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Zolpidem

Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA Class: CN309
Chemical Name: Imidazo(1,2-a)pyridine-3-acetamide,N,N,6-trimethyl-2-(4-methylphenyl)-,(R-(R*,R*))-2,3-dihydroxybutanedioate (2:1)
Molecular Formula: C19H21N3O•½C4H6O
CAS Number: 103188-50-7
Brands: Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist

Medically reviewed by Drugs.com. Last updated on Oct 21, 2019.

Warning

    Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors
  • Serious injuries and/or death resulting from complex sleep behaviors (e.g., sleepwalking, sleep driving, and engaging in other activities while not fully awake) can occur following use of eszopiclone, zaleplon, and zolpidem.

  • Complex sleep behaviors have occurred in patients with and without a history of such behaviors and can occur even at the lowest recommended doses and after just one dose of these drugs.

  • Discontinue drug if a complex sleep behavior occurs. (See Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors under Cautions.)

Introduction

Imidazopyridine-derivative sedative and hypnotic; type A GABA (GABAA)-receptor agonist; structurally unrelated to benzodiazepines and other sedatives and hypnotics.

Uses for Zolpidem

Insomnia

Conventional tablets, oral spray, or sublingual tablets (Edluar) used for short-term management of insomnia characterized by difficulties with sleep initiation. Decreases sleep latency in patients with chronic or transient insomnia; no substantial evidence of diminished effectiveness during the end of each night’s use (early morning insomnia) despite short half-life.

Extended-release tablets used for management of insomnia characterized by difficulty with sleep onset or sleep maintenance. May not be an appropriate treatment choice for patients (men or women) who need to drive or perform activities that require full alertness the next morning (see CNS Depression and Next-day Impairment under Cautions).

Sublingual tablets (Intermezzo) used as needed for management of insomnia when middle-of-the-night awakening is followed by difficulty returning to sleep; for use only when ≥4 hours remain before planned time of awakening.

Zolpidem Dosage and Administration

General

  • Reevaluate patient if zolpidem is to be used for more than 2–3 weeks. (See Adequate Patient Evaluation under Cautions.)

  • Consider gradual dosage reduction (e.g., over several nights) when discontinuing therapy. (See Withdrawal Effects under Cautions.)

Administration

Administer orally (as conventional tablets, extended-release tablets, or an oral solution using a metered-dose spray pump) or sublingually (as sublingual tablets).

Oral Administration

Do not administer with or immediately after a meal in order to facilitate onset of sleep. (See Food under Pharmacokinetics.)

Conventional Tablets

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.

Extended-release Tablets

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.

Swallow extended-release tablets whole; do not divide, crush, or chew.

Oral Spray

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.

Consult the manufacturer’s patient instructions for detailed information on use of the spray pump.

Prior to initial use, prime spray pump by actuating 5 sprays. If not used for ≥14 days, prime spray pump again by actuating 1 spray.

To administer, hold container upright with spray opening pointed directly into the mouth and fully press down on pump to ensure that a full dose is sprayed directly into the mouth over the tongue. Administer 1 or 2 sprays (5 mg per spray) based on indicated dose.

Each 8.2-g container delivers about 60 metered sprays after initial priming. Number of available doses depends on number of sprays per dose and frequency of priming. Discard oral spray when labeled number of actuations (60 sprays) used.

No special requirements for cleaning and maintaining the spray pump.

Sublingual Administration

Do not administer with or immediately after a meal in order to facilitate onset of sleep. (See Food under Pharmacokinetics.)

Sublingual Tablets (Edluar)

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.

Place tablet under tongue, where it will disintegrate. Do not swallow or administer tablet with water.

Sublingual Tablets (Intermezzo)

Administer in bed, only once per night as needed if middle-of-the-night awakening is followed by difficulty returning to sleep, and only if ≥4 hours remain before planned time of awakening.

Place tablet under tongue and allow to disintegrate completely before swallowing. Do not swallow tablet whole.

Remove tablet from pouch just prior to administration.

Dosage

Available as zolpidem tartrate; dosage expressed in terms of the salt.

Use the lowest effective dosage.

Adults

Insomnia
Difficulty with Sleep Initiation
Oral (Conventional Tablets, Oral Spray) or Sublingual (Edluar Sublingual Tablets)

Women: Initially, 5 mg.

Men: Initially, 5 or 10 mg.

Dose of 5 mg should be effective in most women and many men. If 5 mg is not effective in men or women, may increase dose to 10 mg.

In some patients, higher morning blood concentrations following a 10-mg dose increase risk of next-day impairment of driving and other activities requiring full alertness. (See CNS Depression and Next-day Impairment under Cautions.)

Initial doses for women and men differ because clearance is slower in women. (See Elimination: Special Populations, under Pharmacokinetics.)

Difficulty with Sleep Initiation or Sleep Maintenance
Oral (Extended-release Tablets)

Women: Initially, 6.25 mg.

Men: Initially, 6.25 or 12.5 mg.

Dose of 6.25 mg should be effective in most women and many men. If 6.25 mg is not effective in men or women, may increase dose to 12.5 mg.

In some patients, higher morning blood concentrations following a 12.5-mg dose increase risk of next-day impairment of driving and other activities requiring full alertness. (See CNS Depression and Next-day Impairment under Cautions.)

Initial doses for women and men differ because clearance is slower in women. (See Elimination: Special Populations, under Pharmacokinetics.)

Middle-of-the-Night Awakening
Sublingual (Intermezzo Sublingual Tablets)

Women: 1.75 mg.

Men: 3.5 mg.

Doses for women and men differ because clearance is slower in women. (See Elimination: Special Populations, under Pharmacokinetics and also see CNS Depression and Next-day Impairment under Cautions.)

Men or women receiving concomitant CNS depressant: 1.75 mg. (See CNS Depression and Next-day Impairment under Cautions and also see Specific Drugs under Interactions.)

Prescribing Limits

Adults

Insomnia
Difficulty with Sleep Initiation
Oral (Conventional Tablets, Oral Spray) or Sublingual (Edluar Sublingual Tablets)

Maximum 10 mg once daily immediately before bedtime.

Difficulty with Sleep Initiation or Sleep Maintenance
Oral (Extended-release Tablets)

Maximum 12.5 mg once daily immediately before bedtime.

Middle-of-the-Night Awakening
Sublingual (Intermezzo Sublingual Tablets)

Women: Maximum 1.75 mg once per night.

Men: Maximum 3.5 mg once per night.

Special Populations

Hepatic Impairment

Prolonged elimination. (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.

Extended-release tablets: 6.25 mg once daily immediately before bedtime.

Sublingual tablets (Intermezzo): 1.75 mg only once per night if needed.

Renal Impairment

Possible pharmacokinetic alterations. (See Elimination: Special Populations, under Pharmacokinetics.) Manufacturers state that dosage adjustment is not necessary; some clinicians recommend that dosage reduction be considered.

Geriatric Patients

Possible increased sensitivity to sedatives and hypnotics. (See Geriatric Use under Cautions.)

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.

Extended-release tablets: 6.25 mg once daily immediately before bedtime.

Sublingual tablets (Intermezzo): In men and women >65 years of age, 1.75 mg only once per night if needed.

Debilitated Patients

Possible increased sensitivity to sedatives and hypnotics.

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.

Extended-release tablets: 6.25 mg once daily immediately before bedtime.

Cautions for Zolpidem

Contraindications

  • History of a complex sleep behavior while taking eszopiclone, zaleplon, or zolpidem. (See Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors under Cautions.)

  • Known hypersensitivity to zolpidem.

Warnings/Precautions

Warnings

Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors

Complex sleep behaviors, in which patients engage in activities while they are not fully awake, sometimes resulting in serious injuries and/or death reported rarely with eszopiclone, zaleplon, and zolpidem. Such behaviors may include sleepwalking, sleep driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), and engaging in other activities (e.g., making phone calls, preparing and eating food). These behaviors can occur when these drugs are taken alone or with alcohol or other CNS depressants. (See Specific Drugs under Interactions.)

FDA states that serious injuries and fatalities from complex sleep behaviors have occurred in patients with and without a history of such behaviors and can occur even at the lowest recommended dosages and after just one dose of eszopiclone, zaleplon, and zolpidem. Falls with serious injuries such as intracranial hemorrhages, vertebral fractures, and hip fractures as well as fatal falls, self-injuries, accidental overdoses, hypothermia, suicide attempts and apparent completed suicides, fatal motor vehicle collisions, gunshot wounds, carbon monoxide poisoning, drowning or near drowning, burns, and homicide have been reported.

Warn patients about risk of complex sleep behaviors. Discontinue zolpidem if a complex sleep behavior occurs. (See Contraindications under Cautions and also see Advice to Patients.)

Other Warnings and Precautions

CNS Depression and Next-day Impairment

CNS depressant; may impair daytime function in some patients even when used as prescribed.

Zolpidem blood concentrations >50 ng/mL may impair driving to a degree that increases risk of a motor vehicle accident. Concentrations >50 ng/mL reported at 8 hours after a dose in 15% of women and 3% of men receiving 10 mg (as conventional tablets); in 33% of women and 25% of men receiving 12.5 mg (as extended-release tablets); and in 15% of nongeriatric women, 5% of nongeriatric men, and 10% of both geriatric men and women receiving 6.25 mg (as extended-release tablets). Some patients had concentrations ≥90 or ≥100 ng/mL. Because of these findings, bedtime dosages currently recommended by the manufacturers and FDA are lower than original labeled dosages.

Impaired driving reported when driving test administered to healthy individuals <4 hours after a 3.5-mg sublingual dose; potential driving impairment at 4 hours after recommended 1.75-mg dose in women or 3.5-mg dose in men cannot be completely excluded.

Use smallest effective dose to decrease potential risk of next-day impairment. (See Dosage under Dosage and Administration.)

Monitor patients for excessive CNS depression; however, impairment may occur in the absence of symptoms and may not be reliably detected by ordinary clinical examination (i.e., formal psychomotor testing may be required).

Concurrent use of other CNS depressants (e.g., alcohol, benzodiazepines, opiates, tricyclic antidepressants) increases risk of CNS depression. Dosage adjustments of zolpidem and concurrent CNS depressants may be necessary. (See Specific Drugs under Interactions.)

Concomitant use with other sedatives and hypnotics (including other zolpidem-containing preparations and OTC preparations used to treat insomnia [e.g., diphenhydramine, doxylamine succinate]) at bedtime or in middle of the night is not recommended. (See Specific Drugs under Interactions.)

Women appear to be more susceptible to next-day psychomotor impairment because zolpidem clearance is slower in women than in men. (See Elimination: Special Populations, under Pharmacokinetics.)

Administration as extended-release tablets increases risk of next-day impairment. Extended-release zolpidem may not be an appropriate treatment choice for patients who need to drive or perform activities that require full alertness the next morning. Drug concentrations may remain high enough the next day to impair performance. (See Advice to Patients.)

Risk of next-day impairment is increased if preparations intended for bedtime administration (e.g., conventional or extended-release tablets, oral spray, 5- or 10-mg sublingual tablets) are administered with less than 7–8 hours of sleep time remaining, if preparations intended for middle-of-the-night administration (1.75- or 3.5-mg sublingual tablets) are administered with <4 hours of sleep time remaining, if higher than recommended dose is administered, or if used concomitantly with other CNS depressants or drugs that increase zolpidem concentrations.

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new thinking or behavioral abnormalities may indicate the presence of an underlying psychiatric and/or medical condition that requires evaluation.

Sensitivity Reactions

Angioedema involving the tongue, glottis, or larynx reported following initial or subsequent doses of sedative and hypnotic drugs, including zolpidem; may result in airway obstruction and death. Anaphylaxis also reported.

Do not rechallenge with the drug if angioedema occurs.

Abnormal Thinking and Behavioral Changes

Abnormal thinking and behavioral changes (e.g., decreased inhibition, aggressiveness, uncharacteristic extroversion, bizarre behavior, agitation, depersonalization, visual and auditory hallucinations) reported in patients receiving sedative and hypnotic drugs, including zolpidem. Amnesia, anxiety, and other neuropsychiatric symptoms may occur.

Carefully and immediately evaluate any new and concerning behavioral sign or symptom.

Complex behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative and hypnotic drug, with no memory of the event), preparing and eating food, making phone calls, or having sex while not fully awake after taking a sedative and hypnotic drug, and usually with no memory of the event, reported.

Complex sleep behaviors may occur in sedative and hypnotic drug-naive or drug-experienced patients.

Increased risk of complex sleep behaviors with concomitant use of alcohol and other CNS depressants or use of the drug at doses exceeding the maximum recommended dose; however, may occur with the drug alone at therapeutic doses.

Discontinue drug if a complex sleep behavior occurs. (See Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors under Cautions.)

Depression

Worsening of depression and suicidal thoughts and actions (including completed suicides) reported in primarily depressed patients receiving sedatives and hypnotics. Suicidal tendencies may be present; intentional overdosage more frequent in such patients. Protective measures may be required. Prescribe and dispense drug in the smallest feasible quantity.

Respiratory Depression

No respiratory depressant effects reported following 10-mg doses in healthy individuals or patients with mild to moderate COPD; however, decreased oxygen saturation reported in patients with mild to moderate sleep apnea. Respiratory insufficiency reported, mostly in patients with preexisting respiratory impairment.

Use with caution in patients with compromised respiratory function; sedatives and hypnotics may depress respiratory drive.

Consider risk of respiratory depression prior to use in patients with respiratory impairment (e.g., sleep apnea, myasthenia gravis).

Withdrawal Effects

Signs and symptoms of withdrawal reported following rapid dosage reduction or abrupt discontinuance; monitor patients for tolerance and dependence.

Abuse Potential

Zolpidem tartrate 40 mg and diazepam 20 mg (as single doses) had similar effects in former drug abusers; effects of zolpidem tartrate 10 mg and placebo were difficult to distinguish. Monitor patients for abuse.

Increased risk for misuse and abuse of and addiction to zolpidem in patients with a history of addiction to or abuse of drugs or alcohol; carefully monitor such patients.

Specific Populations

Pregnancy

Category C.

No established use in labor and delivery.

Lactation

Distributed into milk in small amounts; potential effects on nursing infants are not known. Use with caution in nursing women. Closely monitor infant for increased sedation, lethargy, and changes in feeding habits.

Pediatric Use

Not recommended in pediatric patients.

Safety and efficacy not established in pediatric patients <18 years of age. Dizziness, headache, and hallucinations reported.

Geriatric Use

Pharmacokinetic changes in geriatric patients compared with younger adults. (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Potential increased sensitivity to zolpidem. Adverse effects tend to be dose related, particularly in geriatric patients. Adverse effect profile in patients ≥65 years of age receiving 6.25-mg dose (as extended-release tablets) similar to that in younger adults receiving 12.5-mg dose.

Use reduced dose to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative and hypnotic drugs. (See Geriatric Patients under Dosage and Administration.) Sedatives may cause confusion and oversedation in geriatric patients; observe closely.

Hepatic Impairment

Prolonged elimination; reduce dose. (See Hepatic Impairment under Dosage and Administration and also see Elimination: Special Populations and Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Possible pharmacokinetic alterations. (See Elimination: Special Populations, under Pharmacokinetics.) Manufacturers state that dosage adjustment is not necessary; however, some clinicians recommend that dosage reduction be considered.

Common Adverse Effects

Drowsiness, dizziness, headache, drugged feeling, next-day somnolence, fatigue, nausea, diarrhea.

Interactions for Zolpidem

Metabolized principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.

Drugs Affecting Hepatic Microsomal Enzymes

Some drugs that inhibit CYP3A may increase systemic exposure to zolpidem.

Effect of inhibitors of other CYP isoenzymes on pharmacokinetics (e.g., systemic exposure) of zolpidem not known.

Specific Drugs

Drug

Interaction

Comments

Chlorpromazine

Pharmacokinetic interactions unlikely; however, additive effects in reducing alertness and psychomotor performance

Cimetidine

No effect on zolpidem pharmacokinetics or pharmacodynamics

CNS depressants (e.g., alcohol, benzodiazepines, opiates, sedating antihistamines, sedatives and hypnotics, tricyclic antidepressants)

Increased risk of CNS depression

Extended-release zolpidem: Additive effects with concomitant use, including daytime use, of other CNS depressants

Alcohol: Additive adverse effect on psychomotor performance

Avoid concomitant use of other sedatives and hypnotics (including other zolpidem-containing preparations and OTC preparations used to treat insomnia [e.g., diphenhydramine, doxylamine succinate]) at bedtime or in middle of the night

Dosage adjustment of zolpidem and other concomitant CNS depressants may be necessary

When zolpidem used for middle-of-the-night awakening, recommended dose in men or women receiving concomitant CNS depressants is 1.75 mg; dosage adjustment of concomitant CNS depressant may be necessary

Digoxin

No effect on digoxin pharmacokinetics

Fluoxetine

Clinically important pharmacokinetic or pharmacodynamic (e.g., psychomotor function) interactions not observed in healthy individuals

Haloperidol

No effect on zolpidem pharmacokinetics or pharmacodynamics following single dose; does not exclude effect following chronic use

Imipramine

Decreased imipramine peak concentration but no other pharmacokinetic interactions; however, additive effect in reducing alertness

Itraconazole

Increased zolpidem AUC, but no changes in psychomotor performance, postural sway, or self-perceived drowsiness

Ketoconazole

Increased peak concentration, AUC, elimination half-life, and pharmacodynamic effects of zolpidem; possible increased hypnotic effects

Consider lower dose of zolpidem

Ranitidine

No effect on zolpidem pharmacokinetics or pharmacodynamics

Rifampin

Decreased AUC, peak concentration, half-life, and pharmacodynamic effects of zolpidem; possible decreased hypnotic efficacy

Sertraline

Earlier and higher peak zolpidem concentrations; possible earlier hypnotic onset and greater hypnotic effect

No clinically important effects on pharmacokinetics of sertraline or N-desmethylsertraline

Warfarin

No effect on PT in healthy individuals

Zolpidem Pharmacokinetics

Absorption

Bioavailability

Conventional tablets: Rapidly absorbed from GI tract following oral administration, with peak plasma concentrations attained in about 1.6 hours. Absolute bioavailability is about 70%.

Extended-release tablets: Exhibit biphasic absorption characteristics; rapid initial absorption following oral administration (similar to conventional tablets), but with extended plasma concentrations beyond 3 hours after administration. Peak plasma concentrations are attained in about 1.5 hours.

Oral spray: Bioequivalent to conventional tablets. Rapidly absorbed from oral mucosa and GI tract, with peak plasma concentrations attained in about 0.9 hours.

Sublingual tablets (Edluar): Bioequivalent to conventional tablets with respect to peak concentration and AUC. Rapidly absorbed, with peak plasma concentrations attained in about 82 minutes.

Sublingual tablets (Intermezzo): Rapidly absorbed, with peak plasma concentrations attained in about 35–75 minutes.

Food

Conventional tablets: Food decreases AUC by 15%, decreases peak plasma concentration by 25%, and prolongs time to peak plasma concentration by 60%.

Extended-release tablets: Food decreases AUC by 23%, decreases peak plasma concentration by 30%, and prolongs time to peak plasma concentration by about 2 hours (from 2 hours to 4 hours).

Oral spray: Food decreases AUC by 27%, decreases peak plasma concentration by 58%, and prolongs time to peak plasma concentration by 225% (from 0.8 hours to 2.6 hours).

Sublingual tablets (Edluar): Food decreases AUC by 20%, decreases peak plasma concentration by 31%, and prolongs time to peak plasma concentration by 28% (from 82 minutes to 105 minutes).

Sublingual tablets (Intermezzo): Food decreases AUC by 19%, decreases peak plasma concentration by 42%, and prolongs time to peak plasma concentration to nearly 3 hours.

Plasma Concentrations

Blood concentrations >50 ng/mL may impair driving to a degree that increases risk of a motor vehicle accident. (See CNS Depression and Next-day Impairment under Cautions.)

Special Populations

Zolpidem exposure is greater in women than in men receiving the same dose. Peak concentration and AUC are increased by 45% (for immediate-release formulation) or by 50 and 75%, respectively (for extended-release tablets), in women compared with men; concentrations 6–12 hours after a dose of extended-release zolpidem are 2–3 times higher in women than in men.

Zolpidem exposure is greater in geriatric patients than in younger adults receiving the same dose. Peak concentration and AUC are increased by 50 and 64%, respectively (for conventional tablets), and by 34 and 30%, respectively (for 3.5-mg sublingual tablets), in geriatric individuals compared with younger adults. Peak concentrations and AUC are lower in geriatric individuals receiving 1.75-mg dose than in younger adults receiving 3.5-mg dose.

In patients with chronic hepatic impairment, peak plasma concentration and AUC (for conventional tablets) are 2 and 5 times higher, respectively, than in healthy individuals. Extended-release tablets not studied to date in patients with hepatic impairment.

Distribution

Extent

Distributed into milk in small amounts.

Plasma Protein Binding

Approximately 92–93%.

Elimination

Metabolism

Metabolized in the liver via oxidation and hydroxylation, principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. No active metabolites.

Elimination Route

Excreted principally in urine as inactive metabolites.

Half-life

Approximately 2.5–3 hours.

Special Populations

Eliminated more slowly in women than in men; lower doses recommended for women since use of same dose in women and men would result in greater drug exposure and increased susceptibility to next-day impairment in women. In geriatric patients, clearance is similar in men and women, and dosage is not gender specific. (See Special Populations: Absorption, under Pharmacokinetics; see CNS Depression and Next-day Impairment under Cautions; and see Dosage under Dosage and Administration.)

In geriatric patients receiving zolpidem as conventional or extended-release tablets, half-life is 2.9 hours. Half-life in geriatric patients reportedly is increased by 32% (for conventional tablets) or unchanged (for sublingual tablets [Intermezzo]) compared with younger adults.

In patients with cirrhosis receiving zolpidem as conventional tablets, half-life is about 9.9 hours. Extended-release tablets not studied to date in patients with hepatic impairment.

In nondialyzed patients with chronic renal disease and in patients undergoing periodic dialysis, slower elimination rates reported with IV zolpidem (not commercially available in the US). No substantial pharmacokinetic alterations reported with oral zolpidem in patients with end-stage renal failure undergoing hemodialysis. Extended-release tablets not studied to date in patients with renal impairment.

Not removed by hemodialysis.

Stability

Storage

Oral

Conventional Tablets

20–25°C.

Extended-release Tablets

15–25°C (may be exposed to temperatures up to 30°C).

Oral Spray

25°C (may be exposed to 15–30°C); avoid prolonged exposure to temperatures >30°C. Store upright. Do not freeze.

Sublingual

Sublingual Tablets (Edluar)

20–25°C. Protect from light and moisture.

Sublingual Tablets (Intermezzo)

20–25°C (may be exposed to 15–30°C). Protect from moisture.

Store tablet in pouch until just prior to administration.

Actions

  • Interacts with the CNS GABA-benzodiazepine-chloride ionophore receptor complex.

  • Selectivity for the type 1 benzodiazepine (BZ1) receptor not absolute, but may account for the decreased muscle relaxant, anxiolytic, and anticonvulsant effects compared with benzodiazepines reported in animal studies, as well as the preservation of deep sleep (stages 3 and 4) reported in human studies.

Advice to Patients

  • Importance of providing patients with a copy of the medication guide and discussing the contents with every patient prior to initiation of therapy. Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.

  • Importance of informing patients and their families of the benefits and risks of zolpidem therapy.

  • Importance of informing all patients (men and women) of the potential for next-day impairment, that the risk is increased if dosing instructions are not carefully followed, and that impairment may be present despite feeling fully awake.

  • Importance of administering immediate-release zolpidem preparations intended for bedtime administration (conventional tablets, oral spray, 5- and 10-mg sublingual tablets [Edluar]) immediately before getting into bed, at least 7–8 hours before being active again. Wait ≥8 hours after taking the drug before driving or engaging in other activities requiring full mental alertness.

  • Importance of administering extended-release zolpidem immediately before getting into bed, at least 7–8 hours before being active again. Avoid driving or engaging in other activities requiring complete mental alertness the day after taking this preparation.

  • Importance of administering the 1.75- or 3.5-mg sublingual tablets (Intermezzo) in bed, only once per night as needed, if middle-of-the-night awakening is followed by difficulty returning to sleep, and only if ≥4 hours remain before planned time of awakening. Wait ≥4 hours after taking this preparation and until feeling fully awake before driving or engaging in other activities requiring full mental alertness.

  • Risk of serious injury and/or death resulting from complex sleep behaviors. Importance of discontinuing zolpidem and notifying a clinician immediately if an episode of complex sleep behavior occurs during therapy, even if it did not result in serious injury.

  • Potential risk of abnormal thinking and behavioral changes; importance of immediately informing clinician if any such changes occur.

  • Importance of immediately informing clinician of any suicidal thoughts or memory impairment.

  • Potential risk of severe anaphylactic and anaphylactoid reactions; importance of immediately seeking medical attention if manifestations of such reactions occur.

  • Importance of taking zolpidem only as prescribed; do not increase dosage unless otherwise instructed by a clinician; inform clinician if the drug is not effective.

  • Risk of withdrawal symptoms following abrupt discontinuance or rapid reduction in dosage. Importance of informing clinician of any tolerance or dependence/withdrawal symptoms.

  • Importance of not taking zolpidem with or immediately after a meal.

  • Importance of placing the zolpidem sublingual tablet (Edluar) under the tongue and allowing it to disintegrate; do not swallow or take with water.

  • Importance of placing the zolpidem sublingual tablet (Intermezzo) under the tongue and allowing it to disintegrate completely before swallowing; do not swallow whole. Remove the tablet from the pouch just prior to dosing.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses, particularly depression.

  • Importance of not taking zolpidem after consuming alcohol in the evening or before bedtime. Importance of advising patients to avoid concurrent use of other sedative and hypnotic drugs used to treat insomnia (including OTC preparations such as diphenhydramine or doxylamine succinate) or CNS depressants during therapy unless otherwise instructed by a clinician.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Zolpidem Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

5 mg/metered spray

Zolpimist (C-IV)

ECR

Tablets, extended-release, film-coated

6.25 mg

Ambien CR (C-IV)

Sanofi-Aventis

Zolpidem Tartrate Extended-release Tablets (C-IV)

12.5 mg

Ambien CR (C-IV)

Sanofi-Aventis

Zolpidem Tartrate Extended-release Tablets (C-IV)

Tablets, film-coated

5 mg

Ambien (C-IV)

Searle

Zolpidem Tartrate Tablets (C-IV)

10 mg

Ambien (C-IV)

Searle

Zolpidem Tartrate Tablets (C-IV)

Sublingual

Tablets

1.75 mg*

Intermezzo (C-IV)

Purdue

Zolpidem Tartrate Sublingual Tablets (C-IV)

3.5 mg*

Intermezzo ( C-IV)

Purdue

Zolpidem Tartrate Sublingual Tablets (C-IV)

5 mg*

Edluar (C-IV)

Meda

Zolpidem Tartrate Sublingual Tablets (C-IV)

10 mg*

Edluar (C-IV)

Meda

Zolpidem Tartrate Sublingual Tablets (C-IV)

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 21, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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