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Zolpidem: Pediatric drug information

Zolpidem: Pediatric drug information
(For additional information see "Zolpidem: Drug information" and see "Zolpidem: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Complex sleep behaviors:

Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following the use of zolpidem. Some of these events may result in serious injuries, including death. Discontinue zolpidem immediately if a patient experiences a complex sleep behavior.

Brand Names: US
  • Ambien;
  • Ambien CR;
  • Edluar;
  • Intermezzo [DSC];
  • Zolpimist
Brand Names: Canada
  • APO-Zolpidem ODT;
  • MINT-Zolpidem ODT;
  • PMS-Zolpidem ODT;
  • Sublinox
Therapeutic Category
  • Nonbenzodiazepine Benzodiazepine Receptor Agonist
Dosing: Pediatric

Note: The lowest effective dose should be used; higher doses may be more likely to impair next-morning activities.

Insomnia

Insomnia:

Children and Adolescents ≤17 years: Limited data available; efficacy results variable and have not been demonstrated in randomized placebo-controlled trials (Anand 2017). Oral: Immediate-release tablets: Usual reported dose: 0.25 mg/kg at bedtime; maximum dose: 10 mg/dose (Blumer 2008; Blumer 2009; Hanna 2018); dosing based on reported experience from an open-label, dose escalation pharmacokinetic evaluation showed zolpidem was well-tolerated in pediatric patients 2 to 18 years of age and recommended a dose of 0.25 mg/kg at bedtime for evaluation in future efficacy trials (Blumer 2008). However, zolpidem has not been shown to be effective in a randomized placebo-controlled trial (n=201) of children aged 6 to 17 years with ADHD-associated insomnia; zolpidem 0.25 mg/kg/dose (maximum dose: 10 mg) administered nightly did not decrease sleep latency; in addition, hallucinations occurred in 7.4% of patients (Blumer 2009). A comparative, randomized controlled trial of zolpidem and haloperidol in pediatric burn patients (n=40, mean age: 9.4 ± 0.7 years) showed zolpidem dosed at 0.5 mg/kg nightly for 1 week (maximum dose: 20 mg) minimally increased Stage 3/4 sleep and REM but not total sleep time; the authors no longer use zolpidem to try to improve sleep in their pediatric burn patients (Armour 2008). A retrospective study compared effectiveness of zolpidem (no dose noted in study) in pediatric burn patients (n=46, mean age: 11 ± 3.7 years) with and without ADHD and found that sleep dysfunction was similar between the groups and those with ADHD required a sleep medication change sooner, concluding that zolpidem was not an effective drug in managing sleep in pediatric burn patients with or without ADHD (Cronin 2015). A prospective, randomized double-blind clinical trial of children between ages 2 to 9 years reported that zolpidem at 0.25 mg/kg (maximum dose: 10 mg/dose) was similar to midazolam with regards to anxiety scoring and inferior with regard to mask acceptance score when used as premedication for perioperative anxiety (Hanna 2018).

Adolescents ≥18 years (non-debilitated patients): Note: The lowest effective dose should be used; higher doses may be more likely to impair next morning activities.

Oral:

Immediate-release tablet (eg, Ambien), spray (Zolpimist): 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum dose: 10 mg/dose.

Extended-release tablet (eg, Ambien CR): 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime; maximum dose: 12.5 mg/dose.

Sublingual tablet:

Edluar: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum daily dose: 10 mg/day.

Intermezzo: Note: Should be taken if patient awakens in middle of night, has difficulty returning to sleep, and has at least 4 hours left before waking.

Females: 1.75 mg once per night as needed; maximum dose: 1.75 mg/night.

Males: 3.5 mg once per night as needed; maximum dose: 3.5 mg/night.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, no adjustment may be necessary.

Hemodialysis: Not dialyzable.

Dosing: Hepatic Impairment: Pediatric

Adolescents ≥ 18 years:

Immediate-release tablet:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Avoid use

Extended-release tablet:

Mild to moderate impairment: 6.25 mg immediately before bedtime

Severe impairment: Avoid use

Oral spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar: 5 mg immediately before bedtime

Intermezzo: Females and males: 1.75 mg once per night as needed. Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Dosing: Adult

(For additional information see "Zolpidem: Drug information")

Insomnia

Insomnia:

Note: Limit long-term use (>4 weeks) to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (ACP [Qaseem 2016]; ESRS [Riemann 2017]). Use of the higher dose can increase the risk of next-day impairment of driving and activities requiring full alertness.

Sleep-onset insomnia:

ER tablet: Oral: Initial: 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime with ≥7 to 8 hours of planned sleep before waking. Use lowest effective dose, not to exceed 12.5 mg.

IR tablet, spray, sublingual tablet: Oral: Initial: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime with ≥7 to 8 hours of planned sleep before waking. Use lowest effective dose, not to exceed 10 mg.

Sleep-maintenance insomnia, 7 to 8 hours planned sleep:

ER tablet: Oral: Initial: 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime with ≥7 to 8 hours of planned sleep before waking. Use lowest effective dose, not to exceed 12.5 mg.

IR tablet, spray, sublingual tablet (off-label use): Oral: Initial: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime with ≥7 to 8 hours of planned sleep before waking. Use lowest effective dose, not to exceed 10 mg.

Sleep-maintenance insomnia, awakening with 4 hours planned sleep: IR sublingual tablet: Oral: 1.75 mg (females) or 1.75 to 3.5 mg (males) once per night upon awakening in the middle of the night with ≥4 hours of planned sleep remaining.

Discontinuation of therapy: Reduce by the smallest available dosage form every week or every other week; ER tablets cannot be split. For patients taking higher doses of zolpidem (eg, 10 to 12.5 mg/day) for an extended period, tapering zolpidem even more slowly in conjunction with cognitive behavioral therapy for insomnia is encouraged (Bélanger 2009). Because the ER tablets cannot be split, the taper is generally done with IR tablets.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Fillastre 1993; manufacturer's labeling).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Fillastre 1993; manufacturer's labeling): No supplemental dose or dosage adjustment necessary (expert opinion).

Peritoneal dialysis: Unlikely to be significantly dialyzed: No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

ER tablet:

Mild to moderate impairment: 6.25 mg immediately before bedtime.

Severe impairment: Avoid use.

IR tablet:

Mild to moderate impairment: 5 mg immediately before bedtime.

Severe impairment: Avoid use.

Oral spray: 5 mg immediately before bedtime.

Sublingual tablet:

Edluar: 5 mg immediately before bedtime.

Intermezzo: Females and males: 1.75 mg once per night as needed. Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Sublinox [Canadian product]:

Mild to moderate impairment: 5 mg immediately before bedtime.

Severe impairment: Use is contraindicated.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Oral, as tartrate:

Zolpimist: 5 mg/actuation (4.5 mL [DSC], 7.7 mL [DSC]) [contains benzoic acid, propylene glycol]

Zolpimist: 5 mg/actuation (4.5 mL, 7.7 mL) [contains benzoic acid, propylene glycol; cherry flavor]

Tablet, Oral, as tartrate:

Ambien: 5 mg [contains fd&c red #40 (allura red ac dye), polysorbate 80]

Ambien: 10 mg

Generic: 5 mg, 10 mg

Tablet Extended Release, Oral, as tartrate:

Ambien CR: 6.25 mg

Ambien CR: 12.5 mg [contains fd&c blue #2 (indigotine)]

Generic: 6.25 mg, 12.5 mg

Tablet Sublingual, Sublingual, as tartrate:

Edluar: 5 mg, 10 mg [contains saccharin sodium]

Intermezzo: 1.75 mg [DSC]

Generic: 1.75 mg, 3.5 mg

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Sublingual, Sublingual, as tartrate:

Sublinox: 5 mg, 10 mg [contains saccharin sodium]

Generic: 5 mg, 10 mg

Dosage Forms Considerations

Zolpimist oral spray 4.5 mL containers contain 30 actuations and 7.7 mL containers contain 60 actuations.

Controlled Substance

C-IV

Administration: Pediatric

Oral:

All formulations: Regardless of dosage form, do not administer with or immediately after a meal (may delay onset). With the exception of Intermezzo, zolpidem should be taken as a single dose immediately before bedtime (due to rapid onset) with at least 7 to 8 hours remaining before planned time of awakening and should not be readministered during the same night. Intermezzo should be taken in bed if patient awakens in the middle of the night (ie, if ≥4 hours left before waking) and there is difficulty in returning to sleep.

Extended-release tablets (Ambien CR): Swallow whole; do not divide, crush, or chew.

Sublingual tablets (Edluar, Intermezzo): Examine blisterpack before use; do not use if blisters are broken, torn, or missing. Separate individual blisters at perforation; peel off top layer of paper; push tablet through foil. Place under the tongue and allow to disintegrate; do not swallow or administer with water.

Oral spray (Zolpimist): Spray directly into the mouth over the tongue. Prior to initial use, pump should be primed by spraying 5 times. If pump is not used for at least 14 days, reprime pump with 1 spray.

Administration: Adult

Oral: Administer immediately before bedtime due to rapid onset of action. Regardless of dosage form, do not administer with or immediately after a meal (may delay onset). With the exception of Intermezzo, zolpidem should be taken as a single dose at bedtime with at least 7 to 8 hours remaining before planned time of awakening and should not be readministered during the same night. Intermezzo should be taken in bed if patient awakes in the middle of the night (ie, if ≥4 hours left before waking) and there is difficulty in returning to sleep.

ER tablet: Swallow tablet whole; do not divide, crush, or chew.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet, sublingual tablet, and oral spray formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Sublingual tablet: Place sublingual tablet under the tongue and allow to disintegrate; do not swallow or administer Edluar or Sublinox with water.

Oral spray: Spray directly into the mouth over the tongue. Prior to initial use, prime pump by spraying 5 times. If pump is not used for at least 14 days, reprime pump with 1 spray.

Storage/Stability

IR and sublingual tablets: Store at 20°C to 25°C (68°F to 77°F). Protect sublingual tablets from light and moisture.

ER tablet: Store at 15°C to 25°C (59°F to 77°F); limited excursions permitted up to 30°C (86°F).

Oral spray: Store upright at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Avoid prolonged exposure to temperatures >30°C (86°F).

Sublingual tablet (Sublinox [Canadian product]): Store at 15°C to 30°C (59°F to 86°F); protect from light and moisture.

Use

Oral:

Tablets:

Immediate release (eg, Ambien): Short-term treatment of insomnia (with difficulty of sleep onset) (FDA approved in age ≥18 years and adults).

Extended release (eg, Ambien CR): Treatment of insomnia (with difficulty of sleep onset and/or sleep maintenance) (FDA approved in age ≥18 years and adults).

Sublingual:

Edluar: Short-term treatment of insomnia (with difficulty of sleep onset) (FDA approved in age ≥18 years and adults).

Intermezzo: "As needed" treatment of middle-of-the-night insomnia with ≥4 hours of sleep time remaining (FDA approved in age ≥18 years and adults).

Oral spray: Zolpimist: Short-term treatment of insomnia (with difficulty of sleep onset) (FDA approved in age ≥18 years and adults).

Medication Safety Issues
Sound-alike/look-alike issues:

Ambien may be confused with Abilify, Ativan, Ambi 10

Sublinox may be confused with Suboxone

Zolpidem may be confused with lorazepam, zaleplon, Zyloprim

Older Adult: High-Risk Medication:

Beers Criteria: Zolpidem, a nonbenzodiazepine benzodiazepine-receptor agonist hypnotic, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to adverse events similar to benzodiazepines in older adults (eg, delirium, falls, fractures) and an increase in emergency room visits, hospitalizations, and motor vehicle crashes. In addition, improvement in sleep latency and duration is minimal (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Zolpidem (when cumulative day supply is >90 days) is identified as a high-risk medication in patients 65 years and older on the PQA’s, Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).

International issues:

Ambien [US, Argentina, Israel] may be confused with Amyben brand name for amiodarone [Great Britain]

Adverse Reactions (Significant): Considerations
CNS depression

Sedative-hypnotic agents, including zolpidem, are associated with next-day drowsiness, and decreased mental alertness (Ref). In patients taking zolpidem, these effects have led to impaired driving, accidental injury, and trauma, such as motor vehicle accidents, falling, bone fracture (including femoral neck fracture), and intracranial injuries (Ref). Patients may feel fully awake, despite this impairment in mental alertness. Zolpidem is included in the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (Ref).

Mechanism: Serum concentration-related; related to the pharmacologic action (ie, sedative-hypnotic effects).

Onset: Rapid; occurs within 24 hours after dose; may occur after the first dose (Ref).

Risk factors:

• Conditions or states leading to increased serum concentrations (eg, age ≥65 years, females) (Ref)

• Concurrent CNS depressants (eg, medications, alcohol)

• Concurrent drugs that increase zolpidem concentrations (eg, CYP 3A4 inhibitors)

• Extended-release formulation (Ref)

• Sleeping less than 7 to 8 hours after zolpidem administration

Complex sleep behaviors

Complex sleep-related disorder may occur, including somnambulism, and eating, driving, cooking, and having sex while sleeping have been reported (Ref). Patients usually have no recollection of these sleep-related behaviors (Ref). In some cases, these behaviors led to serious injury or death (Ref). Non-fatal effects were reversible upon drug discontinuation (Ref).

Mechanism: Dose-related; idiosyncratic (Ref).

Onset: Varied; typically occurs 30 minutes after a single dose (Ref). May occur after years of therapy (Ref).

Risk factors:

• Dose: May occur at any dose; more likely with higher doses (Ref)

• Females (Ref)

• Concurrent use of serotonergic antidepressants (Ref)

• Concurrent use of alcohol or CNS depressants (Ref)

• Concurrent use of CYP3A4 inhibitors (Ref)

• Preexisting sleep disorder (eg, obstructive sleep apnea, restless leg syndrome) (Ref)

• Administration earlier than immediately before sleep (Ref)

• Substance use disorder (Ref)

Other psychiatric/behavioral effects

Various other psychiatric and behavioral effects (aside from complex sleep-related disorder; see above for more information) have been reported, including hallucination (visual and auditory), delirium, abnormality in thinking, increased aggressive behavior, disinhibition, bizarre behavior, agitation, amnesia, anxiety, and worsening of depression in pediatric and adult patients (Ref). These effects have occurred unpredictably in patients with and without previously diagnosed psychiatric illness or risk factors. Hallucination was reported more frequently with zolpidem than placebo in pediatric patients treated for insomnia associated with attention-deficit/hyperactivity disorder (ADHD) (Ref). These effects were reversible upon discontinuation (Ref).

Mechanism: Dose-related; idiosyncratic (Ref).

Onset: Varied; typically occurs within 15 to 30 minutes after initial dose (Ref).

Risk factors:

• Dose: May occur at any dose; more likely with higher doses (Ref)

• Females (Ref)

• Age ≥65 years (Ref)

• Concurrent psychoactive medications (eg, SSRIs, opioids, other anti-anxiety or insomnia medications) (Ref)

• Concurrent alcohol (Ref)

• Concurrent ADHD, neurodevelopmental disorder, or other underlying psychiatric illness (Ref)

• Substance use disorder (Ref)

Suicidal ideation and behavior

Suicidal ideation and suicidal tendencies have occurred in patients with and without previously diagnosed psychiatric illness (Ref). May be related to zolpidem-induced “dream-like” confusion, bizarre behavior, hallucination, or paranoia (Ref). Some reports have been connected to complex sleep-related disorder (see above for more information) (Ref).

Mechanism: Dose-related; idiosyncratic (Ref).

Onset: Intermediate; typically occurs within the first 7 days of therapy (Ref).

Risk factors:

• Dose: May occur at any dose; more likely with higher doses (Ref)

• History of psychiatric illness (eg, anxiety, bipolar disorder, depression, schizophrenia) (Ref)

• Concurrent alcohol or illicit drug use (Ref)

Withdrawal

Withdrawal symptoms following discontinuation of GABA-mediate (GABAergic) medications are generally mild and infrequent (Ref). Transient rebound sleep disturbances (eg, longer sleep-onset latency and increased awakenings) may occur for 1 to 2 days after discontinuation (Ref). Less commonly, a withdrawal syndrome, with symptoms including abdominal cramps, anxiety, disorientation, dysphoria, insomnia, irritability, muscle cramps, restlessness, seizures, sweating, tremor, and vomiting may occur, especially after rapid dose decreases or abrupt discontinuation of chronic supratherapeutic doses (Ref). Withdrawal syndrome symptoms generally resolve within a few weeks of drug discontinuation or with resumption of therapy (Ref).

Mechanism: Withdrawal; long-term therapy induces changes in the GABAA benzodiazepine receptor that decrease the effects of endogenous GABA after drug discontinuation (Ref). Chronic use of supratherapeutic zolpidem doses may result in loss of receptor selectivity and benzodiazepine-like drug effects (Ref). Therefore, rapid dose decreases or abrupt discontinuation may mimic benzodiazepine withdrawal.

Onset: Rapid; typically occurs within 48 hours of rapid dose decrease or abrupt drug discontinuation (Ref).

Risk factor:

• Chronic administration of supratherapeutic doses (eg, >100 mg/day for months to years) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with oral administration, unless otherwise noted.

>10%: Nervous system: Dizziness (1% to 12%) (Blumer 2009), drowsiness (2% to 15%) (table 1), headache (oral: 7% to 19%; sublingual: 3%)

Zolpidem: Adverse Reaction: Drowsiness

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

15%

2%

12.5 mg

Extended-release oral

102

110

8%

5%

≤10 mg

Immediate-release oral

152

161

2%

0%

≤10 mg

Immediate-release oral

685

473

1% to 10%:

Cardiovascular: Chest discomfort (1%), chest pain (1%), edema (≤1%), hypertension (≤1%), increased blood pressure (1%), orthostatic hypotension (≤1%), palpitations (2%), syncope (≤1%), tachycardia (≤1%)

Dermatologic: Diaphoresis (≤1%), pallor (≤1%), pruritus (≤1%), skin rash (1% to 2%), urticaria (≤1%), wrinkling of skin (1%)

Endocrine & metabolic: Heavy menstrual bleeding (1%), hyperglycemia (≤1%), increased thirst (≤1%), menstrual disease (≤1%)

Gastrointestinal: Abdominal distress (1%), abdominal tenderness (1%), anorexia (≤1%), change in appetite (1%), constipation (2%), diarrhea (1% to 3%), dysgeusia (≤1%), dyspepsia (>1%), dysphagia (≤1%), flatulence (≤1%), frequent bowel movements (1%), gastroenteritis (1%) (Blumer 2009), gastroesophageal reflux disease (1%), hiccups (>1%), nausea (7%), vomiting (1%), xerostomia (3%)

Genitourinary: Cystitis (≤1%), urinary incontinence (≤1%) (Blumer 2009), urinary tract infection (>1%), vaginitis (≤1%)

Hematologic & oncologic: Bruise (1%)

Hepatic: Abnormal hepatic function tests (≤1%)

Hypersensitivity: Hypersensitivity reaction (4%)

Infection: Infection (≤1%), influenza (3%)

Nervous system: Abnormal dreams (1%), agitation (≤1%), amnesia (1%) (table 2), anxiety (2% to 6%) (table 3), ataxia (1%) (table 4), balance impairment (2%) (table 5), cerebrovascular disease (≤1%), cognitive dysfunction (≤1%), confusion (>1%), depersonalization (1%), depression (2%) (table 6), disinhibition (1%) (table 7), disorientation (3%), disturbance in attention (2%) (table 8), dysarthria (≤1%), eating disorder (1%; binge eating), emotional lability (≤1%), euphoria (>1%), falling (≤1%), fatigue (oral: 3%; sublingual: 1%) (table 9), hallucination (4%), hypoesthesia (2%), illusion (≤1%), increased body temperature (1%), insomnia (>1%), intoxicated feeling (3%), lethargy (3%), malaise (≤1%), memory impairment (3%), migraine (≤1%), nervousness (≤1%), paresthesia (1%), psychomotor impairment (2%), sleep disorder (1%), speech disturbance (≤1%), stress (1%), stupor (≤1%), vertigo (2%)

Zolpidem: Adverse Reaction: Amnesia

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

1%

0%

≤10 mg

Immediate-release oral

152

161

Zolpidem: Adverse Reaction: Anxiety

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

6%

3%

12.5 mg

Extended-release oral

N/A

N/A

2%

0%

12.5 mg

Extended-release oral

102

110

Zolpidem: Adverse Reaction: Ataxia

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

1%

0%

12.5 mg

Extended-release oral

102

110

Zolpidem: Adverse Reaction: Balance Impairment

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

2%

0%

12.5 mg

Extended-release oral

102

110

Zolpidem: Adverse Reaction: Depression

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

2%

0%

12.5 mg

Extended-release oral

102

110

2%

1%

≤10 mg

Immediate-release oral

152

161

Zolpidem: Adverse Reaction: Disinhibition

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

1%

0%

12.5 mg

Extended-release oral

102

110

Zolpidem: Adverse Reaction: Disturbance in Attention

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

2%

0%

12.5 mg

Extended-release oral

102

110

Zolpidem: Adverse Reaction: Fatigue

Drug (Zolpidem)

Placebo

Dose

Dosage Form

Number of Patients (Zolpidem)

Number of Patients (Placebo)

3%

2%

12.5 mg

Extended-release oral

102

110

1%

0%

3.5 mg

Sublingual

150

145

Neuromuscular & skeletal: Arthralgia (>1%), arthritis (≤1%), asthenia (1%), back pain (3% to 4%), lower limb cramp (≤1%), myalgia (4%), neck pain (1%), tremor (≤1%)

Ophthalmic: Asthenopia (1%), blurred vision (2%), diplopia (>1%), eye irritation (≤1%), eye pain (≤1%), eye redness (2%), scleritis (≤1%), visual disturbance (1% to 3%; including altered depth perception)

Otic: Labyrinthitis (1%), tinnitus (1%)

Respiratory: Bronchitis (≤1%), cough (≤1%), dyspnea (≤1%), flu-like symptoms (1% to 2%), lower respiratory tract infection (>1%), pharyngitis (3%), rhinitis (≤1%), sinusitis (4%), throat irritation (1%), upper respiratory tract infection (>1%)

Miscellaneous: Fever (≤1%), trauma (≤1%)

<1%:

Cardiovascular: Acute myocardial infarction, angina pectoris, arteritis, cardiac arrhythmia, circulatory shock, exacerbation of hypertension, extrasystoles, facial edema, flushing, hypotension, phlebitis, pulmonary embolism, thrombosis, varicose veins, ventricular tachycardia

Dermatologic: Acne vulgaris, bullous rash, dermatitis, furunculosis, skin photosensitivity

Endocrine & metabolic: Decreased libido, gout, hot flash, hypercholesteremia, hyperlipidemia, weight loss

Gastrointestinal: Alteration of saliva, dental caries, enteritis, eructation, esophageal spasm, gastritis, hemorrhoids, increased appetite, intestinal obstruction, sialorrhea, tenesmus

Genitourinary: Breast fibroadenosis, dysuria, impotence, mastalgia, nocturia, urinary frequency, urinary retention

Hematologic & oncologic: Anemia, breast neoplasm, hyperhemoglobinemia, increased erythrocyte sedimentation rate, leukopenia, lymphadenopathy, macrocytic anemia, purpuric disease, rectal hemorrhage

Hepatic: Hyperbilirubinemia, increased serum alkaline phosphatase

Hypersensitivity: Anaphylactic shock

Infection: Abscess, herpes simplex infection, herpes zoster infection

Nervous system: Abnormal gait, abnormality in thinking, aggressive behavior, altered sense of smell, apathy, delusion, dementia, drug dependence, dysphasia, hypotonia, hysteria, manic reaction, myasthenia, neuralgia, neuritis, neuropathy, neurosis, numbness of tongue, pain, panic disorder, paresis, personality disorder, restless leg syndrome, rigors, sciatica, strange feeling, yawning

Neuromuscular & skeletal: Hypokinesia, osteoarthritis, tendinopathy, tetany

Ophthalmic: Abnormal lacrimation, accommodation disturbance, conjunctivitis, corneal ulcer, glaucoma, periorbital edema, photopsia

Otic: Otitis externa, otitis media

Renal: Acute kidney injury, polyuria, pyelonephritis, renal pain

Respiratory: Bronchospasm, epistaxis, hypoxia, laryngitis, pneumonia, pulmonary edema, respiratory depression

Postmarketing:

Hepatic: Cholestatic hepatitis, hepatocellular hepatitis

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Complex sleep-related disorder (Harbourt 2020), delirium (Inagaki 2010), somnambulism (Inagaki 2010), suicidal ideation, suicidal tendencies, withdrawal syndrome (Wilson 2019)

Neuromuscular & skeletal: Bone fracture (Treves 2018), femoral neck fracture (Wang 2001)

Miscellaneous: Accidental injury (Chung 2013)

Contraindications

Hypersensitivity to zolpidem or any component of the formulation; patients who have experienced complex sleep behaviors after taking zolpidem

Canadian labeling: Additional contraindications (not in US labeling): Significant obstructive sleep apnea syndrome and acute and/or severe impairment of respiratory function; myasthenia gravis; severe hepatic impairment; personal or family history of sleepwalking

Warnings/Precautions

Disease-related concerns:

• Depression: Use with caution in patients with depression, particularly if suicidal risk may be present.

• Drug abuse: Use with caution in patients with a history of drug dependence. Risk of abuse is increased in patients with a history or family history of alcohol or drug abuse or mental illness.

• Hepatic impairment: GABA agonists, including zolpidem, have been associated with precipitation of hepatic encephalopathy in patients with hepatic impairment. Patients with hepatic impairment do not clear zolpidem as rapidly as patients with normal hepatic function. Use with caution in patients with mild to moderate hepatic impairment; dose adjustment recommended. Avoid use of immediate and extended-release tablets in patients with severe hepatic impairment; may result in encephalopathy.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Respiratory disease: Use with caution in patients with respiratory compromise, COPD, or sleep apnea.

Special populations:

• Debilitated: Use with caution in debilitated patients; potential for oversedation, impaired coordination, and confusion with use; dosage adjustment recommended.

• Older adult: Use with caution in older adult patients; dose adjustment recommended. Monitor for impaired cognitive and/or motor performance, confusion, and potential for falling.

• Females: Dosage adjustment is recommended for females; pharmacokinetic studies involving zolpidem showed a significant increase in maximum concentration and exposure in females compared to males at the same dose.

• Pediatric: When studied for the unapproved use of insomnia associated with ADHD in children, a higher incidence (~7%) of hallucinations was reported. In addition, sleep latency did not decrease compared to placebo.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate the need for psychiatric and/or medical illness reevaluation. Long-term use is not recommended; reevaluation of patient’s status should occur before extending treatment due to risk of abuse and dependence.

• Rapid onset: Because of the rapid onset of action, administer Intermezzo immediately prior to bedtime, after the patient has gone to bed and is having difficulty falling asleep, or during the middle of the night when at least 4 hours are left before waking.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Zolpidem. Management: Consider avoiding the combination of ciprofloxacin and zolpidem if possible. If combined, monitor for signs of zolpidem toxicity (eg, somnolence, dizziness, lethargy). Risk D: Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Zolpidem. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Zolpidem. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

FluvoxaMINE: May enhance the CNS depressant effect of Zolpidem. FluvoxaMINE may increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Zolpidem. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Food Interactions

Maximum plasma concentration and bioavailability are decreased with food; time to peak plasma concentration is increased; half-life remains unchanged. Management: Do not administer with (or immediately after) a meal.

Dietary Considerations

Do not administer with or immediately after a meal (may delay onset).

Pregnancy Considerations

Zolpidem crosses the placenta (Juric 2009; Saito 2021).

According to product labeling, severe neonatal respiratory depression (requiring artificial ventilation or intratracheal intubation) and sedation have been reported following maternal use late in the third trimester. Exposed neonates should be monitored for excess sedation, hypotonia, and respiratory depression. Additional adverse effects, including low birth weight or preterm delivery, have been observed in some studies (Juric 2009; Sharma 2011; Wang 2010; Wikner 2011).

Monitoring Parameters

Daytime alertness; respiratory rate; behavior profile (eg, including hallucinations and other psychiatric and/or nervous system adverse reactions, especially in pediatric patients with ADHD) (Cronin 2015)

Mechanism of Action

Zolpidem, an imidazopyridine hypnotic that is structurally dissimilar to benzodiazepines, enhances the activity of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), via selective agonism at the benzodiazepine-1 (BZ1) receptor; the result is increased chloride conductance, neuronal hyperpolarization, inhibition of the action potential, and a decrease in neuronal excitability leading to sedative and hypnotic effects. Because of its selectivity for the BZ1 receptor site over the BZ2 receptor site, zolpidem exhibits minimal anxiolytic, myorelaxant, and antiseizure properties (effects largely attributed to agonism at the BZ2 receptor site).

Pharmacokinetics (Adult data unless noted)

Onset of action: Immediate release: 30 minutes.

Duration: Immediate release: 6 to 8 hours.

Absorption: Cmax and AUC is increased by ~45% in females compared to male subjects.

Immediate release and sublingual: Rapid.

Extended release: Biphasic absorption; rapid initial absorption (similar to immediate release product); then provides extended concentrations in the plasma beyond 3 hours postadministration.

Distribution: Vd:

Children 2 to 6 years: 1.8 ± 0.8 L/kg (Blumer 2008).

Children >6 to 12 years: 2.2 ± 1.7 L/kg (Blumer 2008).

Adolescents: 1.2 ± 0.4 L/kg (Blumer 2008).

Adults: 0.54 L/kg after an IV dose (Holm 2000).

Protein binding: ~93%.

Metabolism: Hepatic methylation and hydroxylation via CYP3A4 (~60%), CYP2C9 (~22%), CYP1A2 (~14%), CYP2D6 (~3%), and CYP2C19 (~3%) to 3 inactive metabolites (Holm 2000).

Bioavailability: Immediate release: 70% (Holm 2000).

Half-life elimination:

Children 2 to 6 years: Immediate release: 1.8 hours (Blumer 2008).

Children >6 years and Adolescents: Immediate release: 2.3 hours (Blumer 2008).

Adults:

Immediate release, Extended release: ~2.5 hours (range: 1.4 to 4.5 hours); Cirrhosis: Up to 9.9 hours; Elderly: Prolonged up to 32%.

Spray: ~3 hours (range: 1.7 to 8.4).

Sublingual tablet: ~3 hours (range: 1.4 to 6.7 hours).

Time to peak, plasma:

Children 2 to 6 years: Immediate release: 0.9 hours (Blumer 2008).

Children >6 to 12 years: Immediate release: 1.1 hours (Blumer 2008).

Adolescents: Immediate release: 1.3 hours (Blumer 2008).

Adults:

Immediate release: 1.6 hours; 2.2 hours with food.

Extended release: 1.5 hours; 4 hours with food.

Spray: ~0.9 hours.

Sublingual tablet: Edluar: ~1.4 hours, ~1.8 hours with food; Intermezzo: 0.6 to 1.3 hours, ~3 hours with food.

Excretion: Urine (48% to 67%, primarily as metabolites); feces (29% to 42%, primarily as metabolites).

Clearance, apparent:

Children 2 to 6 years: 11.7 ± 7.9 mL/minute/kg (Blumer 2008).

Children >6 to 12 years: 9.7 ± 10.3 mL/minute/kg (Blumer 2008).

Adolescents: 4.8 ± 2 mL/minute/kg (Blumer 2008).

Adults: Intermezzo: Males: 4 mL/minute/kg; Females: 2.7 mL/minute/kg.

Pharmacokinetics: Additional Considerations

Hepatic function impairment: Cmax and AUC were found to be 2 and 5 times higher, respectively, in hepatically compromised patients. The mean half-life in cirrhotic patients of 9.9 hours was greater than that observed in normal subjects of 2.2 hours.

Older adult:

Immediate release: Cmax, half-life, and AUC were significantly increased when compared with results in younger adults.

Extended release: Mean Cmax and mean AUC are 70.6 ng/mL and 413 ng•h/mL, respectively, while the median Tmax is 2 hours.

Sex: Cmax and AUC were higher when comparing the same dose in women with men. Women clear zolpidem from the body at a lower rate than men. In geriatric patients, clearance is similar between men and women.

Pricing: US

Solution (Zolpimist Oral)

5 mg/ACT (per mL): $96.56

Sublingual (Edluar Sublingual)

5 mg (per each): $14.96

10 mg (per each): $15.70

Sublingual (Zolpidem Tartrate Sublingual)

1.75 mg (per each): $10.04

3.5 mg (per each): $10.04

Tablet, controlled release (Ambien CR Oral)

6.25 mg (per each): $24.56

12.5 mg (per each): $24.56

Tablet, controlled release (Zolpidem Tartrate ER Oral)

6.25 mg (per each): $1.61 - $6.12

12.5 mg (per each): $1.61 - $6.12

Tablets (Ambien Oral)

5 mg (per each): $24.56

10 mg (per each): $24.56

Tablets (Zolpidem Tartrate Oral)

5 mg (per each): $0.10 - $5.14

10 mg (per each): $4.62 - $5.14

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Adorma (CZ);
  • Ambien (BB, BM, BS, BZ, GY, IL, JM, PR, SR, TT);
  • Ambien CR (AR);
  • Ambulax-2 (IN);
  • Conyx (KR);
  • Dactive (PH);
  • Dalparan (ES);
  • Dormeben (CO);
  • Dormizol (AU);
  • Flazinil (EC);
  • Fulsadem (AR);
  • Hypnogen (EE);
  • Ivadal (AT);
  • Ivedal (ZA);
  • Jonfa (VN);
  • Le Tan (CN);
  • Lioram (BR);
  • Lunata (HR);
  • Nidraj (BD);
  • Nitrest (BD, CR, DO, GT, HN, IN, NI, PA, SV);
  • Nocte (CR, DO, GT, HN, LK, NI, PA, SV);
  • Nocte Sublingual (AR);
  • Nottem (IT);
  • Nuo Bin (CN);
  • Nytamel (IE);
  • Nyxe (ZA);
  • Oniria (GR);
  • Sanval (HR, RU);
  • Sleepman (TW);
  • Slepzol (ID);
  • Somidem (AU, MY);
  • Somit (AR, PY, UY);
  • Somnil (CL, CO);
  • Somno (PE);
  • Sove (LK);
  • Stildem (AU);
  • Stilnix (IL);
  • Stilnoct (BE, DK, FI, GB, IE, IS, LU, NL, NO, SE);
  • Stilnox (AU, BF, BG, BJ, BR, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EE, ES, ET, FR, GH, GM, GN, GR, GT, HK, HN, HU, ID, IT, JO, KE, KR, KW, LB, LR, LT, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, PA, PE, PH, PK, PL, PT, PY, QA, RO, SA, SC, SD, SK, SL, SN, SV, TN, TR, TW, TZ, UG, VE, VN, ZA, ZM);
  • Stilnox CR (BR, CO, CR, DO, GT, HN, KR, MY, NI, PA, SG, SV);
  • Sucedal (EC);
  • Vicknox (HK);
  • Ziohex (PH);
  • Zodenox (MY);
  • Zodium (EG);
  • Zodorm (IL);
  • Zoldem (AT, BD, DE, IE);
  • Zoldorm (CH);
  • Zoldox (TW);
  • Zolep (HU);
  • Zoliprex (LK);
  • Zolmia (ID);
  • Zolnod (IE);
  • Zolnox (PY, UY);
  • Zolpicin (TW);
  • Zolpid (BD, KR);
  • Zolpihexal (ZW);
  • Zolpinox (DE);
  • Zolpirest (PH);
  • Zolpista (EG);
  • Zolpitop (BE);
  • Zolsana (BG);
  • Zonoct (DK);
  • Zopidem (TW);
  • Zopim (MY);
  • Zorimin (TW)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767. [PubMed 30693946]
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  22. Edluar (zolpidem tartrate sublingual tablet) [prescribing information]. Somerset, NJ: Meda Pharmaceuticals Inc; September 2021.
  23. FDA Drug Safety Communication. Risk of next‐morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). Food and Drug Administration website. https://www.fda.gov/files/drugs/published/Drug-Safety-Communication--Risk-of-next-morning-impairment-after-use-of-insomnia-drugs--FDA-requires-lower-recommended-doses-for-certain-drugs-containing-zolpidem-%28Ambien--Ambien-CR--Edluar--and-Zolpimist%29.pdf. January 10, 2013. Accessed March 3, 2021.
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  27. Greenblatt DJ, Harmatz JS, Roth T, et al. Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults. Clin Ther. 2013;35(5):604-611. doi:10.1016/j.clinthera.2013.03.007 [PubMed 23541711]
  28. Grzegorzewska AM, Landowski JJ, Cubala WJ. Clinical considerations of sleep related amnestic behaviours associated with zolpidem. Farmakoterapia w Psychiatrii i Neurologii. 2020;36(1):23–31. doi:10.33450/fpn.2020.04.001
  29. Gunja N. In the Zzz zone: the effects of Z-drugs on human performance and driving. J Med Toxicol. 2013;9(2):163-171. doi:10.1007/s13181-013-0294-y [PubMed 23456542]
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