Zolpidem

Aka: Zolpidem, Zolpidem CR, Ambien, Ambien CR, Intermezzo

1. Indication
   1. Insomnia
   2. Sleep maintenance
      1. Standard Ambien and Ambien CR have similar effect on sleep maintenance
   3. Early awakening (Intermezzo)
      1. Contraindicated if other Sedative-Hypnotic used earlier in evening
      2. Similar to Sonata (generic in 2012), but Intermezzo costs significantly more
2. Preparations
   1. Standard dose Zolpidem (Ambien)
      1. Younger Adult
         1. Men: 5-10 mg (or 6.25 to 12.5 mg for CR) orally at bedtime
         2. Women: 5 mg (or 6.25 mg for CR) orally at bedtime
            1. May increase to 10 mg (12.5 mg CR) if ineffective at lower dose
            2. Dose decreased by FDA in 2013 due to next-morning Impairment
               1. See below under precautions
               2. http://www.fda.gov/Drugs/DrugSafety/ucm334033.htm
      2. Elderly: 2.5 to 5 mg orally at bedtime
   2. Controlled release (CR)
      1. Adult: 12.5 mg orally at bedtime
   3. Intermezzo (low dose Zolpidem)
      1. Regular dose: 3.5 mg orally on early awakening
         1. Indicated in men
      2. Low dose: 1.75 mg orally on early awakening
         1. Indicated in women, elderly, liver disease, use of other CNS depressants
      3. References
         1. (2012) Presc Lett 19(5): 26
3. Precautions
   1. FDA decreased recommended Zolpidem dose in 2013 from 10 mg (12.5 mg CR) to 5 mg (or 6.25 mg CR)
      1. Reduced dose in women due to next-morning Impairment (also occurs in 25% of men)
      2. Women metabolize Zolpidem more slowly resulting in blood levels twice as high as men
      3. Levels are even higher and prolonged with the controlled release preparations
   2. References
      1. FDA website
         1. http://www.fda.gov/Drugs/DrugSafety/ucm334033.htm
4. Pharmacokinetics
   1. Peak onset: <30 minutes
   2. Duration: 4-8 hours (6-8 hours with CR version)
   3. Half-Life: 2-3 hours (longer with CR version)
   4. Metabolized by CYP450 3A4
5. Mechanism
   1. Nonbenzodiazepine hypnotic agent
   2. Acts at omega 1 subtype Benzodiazepine receptor
   3. No anticonvulsant or myorelaxant effects
6. Lactation
   1. Compatible with Breast Feeding per AAP
   2. Lack of longterm data - other medications are preferred
7. Pregnancy
   1. Pregnancy Class B (not CR version)
   2. Lack of longterm data - other medications are preferred
8. Drug Interactions
   1. Avoid taking with food or immediately after a meal
      1. Delays onset of action
      2. Decreases maximal concentration
   2. Avoid taking with Alcohol
      1. May increase CNS depression
9. Adverse effects
   1. See Nonbenzodiazepine hypnotic agent for common effects
   2. Abdominal Pain or gastrointestinal upset
   3. Rebound Insomnia
   4. Nightmares
   5. Sleep-eating is more common