment: Especially with higher doses, ER formulation, and in women
• Depression: May worsen; suicidal ideation reported
• Respiratory depression: Use caution in compromised respiratory function
• Dependence: Physical and psychological dependence possible

Drug Interactions

• CNS depressants (alcohol, opioids, benzodiazepines): Additive CNS depression; avoid alcohol
• CYP3A4 inhibitors (ketoconazole): May increase zolpidem levels
• CYP3A4 inducers (rifampin): May decrease zolpidem effectiveness
• Chlorpromazine: Decreased alertness and psychomotor performance
• Sertraline: May increase zolpidem exposure

Special Populations

• Hepatic Impairment: 5 mg IR or 6.25 mg ER; avoid in severe impairment
• Renal Impairment: No adjustment for mild to moderate
• Elderly: Start with lowest dose; increased sensitivity
• Women: Lower doses recommended (slower metabolism)
• Pregnancy: May cause respiratory depression and sedation in neonates
• Lactation: Present in milk; consider timing and infant monitoring
• Pediatric: Not approved for children