Zolpidem (Stilnox) Interactions with Grapefruit Juice and Milk

Zolpidem is a non-benzodiazepine hypnotic (Z-drug) for short-term insomnia. It is metabolized primarily by CYP3A4 (and CYP1A2, CYP2C9).

Grapefruit Juice Interaction

• Furanocoumarins in grapefruit irreversibly inhibit intestinal CYP3A4.
• Result: ↑ Zolpidem bioavailability, ↑ Cmax, ↑ AUC → excessive sedation, respiratory depression, next-day impairment, falls.
• Recommendation: Avoid grapefruit juice entirely during zolpidem therapy, or separate by ≥4 hours (ideally avoid).

Milk Interaction

• Casein binds zolpidem? Evidence is weak. One study showed slight ↓ clearance, ↑ half-life with milk co-administration.
• Clinical significance uncertain; likely minor for most.
• Recommendation: Separate by 1–2 hours if concerned; not a major contraindication.

General Safety

• Take immediately before bed; ensure 7–8h sleep window.
• Avoid alcohol, other CNS depressants.
• Caution in elderly, hepatic impairment, respiratory disease.
• Risk of complex sleep behaviors (sleepwalking, sleep-driving).
• Short-term use only (≤4 weeks); taper to avoid rebound insomnia.

Always consult prescriber/pharmacist about specific interactions.