Dosing and uses of Ambien, Ambien CR (zolpidem)
Adult dosage forms and strengths
tablet, immediate-release: Schedule IV
- 5mg (Ambien)
- 10mg (Ambien)
tablet, extended-release: Schedule IV
- 6.25mg (Ambien CR)
- 12.5mg (Ambien CR)
tablet, sublingual: Schedule IV
- 1.75mg (Intermezzo)
- 3.5mg (Intermezzo)
- 5mg (Edluar)
- 10mg (Edluar)
oral spray: Schedule IV
- 5mg/spray (Zolpimist)
Insomnia
Sleep initiation
Immediate-release tablet, sublingual tablet, and oral spray
- Dosing for PO (Ambien), SL (Edluar), and oral spray (Zolpimist)
- Women: 5 mg PO/SL/oral spray qHS
- Men: Consider 5 mg PO/SL/oral spray qHS; may use 10 mg PO/SL/oral spray qHS if needed
Extended-release (Ambien CR)
- Women: 6.25 mg PO qHS
- Men: Consider 6.25 mg PO qHS; may use 12.5 mg PO qHS; not to exceed 12.5 mg/day
Dosing considerations (Ambien, Ambien CR)
- Use lowest effective dose; take only once per night immediately before bedtime with at least 7-8 hr remaining before the planned time of awakening
- In some patients, higher morning blood levels following use of 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness
- Total dose should not exceed 10 mg once daily immediately before bedtime; should be taken as single dose and should not be readministered during same night
Insomnia (Intermezzo)
Insomnia when a middle of the night awakening is followed by difficulty returning to sleep
Women: 1.75 mg SL PRN; not to exceed 1 dose/night
Men: 3.5 mg SL PRN; not to exceed 1 dose/night
Dosing considerations (Intermezzo)
- Use only when ≥4 hr of bedtime remain before awakening
- Do not take if alcohol has been consumed or with any other sleep aid
- Concomitant with CNS depressants: 1.75 mg SL PRN; not to exceed 1 dose/night
Dosing Modifications
Renal impairment
- Dose adjustment may not be necessary; monitor
Hepatic impairment
- Immediate-release: 5 mg immediately before bedtime
- Extended-release: 6.25 mg immediately before bedtime
- Sublingual (Edluar): 5 mg immediately before bedtime
- Sublingual (Intermezzo): 1.75 mg once at night if ≥4 hr remain before awakening
Pediatric dosage forms and strengths
Not recommended
Geriatric dosage forms and strengths
Drug of choice when hypnotic indicated in elderly
Insomnia
Sleep initiation
Immediate-release, oral spray: 5 mg PO/SL immediately before bedtime
Extended-release: 6.25 mg PO immediately before bedtime
Insomnia (Intermezzo)
Middle of the night awakening
Men and women: 1.75 mg SL PRN; not to exceed 1 dose/night
Dosing Considerations
Ambien, Ambien CR: Use lowest effective dose; take only once per night immediately before bedtime with at least 7-8 hr remaining before the planned time of awakening
Intermezzo: Use only when ≥4 hours of bedtime remain before awakening; do not take if alcohol has been consumed or with any other sleep aid
Ambien, Ambien CR (zolpidem) adverse (side) effects
>10%
Dizziness (5-12%)
Headache (7-19%)
Drowsiness (6-15%)
1-10%
Allergy (4%)
Hallucinations (4%)
Myalgia (4%)
Sinusitis (4%)
Memory disorder (3%)
Visual disturbance (3%)
Pharyngitis (3%)
Lightheadedness (2%)
Palpitation (2%)
Rash (2%)
Constipation (2%)
Depression (2%)
Drowsiness (2%)
Asthenia (1%)
Diarrhea (1%)
Dry mouth (1%)
Flu-like symptoms (1%)
Postmarketing reports
Respiratory depression
Sublingual tablet: Oral ulcers, blisters, and mucosal inflammation
Warnings
Contraindications
Contraindicated in patients with known hypersensitivity to zolpidem; observed reactions include anaphylaxis and angioedema
Cautions
The risk of next-day psychomotor impairment, including impaired driving, is increased if taken with less than a full night of sleep remaining (7 to 8 hours); if a higher than the recommended dose is taken; if co-administered with other CNS depressants or alcohol; or if co-administered with other drugs that increase blood levels of zolpidem; patients should be warned against driving and other activities requiring complete mental alertness if drug taken in these circumstances
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression; dosage adjustments of zolpidem and of other concomitant CNS depressants may be necessary when zolpidem is administered with such agents because of the potentially additive effects; the use of zolpidem with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended
Vehicle drivers and machine operators should be warned that, there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness and impaired driving the morning after therapy; to minimize risk, a full night of sleep (7-8 hours) recommended; this next-morning impairment is highest for the extended-release dosage form and is more prevalent in women because they eliminate more slowly than men
Can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries; severe injuries such as hip fractures and intracranial hemorrhage have been reported
Use caution in patients with history of drug dependence (increases risk of abuse)
Food increases time to attain peak plasma level and decreases peak plasma concentration
Need to evaluate for comorbid diagnoses; reevaluate if insomnia persists after 7-10 days of use
Severe anaphylactic/anaphylactoid reactions including angioedema and anaphylaxis reported; do not rechallenge if such reactions occur
Abnormal thinking, behavioral changes, complex behaviors: May include “sleep driving” and hallucinations; coadministration of alcohol and other CNS depressants appears to increase the risk of such behaviors
Do not use with alcohoL
Use can impair respiratory drive, alertness, and motor coordination; if used in combination with other CNS depressants, dose reductions of 50% may be needed due to additive effects
Consider risk of respiratory depression before prescribing in patients with compromised regulatory functions
Worsening of depression or suicidal thinking may occur; prescribe the least amount feasible to avoid intentional overdose
Withdrawal symptoms may occur with rapid dose reduction or discontinuation
Use lower dose in elderly/debilitated patients due to impaired motor, cognitive performance and increased sensitivity
Use with caution and monitor closely in patients with hepatic impairment, mild to moderate COPD, impaired drug metabolism or hemodynamic responses, or mild to moderate sleep apnea
Use with caution in patients with myasthenia gravis
Pregnancy and lactation
Pregnancy category: C; cases of severe neonatal respiratory depression reported when zolpidem used near term, especially when taken with other CNS depressants
Lactation: Very low amounts secreted in breast milk; effect on infant unknown; use caution; advise mother to observe breastfeeding infant for lethargy, increased sedation, and changes in feeding habits
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ambien, Ambien CR (zolpidem)
Mechanism of action
Imidazopyridine; modulates omega-1 type GABA receptor via selective antagonism, resulting in increased chloride conductance, neuronal hyperpolarization, inhibition of action potential, and a decrease in neuronal excitability that in turn produce sedative and hypnotic effects
Absorption
Bioavailability: 70%
Peak plasma time: 1.6 hr (immediate-release); 1.5 hr (extended-release); 0.9 hr (spray); 1.4 hr (sublingual Edluar); 0.6-1.3 hr (sublingual Intermezzo)
Peak plasma time delayed by food intake
Peak plasma concentration: (5 mg dose) 59 ng/mL; (10 mg) 121 ng/mL; (12.5 mg CR) 134 ng/mL
Distribution
Protein bound: 92.5%
Metabolism
Metabolized by CYP3A4 (60%), CYP2C9 (22%), CYP1A2 (14%), CYP2D6 (3%), CYP2C (3%)
Metabolized to inactive metabolites
Elimination
Half-life
- Immediate release: 2.5 hr (normal liver function); 9.9 hr (cirrhosis)
- Spray: 1.7-8.4 hr
- Sublingual: 1.4-6.7 hr
Excretion
- Urine (48-67%)
- Feces (29-42%)
Administration
Oral Administration
Extended-release tablet: Swallow whole; do not chew, crush, or split
