Zolpidem

Zolpidem is used to treat sleep problems (insomnia) in adults. It helps you fall asleep faster and stay asleep longer, so you can get a better night's sleep. It may also reduce the number of times you wake up during the night. Zolpidem belongs to a class of drugs called sedative-hypnotics. It acts on your brain to produce a calming effect.

Zolpidem is available under the following different brand names: Ambien, Ambien CR, Edluar, Intermezzo, and Zolpimist.

Adult Dosage Forms and Strengths

Tablet, immediate-release: Schedule IV

• 5 mg (Ambien)
• 10 mg (Ambien)

Tablet, extended-release: Schedule IV

• 6.25 mg (Ambien CR)
• 12.5 mg (Ambien CR)

Tablet, sublingual: Schedule IV

• 1.75 mg (Intermezzo)
• 3.5 mg (Intermezzo)
• 5 mg (Edluar)
• 10 mg (Edluar)

Oral spray: Schedule IV

• 5 mg/spray (Zolpimist)

Dosage Considerations – Should be Given as Follows:

Not recommended for pediatric use.

Insomnia

Sleep initiation

Immediate-release tablet, sublingual tablet, and oral spray

• Dosing for orally (Ambien), sublingually (SL) (Edluar), and oral spray (Zolpimist)
• Women: 5 mg orally/sublingual/oral spray at bedtime
• Men: Consider 5 mg orally/sublingual/oral spray at bedtime; may use 10 mg orally/sublingual/oral spray at bedtime if needed

Extended-release (Ambien CR)

• Women: 6.25 mg orally at bedtime
• : Consider 6.25 mg orally at bedtime; may use 12.5 mg orally at bedtime; not to exceed 12.5 mg/day

Dosing considerations (Ambien, Ambien CR)

• lowest effective dose; take only once per night immediately before bedtime with at least 7-8 hours 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 re-administered during same night

Geriatric dosing

Immediate-release, oral spray: 5 mg orally/sublingually immediately before bedtime

Extended-release: 6.25 mg orally immediately before bedtime

Insomnia (Intermezzo)

Insomnia when a middle of the night awakening is followed by difficulty returning to sleep

Women: 1.75 mg sublingually (SL) as needed; not to exceed 1 dose/night

Men: 3.5 mg SL as needed; not to exceed 1 dose/night

Geriatric: Men and women: 1.75 mg sublingually as needed; not to exceed 1 dose/night

Dosing considerations (Intermezzo)

• Use only when 4 hours or more 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 as needed; 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 hours or more remain before awakening

Geriatric dosing considerations

Drug of choice when hypnotic indicated in elderly

Ambien, Ambien CR: Use lowest effective dose; take only once per night immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening

Intermezzo: Use only when 4 hours or more of bedtime remain before awakening; do not take if alcohol has been consumed or with any other sleep aid

Side effects associated with use of Zolpidem, include the following:

• Dizziness
• Headache
• Drowsiness
• Allergy
• Hallucinations
• Muscle pain
• Sinus infection (sinusitis)
• Memory disorder
• Visual disturbance
• Sore throat
• Lightheadedness
• Palpitations
• Rash
• Constipation
• Depression
• Drowsiness
• Weakness
• Diarrhea
• Dry mouth
• Flu-like symptoms

Postmarketing side effects of zolpidem reported include:

• Respiratory depression
• Sublingual tablet: Oral ulcers, blisters, and mucosal inflammation
• Liver and biliary system: Acute hepatocellular, cholestatic or mixed liver injury with or without jaundice (i.e., bilirubin greater than 2x ULN, alkaline phosphatase greater than or equal to 2x ULN, transaminase greater than or equal to 5x ULN)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe Interactions of Zolpidem Include:

• sodium oxybate

Serious Interactions of zolpidem include:

• fentanyl
• fentanyl intranasal
• fentanyl iontophoretic transdermal system
• fentanyl transdermal
• fentanyl transmucosal
• idelalisib
• ivacaftor
• nefazodone
• valerian

Zolpidem has moderate interactions with at least 30 different drugs.

Zolpidem has mild interactions with at least 98 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

• This medication contains zolpidem. Do not take Ambien, Ambien CR, Edluar, Intermezzo, or Zolpimist if you are allergic to zolpidem or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Contraindicated in patients with known hypersensitivity to zolpidem; observed reactions include anaphylaxis and angioedema

Short-Term Effects

• 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.
• 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.
• See "What Are Side Effects Associated with Using Zolpidem?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Zolpidem?”

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 re-challenge if such reactions occur
• Abnormal thinking, behavioral changes, complex behaviors: May include “sleep driving” and hallucinations; co-administration 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
• GABA agonists such as zolpidem tartrate have been associated with precipitation of hepatic encephalopathy in patients with hepatic insufficiency; patients with hepatic insufficiency do not clear zolpidem tartrate as rapidly as patients with normal hepatic function; avoid zolpidem use in patients with severe hepatic impairment as it may contribute to encephalopathy

Pregnancy and Lactation

• Use zolpidem with caution during pregnancy if benefits outweigh risks
• Animal studies show risk and human studies not available or neither animal nor human studies done
• Cases of severe neonatal respiratory depression reported when zolpidem is used near term, especially when taken with other CNS depressants
• Very low amounts of zolpidem are secreted in breast milk; the effect on infants is unknown; use caution if breastfeeding; advise mother to observe breastfeeding infant for lethargy, increased sedation, and changes in feeding habits