Zolpidem (Oral)

Generic name: Zolpidem

Drug class: Non-benzodiazepine hypnotic

Dosage form: Oral tablet, extended-release tablet, sublingual tablet, oral spray

Route of administration: Oral (tablet, sublingual tablet, oral spray)

Dose:

• Immediate-release tablets: 5 mg for women; 5 mg or 10 mg for men, taken once per night immediately before bedtime. Maximum dose: 10 mg/day.
• Extended-release tablets: 6.25 mg for women; 6.25 mg or 12.5 mg for men, taken once per night immediately before bedtime. Maximum dose: 12.5 mg/day.
• Sublingual tablets: 1.75 mg for women; 3.5 mg for men, taken once per night as needed after waking in the middle of the night. Maximum dose: 1.75 mg/day for women; 3.5 mg/day for men.
• Oral spray: 5 mg per actuation, taken once per night immediately before bedtime. Maximum dose: 5 mg/day.

Mechanism of action: Zolpidem enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by selectively binding to the benzodiazepine-1 (BZ1) receptor subtype. This binding increases chloride ion conductance, leading to neuronal hyperpolarization, inhibition of action potentials, and decreased neuronal excitability, resulting in sedative and hypnotic effects.

Drug usage cases:

• Short-term treatment of insomnia characterized by difficulties with sleep initiation.
• Short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (extended-release formulation).
• As needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep (sublingual formulation).

Drug contraindications:

• Hypersensitivity to zolpidem or any component of the formulation.
• Sleep apnea syndrome.
• Severe hepatic impairment.
• Myasthenia gravis.
• Acute and/or intermittent porphyria.

Side effects:

• Drowsiness.
• Headache.
• Dizziness.
• Fatigue.
• Gastrointestinal disturbances (e.g., nausea, diarrhea).
• Allergic reactions (e.g., rash, pruritus, angioedema).
• Complex sleep-related behaviors (e.g., sleepwalking, sleep driving, sleep eating).
• Memory impairment.
• Depression or mood changes.
• Visual disturbances (e.g., double vision, blurred vision).

Warnings:

• Risk of complex sleep-related behaviors, including sleepwalking, sleep driving, and sleep eating; patients should be monitored for these behaviors.
• Potential for abuse, misuse, and physical dependence; use with caution in individuals with a history of substance abuse.
• May cause next-day drowsiness or impaired alertness; patients should be cautioned against engaging in activities requiring full alertness until they know how the drug affects them.
• Use with caution in patients with hepatic impairment; dosage adjustments may be necessary.
• Risk of withdrawal symptoms upon abrupt discontinuation after prolonged use; gradual dose reduction is recommended.
• May interact with other central nervous system depressants, including alcohol, leading to enhanced sedative effects; concurrent use should be avoided.
• Not recommended for use in children under 18 years of age.

Use during pregnancy or breastfeeding:

Pregnancy: Zolpidem is classified as a Category C drug during pregnancy, indicating that risk to the fetus cannot be ruled out. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Zolpidem crosses the placenta, and its use, especially during the third trimester, may lead to neonatal withdrawal symptoms. Pregnant women should consult their healthcare provider before using zolpidem.

Breastfeeding: Zolpidem is excreted in breast milk in small amounts. While the risk to nursing infants is presumed to be low, caution is advised. The American Academy of Pediatrics considers zolpidem compatible with breastfeeding, but nursing mothers should monitor their infants for any adverse effects. It is recommended to consult a healthcare provider before using zolpidem while breastfeeding.