Clinical Overview
Zaleplon is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia, specifically for difficulty with sleep initiation. It has the shortest half-life (1 hour) among the Z-drugs, making it suitable for patients who need to fall asleep quickly but may need to wake up within a few hours without next-day impairment.
Primary Clinical Applications
Zaleplon is indicated for the short-term treatment of insomnia characterized by difficulty with sleep initiation. Its ultra-short duration of action makes it particularly suitable for patients with sleep-onset insomnia who need to maintain early morning alertness, shift workers, or those who experience middle-of-the-night insomnia with at least 4 hours of sleep time remaining.
Mechanism and Clinical Benefits
Zaleplon selectively binds to GABA-A receptors containing alpha-1 subunits, promoting sleep initiation with minimal effects on sleep architecture. Its very short half-life (1 hour) allows for rapid elimination, reducing the risk of next-day sedation and making it suitable for flexible dosing schedules.
Clinical Considerations
The ultra-short half-life means zaleplon can be taken at bedtime or even in the middle of the night if at least 4 hours of sleep time remain. It should be taken on an empty stomach for optimal absorption. While the short duration reduces next-day effects, it also means the medication may not help with sleep maintenance issues.
Prescribing Information
Dosing & Administration
Insomnia – Adults:
- Recommended dose: 10 mg immediately before bedtime
- Range: 5-20 mg once daily
- Low weight patients: 5 mg may be sufficient
Elderly:
- Recommended dose: 5 mg immediately before bedtime
- Maximum: 10 mg once daily
Hepatic Impairment:
- Mild-moderate: 5 mg immediately before bedtime
- Severe: Not recommended
Administration:
- Take immediately before bedtime or when experiencing difficulty falling asleep
- Take on empty stomach for faster onset
- Can be taken middle-of-night if ≥4 hours sleep time remaining
- Do not take with or after a high-fat meal
Indications
- Short-term treatment of insomnia (sleep initiation)
- Difficulty falling asleep
Contraindications
- Known hypersensitivity to zaleplon
- Severe hepatic impairment
Warnings & Precautions
- Complex sleep behaviors: Sleep-driving, sleep-eating reported but less common than with longer-acting agents
- CNS depression: Risk increased with alcohol and other CNS depressants
- Abnormal thinking and behavior: May cause bizarre behavior, agitation, hallucinations
- Withdrawal effects: May occur with abrupt discontinuation after prolonged use
- Memory impairment: Anterograde amnesia possible
Drug Interactions
- CNS depressants: Enhanced sedation
- Alcohol: Additive CNS depression
- CYP3A4 inhibitors: May increase zaleplon levels
- Rifampin: Significantly reduces zaleplon levels (80% reduction)
- Cimetidine: Increases zaleplon levels by 85%
Adverse Reactions
Common (≥2%):
- Headache, dizziness, somnolence, nausea
- Asthenia, abdominal pain, amnesia
Advantages:
- Minimal next-day impairment due to short half-life
- Can be taken middle-of-night
- Less rebound insomnia
Special Populations
- Elderly: Increased sensitivity, maximum 10 mg daily
- Hepatic Impairment: Reduce dose for mild-moderate, avoid in severe
- Pregnancy: Category C – use only if benefits outweigh risks
- Short half-life: Suitable for patients needing early morning alertness
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.
